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Peer-reviewed works with DOI and abstract, discovered from MEDLINE-indexed literature. Candidates: no tier, no stated finding, not yet read.
Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews.
Background: Chronic pain is defined as pain lasting beyond normal tissue healing time, generally taken to be 12 weeks. It contributes to disability, anxiety, depression, sleep disturbances, poor quality of life, and healthcare costs. Chronic pain has a weighted mean prevalence in adults of 20%.For many years, the treatment choice for chronic pain included recommendations for rest and inactivity. However, exercise may have specific benefits in reducing the severity of chronic pain, as well as more general benefits associated with improved overall physical and mental health, and physical functioning. Physical activity and exercise programmes are increasingly being promoted and offered in various healthcare systems, and for a variety of chronic pain conditions. It is therefore important at this stage to establish the efficacy and safety of these programmes, and furthermore to address the critical factors that determine their success or failure.
Objectives: To provide an overview of Cochrane Reviews of adults with chronic pain to determine (1) the effectiveness of different physical activity and exercise interventions in reducing pain severity and its impact on function, quality of life, and healthcare use; and (2) the evidence for any adverse effects or harm associated with physical activity and exercise interventions.
Methods: We searched theCochrane Database of Systematic Reviews (CDSR) on the Cochrane Library (CDSR 2016, Issue 1) for systematic reviews of randomised controlled trials (RCTs), after which we tracked any included reviews for updates, and tracked protocols in case of full review publication until an arbitrary cut-off date of 21 March 2016 (CDSR 2016, Issue 3). We assessed the methodological quality of the reviews using the AMSTAR tool, and also planned to analyse data for each painful condition based on quality of the evidence. We extracted data for (1) self-reported pain severity, (2) physical function (objectively or subjectively measured), (3) psychological function, (4) quality of life, (5) adherence to the prescribed intervention, (6) healthcare use/attendance, (7) adverse events, and (8) death. Due to the limited data available, we were unable to directly compare and analyse interventions, and have instead reported the evidence qualitatively.
Main results: We included 21 reviews with 381 included studies and 37,143 participants. Of these, 264 studies (19,642 participants) examined exercise versus no exercise/minimal intervention in adults with chronic pain and were used in the qualitative analysis. Pain conditions included rheumatoid arthritis, osteoarthritis, fibromyalgia, low back pain, intermittent claudication, dysmenorrhoea, mechanical neck disorder, spinal cord injury, postpolio syndrome, and patellofemoral pain. None of the reviews assessed 'chronic pain' or 'chronic widespread pain' as a general term or specific condition. Interventions included aerobic, strength, flexibility, range of motion, and core or balance training programmes, as well as yoga, Pilates, and tai chi. Reviews were well performed and reported (based on AMSTAR), and included studies had acceptable risk of bias (with inadequate reporting of attrition and reporting biases). However the quality of evidence was low due to participant numbers (most included studies had fewer than 50 participants in total), length of intervention and follow-up (rarely assessed beyond three to six months). We pooled the results from relevant reviews where appropriate, though results should be interpreted with caution due to the low quality evidence. Pain severity: several reviews noted favourable results from exercise: only three reviews that reported pain severity found no statistically significant changes in usual or mean pain from any intervention. However, results were inconsistent across interventions and follow-up, as exercise did not consistently bring about a change (positive or negative) in self-reported pain scores at any single point. Physical function: was the most commonly reported outcome measure. Physical function was significantly improved as a result of the intervention in 14 reviews, though even these statistically significant results had only small-to-moderate effect sizes (only one review reported large effect sizes). Psychological function and quality of life: had variable results: results were either favourable to exercise (generally small and moderate effect size, with two reviews reporting significant, large effect sizes for quality of life), or showed no difference between groups. There were no negative effects. Adherence to the prescribed intervention: could not be assessed in any review. However, risk of withdrawal/dropout was slightly higher in the exercising group (82.8/1000 participants versus 81/1000 participants), though the group difference was non-significant. Healthcare use/attendance: was not reported in any review. Adverse events, potential harm, and death: only 25% of included studies (across 18 reviews) actively reported adverse events. Based on the available evidence, most adverse events were increased soreness or muscle pain, which reportedly subsided after a few weeks of the intervention. Only one review reported death separately to other adverse events: the intervention was protective against death (based on the available evidence), though did not reach statistical significance.
Authors' conclusions: The quality of the evidence examining physical activity and exercise for chronic pain is low. This is largely due to small sample sizes and potentially underpowered studies. A number of studies had adequately long interventions, but planned follow-up was limited to less than one year in all but six reviews. There were some favourable effects in reduction in pain severity and improved physical function, though these were mostly of small-to-moderate effect, and were not consistent across the reviews. There were variable effects for psychological function and quality of life. The available evidence suggests physical activity and exercise is an intervention with few adverse events that may improve pain severity and physical function, and consequent quality of life. However, further research is required and should focus on increasing participant numbers, including participants with a broader spectrum of pain severity, and lengthening both the intervention itself, and the follow-up period.
The Cochrane database of systematic reviews · meta-analysis · 484 citationsread the source →
Behavioural, educational and respiratory outcomes of antenatal betamethasone for term caesarean section (ASTECS trial).
Objectives: To determine whether antenatal betamethasone prior to elective term caesarean section (CS) affects long term behavioural, cognitive or developmental outcome, and whether the risk of asthma or atopic disease is reduced.
Design: A questionnaire based follow-up of a multicentre randomised controlled trial (Antenatal Steroids for Term Elective Caesarean Section, BMJ 2005).
Setting: Four UK study centres from the original trial.
Participants: 862 participants from the four largest recruiting centres, 92% of the original study. 824 (96%) were traced and 799 (93%) were successfully contacted. Fifty-one percent (407/799) completed and returned the questionnaire. The children were aged 8-15 years (median 12.2 years, 52% girls). 386 gave consent to contact schools with 352 (91%) reports received.
Main outcome measures: Questionnaires including a strengths and difficulties questionnaire, International Study of Asthma and Allergies in Childhood, general health and school performance.
Results: There were no significant differences between children whose mothers received betamethasone and controls for the mean total strengths and difficulties questionnaire scores and subscores for hyperactivity, emotional symptoms, prosocial behaviour, conduct or peer problems. 25 (12%) children whose mothers received betamethasone had reported learning difficulties compared with 27 (14%) control children. The proportion of children who achieved standard assessment tests KS2 exams level 4 or above for mathematics, English or science was similar as were the rates of ever reported wheeze (30% vs 30%), asthma (24% vs 21%), eczema (34% vs 37%) and hay fever (25% vs 27%).
Conclusions: Antenatal betamethasone did not result in any adverse outcomes or reduction in asthma or atopy. It should be considered for elective CS at 37-38 weeks of gestation.
Trial registration: : Original trial was preregistration, the trial publication is BMJ. 2005 Sep 24;331(7518):662.
Archives of disease in childhood. Fetal and neonatal edition · randomised controlled trial · 105 citationsread the source →
Lewis RA, Johns CS, Cogliano M, Capener D, Tubman E, Elliot CA, Charalampopoulos A, Sabroe I, Thompson AAR, Billings CG, Hamilton N, Baster K, Laud PJ, Hickey PM, Middleton J, Armstrong IJ, Hurdman JA, Lawrie A, Rothman AMK, Wild JM, Condliffe R, Swift AJ, Kiely DG. (2020)MEDLINE-indexed journal, not yet read by usAmerican journal of respiratory and critical care medicine Identification of Cardiac Magnetic Resonance Imaging Thresholds for Risk Stratification in Pulmonary Arterial Hypertension.
Rationale: Pulmonary arterial hypertension (PAH) is a life-shortening condition. The European Society of Cardiology and European Respiratory Society and the REVEAL (North American Registry to Evaluate Early and Long-Term PAH Disease Management) risk score calculator (REVEAL 2.0) identify thresholds to predict 1-year mortality. Objectives: This study evaluates whether cardiac magnetic resonance imaging (MRI) thresholds can be identified and used to aid risk stratification and facilitate decision-making. Methods: Consecutive patients with PAH (n = 438) undergoing cardiac MRI were identified from the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Center) MRI database. Thresholds were identified from a discovery cohort and evaluated in a test cohort. Measurements and Main Results: A percentage-predicted right ventricular end-systolic volume index threshold of 227% or a left ventricular end-diastolic volume index of 58 ml/m2 identified patients at low (<5%) and high (>10%) risk of 1-year mortality. These metrics respectively identified 63% and 34% of patients as low risk. Right ventricular ejection fraction >54%, 37-54%, and <37% identified 21%, 43%, and 36% of patients at low, intermediate, and high risk, respectively, of 1-year mortality. At follow-up cardiac MRI, patients who improved to or were maintained in a low-risk group had a 1-year mortality <5%. Percentage-predicted right ventricular end-systolic volume index independently predicted outcome and, when used in conjunction with the REVEAL 2.0 risk score calculator or a modified French Pulmonary Hypertension Registry approach, improved risk stratification for 1-year mortality. Conclusions: Cardiac MRI can be used to risk stratify patients with PAH using a threshold approach. Percentage-predicted right ventricular end-systolic volume index can identify a high percentage of patients at low-risk of 1-year mortality and, when used in conjunction with current risk stratification approaches, can improve risk stratification. This study supports further evaluation of cardiac MRI in risk stratification in PAH.
American journal of respiratory and critical care medicine · 115 citationsread the source →
Telemedicine Applications for Cancer Rehabilitation: Scoping Review.
Background: Cancer is a significant public health issue worldwide. Treatments such as surgery, chemotherapy, and radiation therapy often cause psychological and physiological side effects, affecting patients' ability to function and their quality of life (QoL). Physical activity is crucial to cancer rehabilitation, improving physical function and QoL and reducing cancer-related fatigue. However, many patients face barriers to accessing cancer rehabilitation due to socioeconomic factors, transportation issues, and time constraints. Telerehabilitation can potentially overcome these barriers by delivering rehabilitation remotely.
Objective: The aim of the study is to identify how telemedicine is used for the rehabilitation of patients with cancer.
Methods: This scoping review followed recognized frameworks. We conducted an electronic literature search on PubMed for studies published between January 2015 and May 2023. Inclusion criteria were studies reporting physical therapy telerehabilitation interventions for patients with cancer, including randomized and nonrandomized controlled trials, feasibility studies, and usability studies. In total, 21 studies met the criteria and were included in the final review.
Results: Our search yielded 37 papers, with 21 included in the final review. Randomized controlled trials comprised 47% (n=10) of the studies, with feasibility studies at 33% (n=7) and usability studies at 19% (n=4). Sample sizes were typically 50 or fewer participants in 57% (n=12) of the reports. Participants were generally aged 65 years or younger (n=17, 81%), with a balanced gender distribution. Organ-specific cancers were the focus of 66% (n=14) of the papers, while 28% (n=6) included patients who were in the posttreatment period. Web-based systems were the most used technology (n=13, 61%), followed by phone call or SMS text messaging-based systems (n=9, 42%) and mobile apps (n=5, 23%). Exercise programs were mainly home based (n=19, 90%) and included aerobic (n=19, 90%), resistance (n=13, 61%), and flexibility training (n=7, 33%). Outcomes included improvements in functional capacity, cognitive functioning, and QoL (n=10, 47%); reductions in pain and hospital length of stay; and enhancements in fatigue, physical and emotional well-being, and anxiety. Positive effects on feasibility (n=3, 14%), acceptability (n=8, 38%), and cost-effectiveness (n=2, 9%) were also noted. Functional outcomes were frequently assessed (n=19, 71%) with tools like the 6-minute walk test and grip strength tests.
Conclusions: Telerehabilitation for patients with cancer is beneficial and feasible, with diverse approaches in study design, technologies, exercises, and outcomes. Future research should focus on developing standardized methodologies, incorporating objective measures, and exploring emerging technologies like virtual reality, wearable or noncontact sensors, and artificial intelligence to optimize telerehabilitation interventions. Addressing these areas can enhance clinical practice and improve outcomes for remote rehabilitation with patients.
JMIR cancer · review · 17 citationsread the source →
Positive childhood experiences predict less psychopathology and stress in pregnant women with childhood adversity: A pilot study of the benevolent childhood experiences (BCEs) scale.
This pilot study examined the psychometric properties of the Benevolent Childhood Experiences (BCEs) scale, a new instrument designed to assess positive early life experiences in adults with histories of childhood maltreatment and other adversities. A counterpart to the Adverse Childhood Experiences (ACEs) questionnaire, the BCEs was developed to be multiculturally-sensitive and applicable regardless of socioeconomic position, urban-rural background, or immigration status. Higher levels of BCEs were hypothesized to predict lower levels of psychopathology and stress beyond the effects of ACES in a sample of ethnically diverse, low-income pregnant women. BCEs were also expected to show adequate internal validity across racial/ethnic groups and test-retest stability from the prenatal to the postnatal period. Participants were 101 pregnant women (M=29.10years, SD=6.56, range=18-44; 37% Latina, 22% African-American, 20% White, 21% biracial/multiracial/other; 37% foreign-born, 26% Spanish-speaking) who completed the BCEs and ACEs scales; assessments of prenatal depression and post-traumatic stress disorder (PTSD) symptoms, perceived stress, and exposure to stressful life events (SLEs) during pregnancy; and demographic information. Higher levels of BCEs predicted less PTSD symptoms and SLEs, above and beyond ACEs. The BCEs showed excellent test-retest reliability, and mean levels were comparable across racial/ethnic and Spanish-English groups of women. Person-oriented analyses also showed that higher levels of BCEs offset the effects of ACEs on prenatal stress and psychopathology. The BCEs scale indexes promising promotive factors associated with lower trauma-related symptomatology and stress exposure during pregnancy and illuminates how favorable childhood experiences may counteract long-term effects of childhood adversity.
Child abuse & neglect · 271 citationsread the source →
Physical activity for women with breast cancer after adjuvant therapy.
Background: Women with a diagnosis of breast cancer may experience short- and long-term disease and treatment-related adverse physiological and psychosocial outcomes. These outcomes can negatively impact prognosis, health-related quality of life (HRQoL), and psychosocial and physical function. Physical activity may help to improve prognosis and may alleviate the adverse effects of adjuvant therapy.
Objectives: To assess effects of physical activity interventions after adjuvant therapy for women with breast cancer.
Search methods: We searched the Cochrane Breast Cancer Group (CBCG) Specialised Registry, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Physiotherapy Evidence Database (PEDro), SPORTDiscus, PsycINFO, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform, on 18 September 2015. We also searched OpenGrey and Healthcare Management Information Consortium databases.
Selection criteria: We searched for randomised and quasi-randomised trials comparing physical activity interventions versus control (e.g. usual or standard care, no physical activity, no exercise, attention control, placebo) after adjuvant therapy (i.e. after completion of chemotherapy and/or radiation therapy, but not hormone therapy) in women with breast cancer.
Data collection and analysis: Two review authors independently selected studies, assessed risk of bias, and extracted data. We contacted trial authors to ask for additional information when needed. We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome and used GRADE to assess the quality of evidence for the most important outcomes.
Main results: We included 63 trials that randomised 5761 women to a physical activity intervention (n = 3239) or to a control (n = 2524). The duration of interventions ranged from 4 to 24 months, with most lasting 8 or 12 weeks (37 studies). Twenty-eight studies included aerobic exercise only, 21 involved aerobic exercise and resistance training, and seven used resistance training only. Thirty studies described the comparison group as usual or standard care, no intervention, or control. One-fifth of studies reported at least 20% intervention attrition and the average physical activity adherence was approximately 77%.No data were available on effects of physical activity on breast cancer-related and all-cause mortality, or on breast cancer recurrence. Analysis of immediately postintervention follow-up values and change from baseline to end of intervention scores revealed that physical activity interventions resulted in significant small-to-moderate improvements in HRQoL (standardised mean difference (SMD) 0.39, 95% CI 0.21 to 0.57, 22 studies, 1996 women; SMD 0.78, 95% CI 0.39 to 1.17, 14 studies, 1459 women, respectively; low-quality evidence), emotional function (SMD 0.21, 95% CI 0.10 to 0.32, 26 studies, 2102 women, moderate-quality evidence; SMD 0.31, 95% CI 0.09 to 0.53, 15 studies, 1579 women, respectively; low-quality evidence), perceived physical function (SMD 0.33, 95% CI 0.18 to 0.49, 25 studies, 2129 women; SMD 0.60, 95% CI 0.23 to 0.97, 13 studies, 1433 women, respectively; moderate-quality evidence), anxiety (SMD -0.57, 95% CI -0.95 to -0.19, 7 studies, 326 women; SMD -0.37, 95% CI -0.63 to -0.12, 4 studies, 235 women, respectively; low-quality evidence), and cardiorespiratory fitness (SMD 0.44, 95% CI 0.30 to 0.58, 23 studies, 1265 women, moderate-quality evidence; SMD 0.83, 95% CI 0.40 to 1.27, 9 studies, 863 women, respectively; very low-quality evidence).Investigators reported few minor adverse events. Small improvements in physical activity interventions were sustained for three months or longer postintervention in fatigue (SMD -0.43, 95% CI -0.60 to -0.26; SMD -0.47, 95% CI -0.84 to -0.11, respectively), cardiorespiratory fitness (SMD 0.36, 95% CI 0.03 to 0.69; SMD 0.42, 95% CI 0.05 to 0.79, respectively), and self-reported physical activity (SMD 0.44, 95% CI 0.17 to 0.72; SMD 0.51, 95% CI 0.08 to 0.93, respectively) for both follow-up values and change from baseline scores. However, evidence of heterogeneity across trials was due to variation in intervention components (i.e. mode, frequency, intensity, duration of intervention and sessions) and measures used to assess outcomes. All trials reviewed were at high risk of performance bias, and most were also at high risk of detection, attrition, and selection bias. In light of the aforementioned issues, we determined that the evidence was of very low, low, or moderate quality.
Authors' conclusions: No conclusions regarding breast cancer-related and all-cause mortality or breast cancer recurrence were possible. However, physical activity interventions may have small-to-moderate beneficial effects on HRQoL, and on emotional or perceived physical and social function, anxiety, cardiorespiratory fitness, and self-reported and objectively measured physical activity. The positive results reported in the current review must be interpreted cautiously owing to very low-to-moderate quality of evidence, heterogeneity of interventions and outcome measures, imprecision of some estimates, and risk of bias in many trials. Future studies with low risk of bias are required to determine the optimal combination of physical activity modes, frequencies, intensities, and durations needed to improve specific outcomes among women who have undergone adjuvant therapy.
The Cochrane database of systematic reviews · meta-analysis · 165 citationsread the source →
A novel perspective for an orphan problem: old and new drugs for the medical management of malignant ascites.
Malignant ascites is defined as a condition in which fluid containing cancer cells accumulates in the abdomen. The cancers most commonly associated to ascites are ovarian (37%), pancreato-biliary (21%), gastric (18%), oesophageal (4%), colorectal (4%), and breast (3%). Treatment of malignant ascites remains a challenge. In the majority of patients systemic chemotherapy is ineffective and diuretics and paracentesis are still the only approaches, but new promising option are appearing, as cytoreductive debulking surgery and intraperitoneal (IP) or intravenous biological (target) therapies. More promising, after the recognition of potential epithelial targets as Epithelial Cell Adhesion Molecule (EpCAM), are the trifunctional antibodies able to bind these cell adhesion molecules and, at the same, time the immune system cells. These agents have been developed for malignant ascites with the aim also to prolong the need for subsequent paracentesis. So patients with malignant ascites may look at the future with hope and growing optimism.
Critical reviews in oncology/hematology · review · 26 citationsread the source →
Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews.
Background: Chronic pain is defined as pain lasting beyond normal tissue healing time, generally taken to be 12 weeks. It contributes to disability, anxiety, depression, sleep disturbances, poor quality of life, and healthcare costs. Chronic pain has a weighted mean prevalence in adults of 20%.For many years, the treatment choice for chronic pain included recommendations for rest and inactivity. However, exercise may have specific benefits in reducing the severity of chronic pain, as well as more general benefits associated with improved overall physical and mental health, and physical functioning. Physical activity and exercise programmes are increasingly being promoted and offered in various healthcare systems, and for a variety of chronic pain conditions. It is therefore important at this stage to establish the efficacy and safety of these programmes, and furthermore to address the critical factors that determine their success or failure.
Objectives: To provide an overview of Cochrane Reviews of adults with chronic pain to determine (1) the effectiveness of different physical activity and exercise interventions in reducing pain severity and its impact on function, quality of life, and healthcare use; and (2) the evidence for any adverse effects or harm associated with physical activity and exercise interventions.
Methods: We searched theCochrane Database of Systematic Reviews (CDSR) on the Cochrane Library (CDSR 2016, Issue 1) for systematic reviews of randomised controlled trials (RCTs), after which we tracked any included reviews for updates, and tracked protocols in case of full review publication until an arbitrary cut-off date of 21 March 2016 (CDSR 2016, Issue 3). We assessed the methodological quality of the reviews using the AMSTAR tool, and also planned to analyse data for each painful condition based on quality of the evidence. We extracted data for (1) self-reported pain severity, (2) physical function (objectively or subjectively measured), (3) psychological function, (4) quality of life, (5) adherence to the prescribed intervention, (6) healthcare use/attendance, (7) adverse events, and (8) death. Due to the limited data available, we were unable to directly compare and analyse interventions, and have instead reported the evidence qualitatively.
Main results: We included 21 reviews with 381 included studies and 37,143 participants. Of these, 264 studies (19,642 participants) examined exercise versus no exercise/minimal intervention in adults with chronic pain and were used in the qualitative analysis. Pain conditions included rheumatoid arthritis, osteoarthritis, fibromyalgia, low back pain, intermittent claudication, dysmenorrhoea, mechanical neck disorder, spinal cord injury, postpolio syndrome, and patellofemoral pain. None of the reviews assessed 'chronic pain' or 'chronic widespread pain' as a general term or specific condition. Interventions included aerobic, strength, flexibility, range of motion, and core or balance training programmes, as well as yoga, Pilates, and tai chi. Reviews were well performed and reported (based on AMSTAR), and included studies had acceptable risk of bias (with inadequate reporting of attrition and reporting biases). However the quality of evidence was low due to participant numbers (most included studies had fewer than 50 participants in total), length of intervention and follow-up (rarely assessed beyond three to six months). We pooled the results from relevant reviews where appropriate, though results should be interpreted with caution due to the low quality evidence. Pain severity: several reviews noted favourable results from exercise: only three reviews that reported pain severity found no statistically significant changes in usual or mean pain from any intervention. However, results were inconsistent across interventions and follow-up, as exercise did not consistently bring about a change (positive or negative) in self-reported pain scores at any single point. Physical function: was the most commonly reported outcome measure. Physical function was significantly improved as a result of the intervention in 14 reviews, though even these statistically significant results had only small-to-moderate effect sizes (only one review reported large effect sizes). Psychological function and quality of life: had variable results: results were either favourable to exercise (generally small and moderate effect size, with two reviews reporting significant, large effect sizes for quality of life), or showed no difference between groups. There were no negative effects. Adherence to the prescribed intervention: could not be assessed in any review. However, risk of withdrawal/dropout was slightly higher in the exercising group (82.8/1000 participants versus 81/1000 participants), though the group difference was non-significant. Healthcare use/attendance: was not reported in any review. Adverse events, potential harm, and death: only 25% of included studies (across 18 reviews) actively reported adverse events. Based on the available evidence, most adverse events were increased soreness or muscle pain, which reportedly subsided after a few weeks of the intervention. Only one review reported death separately to other adverse events: the intervention was protective against death (based on the available evidence), though did not reach statistical significance.
Authors' conclusions: The quality of the evidence examining physical activity and exercise for chronic pain is low. This is largely due to small sample sizes and potentially underpowered studies. A number of studies had adequately long interventions, but planned follow-up was limited to less than one year in all but six reviews. There were some favourable effects in reduction in pain severity and improved physical function, though these were mostly of small-to-moderate effect, and were not consistent across the reviews. There were variable effects for psychological function and quality of life. The available evidence suggests physical activity and exercise is an intervention with few adverse events that may improve pain severity and physical function, and consequent quality of life. However, further research is required and should focus on increasing participant numbers, including participants with a broader spectrum of pain severity, and lengthening both the intervention itself, and the follow-up period.
The Cochrane database of systematic reviews · meta-analysis · 377 citationsread the source →
Meta-analysis of technology-assisted interventions for social anxiety disorder.
This meta-analysis investigated the efficacy of technology-assisted interventions for individuals with social anxiety disorder (SAD). A systematic literature search in the databases Medline, PsychInfo, and Web of Science revealed 37 randomized controlled trials (2991 participants) that were grouped into internet delivered cognitive behavior therapy (ICBT; 21 trials), virtual reality exposure therapy (VRET; 3 trials), and cognitive bias modification (CBM; 13 trials). Patients undergoing ICBT and VRET showed significantly less SAD symptoms at postassessment than passive control conditions (g=0.84 and 0.82, respectively). Compared to active control conditions, ICBT had a small advantage (g=0.38) and VRET showed comparable effects (p>0.05). CBM was not more effective than passive control conditions, except when delivered in the laboratory (g=0.35). While the efficacy of CBM was limited, substantial evidence for ICBT and preliminary evidence for VRET suggests that both can effectively reduce SAD symptoms indicating the potential of technology-assisted interventions for SAD.
Journal of anxiety disorders · meta-analysis · 87 citationsread the source →
Mshamu S, Meta J, Adhikari B, Halifa S, Mmbando A, Wood HS, Wood OS, Bøjstrup TC, Day NPJ, Lindsay SW, Knudsen J, Deen J, Seidlein LV, Pell C. (2025)MEDLINE-indexed journal, not yet read by usPloS one Community responses to a novel house design: A qualitative study of "Star Homes" in Mtwara, southeastern Tanzania.
Introduction: To evaluate the impact of a novel design "Star Home" on the incidence of malaria, respiratory tract infections and diarrheal diseases among children, randomly selected households in Mtwara, Tanzania were offered a free, new Star Home. Drawing on longitudinal qualitative research that accompanied the Star Homes study, this article describes the experiences of residents and the wider community of living with these buildings.
Methods: A total of four rounds of face-to-face interviews were undertaken with residents of Star Homes (n = 37), control (wattle/daub) homes (n = 21), neighboring households n = 6), community members (n = 17) and community leaders (n = 6). The use of Star Homes was also observed over these four time periods between 2021 and 2023. Interviews were conducted in Swahili, transcribed, and translated into English for thematic analysis.
Results: Star Homes residents appreciated several aspects of the Star Homes, including overall comfort, access to water and electricity, and clean toilets. There were concerns about some design elements, such as poorly closing doors, stoves perceived as inefficient, and the façade, which was susceptible to rainwater ingress. The houses were not always used as intended by their developers, for example, residents were sleeping downstairs instead of upstairs because of cold floors or difficulties using the stairs. Star Homes residents described how the structures triggered praise but also envy from other community members.
Conclusions: The findings highlight the need for close attention to the use of novel design houses and careful sensitization around the potential benefits of dwellings to ensure that the intended health impacts of interventions are achieved.
PloS one · 4 citationsread the source →
The effectiveness of third wave cognitive behavioural therapies for children and adolescents: A systematic review and meta-analysis.
Objectives: Third wave cognitive behavioural therapies are increasingly used with children and adolescents. This meta-analysis aimed to determine the effectiveness of four third-wave interventions (acceptance and commitment therapy, compassion focused therapy, mindfulness-based cognitive therapy, and metacognitive therapy) for youth.
Methods: Four electronic databases were used to identify randomized controlled trials, which tested effects related to health, well-being and functioning. Sensitivity analyses considering study quality were conducted and moderators were explored.
Results: The results based on 50 RCTs meeting inclusion criteria indicated emotional symptoms/internalizing problems (g = -.68, 95% CI -.98 to -.37, k = 43, N = 3265), behavioural difficulties/externalizing problems (g = -.62, 95% CI -1.01 to -.22, k = 23, N = 1659), interference from difficulties (g = -.46, 95% CI -.87 to -.05, k = 21, N = 1786), third wave processes (g = .39, 95% CI .17 to .62, k = 22, N = 1900), wellbeing/flourishing (g = .76, 95% CI .35 to 1.17, k = 21, N = 1303) and physical health/pain (g = .72, 95% CI .01 to 1.44, k = 9, N = 1171) yielded significant effects. Effect for quality of life (g = .62, 95% CI -.08 to 1.31, k = 12, N = 1271) was non-significant. When analysing only those studies rated moderate-high quality, third wave interventions yielded significant superiority effects compared to controls for emotional symptoms/internalizing problems (g = -.55, 95% CI -.82 to -.27, k = 28, N = 2110), interference from difficulties (g = -.48, 95% CI -.90 to -.05, k = 21, N = 1605), third wave processes (g = .27, 95% CI .11 to .43, k = 18, N = 1692), well-being/flourishing (g = .50, 95% CI .18 to .81, k = 16, N = 1063), and quality of life (g = .32, 95% CI .04 to .60, k = 10, N = 1212). Behavioural difficulties/externalizing problems (g = -.38, 95% CI -.86 to .10, k = 15, N = 1351) and physical health/pain (g = .52, 95% CI -.14 to 1.17, k = 8, N = 1139) ceased to be significant. Widespread heterogeneity raised concerns about generalizability and follow-up data was relatively sparse.
Conclusions: This meta-analysis finds promising results for use of third wave CBT with youth, though the review has limitations.
The British journal of clinical psychology · meta-analysis · 19 citationsread the source →
Turnover intention among primary health workers in China: a systematic review and meta-analysis.
Objectives: To analyse the prevalence and determinants of turnover intention (TI) among primary health workers (PHWs) in China to provide evidence for improving retention measures.
Design: Systemic review and meta-analysis.
Data sources: Four English-language databases (PubMed, EMBASE, Cochrane Library, PsycINFO) and three Chinese databases (CNKI, CSPD, CBM) were searched up to October 2019.
Eligibility criteria: Eligible studies were observational or descriptive studies conducted in mainland China. The prevalence of TI among health workers and related factors had to be explicitly reported in each included study.
Data extraction and synthesis: Data were extracted by one author and reviewed independently by two other authors. For each factor analysed by a meta-analysis, the factor was required to be the same across different studies, and at least three studies had to include it. The quality of studies was assessed using the Newcastle-Ottawa Scale and heterogeneity was evaluated using the I2 statistic.
Results: We identified 16 cross-sectional studies investigating a total of 37 672 PHWs. The prevalence of TI was 30.4%. Subgroup analysis revealed that the highest prevalence was observed in the community primary healthcare institutions and the eastern provinces of China. Meta-analyses indicated that 21 factors were significantly associated with TI, including demographic factors (gender, age, education, marital status), job characteristic factors (title, work seniority, remuneration, social status, organisational affiliation, work stress) and job satisfaction factors (learning and training opportunity, interpersonal relationship, work condition and environment, and so on).
Conclusion: This study highlights the problem of TI among PHWs in China. Efforts should be made to improve conditions in both work-related areas and areas outside of work. Policymakers should continue to improve reward systems, the construction of infrastructure and promotion systems, and pay more attention to PHWs' lives outside of work and meet their living needs.
BMJ open · meta-analysis · 70 citationsread the source →
Prevalence of low-grade inflammation in depression: a systematic review and meta-analysis of CRP levels.
Background: Peripheral low-grade inflammation in depression is increasingly seen as a therapeutic target. We aimed to establish the prevalence of low-grade inflammation in depression, using different C-reactive protein (CRP) levels, through a systematic literature review and meta-analysis.
Methods: We searched the PubMed database from its inception to July 2018, and selected studies that assessed depression using a validated tool/scale, and allowed the calculation of the proportion of patients with low-grade inflammation (CRP >3 mg/L) or elevated CRP (>1 mg/L).
Results: After quality assessment, 37 studies comprising 13 541 depressed patients and 155 728 controls were included. Based on the meta-analysis of 30 studies, the prevalence of low-grade inflammation (CRP >3 mg/L) in depression was 27% (95% CI 21-34%); this prevalence was not associated with sample source (inpatient, outpatient or population-based), antidepressant treatment, participant age, BMI or ethnicity. Based on the meta-analysis of 17 studies of depression and matched healthy controls, the odds ratio for low-grade inflammation in depression was 1.46 (95% CI 1.22-1.75). The prevalence of elevated CRP (>1 mg/L) in depression was 58% (95% CI 47-69%), and the meta-analytic odds ratio for elevated CRP in depression compared with controls was 1.47 (95% CI 1.18-1.82).
Conclusions: About a quarter of patients with depression show evidence of low-grade inflammation, and over half of patients show mildly elevated CRP levels. There are significant differences in the prevalence of low-grade inflammation between patients and matched healthy controls. These findings suggest that inflammation could be relevant to a large number of patients with depression.
Psychological medicine · meta-analysis · 606 citationsread the source →
Prevalence of Depression, Depressive Symptoms, and Suicidal Ideation Among Medical Students: A Systematic Review and Meta-Analysis.
Importance: Medical students are at high risk for depression and suicidal ideation. However, the prevalence estimates of these disorders vary between studies.
Objective: To estimate the prevalence of depression, depressive symptoms, and suicidal ideation in medical students.
Data sources and study selection: Systematic search of EMBASE, ERIC, MEDLINE, psycARTICLES, and psycINFO without language restriction for studies on the prevalence of depression, depressive symptoms, or suicidal ideation in medical students published before September 17, 2016. Studies that were published in the peer-reviewed literature and used validated assessment methods were included.
Data extraction and synthesis: Information on study characteristics; prevalence of depression or depressive symptoms and suicidal ideation; and whether students who screened positive for depression sought treatment was extracted independently by 3 investigators. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were estimated using stratified meta-analysis and meta-regression.
Main outcomes and measures: Point or period prevalence of depression, depressive symptoms, or suicidal ideation as assessed by validated questionnaire or structured interview.
Results: Depression or depressive symptom prevalence data were extracted from 167 cross-sectional studies (n = 116 628) and 16 longitudinal studies (n = 5728) from 43 countries. All but 1 study used self-report instruments. The overall pooled crude prevalence of depression or depressive symptoms was 27.2% (37 933/122 356 individuals; 95% CI, 24.7% to 29.9%, I2 = 98.9%). Summary prevalence estimates ranged across assessment modalities from 9.3% to 55.9%. Depressive symptom prevalence remained relatively constant over the period studied (baseline survey year range of 1982-2015; slope, 0.2% increase per year [95% CI, -0.2% to 0.7%]). In the 9 longitudinal studies that assessed depressive symptoms before and during medical school (n = 2432), the median absolute increase in symptoms was 13.5% (range, 0.6% to 35.3%). Prevalence estimates did not significantly differ between studies of only preclinical students and studies of only clinical students (23.7% [95% CI, 19.5% to 28.5%] vs 22.4% [95% CI, 17.6% to 28.2%]; P = .72). The percentage of medical students screening positive for depression who sought psychiatric treatment was 15.7% (110/954 individuals; 95% CI, 10.2% to 23.4%, I2 = 70.1%). Suicidal ideation prevalence data were extracted from 24 cross-sectional studies (n = 21 002) from 15 countries. All but 1 study used self-report instruments. The overall pooled crude prevalence of suicidal ideation was 11.1% (2043/21 002 individuals; 95% CI, 9.0% to 13.7%, I2 = 95.8%). Summary prevalence estimates ranged across assessment modalities from 7.4% to 24.2%.
Conclusions and relevance: In this systematic review, the summary estimate of the prevalence of depression or depressive symptoms among medical students was 27.2% and that of suicidal ideation was 11.1%. Further research is needed to identify strategies for preventing and treating these disorders in this population.
JAMA · meta-analysis · 1429 citationsread the source →
Transdiagnostic computerised cognitive behavioural therapy for depression and anxiety: A systematic review and meta-analysis.
An increasing number of computerised transdiagnostic cognitive behavioural therapy programs (TD-cCBT) have been developed in the past decade, but there are no meta-analyses to explore the efficacy of these programs, nor moderators of the effects. The current meta-analysis focused on studies evaluating TD-cCBT interventions to examine their effects on anxiety, depression and quality of life (QOL). Results from 17 RCTs showed computerised TD-cCBT outperformed control conditions on all outcome measures at post-treatment, with large effect sizes for depression (g's=.84), and medium effect sizes for anxiety (g=.78) and QOL (g=.48). RCT quality was generally good, although heterogeneity was moderate to high. Further analyses revealed that studies comparing TD-cCBT to waitlist controls had the largest differences (g=.93) compared to active (g=.59) and usual care control groups (g=.37) on anxiety outcomes, but there was no influence of control group subtype on depression outcomes. Treatment length, symptom target (mixed versus anxiety only), treatment design (standardised versus tailored), and therapist experience (students versus qualified therapists) did not influence the results. Preliminary evidence from 4 comparisons with disorder-specific treatments suggests transdiagnostic treatments are as effective for reducing anxiety, and there may be small but superior outcomes for TD-cCBT programs for reducing depression (g=.21) and improving QOL (g=.21) compared to disorder-specific cCBT. These findings show that TD-cCBT programs are efficacious, and have comparable effects to disorder-specific cCBT programs.
Journal of affective disorders · meta-analysis · 114 citationsread the source →
Yao CA, Rhodes RE. (2015)MEDLINE-indexed journal, not yet read by usThe international journal of behavioral nutrition and physical activity · meta-analysis Parental correlates in child and adolescent physical activity: a meta-analysis.
Objective: Physical activity (PA) has a profound impact on health and development in children. Parental behaviors (i.e., modeling and support) represent an obvious important factor in child PA. The purpose of this paper was to provide a comprehensive meta-analysis that overcomes the limitations of prior narrative reviews and quantitative reviews with small samples.
Methods: Ten major databases were used in the literature search. One-hundred and fifteen studies passed the eligibility criteria. Both fixed and random effects models with correction for sampling and measurement error were examined in the analysis. Moderator analyses investigating the effects of child's developmental age, study design, parental gender, measurement of child PA, and quality rating were performed.
Results: Based on the random effects model, the results showed that parental modeling was weakly associated with child PA (summary r = .16, 95% CI .09-.24) and none of the proposed moderators were significant. Separate analyses examining the moderating effects of parental gender and boys' PA found that that father-son PA modeling (r = .29, 95% CI .21-.36) was significantly higher compared to mother-son PA (r = .19, 95% CI .14-.23; p < .05). However, parental gender did not moderate the relationship between parental modeling and girls' PA (p > .05). The random effects model indicated an overall moderate effect size for the parental support and child PA relationship (summary r = .38, 95% CI .30-.46). Here, the only significant moderating variable was the measurement of child PA (objective: r = .20, 95% CI .13-.26; reported: r = .46, 95% CI .37-.55; p < .01).
Conclusions: Parental support and modeling relate to child PA, yet our results revealed a significant degree of heterogeneity among the studies that could not be explained well by our proposed moderators.
The international journal of behavioral nutrition and physical activity · meta-analysis · 282 citationsread the source →
Effects of non-health-targeted policies on migrant health: a systematic review and meta-analysis.
Background: Government policies can strongly influence migrants' health. Using a Health in All Policies approach, we systematically reviewed evidence on the impact of public policies outside of the health-care system on migrant health.
Methods: We searched the PubMed, Embase, and Web of Science databases from Jan 1, 2000, to Sept 1, 2017, for quantitative studies comparing the health effects of non-health-targeted public policies on migrants with those on a relevant comparison population. We searched for articles written in English, Swedish, Danish, Norwegian, Finnish, French, Spanish, or Portuguese. Qualitative studies and grey literature were excluded. We evaluated policy effects by migration stage (entry, integration, and exit) and by health outcome using narrative synthesis (all included studies) and random-effects meta-analysis (all studies whose results were amenable to statistical pooling). We summarised meta-analysis outcomes as standardised mean difference (SMD, 95% CI) or odds ratio (OR, 95% CI). To assess certainty, we created tables containing a summary of the findings according to the Grading of Recommendations Assessment, Development, and Evaluation. Our study was registered with PROSPERO, number CRD42017076104.
Findings: We identified 43 243 potentially eligible records. 46 articles were narratively synthesised and 19 contributed to the meta-analysis. All studies were published in high-income countries and examined policies of entry (nine articles) and integration (37 articles). Restrictive entry policies (eg, temporary visa status, detention) were associated with poor mental health (SMD 0·44, 95% CI 0·13-0·75; I2=92·1%). In the integration phase, restrictive policies in general, and specifically regarding welfare eligibility and documentation requirements, were found to increase odds of poor self-rated health (OR 1·67, 95% CI 1·35-1·98; I2=82·0%) and mortality (1·38, 1·10-1·65; I2=98·9%). Restricted eligibility for welfare support decreased the odds of general health-care service use (0·92, 0·85-0·98; I2=0·0%), but did not reduce public health insurance coverage (0·89, 0·71-1·07; I2=99·4%), nor markedly affect proportions of people without health insurance (1·06, 0·90-1·21; I2=54·9%).
Interpretation: Restrictive entry and integration policies are linked to poor migrant health outcomes in high-income countries. Efforts to improve the health of migrants would benefit from adopting a Health in All Policies perspective.
Funding: Swedish Council for Health, Working Life, and Social Research; UK Medical Research Council; Scottish Government Chief Scientist Office.
The Lancet. Global health · meta-analysis · 123 citationsread the source →
Suicide risk in long-term care facilities: a systematic review.
Objective: Suicide risk is highest in later life; however, little is known about the risk of suicide among older adults in long-term care facilities (e.g., nursing homes and assisted living facilities). The goal of this paper is to review and synthesize the descriptive and analytic epidemiology of suicide in long-term care settings over the past 25 years.
Methods: Four databases (PubMed, CINAHL Plus, Web of Knowledge, and EBSCOHost Academic Search Complete) were searched for empirical studies of suicide risk in nursing homes, assisted living, and other residential facilities from 1985 to 2013. Of the 4073 unique research articles identified, 37 were selected for inclusion in this review.
Results: Of the included reports, 21 were cross-sectional, 8 cohort, 3 qualitative, and 5 intervention studies. Most studies indicate that suicidal thoughts (active and passive) are common among residents (prevalence in the past month: 5-33%), although completed suicide is rare. Correlates of suicidal thoughts among long-term care residents include depression, social isolation, loneliness, and functional decline. Most studies examined only individual-level correlates of suicide, although there is suggestive evidence that organizational characteristics (e.g., bed size and staffing) may also be relevant.
Conclusions: Existing research on suicide risk in long-term care facilities is limited but suggests that this is an important issue for clinicians and medical directors to be aware of and address. Research is needed on suicide risk in assisted living and other non-nursing home residential settings, as well as the potential role of organizational characteristics on emotional well-being for residents.
International journal of geriatric psychiatry · systematic review · 55 citationsread the source →
Predictors of treatment resistance in patients with schizophrenia: a population-based cohort study.
Background: Identification of patients at high risk of treatment-resistant schizophrenia at the time of schizophrenia diagnosis would be of great clinical benefit in minimising the delay to clozapine treatment in patients unlikely to respond to non-clozapine antipsychotics. However, little is known about predictors of treatment resistance in this patient population. We used a treatment-based proxy for treatment-resistant schizophrenia to identify candidate predictors of treatment resistance at first hospital contact with a schizophrenia diagnosis.
Methods: In this population-based cohort study, we obtained Danish national registry data for all adult patients (≥18 years) with incident schizophrenia diagnosed between Jan 1, 1996, and Dec 31, 2006, and followed up until Dec 31, 2010. Our main proxy definition of treatment-resistant schizophrenia was the earliest instance of either clozapine initiation or hospital admission for schizophrenia after having had two periods of different antipsychotic monotherapy. We did multivariable Cox proportional hazards regression analysis to estimate the association between baseline candidate predictors and treatment resistance.
Findings: 8624 patients fulfilled the criteria for inclusion. In multivariable complete-case analyses, 1703 (21%) of 8044 patients fulfilled the main proxy definition of treatment-resistant schizophrenia during a median follow-up of 9·1 years (IQR 6·3-11·9). Younger age (hazard ratio 0·96 [95% CI 0·95-0·97]), living in a less urban area (provincial 1·38 [1·23-1·56], rural 1·44 [1·25-1·65]), primary education level (0·88 [0·79-0·98]), more than 30 bed-days in psychiatric hospital in the year before first schizophrenia diagnosis (1·54 [1·35-1·75]), inpatient at first schizophrenia diagnosis (2·07 [1·87-2·29]), paranoid subtype (1·24 [1·13-1·37]), comorbid personality disorder (1·24 [1·11-1·39]), psychotropic drug use (antipsychotics 1·51 [1·35-1·69], antidepressants 1·15 [1·03-1·29], and benzodiazepines 1·22 [1·10-1·37]), and previous suicide attempt (1·21 [1·07-1·39]) were all significantly associated with treatment-resistant schizophrenia.
Interpretation: Our study identifies several candidate predictors that could potentially be included in future prediction models for treatment-resistant schizophrenia. Notably, established risk factors for schizophrenia did not predict treatment resistance, suggesting that treatment-resistant disease might be a distinct subtype of schizophrenia and not merely a more severe form.
Funding: European Community's Seventh Framework Programme.
The lancet. Psychiatry · 127 citationsread the source →
Skapinakis P, Caldwell DM, Hollingworth W, Bryden P, Fineberg NA, Salkovskis P, Welton NJ, Baxter H, Kessler D, Churchill R, Lewis G. (2016)MEDLINE-indexed journal, not yet read by usThe lancet. Psychiatry · systematic review Pharmacological and psychotherapeutic interventions for management of obsessive-compulsive disorder in adults: a systematic review and network meta-analysis.
Background: Several interventions are available for management of obsessive-compulsive disorder in adults, but few studies have compared their relative efficacy in a single analysis. We aimed to simultaneously compare all available treatments using both direct and indirect data.
Methods: In this systematic review and network meta-analysis, we searched the two controlled trials registers maintained by the Cochrane Collaboration Common Mental Disorders group for trials published up to Feb 16, 2016. We selected randomised controlled trials in which an active psychotherapeutic or pharmacological intervention had been used in adults with obsessive-compulsive disorder. We allowed all comorbidities except for schizophrenia or bipolar disorder. We excluded studies that focused exclusively on treatment-resistant patient populations defined within the same study. We extracted data from published reports. The primary outcome was symptom severity as measured by the Yale-Brown Obsessive Compulsive Scale. We report mean differences with 95% credible intervals compared with placebo. This study is registered with PROSPERO, number CRD42012002441.
Findings: We identified 1480 articles in our search and included 53 articles (54 trials; 6652 participants) in the network meta-analysis. Behavioural therapy (mean difference -14·48 [95% credible interval -18·61 to -10·23]; 11 trials and 287 patients), cognitive therapy (-13·36 [-18·40 to -8·21]; six trials and 172 patients), behavioural therapy and clomipramine (-12·97 [-19·18 to -6·74]; one trial and 31 patients), cognitive behavioural therapy and fluvoxamine (-7·50 [-13·89 to -1·17]; one trial and six patients), cognitive behavioural therapy (-5·37 [-9·10 to -1·63]; nine trials and 231 patients), clomipramine (-4·72 [-6·85 to -2·60]; 13 trials and 831 patients), and all SSRIs (class effect -3·49 [95% credible interval -5·12 to -1·81]; 37 trials and 3158 patients) had greater effects than did drug placebo. Clomipramine was not better than were SSRIs (-1·23 [-3·41 to 0·94]). Psychotherapeutic interventions had a greater effect than did medications, but a serious limitation was that most psychotherapeutic trials included patients who were taking stable doses of antidepressants (12 [80%] of the 15 psychotherapy trials explicitly allowed antidepressants).
Interpretation: A range of interventions is effective in the management of obsessive-compulsive disorder, but considerable uncertainty and limitations exist regarding their relative efficacy. Taking all the evidence into account, the combination of psychotherapeutic and psychopharmacological interventions is likely to be more effective than are psychotherapeutic interventions alone, at least in severe obsessive-compulsive disorder.
Funding: National Institute for Health Research.
The lancet. Psychiatry · systematic review · 236 citationsread the source →
Stigma reduction interventions for children and adolescents in low- and middle-income countries: Systematic review of intervention strategies.
Stigmatisation and discrimination are common worldwide, and have profound negative impacts on health and quality of life. Research, albeit limited, has focused predominantly on adults. There is a paucity of literature about stigma reduction strategies concerning children and adolescents, with evidence especially sparse for low- and middle-income countries (LMIC). This systematic review synthesised child-focused stigma reduction strategies in LMIC, and compared these to adult-focused interventions. Relevant publications were systematically searched in July and August 2018 in the following databases; Cochrane, Embase, Global Health, HMIC, Medline, PsycINFO, PubMed and WorldWideScience.org, and through Google Custom Search. Included studies and identified reviews were cross-referenced. Three categories of search terms were used: (i) stigma, (ii) intervention, and (iii) LMIC settings. Data on study design, participants and intervention details including strategies and implementation factors were extracted. Within 61 unique publications describing 79 interventions, utilising 14 unique stigma reduction strategies, 14 papers discussed 21 interventions and 10 unique strategies involving children. Most studies targeted HIV/AIDS (50% for children, 38% for adults) or mental illness (14% vs 34%) stigma. Community education (47%), individual empowerment (15%) and social contact (12%) were most employed in child-focused interventions. Most interventions were implemented at one socio-ecological level; child-focused interventions mostly employed community-level strategies (88%). Intervention duration was mostly short; between half a day and a week. Printed or movie-based material was key to deliver child-focused interventions (37%), while professionals most commonly implemented adult-focused interventions (53%). Ten unique, child-focused strategies were all evaluated positively, using a diverse set of scales. Children and adolescents are under-represented in stigma reduction in LMIC. More stigma reduction interventions in LMIC, addressing a wider variety of stigmas, with children as direct and indirect target group, are needed. This systematic review is registered under International Prospective Register of Systematic Reviews PROSPERO, reference number #CRD42018094700.
Social science & medicine (1982) · systematic review · 77 citationsread the source →
Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, Leucht S, Ruhe HG, Turner EH, Higgins JPT, Egger M, Takeshima N, Hayasaka Y, Imai H, Shinohara K, Tajika A, Ioannidis JPA, Geddes JR. (2018)MEDLINE-indexed journal, not yet read by usLancet (London, England) · systematic review Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.
Background: Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder.
Methods: We did a systematic review and network meta-analysis. We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016. We included placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults (≥18 years old and of both sexes) with major depressive disorder diagnosed according to standard operationalised criteria. We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; or patients with a serious concomitant medical illness. We extracted data following a predefined hierarchy. In network meta-analysis, we used group-level data. We assessed the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Primary outcomes were efficacy (response rate) and acceptability (treatment discontinuations due to any cause). We estimated summary odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO, number CRD42012002291.
Findings: We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89-2·41) for amitriptyline and 1·37 (1·16-1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72-0·97) and fluoxetine (0·88, 0·80-0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01-1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19-1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51-0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43-0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30-2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low.
Interpretation: All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants.
Funding: National Institute for Health Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science.
Lancet (London, England) · systematic review · 2220 citationsread the source →
Falk DE, O'Malley SS, Witkiewitz K, Anton RF, Litten RZ, Slater M, Kranzler HR, Mann KF, Hasin DS, Johnson B, Meulien D, Ryan M, Fertig J, Alcohol Clinical Trials Initiative (ACTIVE) Workgroup. (2019)MEDLINE-indexed journal, not yet read by usJAMA psychiatry · randomised controlled trial Evaluation of Drinking Risk Levels as Outcomes in Alcohol Pharmacotherapy Trials: A Secondary Analysis of 3 Randomized Clinical Trials.
Importance: The US Food and Drug Administration recognizes total abstinence and no heavy drinking days as outcomes for pivotal pharmacotherapy trials for alcohol use disorder (AUD). Many patients have difficulty achieving these outcomes, which can discourage seeking treatment and has slowed the development of medications that affect alcohol use.
Objective: To compare 2 drinking-reduction outcomes with total abstinence and no heavy drinking outcomes.
Design, setting, and participants: Data were obtained from 3 multisite, randomized, placebo-controlled clinical trials of medications for treating alcohol dependence (naltrexone, varenicline, and topiramate) in adults with DSM-IV-categorized alcohol dependence.
Main outcomes and measures: Within each trial, the percentage of participants in active and placebo conditions who met responder definitions of abstinence, no heavy drinking days, a WHO 1-level reduction, and a WHO 2-level reduction was computed by month with corresponding effect sizes (Cohen h).
Results: Across the 3 trials (N = 1169; mean [SD] age, 45 [10] years; 824 [70.5%] men), the percentage of participants classified as responders during the last 4 weeks of treatment was lowest for abstinence (naltrexone, 34.7% [100 of 288]; varenicline, 7.3% [7 of 96]; topiramate, 11.7% [21 of 179]) followed by no heavy drinking days (naltrexone, 51.0% [147 of 288]; varenicline, 24.0% [23 of 96]; topiramate, 20.7% [37 of 179]), WHO 2-level reduction (naltrexone, 75.0% [216 of 288]; varenicline, 55.2% [53 of 96]; topiramate, 44.7% [80 of 179]), and WHO 1-level reduction (naltrexone, 83.3% [240 of 288]; varenicline, 69.8 [67 of 96]; topiramate, 54.7% [98 of 179]) outcomes. Standardized treatment effects observed for the WHO 2-level reduction outcomes (naltrexone, Cohen h = 0.214 [95% CI, 0.053 -0.375]; varenicline, 0.273 [95% CI, -0.006 to 0.553]; topiramate, 0.230 [95% CI, 0.024-0.435]) and WHO 1-level reduction (naltrexone, Cohen h = 0.116 [95% CI, -0.046 to 0.277]; varenicline, 0.338 [95% CI, 0.058-0.617]; topiramate, 0.014 [95% CI, -0.192 to 0.219]) were comparable with those obtained using abstinence (naltrexone, Cohen h = 0.142 [95% CI, -0.020 to 0.303]; varenicline, 0.146 [95% CI, -0.133 to 0.426]; topiramate, 0.369 [95% CI, 0.163-0.574]) and no heavy drinking days (naltrexone, Cohen h = 0.140 [95% CI, -0.021 to 0.302]; varenicline, 0.232 [95% CI, -0.048 to 0.511]; topiramate, 0.207 [95% CI, 0.002-0.413]).
Conclusions and relevance: WHO drinking risk level reductions appear to be worthwhile indicators of treatment outcome in AUD pharmacotherapy trials. These outcomes may align with drinking reduction goals of many patients and capture clinically meaningful improvements experienced by more patients than either abstinence or no heavy drinking days.
Trial registration: ClinicalTrials.gov identifiers: NCT00006206; NCT01146613; NCT00210925.
JAMA psychiatry · randomised controlled trial · 98 citationsread the source →
Salum GA, Petersen CS, Jarros RB, Toazza R, DeSousa D, Borba LN, Castro S, Gallegos J, Barrett P, Abend R, Bar-Haim Y, Pine DS, Koller SH, Manfro GG. (2018)MEDLINE-indexed journal, not yet read by usJournal of child and adolescent psychopharmacology · randomised controlled trial Group Cognitive Behavioral Therapy and Attention Bias Modification for Childhood Anxiety Disorders: A Factorial Randomized Trial of Efficacy.
Background: The objective of this study is to assess group differences in symptom reduction between individuals receiving group cognitive behavioral therapy (G-CBT) and attention bias modification (ABM) compared to their respective control interventions, control therapy (CT), and attention control training (ACT), in a 2 × 2 factorial design.
Methods: A total of 310 treatment-naive children (7-11 years of age) were assessed for eligibility and 79 children with generalized, separation or social anxiety disorder were randomized and received G-CBT (n = 42) or CT (n = 37). Within each psychotherapy group, participants were again randomized to ABM (n = 38) or ACT (n = 41) in a 2 × 2 factorial design resulting in four groups: G-CBT + ABM (n = 21), G-CBT + ACT (n = 21), CT + ABM (n = 17), and CT + ACT (n = 20). Primary outcomes were responder designation as defined by Clinical Global Impression-Improvement (CGI-I) scale (≤2) and change on the Pediatric Anxiety Rating Scale (PARS).
Results: There were significant improvements of symptoms in all groups. No differences in response rates or mean differences in PARS scores were found among groups: G-CBT + ABM group (23.8% response; 3.9 points, 95% confidence interval [CI] -0.3 to 8.1), G-CBT + ACT (42.9% response; 5.6 points, 95% CI 2.2-9.0), CT + ABM (47.1% response; 4.8 points 95% CI 1.08-8.57), and CT + ACT (30% response; 0.8 points, 95% CI -3.0 to 4.7). No evidence or synergic or antagonistic effects were found, but the combination of G-CBT and ABM was found to increase dropout rate.
Conclusions: We found no effect of G-CBT or ABM beyond the effects of comparison groups. Results reveal no benefit from combining G-CBT and ABM for anxiety disorders in children and suggest potential deleterious effects of the combination on treatment acceptability.
Journal of child and adolescent psychopharmacology · randomised controlled trial · 15 citationsread the source →
Ponsioen CY, de Groof EJ, Eshuis EJ, Gardenbroek TJ, Bossuyt PMM, Hart A, Warusavitarne J, Buskens CJ, van Bodegraven AA, Brink MA, Consten ECJ, van Wagensveld BA, Rijk MCM, Crolla RMPH, Noomen CG, Houdijk APJ, Mallant RC, Boom M, Marsman WA, Stockmann HB, Mol B, de Groof AJ, Stokkers PC, D'Haens GR, Bemelman WA, LIR!C study group. (2017)MEDLINE-indexed journal, not yet read by usThe lancet. Gastroenterology & hepatology · randomised controlled trial Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial.
Background: Treatment of patients with ileocaecal Crohn's disease who have not responded to conventional therapy is commonly scaled up to biological agents, but surgery can also offer excellent short-term and long-term results. We compared laparoscopic ileocaecal resection with infliximab to assess how they affect health-related quality of life.
Methods: In this randomised controlled, open-label trial, in 29 teaching hospitals and tertiary care centres in the Netherlands and the UK, adults with non-stricturing, ileocaecal Crohn's disease, in whom conventional therapy has failed were randomly allocated (1:1) by an internet randomisation module with biased-coin minimisation for participating centres and perianal fistula to receive laparoscopic ileocaecal resection or infliximab. Eligible patients were aged 18-80 years, had active Crohn's disease of the terminal ileum, and had not responded to at least 3 months of conventional therapy with glucocorticosteroids, thiopurines, or methotrexate. Patients with diseased terminal ileum longer than 40 cm or abdominal abscesses were excluded. The primary outcome was quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ) at 12 months. Secondary outcomes were general quality of life, measured by the Short Form-36 (SF-36) health survey and its physical and mental component subscales, days unable to participate in social life, days on sick leave, morbidity (additional procedures and hospital admissions), and body image and cosmesis. Analyses of the primary outcome were done in the intention-to-treat population, and safety analyses were done in the per-protocol population. This trial is registered at the Dutch Trial Registry (NTR1150).
Findings: Between May 2, 2008, and October 14, 2015, 73 patients were allocated to have resection and 70 to receive infliximab. Corrected for baseline differences, the mean IBDQ score at 12 months was 178·1 (95% CI 171·1-185·0) in the resection group versus 172·0 (164·3-179·6) in the infliximab group (mean difference 6·1 points, 95% CI -4·2 to 16·4; p=0·25). At 12 months, the mean SF-36 total score was 112·1 (95% CI 108·0-116·2) in the resection group versus 106·5 (102·1-110·9) in the infliximab group (mean difference 5·6, 95% CI -0·4 to 11·6), the mean physical component score was 47·7 (45·7-49·7) versus 44·6 (42·5-46·8; mean difference 3·1, 4·2 to 6·0), and the mean mental component score was 49·5 (47·0-52·1) versus 46·1 (43·3-48·9; mean difference 3·5, -0·3 to 7·3). Mean numbers of days of sick leave were 3·4 days (SD 7·1) in the resection group versus 1·4 days (4·7) in the infliximab group (p<0·0001), days not able to take part in social life were 1·8 days (6·3) versus 1·1 days (4·5; p=0·20), days of scheduled hospital admission were 6·5 days (3·8) versus 6·8 days (3·2; p=0·84), and the number of patients who had unscheduled hospital admissions were 13 (18%) of 73 versus 15 (21%) of 70 (p=0·68). Body-image scale mean scores in the patients who had resection were 16·0 (95% CI 15·2-16·8) at baseline versus 17·8 (17·1-18·4) at 12 months, and cosmetic scale mean scores were 17·6 (16·6-18·6) versus 18·6 (17·6-19·6). Surgical intervention-related complications classified as IIIa or worse on the Clavien-Dindo scale occurred in four patients in the resection group. Treatment-related serious adverse events occurred in two patients in the infliximab group. During a median follow-up of 4 years (IQR 2-6), 26 (37%) of 70 patients in the infliximab group had resection, and 19 (26%) of 73 patients in the resection group received anti-TNF.
Interpretation: Laparoscopic resection in patients with limited (diseased terminal ileum <40 cm), non-stricturing, ileocaecal Crohn's disease in whom conventional therapy has failed could be considered a reasonable alternative to infliximab therapy.
Funding: Netherlands Organisation for Health Research and Development.
The lancet. Gastroenterology & hepatology · randomised controlled trial · 228 citationsread the source →
Goldstein LH, Robinson EJ, Mellers JDC, Stone J, Carson A, Reuber M, Medford N, McCrone P, Murray J, Richardson MP, Pilecka I, Eastwood C, Moore M, Mosweu I, Perdue I, Landau S, Chalder T, CODES study group. (2020)MEDLINE-indexed journal, not yet read by usThe lancet. Psychiatry · randomised controlled trial Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.
Background: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency.
Methods: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544.
Findings: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events.
Interpretation: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach.
Funding: National Institute for Health Research, Health Technology Assessment programme.
The lancet. Psychiatry · randomised controlled trial · 192 citationsread the source →
Shinde S, Weiss HA, Varghese B, Khandeparkar P, Pereira B, Sharma A, Gupta R, Ross DA, Patton G, Patel V. (2018)MEDLINE-indexed journal, not yet read by usLancet (London, England) · randomised controlled trial Promoting school climate and health outcomes with the SEHER multi-component secondary school intervention in Bihar, India: a cluster-randomised controlled trial.
Background: School environments affect health and academic outcomes. With increasing secondary school retention in low-income and middle-income countries, promoting quality school social environments could offer a scalable opportunity to improve adolescent health and wellbeing.
Methods: We did a cluster-randomised trial to assess the effectiveness of a multi-component whole-school health promotion intervention (SEHER) with integrated economic and process evaluations in grade 9 students (aged 13-14 years) at government-run secondary schools in the Nalanda district of Bihar state, India. Schools were randomly assigned (1:1:1) to three groups: the SEHER intervention delivered by a lay counsellor (the SEHER Mitra [SM] group), the SEHER intervention delivered by a teacher (teacher as SEHER Mitra [TSM] group), and a control group in which only the standard government-run classroom-based life-skills Adolescence Education Program was implemented. The primary outcome was school climate measured with the Beyond Blue School Climate Questionnaire (BBSCQ). Students were assessed at the start of the academic year (June, 2015) and again 8 months later at the end of the academic year (March, 2016) via self-completed questionnaires. This study is registered with ClinicalTrials.gov, number NCT02484014.
Findings: Of the 112 eligible schools in the Nalanda district, 75 were randomly selected to participate in the trial. We randomly assigned 25 schools to each of the three groups. One school subsequently dropped out of the TSM group, leaving 24 schools in this group. The baseline survey included a total of 13 035 participants, and the endpoint survey included 14 414 participants. Participants in the SM-delivered intervention schools had substantially higher school climate scores at endpoint survey than those in the control group (BBSCQ baseline-adjusted mean difference [aMD] 7·57 [95% CI 6·11-9·03]; effect size 1·88 [95% CI 1·44-2·32], p<0·0001) and the TSM-delivered intervention (aMD 7·57 [95% CI 6·06-9·08]; effect size 1·88 [95% CI 1·43-2·34], p<0·0001). There was no effect of the TSM-delivered intervention compared with control (aMD -0·009 [95% CI -1·53 to 1·51], effect size 0·00 [95% CI -0·45 to 0·44], p=0·99). Compared with the control group, participants in the SM-delivered intervention schools had moderate to large improvements in the secondary outcomes of depression (aMD -1·23 [95% CI -1·89 to -0·57]), bullying (aMD -0·91 [95% CI -1·15 to -0·66]), violence victimisation (odds ratio [OR] 0·62 [95% CI 0·46-0·84]), violence perpetration (OR 0·68 [95% CI 0·48-0·96]), attitude towards gender equity (aMD 0·41 [95% CI 0·21-0·61]), and knowledge of reproductive and sexual health (aMD 0·29 [95% CI 0·06-0·53]). Similar results for these secondary outcomes were noted for the comparison between SM-delivered intervention schools and TSM-delivered intervention schools (depression: aMD -1·23 [95% CI -1·91 to -0·55]; bullying: aMD -0·83 [95% CI -1·08 to -0·57]; violence victimisation: OR 0·49 [95% CI 0·35-0·67]; violence perpetration: OR 0·49 [95% CI 0·34-0·71]; attitude towards gender equity: aMD 0·23 [95% CI 0·02-0·44]; and knowledge of reproductive and sexual health: aMD 0·22 [95% CI -0·02 to 0·47]). However, no effects on these secondary outcomes were observed for the TSM-delivered intervention schools compared with the control group (depression: aMD -0·03 [95% CI -0·70 to 0·65]; bullying: aMD -0·08 [95% CI -0·34 to 0·18]; violence victimisation: OR 1·27 [95% CI 0·93-1·73]; violence perpetration: OR 1·37 [95% CI 0·95-1·95]; attitude towards gender equity: aMD 0·17 [95% CI -0·09 to 0·38]; and knowledge of reproductive and sexual health: aMD 0·06 [95% CI -0·18 to 0·32]).
Interpretation: The multi-component whole-school SEHER health promotion intervention had substantial beneficial effects on school climate and health-related outcomes when delivered by lay counsellors, but no effects when delivered by teachers. Future research should focus on the evaluation of the scaling up of the SEHER intervention in diverse contexts and delivery agents.
Funding: John D. and Catherine T. MacArthur Foundation, USA and the United Nations Population Fund India Office.
Lancet (London, England) · randomised controlled trial · 121 citationsread the source →
Depression and anxiety in labor migrants and refugees--a systematic review and meta-analysis.
Prevalence rates of depression and anxiety among migrants (i.e. refugees, labor migrants) vary among studies and it's been found that prevalence rates of depression and anxiety may be linked to financial strain in the country of immigration. Our aim is to review studies on prevalence rates of depression and/or anxiety (acknowledging that Post-traumatic Stress Disorder (PTSD) is within that class of disorders), and to evaluate associations between the Gross National Product (GNP) of the immigration country as a moderating factor for depression, anxiety and PTSD among migrants. We carried out a systematic literature review in the databases MEDLINE and EMBASE for population based studies published from 1990 to 2007 reporting prevalence rates of depression and/or anxiety and or PTSD according to DSM- or ICD- criteria in adults, and a calculation of combined estimates for proportions using the DerSimonian-Laird estimation. A total of 348 records were retrieved with 37 publications on 35 populations meeting our inclusion criteria. 35 studies were included in the final evaluation. Our meta-analysis shows that the combined prevalence rates for depression were 20 percent among labor migrants vs. 44 percent among refugees; for anxiety the combined estimates were 21 percent among labor migrants vs. 40 percent among (n=24,051) refugees. Higher GNP in the country of immigration was related to lower symptom prevalence of depression and/or anxiety in labor migrants but not in refugees. We conclude that depression and/or anxiety in labor migrants and refugees require separate consideration, and that better economic conditions in the host country reflected by a higher GNP appear to be related to better mental health in labor migrants but not in refugees.
Social science & medicine (1982) · meta-analysis · 385 citationsread the source →
Psychological morbidity and quality of life of ethnic minority patients with cancer: a systematic review and meta-analysis.
Background: Ethnic minority is associated with higher cancer incidence and poorer survival than is being in the majority group. We did a systematic review and meta-analysis to assess whether psychological morbidity and health-related quality of life (HRQoL) were affected by minority status.
Methods: We searched Medline, AMED, PsycINFO, Embase, CENTRAL, CINAHL, PubMed, Sociological Abstracts, and Web of Science for English-language articles published between Jan 1, 1995, and October, 2009. Articles were eligible if they reported original data on anxiety, depression, distress (for psychological morbidity), or HRQoL in minority and majority cancer patients or survivors. Minority status was defined as being an immigrant or having an ethnic, linguistic, or religious background different to the majority of the population in the country where the research was done. We excluded African Americans and indigenous groups. Eligible articles were rated for quality of reporting, external validity, internal validity, sample size, and power. Each quality criterion was rated independently by two reviewers until inter-rater reliability was achieved. In a meta-analysis we compared mean scores adjusted for socioeconomic status and other sociodemographic and clinical variables, where available. Effect sizes greater than 0·5 and 95% CI that included 0·5 or -0·5 were deemed clinically important, with negative values indicating worse outcomes in minority patients. We assessed publication bias by estimating the number of potential unpublished studies and the number of non-signficant studies with p=0·05 required to produce a non-significant overall result.
Findings: We identified 21 eligible articles that included 18 datasets collected in the USA and one in each of Canada, Romania, and the UK. Ethnic minority groups were Hispanic, Asian or Pacific Islander, or Hungarian (one dataset). Overall, we found minority versus majority groups to have significantly worse distress (mean difference -0·37, 95% CI -0·46 to -0·28; p<0·0001), depression (-0·23, -0·36 to -0·11; p=0·0003), and overall HRQoL (-0·33, -0·58 to -0·07; p=0·013). Further analyses found disparities to be specific to Hispanic patients in the USA, in whom poorer outcomes were consistent with potentially clinically important differences for distress (effect size -0·37, 95% CI -0·54 to -0·20; p<0·0001), social HRQoL (-0·45, -0·87 to -0·03; p=0·035), and overall HRQoL (-0·49, -0·78 to -0.20; p=0·0008). Results were significantly heterogeneous for overall HRQoL and all domains. Tests for interaction, for adjusted versus unadjusted and comparisons of high-quality, medium-quality, and low-quality articles, were generally non-significant, which suggests no bias. We found no evidence of any substantive publication bias.
Interpretation: Hispanic cancer patients in the USA, but not other ethnic minority groups, report significantly worse distress, depression, social HRQoL, and overall HRQoL than do majority patients, of which all but depression might be clinically important. Heterogeneous results might, however, have limited the interpretation. Data for other minority groups and for anxiety are scarce. More studies are needed from outside the USA. Future reports should more clearly describe their minority group samples and analyses should control for clinical and sociodemographic variables known to predict outcomes. Understanding of why outcomes are poor in US Hispanic patients is needed to inform the targeting of interventions.
Funding: Prince of Wales Hospital, Sydney, Australia.
The Lancet. Oncology · meta-analysis · 152 citationsread the source →
The Social Epidemiology of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome
Social epidemiology is defined as the study of the distribution of health outcomes and their social determinants (1). It builds on the classic epidemiologic triangle of host, agent, and environment to focus explicitly on the role of social determinants in infectious disease transmission and progression. These determinants are the “features of and pathways by which societal conditions affect health” (2, p. 697). Early studies of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) focused on individual characteristics and behaviors in determining HIV risk, an approach that Fee and Krieger (3) refer to as “biomedical individualism.” Biomedical individualism is the basis of risk factor epidemiology; by contrast, the social epidemiology perspective emphasizes social conditions as fundamental causes of disease (4) (table 1). Social epidemiologists examine how persons become exposed to risk or protective factors and under what social conditions individual risk factors are related to disease. Social factors are thus the focus of analysis and are not simply adjusted for as potentially confounding factors or used as proxies for unavailable individual-level data. Social factors are indeed critical to understanding nonuniform infectious disease patterns that emerge as a result of the dependent nature of disease transmission or the idea that an outcome in one person is dependent upon outcomes and exposures in others (5, 6). Contact patterns that enhance HIV/AIDS vulnerability may be conceptualized at multiple levels. Figure 1 distinguishes determinants of HIV/AIDS at three levels: individual, social, and structural. Individual factors include biologic, demographic, and behavioral risk factors that may influence the risk of HIV acquisition and disease progression. Social-level factors include critical pathways by which community and network structures link persons to society. These structures are central to understanding the diffusion and differential distribution of HIV/AIDS in population subgroups. Structural-level factors include social and economic factors, as well as laws and policies. These factors, in turn, affect HIV transmission dynamics and the differential distribution of HIV/AIDS. Infectious disease epidemiology provides models of the mechanisms through which social determinants affect HIV transmission (7). For example, the basic reproductive number of an infectious disease, R0 (8), describes secondary infections that arise from a primary infection. In the equation R0 = βCD, β is the probability of infection per contact, C is the number of contacts, and D is the duration of infectivity. The goal of intervention efforts is to reduce the empirical value of these terms by modifying the social conditions under which individual risk factors lead to disease. Examples of factors that affect the component terms of R0 in HIV epidemiology are presented in table 2. In this review, we present existing evidence linking social and structural determinants to HIV/AIDS. In addition, we discuss the implications of these findings for future social epidemiology research on HIV/AIDS as well as the design of more effective HIV/AIDS interventions. We searched the published literature to identify conceptual and empirical research reports on the social epidemiology of HIV/AIDS. Five databases were searched: PsycINFO (American Psychological Association, Washington, DC), PubMed (MEDLINE; National Institutes of Health, Bethesda, Maryland), Social Science Citation Index (Web of Science; Thomson ISI, Stamford, Connecticut), Sociological Abstracts (CSA, Bethesda, Maryland), and Digital Dissertations (ProQuest; UMI, Ann Arbor, Michigan). Searches were designed to include the factors we specified in our framework as social or structural factors (figure 1). Searches were limited to published articles in the English language for the period 1981–2003. The following keywords were included in each search: AIDS/acquired immunodeficiency syndrome, HIV, and epidemiol*. Additional searches were conducted by using combinations of keywords listed in Appendix table 1 corresponding with our framework. We identified four categories of social-level factors of importance to HIV/AIDS epidemiology: cultural context, social networks, neighborhood effects, and social capital. Each uses different conceptual and methodological approaches to examine the effects of social forces on population HIV/AIDS vulnerability. Anthropologist Edward Tylor defined culture as “that complex whole which includes knowledge, belief, art, law, morals, custom, and any other capabilities and habits acquired by man as a member of society” (9, p. 1). Anthropologic and epidemiologic approaches may be integrated in a variety of ways to identify features of the social environment that affect HIV/AIDS risk. One way to explore how the social environment affects HIV/AIDS epidemiology is through the use of mixed research methods. Mixed-methods study designs integrate qualitative and quantitative research methods either sequentially or concurrently (10). In sequential study designs, qualitative methods may be used to explore a topic under study or to explain quantitative epidemiologic findings. Concurrent study designs are meant to confirm, cross-validate, or corroborate findings within a single study. A common type of concurrent mixed methods study is “triangulation,” and this approach has been used extensively in rapid assessments of illicit drug use and HIV/AIDS (11–13). Mixed methods approaches are particularly well suited to the investigation of the often hidden and stigmatizing behavioral and social factors underlying HIV epidemics. One exemplary study combining qualitative methods with quantitative methods was conducted by Beyrer et al. (14) to examine the role of overland heroin trafficking routes in shaping explosive HIV/AIDS epidemics among injection drug users in Southeast Asia. Piecing together data from a variety of sources, including existing epidemiologic data, key informant interviews, and laboratory data, this study revealed that distinct HIV subtypes emerged and recombined along drug trafficking routes originating in Myanmar, one of the world’s largest heroin producers. Along these trafficking routes, communities of injection drug users formed, facilitating the spread of HIV into local communities in Laos, Thailand, Vietnam, India, and China (refer, for example, to Panda et al. (15)). This illustration highlights the broader understanding of HIV/AIDS epidemiology that can be achieved by examining the interplay between contextual factors and social and behavioral factors. Investigation of social networks in HIV/AIDS began with the mapping of relationships between one of the first identified AIDS cases, an airline steward, and a large number of his male sex partners in the early 1980s (16). Social network analysis generates measures of the quality, density, position, and structure of relationships between persons, including dyads (partnerships), personal networks (“egocentric” networks), and larger communities (“sociometric” networks) (17, 18). Social networks can influence health outcomes in direct and indirect ways, including 1) social influence, 2) social engagement and participation, 3) prevalence of infectious disease and network member mixing, 4) access to material goods and informational resources, and 5) social support (19). Researchers have demonstrated that patterns in the structure of relationships—rather than differences in individual risk behaviors alone—explain observed HIV patterns (20, 21). The theoretical foundation for examining social networks in HIV research is closely tied to advances in sexually transmitted disease (STD) epidemiology. A key concept from STD epidemiology is the notion of the “core group,” a small group of disease transmitters responsible for a large proportion of cases (22). Friedman et al. (23) found that individuals’ locations within sociometric risk networks were associated with HIV risk among a group of injection drug users in New York City. Other concepts from STD epidemiology, such as partner concurrency, bridging, and mixing patterns, are also important in understanding HIV risk (24–29). Specific network characteristics that have been associated with HIV/AIDS include the size of subgroups and their distribution in a network (23), the centrality of HIV-positive persons within networks (30), partner selection patterns (24, 31–33), and concurrent sexual partnerships (28). Inclusion of these variables has been shown to improve transmission estimates in mathematical modeling (34, 35). Social and normative influences have also been associated with individual HIV risks (36, 37). Network-related social and normative influences are predictive of illicit drug use (38) and condom use behavior (37, 39), highlighting the importance of network-based interventions for HIV prevention (18). Kelly et al. (40, 41) developed a popular opinion leader model that has been effective in reducing HIV risk in several populations, including men who have sex with men and women in low-income housing (42). The success of this model has led to its adaption for international use by the National Institute of Mental Health Collaborative HIV/STD Prevention Trial in China, India, Peru, Russia, and Zimbabwe. Neighborhoods represent the intersection of social networks and physical spatial locations, a confluence Wallace (43) has called the “sociogeographic networks” through which infectious diseases spread. Early interest in the role of neighborhood social environment in disease transmission was sparked by a study in Colorado Springs, Colorado, in which researchers found that gonorrhea was highly focused geographically in core residential neighborhoods (44). Both direct and indirect mechanisms may determine how neighborhood-level factors shape population HIV/AIDS patterns. Direct mechanisms are those that increase the likelihood of a person coming into contact with someone who is HIV positive, for example, through residential segregation and the social isolation of marginalized populations. Indirect mechanisms include those that increase population vulnerability to HIV/AIDS, such as exposure to poor socioeconomic conditions, high unemployment, or the proliferation of illicit drug markets. A range of neighborhood-level factors have been examined in relation to infectious disease, including poverty and income (45, 46), residential segregation (47), and neighborhood physical environment (48, 49). Current research in neighborhood and area effects on health emphasizes the importance of moving beyond documentation of associations to analyze the social and epidemiologic mechanisms through which neighborhood effects might operate (50–54). Increasing concentrations of affluence and poverty are contributing to what demographer Douglas Massey has called “a radical change in the geographic basis of human society” (55, p. 395). Powerful social and economic forces in US cities are increasing neighborhood segregation by class and race/ethnicity (56, 57). Resulting social disorganization and loss of resources and services in poor neighborhoods are in turn shaping HIV/AIDS patterns at the neighborhood level. In a number of studies in New York City, for example, Wallace (58–63) has examined the complex interplay of public policies such as “planned shrinkage” with HIV epidemic dynamics in the Bronx, documenting the “synergy of plagues” that has accompanied rapid social change and the destruction of essential protective networks in poor communities. Using AIDS surveillance data, ecologic studies conducted in various US cities have also consistently found significant associations between income and poverty measures and neighborhood-level AIDS incidence and prevalence rates, and these findings have been consistent across census block groups (46), census tracts (64), and zip codes (65, 66). Length of survival an AIDS has also been with neighborhood measures of income and the of highly a of health at the population may also a role in shaping HIV/AIDS patterns, associations between HIV/AIDS and income at the neighborhood have not been well segregation by race/ethnicity is neighborhood-level that may an important role in HIV/AIDS may affect infectious disease patterns through the and isolation of persons in one increasing the probability of transmission within that For example, found that measures of residential isolation were protective for at risk of disease. Indirect effects of segregation are associated with of neighborhood and with for those in poor neighborhoods segregation may to understanding disease we of studies examining neighborhood segregation in relation to HIV/AIDS that have been The physical environment of neighborhoods has also been examined in relation to infectious disease. et al. examined gonorrhea and neighborhood physical environment in New by using an of physical to explore and to this the of physical such as and a in social in a of community this concept to public et al. found a significant between neighborhood physical and gonorrhea rates, a by a ecologic study of US physical environment may HIV risk by illicit drug use such as injection behaviors and of the mechanisms through which the observed associations may be and associations between the physical environment and HIV/AIDS is research is to support the design of neighborhood-level HIV/AIDS interventions. has differences are not result from social and economic by policies. are and to p. The of evidence ecologic associations between neighborhood-level factors and infectious disease that to be to identify of and defined social as of social structures that that is the of that in its not be p. Social may affect health through 1) the of 2) access to services and 3) of in a and 4) participation, to policies that are more to published studies have explicitly examined social in the of HIV/AIDS. 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Mental Health Response to the COVID-19 Outbreak in China
Back to table of contents Previous article Next article CommentaryFull AccessMental Health Response to the COVID-19 Outbreak in ChinaJunying Zhou, M.D., Ph.D., Liu Liu, M.D., Pei Xue, M.D., Xiaorong Yang, B.N., Xiangdong Tang, M.D., Ph.D.Junying Zhou, M.D., Ph.D., Liu Liu, M.D., Pei Xue, M.D., Xiaorong Yang, B.N., Xiangdong Tang, M.D., Ph.D.Published Online:7 May 2020https://doi.org/10.1176/appi.ajp.2020.20030304AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Transmission of the 2019 novel coronavirus (COVID-19) (1) has now widely and rapidly spread around the world. On March 11, 2020, the World Health Organization announced that COVID-19 is a pandemic (2). The rapid transmission and mortality risk of the COVID-19 infection may increase the risk of mental health problems among healthy individuals in the general public and worsen preexisting psychiatric problems in psychiatric patients, although data are still being gathered. A constellation of difficult feelings and psychological distress, including panic, worries, and depression, could be triggered by the fear of possible infection, being quarantined at hospitals and home, social isolation, and even the shortage of protective gear.A number of mental health surveys associated with the COVID-19 outbreak are being conducted in different vulnerable populations, which include infected patients, medical staff, students, and the general population. Liu et al. have reported results from a multicenter survey conducted among 1,563 medical staff members and found that the prevalence of depression and anxiety was 51% and 45%, respectively (3). So far, data on the mental health repercussions of the COVID-19 pandemic in outpatient populations have not been available. Thus, we conducted a questionnaire survey, from February 25 to March 9, 2020, among outpatients who sought care in the Departments of Psychiatry, Neurology, and Sleep Medicine in West China Hospital of Sichuan University (Chengdu, China). A self-report questionnaire was completed by outpatients, who provided consent, via the WeChat-based survey program Questionnaire Star. A total of 2,065 out of 3,441 patients completed the survey, including 589 new patients and 1,476 existing patients. The prevalence rates of mental health problems related to the COVID-19 outbreak, including anxiety (defined as a total score ≥5 on the Generalized Anxiety Disorder 7-item scale), depression (defined as a total score ≥5 on the Patient Health Questionnaire 9-item scale), and insomnia (defined as a total score ≥8 on the Insomnia Severity Index), were 25.5%, 16.9%, and 26.2%, respectively. Furthermore, 20.9% of patients (N=300) with preexisting psychiatric disorders (N=1,434) reported a deterioration of their mental health condition related to the pandemic. In particular, transportation restrictions, isolation at home, and fear of cross-infection in hospitals have inevitably become major concerns and barriers to treatment for these patients during the outbreak. Our survey also showed that 24.5% of new patients, including those with anxiety (N=46), depression (N=37), insomnia (N=79), and psychosis (N=21), could not receive timely diagnoses and treatment. Similarly, 22.0% of existing patients with diagnosed mental disorders, including depression, bipolar disorders, and schizophrenia (N=315), could not receive routine psychiatric care because of suspended hospital visits. Consequently, 18.1% of patients (N=259) have self-reduced medication dosages, and 17.2% of patients (N=247) stopped taking their medication because they could not gain access to prescriptions from physicians during the outbreak. As the lifetime prevalence of mental disorders is 16.6% among adults in China (4), millions of psychiatric patients may face barriers to help seeking for timely management of their mental health condition. The long-term repercussions of the viral pandemic on the management of psychiatric patients warrant further investigation. Nonetheless, our data reiterate the importance of implementing appropriate mental health care measures in the face of the COVID-19 pandemic. In response to the COVID-19 outbreak, there have been ongoing measures and concerted efforts in China that emphasize the importance of dealing with the potentially concurrent mental health crisis. On January 26, 2020, the National Health Commission of China released principles for emergency psychological crisis intervention for the COVID-19 pandemic (5). Mental health hotlines were quickly established across China and provided the public with counseling and psychological services. The telephone and Internet have been widely used to deliver mental health care services, and social media platforms (e.g., WeChat, Weibo) have been used to share strategies, guidelines, and education programs for managing potential mental distress. In addition, a series of self-help handbooks for psychological care associated with COVID-19 have been published by the China Association for Mental Health, medical institutions, and universities. Furthermore, a number of hospitals in China have initiated telemedicine services for patients in need during the outbreak of COVID-19. On January 26, 2020, West China Hospital of Sichuan University, as one of the leading hospitals in China, opened a free online outpatient service involving more than 100 medical doctors across specialties. This online outpatient service was created mainly to provide prescriptions to existing patients and to offer consultation to new patients. Our hospital collaborated with commercial courier services to deliver medication to patients' homes at no cost. To date, thousands of patients have received health care provided by this online outpatient service. Interestingly, only 7.4% of patients with mental disorders (N=136) in our survey have sought online help for medical care. Thus, there is a need to promote online mental health care services across China to manage mental health problems during the pandemic. The long-term outcomes of the mental health interventions in both community and hospital settings need further evaluation to determine how we can ameliorate the negative effects of viral outbreaks in the general public, especially among vulnerable patients with mental health problems. Sleep Medicine Center (Zhou, Xue, Tang), Department of Anesthesiology, Translational Neuroscience Center (Liu), and Outpatient Department (Yang), West China Hospital, Sichuan University, Chengdu, China. Send correspondence to Dr. Zhou ([email protected]).The authors report no financial relationships with commercial interests. The authors thank the clinic nurses in the Departments of Psychiatry, Neurology, and Sleep Medicine, West China Hospital, Sichuan University. References1 Lu R, Zhao X, Li J, et al.: Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395:565–574Crossref, Medline, Google Scholar2 World Health Organization (WHO): WHO director-general's opening remarks at the media briefing on COVID-19: 11 March 2020 (https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020)Google Scholar3 Liu S, Yang L, Zhang C, et al.: Online mental health services in China during the COVID-19 outbreak. Lancet Psychiatry 2020; 7:e17–e18Crossref, Medline, Google Scholar4 Huang Y, Wang Y, Wang H, et al.: Prevalence of mental disorders in China: a cross-sectional epidemiological study. Lancet Psychiatry 2019; 6:211–224Crossref, Medline, Google Scholar5 National Health Commission of China: [Principles for emergency psychological crisis intervention for the new coronavirus pneumonia.] http://www.nhc.gov.cn/jkj/s3577/202001/6adc08b966594253b2b791be5c3b9467.shtml (Chinese)Google Scholar FiguresReferencesCited byDetailsCited byRelationship between depression and burnout among nurses in Intensive Care units at the late stage of COVID-19: a network analysis1 April 2024 | BMC Nursing, Vol. 23, No. 1Effects of Long COVID on Psycho-Physical Conditions in the Italian Population: A Statistical and Large Language Model Combined Description27 April 2024 | European Journal of Investigation in Health, Psychology and Education, Vol. 14, No. 5The efficacy of internet-delivered cognitive-behavioral therapy for posttraumatic stress disorder according to the mean age of patients: a systematic review and meta-analysis11 December 2023 | Psychology, Health & Medicine, Vol. 29, No. 4Descripción de un Programa de Telesalud Mental en el Marco de la Pandemia de COVID-19 en ColombiaRevista Colombiana de Psiquiatría, Vol. 53, No. 2Longitudinal trajectories of anxiety and depression in subjects with different mental disorders after one year in the COVID-19 pandemicPsychiatry Research, Vol. 334The Impact of the COVID-19 Pandemic on the Mental Health of Families16 April 2024Effect of anxiety and depression on self-reported adverse reactions to COVID-19 vaccine: a cross-sectional study in Shanghai, China3 March 2023 | BMC Public Health, Vol. 23, No. 1Evaluation of cognitive functions in a group of Egyptian recovered COVID-19 patients22 May 2023 | Middle East Current Psychiatry, Vol. 30, No. 1Trends in telemedicine utilization for mental illness during the COVID-19 pandemic: an analysis of a nationwide database in Korea24 October 2023 | BMC Psychiatry, Vol. 23, No. 1Investigating the dynamic relationship between stigma of fear, discrimination and employees performance among healthcare workers during Covid-19 pandemic31 July 2023 | Cognition, Technology & Work, Vol. 25, No. 4"I Can't See an End in Sight." How the COVID-19 Pandemic May Influence Suicide RiskCrisis, Vol. 44, No. 6Mental Distress Among Norwegian Adults During the COVID-19 Pandemic: Predictors in Initial Response and Subsequent Trajectories25 October 2023 | International Journal of Public Health, Vol. 68The mediating effect of family health on the relationship between health literacy and mental health: A national cross-sectional survey in China24 April 2023 | International Journal of Social Psychiatry, Vol. 69, No. 6Coronavirus anxiety, fear level, and awareness of nursing students starting face-to-face education28 August 2023 | Journal of Public Health, Vol. 20Unleashing the link between the relaxation of the COVID-19 control policy and residents' mental health in China: the mediating role of family tourism consumption22 August 2023 | Frontiers in Public Health, Vol. 11Impact of the first wave of COVID-19 pandemic on the Hungarian university students' social and health behaviour28 October 2021 | Journal of Public Health, Vol. 31, No. 7Is psychologically vulnerable rural-to-urban migrants' mental health further at stake under China's tightened COVID-19 measures: how should the government respond?5 May 2023 | Frontiers in Sociology, Vol. 8The impact of the COVID-19 pandemic and earthquake on mental health of persons with severe mental illness: A survey study among people receiving community mental health care versus treatment as usual in Croatia1 November 2022 | International Journal of Social Psychiatry, Vol. 69, No. 3Prosocial behavior predicts meaning in life during the COVID-19 pandemic: The longitudinal mediating role of perceived social support16 March 2023 | Frontiers in Public Health, Vol. 11Inter-relationships of depressive and anxiety symptoms with suicidality among adolescents: A network perspectiveJournal of Affective Disorders, Vol. 324The Racial Differences in Impact and Knowledge of COVID-19 Among Patients with Psychiatric IllnessesCurrent Psychiatry Research and Reviews, Vol. 19, No. 1Codesign of a digital health tool for suicide prevention: protocol for a scoping review10 March 2023 | BMJ Open, Vol. 13, No. 3Chinese adolescents' depression, anxiety, and family mutuality before and after COVID ‐19 lockdowns: Longitudinal cross‐lagged relations2 September 2022 | Family Relations, Vol. 72, No. 1Public psychological crisis reports: an investigation during the remission of COVID-19 in China21 January 2022 | Chinese Management Studies, Vol. 17, No. 1"Nice You Share in Return": Informational Sharing, Reciprocal Sharing, and Life Satisfaction Amid COVID-19 Pandemic29 October 2022 | Social Indicators Research, Vol. 165, No. 2Psychological Distress of Healthcare Workers in 4 Hospitals Compared to General Population During the First Italian Wave of COVID-19 Pandemic27 January 2023 | INQUIRY: The Journal of Health Care Organization, Provision, and Financing, Vol. 60Effect of the COVID-19 Lockdown and Post-lockdown on Mental Health Among Diploma in Pharmacy Students27 July 2023Evaluation and Application of Cloud Computing in Mental Health Service PlatformProcedia Computer Science, Vol. 228A mathematical model of coronavirus transmission by using the heuristic computing neural networksEngineering Analysis with Boundary Elements, Vol. 146Complicaciones neuropsiquiátricas por COVID-1931 December 2022 | Salud, Ciencia y Tecnología, Vol. 2, No. S1Network analysis of depressive and anxiety symptoms in adolescents during the later stage of the COVID-19 pandemic10 March 2022 | Translational Psychiatry, Vol. 12, No. 1Impact of housing conditions on changes in youth's mental health following the initial national COVID-19 lockdown: a cohort study4 February 2022 | Scientific Reports, Vol. 12, No. 1COVID-19 behavioral health and quality of life19 January 2022 | Scientific Reports, Vol. 12, No. 1RETRACTED ARTICLE: Type 1 diabetes and the challenges of emotional support in crisis situations: results from a randomized clinical trial of a multidisciplinary teleintervention23 February 2022 | Scientific Reports, Vol. 12, No. 1Type 1 diabetes and the challenges of emotional support in crisis situations: results from a feasibility study of a multidisciplinary teleintervention20 May 2022 | Scientific Reports, Vol. 12, No. 1Prevalence of post-traumatic stress disorder symptoms among patients with mental disorder during the COVID-19 pandemic1 March 2022 | BMC Psychiatry, Vol. 22, No. 1COVID-19 and substance use disorders: a review of international guidelines for frontline healthcare workers of addiction services31 March 2022 | BMC Psychiatry, Vol. 22, No. 1Anxiety and depression in the post-pandemic era: concerns about viral mutation and re-outbreak3 November 2022 | BMC Psychiatry, Vol. 22, No. 1Gender differences in psychiatric outpatients: a before and during COVID-19 pandemic study in general hospitals from China7 September 2022 | Annals of General Psychiatry, Vol. 21, No. 1Public wellbeing analytics framework using social media chatter data3 November 2022 | Social Network Analysis and Mining, Vol. 12, No. 1Association between sedentary time and metabolic syndrome: A cross-sectional study among Chinese Garze Tibetans17 November 2022 | Frontiers in Public Health, Vol. 10COVID-19 pandemic and adolescent mental health in China: Micro evidence and socioeconomic mechanisms14 November 2022 | Frontiers in Psychology, Vol. 13A deep learning-based model for detecting depression in senior population7 November 2022 | Frontiers in Psychiatry, Vol. 13Einfluss der COVID-19-Pandemie auf die ambulante psychotherapeutische Versorgung von Kindern und Jugendlichen27 June 2022 | Die Psychotherapie, Vol. 67, No. 6Family Resilience, Media Exposure, and Children's Mental Health in China During COVID-196 December 2021 | The Family Journal, Vol. 30, No. 4The associations among the stress symptoms, depressive symptoms, anxiety symptoms and insomnia symptoms in depressed patients after the first COVID-19 outbreak was initially controlled in China: A prospective cohort studyJournal of Affective Disorders, Vol. 314Minority and low-SES families' experiences during the early phases of the COVID-19 pandemic crisis: A qualitative studyChildren and Youth Services Review, Vol. 140Network analysis of depression, anxiety, insomnia and quality of life among Macau residents during the COVID-19 pandemicJournal of Affective Disorders, Vol. 311Prevalence of problematic Internet use during the coronavirus disease 2019 pandemicCurrent Opinion in Behavioral Sciences, Vol. 46Prevalence of anxiety symptoms among Chinese university students amid the COVID-19 pandemic: A systematic review and meta-analysisHeliyon, Vol. 8, No. 8Machine learning approach for anxiety and sleep disorders analysis during COVID-19 lockdown30 May 2022 | Health and Technology, Vol. 12, No. 4Mental health of patients with mental illness during the COVID-19 pandemic lockdown: a questionnaire-based survey weighted for attrition17 September 2021 | Nordic Journal of Psychiatry, Vol. 76, No. 5Proposal of a Model for the Analysis of the State of the Use of ICT in Education Applied to Technological Institutes of Higher Education8 July 2022 | Computers, Vol. 11, No. Mental and COVID-19 A in the June 2022 | Frontiers in Public Health, Vol. of Psychiatric in Patients in Hospitals to COVID-19 Outbreak in A Center Longitudinal April 2022 | Vol. No. Use and Mental Health During the COVID-19 Health Vol. No. for During the COVID-19 Pandemic: A April 2022 | Frontiers in Psychiatry, Vol. post-traumatic in the general a cross-sectional study from August 2021 | Psychology, Health & Medicine, Vol. No. as in a with A Reports, Vol. 17, No. of symptoms in Internet and depression among adolescents in A network of Affective Disorders, Vol. March 2022 | University Journal of and of Social Media in for the of the Pandemic among Students27 February 2022 | International Journal of Research and Public Health, Vol. 19, No. of the during the COVID-19 Lockdown by the Mental Health by the of Psychology of March 2022 | International Journal of Research and Public Health, Vol. 19, No. symptoms during the early and late of the COVID-19 pandemic in China: a systematic review and Medicine, Vol. and Sleep of Patients with Sleep February 2022 | Journal of Sleep Medicine, Vol. 9, No. of and psychiatric symptoms in patients with psychiatric disorders during the Covid-19 May 2021 | European of Psychiatry and Vol. No. the Care and Anxiety of Patients with COVID-19 in November 2021 | Journal of and Health, Vol. No. impact of the pandemic on in the with preexisting mental health A longitudinal October 2021 | Journal of Vol. No. of Psychiatric and Psychiatric Among for During the Initial of COVID-19 Pandemic in Vol. 19, No. of the COVID-19 September to the Prevalence of of Mental in the During the COVID-19 Pandemic: December 2022 | Research, Vol. No. in the of the COVID-19 Pandemic in January 2022 | Journal of Science, Vol. No. 6Mental Health and among University during the COVID-19 Pandemic in January 2022 | Journal of Sciences, Vol. No. in the and COVID-19 among patients with psychiatric illness A study from of Psychiatry, Vol. No. on Impact of COVID-19 Pandemic on with their and with Social Psychiatry, Vol. No. and of to Department during COVID-19 Pandemic of December 2021 | Journal of Care Medicine, Vol. 25, No. impact of the COVID-19 pandemic on depression in a prospective cohort December 2021 | Medicine, Vol. impact in patients with mental disorders after of COVID-19 Vol. to the COVID-19 Pandemic Among the General February 2021 | Journal of and Studies, Vol. No. 8The impact of COVID-19 pandemic on symptoms and among patients with medication a cross-sectional May 2021 | The Journal of and Vol. 22, No. reactions and insomnia in adults with mental health disorders during the COVID-19 January 2021 | BMC Psychiatry, Vol. 21, No. and anxiety symptoms in adults before and during the COVID-19 pandemic: evidence from a September 2021 | Annals of General Psychiatry, Vol. No. 1Prevalence of psychiatric and related symptoms among patients with COVID-19 during the wave of the April 2021 | and Health, Vol. 17, No. anxiety, and post-traumatic stress symptoms and COVID-19 patients: a cross-sectional study4 May 2021 | Middle East Current Psychiatry, Vol. No. of a of patients with disorders during the first COVID-19 December 2021 | Scientific Reports, Vol. 11, No. 1Effects of COVID ‐19 pandemic on mental health outcomes in a cohort of early psychosis January 2021 | in Psychiatry, Vol. No. the psychological therapy treatment outcomes for adults who are not in of and be to November 2021 | Medicine, Vol. Health to Social During the COVID-19 Pandemic in a November 2021 | Frontiers in Public Health, Vol. between the COVID-19 and and symptoms in people with November 2021 | impact of and mental health on health during of Psychiatric Research, Vol. and of public health on public new A systematic March 2021 | International Journal of Social Psychiatry, Vol. 67, No. and disorders associated with COVID-19. disorders and Vol. of mental disorders on COVID-19 October 2021 | Neurology, Vol. 13, No. of COVID-19 pandemic on emergency community Psychiatry, Vol. and psychological impact of COVID-19 pandemic in a cohort study Vol. mental health and need for care among psychiatric outpatients during the COVID-19 pandemic: from an in Research, Vol. pandemic in January 2021 | Journal of Social and Vol. 23, No. Psychiatric and the of Mental during the COVID-19 Pandemic: A et la de la COVID-19: January 2021 | The Journal of Psychiatry, Vol. No. Media and Analysis during the Covid-19 September 2021 | Vol. 13, No. Distress During the COVID-19 Pandemic in Patients Mental August 2021 | Frontiers in Psychology, Vol. to Analysis of the of July 2021 | Vol. 13, No. of COVID-19: of and July 2021 | No. 29, of Health for the of July 2021 | Frontiers in Health, Vol. of the Patients in Hospital to the COVID-19 A July 2021 | Frontiers in Psychology, Vol. during the COVID-19 pandemic social July 2021 | Vol. No. COVID-19 in Chinese July 2021 | Frontiers in Medicine, Vol. experiences of and mental health services during the first Covid-19 of Health Vol. 9, No. Health and during the Pandemic in A Questionnaire of Mental Health and Psychiatric July 2021 | International Journal of Research and Public Health, Vol. No. of the COVID-19 pandemic on mental health service use among psychiatric outpatients in a of Affective Disorders, Vol. and Association of Life Among of Patients Psychiatric Services During the COVID-19 June 2021 | Frontiers in Psychiatry, Vol. of Anxiety to the COVID-19 Ph.D., Yang, Ph.D., Ph.D., Ph.D., Ph.D., Yang, Ph.D., Ph.D., Ph.D., Ph.D., Ph.D., Ph.D., Ph.D., Ph.D., Ph.D., Ph.D., Ph.D., M.D., Ph.D., April 2021 | Journal of Psychiatry, Vol. No. in depression & anxiety among mental health service during the COVID-19 pandemicJournal of Affective Disorders, Vol. symptoms and seeking during the Covid-19 May 2021 | Translational Psychiatry, Vol. 11, No. und und February 2021 | der Vol. No. prevalence of depressive and anxiety symptoms and their associations with quality of life among patients with psychiatric disorders during the COVID-19 January 2021 | Translational Psychiatry, Vol. 11, No. COVID-19 pandemic and mental of The Vol. of COVID-19 pandemic on the mental health of May 2021 | Journal of associated with mental health and quality of life during the COVID-19 pandemic in May 2021 | Open, Vol. No. and risk of psychiatric symptoms and diagnoses before and during the COVID-19 pandemic: from the COVID-19 mental health April 2021 | Medicine, Vol. in The impact of protective and on and Medicine in Psychiatry, Vol. COVID-19 the of March 2021 | Current Psychiatry Reports, Vol. 23, No. Medicine in Psychiatry in the COVID-19 era: the impact of the pandemic on mental Medicine in Psychiatry, Vol. and in the age of October 2020 | Psychology & Vol. No. in mental health problems related to COVID-19 in Hospital Psychiatry, Vol. mental health and novel coronavirus: The risk of the Journal of Psychiatry, Vol. for and Mental On the of COVID-19 February 2021 | Frontiers in Vol. of during COVID-19: a an January 2021 | Vol. 44, No. and psychological of students during the early stage of COVID-19 outbreak in China: a cross-sectional February 2021 | BMJ Open, Vol. 11, No. an to Mental Health, and among Youth and February 2021 | International Journal of Research and Public Health, Vol. No. in the and of Mental Health November from July Disorders, and and mental illness: A systematic review and & Health, Vol. and in pandemic: the in mental health October 2020 | International Journal of Vol. No. 1Prevalence and with Insomnia Among the Chinese General Public the 2019 June 2021 | and of Vol. the of December 2021 | and of Vol. Health for to Patients in a of Pandemic: and of Patient July 2021 | Mental Health, Vol. 8, No. impact of COVID-19 pandemic on the of depression among health care cross-sectional May 2021 | Vol. Mental Health the of in the April 2021 | Journal of Education in the Health Vol. No. from November to the Mental Health of by COVID-19 in China: A December 2020 | Frontiers in Psychiatry, Vol. of in 100 Patients Disorder During the COVID-19 Pandemic in December 2020 | Frontiers in Psychiatry, Vol. in of November 2020 | Current Psychiatry Reports, Vol. 22, No. adverse with during COVID-19 Journal of Psychiatry, Vol. of patients with Journal of Psychiatry, Vol. health response for and adolescents during the COVID-19 outbreak in Research, Vol. to COVID-19 to in and from a for Sleep in December 2020 | International Journal of Research and Public Health, Vol. 17, No. awareness of suicide during the October 2020 | Reports, Vol. No. of and health anxiety during COVID pandemic among of a psychiatric an Journal of impact of COVID ‐19 on individuals with disorders: A survey of individuals in the and the July 2020 | International Journal of Disorders, Vol. 53, No. and Distress COVID-19 Among University in the October 2020 | Frontiers in Psychiatry, Vol. pandemic and mental health review of the and Vol. and to the COVID-19 crisis in the of Psychiatric Research, Vol. of COVID-19 on Youth Mental Health, and A of and de la COVID-19 la de et adolescents un et July 2020 | The Journal of Psychiatry, Vol. No. Network Analysis of During the COVID-19 October 2020 | Frontiers in Psychology, Vol. of suicide during and after the COVID ‐19 September 2020 | World Psychiatry, Vol. 19, No. psychological and mental impact of coronavirus disease 2019 (COVID-19) on medical staff and general public A systematic review and Research, Vol. changes during COVID-19 and the potential A June 2020 | Journal of Health Psychology, Vol. 25, No. and July 2020 | Journal of Psychiatry, Vol. No. COVID-19-Pandemie die und Psychotherapie, Vol. No. 2019 (COVID-19) and Psychiatric in Anxiety and Journal of Medicine, Vol. 2, No. of COVID-19 on Mental Health in the September 2020 | Journal of Internet Research, Vol. 22, No. an Outpatient Psychiatric to During the COVID-19 Pandemic: A October 2020 | Journal of Internet Research, Vol. 22, No. disorders in people infected with the coronavirus September 2020 | Journal of Public Health, Vol. No. 4 July authors thank the clinic nurses in the Departments of Psychiatry, Neurology, and Sleep Medicine, West China Hospital, Sichuan April 2020 online May 2020 in 1 July 2020
American Journal of Psychiatry · 294 citationsread the source →
Ehrhardt MJ, Mulrooney DA, Li C, Baassiri MJ, Bjornard K, Sandlund JT, Brinkman TM, Huang IC, Srivastava DK, Ness KK, Robison LL, Hudson MM, Krull KR. (2018)MEDLINE-indexed journal, not yet read by usCancer Neurocognitive, psychosocial, and quality-of-life outcomes in adult survivors of childhood non-Hodgkin lymphoma.
Background: Children with non-Hodgkin lymphoma (NHL) undergo treatment with central nervous system-directed therapy, the potentially neurotoxic effects of which have not been reported in NHL survivors.
Methods: NHL survivors (n = 187) participating in the St. Jude Lifetime Cohort who were 10 or more years from their diagnosis and were 18 years old or older underwent neurocognitive, emotional distress (Brief Symptom Inventory 18), and health-related quality of life (HRQOL) assessments (36-Item Short Form Health Survey). Age-adjusted z scores were compared with community controls (n = 181) and normative data. Treatment exposures were abstracted from medical records. Models adjusted for the age, sex, and time from diagnosis were used to calculate the risk of impairment.
Results: The mean ages at evaluation were similar for the survivors and the controls (35.7 ± 8.9 vs 35.5 ± 11.0 years; P = .86). Survivors were 25.2 ± 8.8 years from their diagnosis: 43 (23%) received cranial radiation, 70 (37%) received high-dose methotrexate, 40 (21%) received high-dose cytarabine, and 151 (81%) received intrathecal chemotherapy. Survivors' intelligence and attention were within normal limits; however, their memory, executive function, processing speed, and academics were impaired in comparison with both population norms and community controls (P values < .05). Treatment-related exposures were not associated with neurocognitive function; however, neurocognitive impairment was associated with lower educational attainment, unemployment, and occupational status (P values < .03). Slower processing speed and worse self-reported executive function were associated with symptoms of depression (P values ≤ .003) and poorer HRQOL (P values < .05).
Conclusions: Adult survivors of childhood NHL experience impaired neurocognitive function, which is associated with lower social attainment and poor HRQOL. Early-detection and intervention strategies are recommended. Cancer 2017. © 2017 American Cancer Society.
Cancer · 34 citationsread the source →
Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial.
Background: Obesity is associated with a reduction in life expectancy and an increase in mortality from cardiovascular diseases, cancer, and other causes. We therefore assessed the efficacy and safety of two doses of phentermine plus topiramate controlled-release combination as an adjunct to diet and lifestyle modification for weight loss and metabolic risk reduction in individuals who were overweight and obese, with two or more risk factors.
Methods: In this 56-week phase 3 trial, we randomly assigned overweight or obese adults (aged 18-70 years), with a body-mass index of 27-45 kg/m(2) and two or more comorbidities (hypertension, dyslipidaemia, diabetes or prediabetes, or abdominal obesity) to placebo, once-daily phentermine 7·5 mg plus topiramate 46·0 mg, or once-daily phentermine 15·0 mg plus topiramate 92·0 mg in a 2:1:2 ratio in 93 centres in the USA. Drugs were administered orally. Patients were randomly assigned by use of a computer-generated algorithm that was implemented through an interactive voice response system, and were stratified by sex and diabetic status. Investigators, patients, and study sponsors were masked to treatment. Primary endpoints were the percentage change in bodyweight and the proportion of patients achieving at least 5% weight loss. Analysis was by intention to treat. This study is registered with Clinical Trials.gov, number NCT00553787.
Findings: Of 2487 patients, 994 were assigned to placebo, 498 to phentermine 7·5 mg plus topiramate 46·0 mg, and 995 to phentermine 15·0 mg plus topiramate 92·0 mg; 979, 488, and 981 patients, respectively, were analysed. At 56 weeks, change in bodyweight was -1·4 kg (least-squares mean -1·2%, 95% CI -1·8 to -0·7), -8·1 kg (-7·8%, -8·5 to -7·1; p<0·0001), and -10·2 kg (-9·8%, -10·4 to -9·3; p<0·0001) in the patients assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively. 204 (21%) patients achieved at least 5% weight loss with placebo, 303 (62%; odds ratio 6·3, 95% CI 4·9 to 8·0; p<0·0001) with phentermine 7·5 mg plus topiramate 46·0 mg, and 687 (70%; 9·0, 7·3 to 11·1; p<0·0001) with phentermine 15·0 mg plus topiramate 92·0 mg; for ≥10% weight loss, the corresponding numbers were 72 (7%), 182 (37%; 7·6, 5·6 to 10·2; p<0·0001), and 467 (48%; 11·7, 8·9 to 15·4; p<0·0001). The most common adverse events were dry mouth (24 [2%], 67 [13%], and 207 [21%] in the groups assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively), paraesthesia (20 [2%], 68 [14%], and 204 [21%], respectively), constipation (59 [6%], 75 [15%], and 173 [17%], respectively), insomnia (47 [5%], 29 [6%], and 102 [10%], respectively), dizziness (31 [3%], 36 [7%], 99 [10%], respectively), and dysgeusia (11 [1%], 37 [7%], and 103 [10%], respectively). 38 (4%) patients assigned to placebo, 19 (4%) to phentermine 7·5 mg plus topiramate 46·0 mg, and 73 (7%) to phentermine 15·0 mg plus topiramate 92·0 mg had depression-related adverse events; and 28 (3%), 24 (5%), and 77 (8%), respectively, had anxiety-related adverse events.
Interpretation: The combination of phentermine and topiramate, with office-based lifestyle interventions, might be a valuable treatment for obesity that can be provided by family doctors.
Funding: Vivus.
Lancet (London, England) · randomised controlled trial · 667 citationsread the source →
Cognitive reappraisal self-efficacy mediates the effects of individual cognitive-behavioral therapy for social anxiety disorder.
OBJECTIVE: To examine whether changes in cognitive reappraisal self-efficacy (CR-SE) mediate the effects of individually administered cognitive-behavioral therapy (I-CBT) for social anxiety disorder (SAD) on severity of social anxiety symptoms. METHOD: A randomized controlled trial in which 75 adult patients (21-55 years of age; 53% male; 57% Caucasian) with a principal diagnosis of generalized SAD were randomly assigned to 16 sessions of I-CBT (n = 38) or a wait-list control (WL) group (n = 37). All patients completed self-report inventories measuring CR-SE and social anxiety symptoms at baseline and post-I-CBT/post-WL, and I-CBT completers were also assessed at 1-year posttreatment. RESULTS: Compared with WL, I-CBT resulted in greater increases in CR-SE and greater decreases in social anxiety. Increases in CR-SE during I-CBT mediated the effect of I-CBT on social anxiety. Gains achieved by patients receiving I-CBT were maintained 1-year posttreatment, and I-CBT-related increases in CR-SE were also associated with reduction in social anxiety at the 1-year follow-up. CONCLUSIONS: Increasing CR-SE may be an important mechanism by which I-CBT for SAD produces both immediate and long-term reductions in social anxiety.
Journal of Consulting and Clinical Psychology · randomised controlled trial · 325 citationsread the source →
Treatment of posttraumatic stress disorder by trained lay counselors in an African refugee settlement: A randomized controlled trial.
Traumatic stress due to conflict and war causes major mental health problems in many resource-poor countries. The objective of this study was to examine whether trained lay counselors can carry out effective treatment of posttraumatic stress disorder (PTSD) in a refugee settlement. In a randomized controlled dissemination trial in Uganda with 277 Rwandan and Somalian refugees who were diagnosed with PTSD the authors investigated the effectiveness of psychotherapy administered by lay counselors. Strictly manualized narrative exposure therapy (NET) was compared with more flexible trauma counseling (TC) and a no-treatment monitoring group (MG). Fewer participants (4%) dropped out of NET treatment than TC (21%). Both active treatment groups were statistically and clinically superior to MG on PTSD symptoms and physical health but did not differ from each other. At follow-up, a PTSD diagnosis could not be established anymore in 70% of NET and 65% TC participants, whereas only 37% in MG did not meet PTSD criteria anymore. Short-term psychotherapy carried out by lay counselors with limited training can be effective to treat war-related PTSD in a refugee settlement.
Journal of Consulting and Clinical Psychology · randomised controlled trial · 395 citationsread the source →
Rumination and perceived impairment associated with depressive symptoms in a verbal adolescent-adult ASD sample.
The aim of this study was to examine the association between depressive symptoms and several psychosocial constructs (insight into autism symptoms, rumination, desire for social interaction, and satisfaction with social support) that may play a role in the development or maintenance of depression in verbally fluent adolescents and adults with ASD. Participants included 50 individuals with ASD and verbal IQ ≥ 70, aged 16-35 (sample size varied by measure). Elevated depressive symptoms on the Beck Depression Inventory, 2nd edition (BDI-II), were associated with greater self-perceived, autism-related impairments (n = 48), greater rumination (n = 21), and lower perceived social support (n = 37). Rumination tended to moderate the association between self-perceived autism symptoms and BDI-II scores (n = 21), and was significantly associated with ASD-related insistence on sameness behaviors (n = 18). An unexpected relationship between depressive features and social participation and motivation will need to be clarified by longitudinal research. These and similar findings contribute to our understanding of the phenomenology of depression in ASD, which is critical to the development of practical prevention and treatment.
Autism research : official journal of the International Society for Autism Research · 95 citationsread the source →
Physical activity maintenance in patients with rheumatoid arthritis: a qualitative study.
Objective: To describe the experience of physical activity maintenance in patients with rheumatoid arthritis.
Design: A qualitative salutogenic-oriented interview study.
Setting: A rheumatology outpatient clinic.
Subjects: A purposive sample of 16 physically active patients (mean age 50, range 37-67) diagnosed with rheumatoid arthritis on average 21 years previously (range 4-46 years).
Methods: In-depth interviews were conducted using a semi-structured interview guide to illuminate how the phenomenon 'physical activity maintenance' was experienced by patients with rheumatoid arthritis. The interviews were analysed using systematic text condensation, inspired by Giorgi's descriptive phenomenological methodology.
Results: The analysis revealed three categories: (1) knowing and enjoying the body; (2) responsibility and challenges; (3) autonomy and social belonging. On the basis of these categories, the essential meaning of the phenomenon of physical activity maintenance for patients with rheumatoid arthritis was summarized into 'striving for a transparent body and participation', pointing to experiences of sensations of wellbeing, liberation from restrictions and social participation on equal terms with non-arthritis populations.
Conclusion: This study demonstrates that physical activity in patients with rheumatoid arthritis may be understood as a resource to resist disability and to feel and stay healthy while creating and sustaining meaningfulness in life.
Clinical rehabilitation · 33 citationsread the source →
Legislative provisions related to marriage and divorce of persons with mental health problems: a global review.
Realization of right to marry by a person is an exercise of personal liberty, even if concepts of marriage and expectations from such commitment vary across cultures and societies. Once married, if an individual develops mental illness the legal system often starts to discriminate against the individual. There is no doubt that every individual's right to marry or remain married is regulated by their country's family codes, civil codes, marriage laws, or divorce laws. Historically mental health condition of a spouse or intending spouse has been of interest to lawmakers in a number of ways from facilitating divorce to helping the individual with mental illness. There is no doubt that there are deeply ingrained stereotypes that persons with mental health problems lack capacity to consent and, therefore, cannot enter into a marital contract of their own free will. These assumptions lead to discrimination both in practice and in law. Furthermore, the probability of mental illness being genetically transmitted and passed on to offspring adds yet another dimension of discrimination. Thus, the system may also raise questions about the ability of persons with mental health problems to care, nurture, and support a family and children. Internationally, rights to marry, the right to remain married, and dissolution of marriage have been enshrined in several human rights instruments. Domestic laws were studied in 193 countries to explore whether laws affected the rights of people with mental illness with respect to marriage; it was found that 37% of countries explicitly prohibit marriage by persons with mental health problems. In 11% (21 countries) the presence of mental health problems can render a marriage void or can be considered grounds for nullity of marriage. Thus, in many countries basic human rights related to marriage are being flouted.
International review of psychiatry (Abingdon, England) · review · 8 citationsread the source →
Evaluation of Parental Dental Fear and Anxiety (DFA) on Adolescent Dental Treatment
INTRODUCTION Dental anxiety is a negative state of mind of a dental patient, which is shown to be excessive and unreasonable.[1] Dental fear is a normal emotional response to particularly alarming stimuli in situations related to dental treatment.[1] Dental fear and anxiety (DFA) are often used together to describe different types of fear experienced in the dental environment.[2] American Academy of Pediatrics divides adolescents into three age groups: early 11–14 years, middle 15–17 years, and late 18–21 years.[3] Five specific pathways for DFA were seen in adolescent dental patients. One of which being the parental pathway plays an important role in the transmission of fear hindering their child’s dental treatment.[4] Parental DFA is usually an excessive perturbing of the things that could go wrong in child’s oral health and is an important factor that has an impact on adolescents receiving dental treatment and maintenance of their oral health. It is necessary to recognize and know how parental DFA affects the dental treatment of adolescents. Thus, this review aimed at evaluating the parental influence of DFA on dental treatment of adolescents. MATERIALS AND METHODS DATA EXTRACTION AND LITERATURE SEARCH STRATEGY A broad search of literature published between 2005 and 2021 from electronic databases through Scopus, PubMed, Google Scholar, and Web of Science was performed. These studies were conducted in different countries as mentioned in Table 1. This review article includes eight cross-sectional studies, three longitudinal studies, and one descriptive study. The age group of children included ranged from 10 to 19 years. Table 1: Summary study design, data collection, dental fear and anxiety assessment scales used analysis, and interpretation of reviewed articlesThe search was carried out using the following keywords: dental anxiety, parental dental anxiety, adolescent, and dental treatment. The terms used to formulate the search strategies were parent OR mother OR father AND dental fear OR dental anxiety AND adolescent AND dental treatment. Data extracted were independently reviewed and disagreements were solved by discussion. A flowchart representing the method of article selection for the review is shown in Figure 1.Figure 1: Flowchart representing the method of article selectionINCLUSION CRITERIA We included the studies in which parental dental anxiety was a major criterion affecting different dental health conditions. Articles referring to adolescents (10–19 years) facing different oral health problems were also included in the study. EXCLUSION CRITERIA Abstracts that were not giving relevant data, data from unpublished articles, parental dental anxiety in medically compromised and specially challenged adolescents, and articles that did not include the adolescent age group were excluded from the study. RESULTS Approximately 83 publications were found related. Screening identified 10 articles that fulfilled the criteria of inclusion; full-text versions were retrieved and their references were screened for further relevant articles. Checking the subreference list, another two relevant articles were found. Thus, 12 articles were considered for this review that met the final inclusion criteria. Of 12 articles reviewed, 8 studies[56789101112] used validated assessment scales as mentioned by authors for measuring parental DFA. The authors have not specified the validation of assessment scales used for the other four studies.[13141516] The various DFA assessment scales used in the reviewed articles are mentioned in Table 2. Summary study design, data collection, analysis, and interpretation of reviewed articles are mentioned in Table 1.Table 2: Tabular representation of dental fear and anxiety assessment scales usedDISCUSSION Dental anxiety being primarily a negative parental factor was found to affect children from assessing regular dental care. Among the reviewed articles based on the outcome, we found that three articles explained about a relationship between parental DFA and adolescent dental treatment,[67,13] and the remaining nine articles explained about the correlation between parental DFA scores with adolescent DFA scores.[6891011,13141516] No significant association was observed between parental DFA and adolescent DFA scores in two of the studies,[78] whereas two studies showed positive association only during early adolescence.[914] Other five studies showed a significant positive correlation of parental DFA with their children’s dental anxiety,[10111215,16] of which three studies also suggested fathers as mediating role in transmission of DFA to their children.[1011,15] RELATIONSHIP BETWEEN PARENTAL DENTAL FEAR AND ANXIETY AND ADOLESCENT DENTAL TREATMENT Adolescent dental treatment utilization mainly depends on parental/caretaker’s decision-making and their dental care obtaining habits. In childhood and even adolescence, this becomes very crucial for the development of good oral health behavior like regular visits to the dentist and preventive dental care.[17] Another postulated process is “social learning” wherein, media, friends, and relatives portray dentists in negative light or image leading to formation of DFA. These processes of information transmission and vicarious experience lead to negative portrayal of dentists and pessimistic expectations about the dentist’s role. All these predispose to DFA.[18] The absence of anxiety among parents would have a positive influence on a child.[19] Parental dental anxiety along with family income, economic stability, parental oral health literacy, and oral health practices is found to be a few factors that affect adolescent’s oral health-related quality of life (QOL).[202122] Dental anxiety being primarily a negative parental factor was found to affect children from accessing regular dental care, whereas parental self-dental utilization being a positive parental factor showed a positive impact on a child’s dental utilization.[23] Parents with higher anxiety levels were found to start brushing their children’s teeth at an earlier age; hence, a significant correlation was found between parent’s anxiety levels and the age at which the child starts to brush.[24] Dental health status of children was found to be better with more a positive attitude of parents toward dentistry.[25] Among the articles reviewed, two articles were found to have parental DFA during fixed orthodontic treatment of the adolescents which included the use of extraoral appliances. These two studies used different anxiety measurement scales for assessing parental DFA before and during the treatment procedures.[513] Poorer QOL is seen in families of adolescents with malocclusion as compared with the families of adolescents without any occlusal variation; the impact may have effects on parental or guardian’s emotions.[26] Both of the studies assessed state and trait dental anxiety of parents (STAI scale). State anxiety is transient, fluctuates, and varies in intensity. Trait anxiety is a personality trait; it is stable with time.[2728] The result showed that parent’s trait anxiety levels did not change during orthodontic treatment.[513] State anxiety was found to be within normal range and changed according to intensity of pressure.[13] There was an incidence of high levels of state anxiety and depression in both parents and patients under treatment with extra oral orthodontic appliances after 1 year of active treatment. Among patients waiting for orthodontic treatment and among their parents no statistically significant differences were noted in their trait anxiety levels.[5] The extra oral appliances had a negative effect on patient’s and parent’s anxiety levels which might indirectly affect the ongoing dental treatment. It was therefore recommended for clinicians to have alternate treatment modalities in mind to address this challenge.[5] Apart from orthodontic treatment, adolescents are also found commonly with traumatic dental injuries (TDIs) involving dentine/pulp or fracture of the root. A family’s QOL in such conditions was assessed using the family impact scale (FIS). This scale had four subscales, in which parental emotion was one of the subscales assessed. Parental emotion had a significant negative impact on the severity of TDI and severe untreated TDI of an adolescent can be a source of family distress.[629,30] EVIDENCE OF ASSOCIATION OF DENTAL FEAR AND ANXIETY BETWEEN PARENTS AND THEIR ADOLESCENTS Previous studies have shown that parents exhibit an influence on their children’s DFA through modeling and information.[31] The DFA experienced in childhood may lead into adulthood causing a predictor for dental treatment avoidance in adulthood.[3233] Among the reviewed articles, we found a correlation between the parental dental DFA scores with their adolescent’s DFA scores. Parent’s DFA and children’s DFA were assessed using the same dental anxiety measuring scale in nine of the studies,[6891011,13141516] and three studies[57,12] used different scales to measure anxiety levels in parents and children’s. Two of the studies showed no significant association between the anxiety level of adolescents and that of their parents.[78] One of the studies suggested that when a child reached adolescence, parental DFA does not directly contribute to child DFA. Other factors such as the presence of a sibling and family structure (single-parent family, nuclear) are found to play a significant role.[7] Lending support to the former findings, there was no relation between anxiety levels of adolescents (12–17 years) and that of their parents, whereas in the same study a positive association was found when the child is 8–11 years of age.[8] Two studies suggested a positive association in early adolescence.[914] In one of these two studies, mother’s and adolescents dental fear scores had a significant association at the age of 12 years and 18 years in given treatment scenarios such as “feeling about having their teeth scraped and polished, having teeth drilled and having an injection in gum,” whereas there was no significant association between dental fear scores of mother’s and adolescence at 15 years of age.[9] In another study reviewed, in early adolescence (11–12 years), there was a statistically significant association between parental and adolescent dental fear but in mid-adolescence (15–16 years) there was only an association with parental dental fear with their daughters.[14] It was found in the Finnish population, by eliminating dental fear among 30 years and elderly population, 41% of irregular attendees could become regular attenders.[34] In contrast, other five studies showed a significant positive correlation of parental DFA with their children’s dental anxiety.[10111215,16] Fearful parents of adolescents of age (11–16 years) assumed that their child had fear irrespective of whether the child had fear or not.[16] Three of these studies, where parental DFA was assessed in both the parents, suggested that the father also has a mediating role in the transmission of DFA to the children of age group 11–17 years,[10] 7–15 years,[11] and 7–12 years,[15] respectively. Father’s DFA is one of the best predictors of adolescence DFA[1035] and it is also found that child’s dental anxiety is best predicted by the parent’s fear of pain.[12] Previous studies have suggested that children experience fear and anxiety in their early life due to a lack of cognitive ability without having a clear perception of fearful situation and have been influenced by their parent’s fear and anxiety.[36] It is still unclear of the association of DFA between parents and late adolescents.[9] It was found that limited studies were found in the area of adolescent oral health. In the available literature, definite assessment methods were not used to assess the anxiety levels among parents. Furthermore, studies focused on late adolescence are indicated to establish the changes in oral health due to parental DFA. Adolescence is the transitional phase between childhood and adulthood and is a crucial period where they develop decision-making and independence; this has an impact on dental treatment-seeking behavior. The influence of parental dental anxiety might worsen the scenario. Parental DFA is seen to have a direct impact on the treatment itself.[56,20] Previously reviewed articles show a strong association of parental DFA and child’s DFA below 8 years of age.[37] In this study, we found parental DFA showed a positive association with their adolescent’s DFA, which thus hinders their dental treatment. There is a need to give attention to psychological parameters before and during the treatment of both parents and adolescents. Therefore, identifying parental dental anxiety prior to the treatment and intervention helps to reduce or eliminate DFA in children and further improves their dental treatment utilization. This study adds value in sensitizing dental professionals toward addressing parental concerns while treating adolescents and recommendations for appropriate implementations in teaching curricula and policies regarding the same. There is more potential to understand the background of parental DFA in single parents and in mother and father alone and also the factors that made them vulnerable. Parental education/counselling regarding various dental treatment procedures using appropriate methods such as focus group discussion will help to reduce DFA among the parental populations. ACKNOWLEDGEMENT We thank Health Sciences Library, Manipal Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, India and Department of Psychiatry, Kasturba Medical College and Hospital, Manipal, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, India. FINANCIAL SUPPORT AND SPONSORSHIP This study was self-funded. CONFLICTS OF INTEREST There are no conflicts of interest. AUTHORS CONTRIBUTIONS Idea and conceptualization: Ramprasad Vasthare. Literature search: Thrisha Hegde, Bhavyashri P. Manuscript writing: Thrisha Hegde, Bhavyashri P, Ramprasad Vasthare, Karthik M, Ravindra Munoli. Editing of the review: Ramprasad Vasthare, Thrisha Hegde, Bhavyashri P, Karthik M, Ravindra Munoli. Intellectual inputs: Ramprasad Vasthare, Ravindra Munoli, Karthik M. ETHICAL POLICY AND INSTITUTIONAL REVIEW BOARD STATEMENT Not applicable as this was a narrative review. PATIENT DECLARATION OF CONSENT Not applicable. DATA AVAILABILITY STATEMENT Data of literature search is available on appropriate request to the corresponding author.
Journal of International Society of Preventive and Community Dentistry · review · 16 citationsread the source →
Inflammation and Schizophrenia
An association between inflammatory abnormalities and schizophrenia has been found repeatedly. The purposes of this special feature are to clarify the key findings on inflammation in schizophrenia, identify major gaps in the literature, and suggest priorities for research in this area. Inflammation is one of the body’s first lines of defense in response to injury or infection, and increased inflammation is found in many diseases. Acute inflammation is a nonspecific response characterized by warmth, pain, and swelling. Leukocytes migrate to the area of injury and become activated, the blood supply to the area increases, and blood vessels become more permeable, allowing cells and molecules to leave blood vessels and enter the injured tissue. The inflammatory response also involves the complement system, a group of proteins that, when activated, combine to form a complex molecular structure that kills cells, usually bacteria and parasites. Cytokines are key molecules that regulate inflammation; they also have important roles in the immune system. They are produced by a wide variety of immune cells and cells outside of the immune system. The term cytokine derives from their ability to influence the movement of inflammatory cells, but they also have other functions. Chronic inflammation is usually a lower grade response, lacks the grossly visible signs of acute inflammation, and may be systemic rather than localized. Chronic inflammation plays a role in the pathophysiology of many chronic diseases, including cardiovascular and cerebrovascular disease, diabetes, Alzheimer’s disease, and some cancers. The characteristics of chronic inflammation differ somewhat in the brain from what occurs in other tissues. An important component of neuroinflammation is the microglial activation. The brain contains relatively few of the inflammatory cells that are found outside the brain. Microglia, which are related to the peripheral inflammatory cells, serve some of the protective functions such cells play in the rest of the body. Microglia are involved in other brain functions, including the pruning and maintenance of synapses, trafficking of neurotransmitters, and devouring—phagocytosis—of cell fragments and damaged cells. Activated microglia produce inflammatory cytokines and the phagocytose cells or proteins that provoke the inflammatory response. Microglial activation and subsequent proinflammatory cytokine production may disrupt the blood-brain barrier (BBB). An intact BBB usually tightly controls the entry of cytokines and leukocytes into brain tissue. Damage to the BBB impairs its ability to control which inflammatory cells and molecules enter the brain; other substances leak into brain tissue, and the brain is unable to function normally. A discussion of prenatal inflammation as a risk factor for schizophrenia is beyond the scope of the present special feature, and the reader is referred to previous reviews of human1,2 and animal studies.3–6 Numerous studies have found that people with schizophrenia have increased blood concentrations of inflammatory cytokines.7 Two important themes emerge from these studies. First, inflammatory abnormalities are present in subjects with first-episode, drug-naive psychosis (FEP) compared with controls, suggesting an association that may be independent of the effects of antipsychotic medications. Second, the concentrations of some inflammatory molecules may vary with the clinical status of patients: ie, there appear to be separate groups of state and trait markers. The state-related markers include interleukin (IL) 1-beta, IL-6, and transforming growth factor-beta. People with schizophrenia have higher concentrations of these cytokines than controls during an exacerbation of symptoms, but there is no difference during periods of clinical stability. IL-12, interferon-gamma, and tumor necrosis factor-alpha (TNF-alpha) appear to be trait markers. Concentrations of these cytokines are higher in patients with FEP than in controls, and in patients with chronic illness, during both periods of symptomatic worsening, than in controls. C-reactive protein (CRP), another proinflammatory molecule, also appears to be a state marker,8 and specific lymphocyte populations may also segregate into state and trait markers.9 Additional evidence for potential state-related markers in schizophrenia has been reviewed elsewhere.10 Two studies suggest that inflammatory molecules may predict subsequent relapse.11,12 Other studies have found abnormal levels of inflammatory parameters in the central nervous system (CNS) in schizophrenia, including cerebrospinal fluid (CSF) cytokine11 and leukocyte levels,13,14 CNS microglia and lymphocytes,15–19 CSF and CNS oxidative stress,20,21 and anti-N-methyl-D-aspartate receptor autoantibodies.22 There is also evidence suggesting that infections may be associated with illness relapse.23 Within schizophrenia, blood cytokine abnormalities have been associated with poorer cognitive function and measures of regional brain volume24–26 and negative symptoms.27–30 There are several randomized clinical trials of the nonsteroidal anti-inflammatory drugs (NSAIDs) celecoxib and aspirin as adjuncts to antipsychotics.31 Interpretation of this evidence is complex, as these studies have not consistently distinguished relapsed from clinically stable patients. Furthermore, if inflammation plays a role in psychotic relapse, the efficacy of anti-inflammatory treatments may “disappear” in a lengthy trial because the treatment would not have any effect once patients have returned to their clinical baseline. However, an adjunctive agent that accelerates a patient’s antipsychotic response would be valuable. Agents other than NSAIDs that have anti-inflammatory properties, used in adjunct to antipsychotics, have been found to be superior to placebo. There have been two trials of minocycline,32,33 a second-generation tetracycline with anti-inflammatory and antimicrobial effects, that were superior to placebo. The efficacy of minocycline may have “disappeared” over the course of one trial,33 raising the possibility of an effect restricted to relapsed patient and not in those at a stable baseline. Adenosine is a purine nucleoside that modulates many physiological processes and has anti-inflammatory effects. A meta-analysis found that adjunctive treatment with adenosine-modulating drugs is superior to the effects of placebo.34 These drugs were associated with significant symptomatic improvement in inpatients, but not in outpatients, supporting the concept that state/trait differences may be an important predictor of antipsychotic response to adjunctive agents. Oxidative stress refers to an increase in free radicals, highly reactive molecules generated from metabolism and environmental exposures that can damage cell membranes. Inflammation and oxidative stress strongly influence each other.35 Antioxidant drugs decrease oxidative stress. One trial found that adjunctive treatment with the antioxidant N-acetylcysteine significantly reduced psychopathology in schizophrenia.36 A trial of fish oil, which also has significant anti-inflammatory effects, was conducted in adolescents and young adults with subthreshold psychotic symptoms,37 ie, “prodromal” patients. Patients receiving fish oil were significantly less likely to progress to a psychotic disorder than subjects receiving a placebo. Interestingly, fish oil was prescribed for 12 weeks, but the protective benefits with regards to transition to psychosis remained significant for 40 weeks after cessation of treatment. Inflammation may be a common mediator of diverse prenatal risk factors for schizophrenia, including preterm labor; preeclampsia (pregnancy-induced hypertension); neonatal birth asphyxia; and maternal gestational diabetes, stress, and depression.2 Maternal serum concentrations of the cytokines IL-838 and TNF-alpha39 during pregnancy were associated with an increased risk of schizophrenia in the offspring. Animal studies suggest that inflammation during critical periods of neurodevelopment may permanently alter the “set-point” of the inflammatory system, with increased inflammation in adult offspring.40–45 Meta-analyses have confirmed the presence of other abnormalities in schizophrenia that are associated with inflammation: increased autoantibodies,22 oxidative stress,46 CRP,8 and circulating lymphocytes.9 Antibodies are crucial “weapons” the immune system uses against foreign proteins. Autoantibodies, antibodies against a person’s own proteins, are associated with cytokine abnormalities.47 Lymphocytes, a group of white blood cells that combat infections, produce antibodies, and are an important source of cytokines, are increased in schizophrenia.9 Some subsets of lymphocytes may be state markers for acute psychosis, whereas others may be trait markers.9 CRP is a protein synthesized by the liver in response to inflammation, particularly IL-6 and other cytokines. Inflammation and oxidative stress may contribute to the decreased blood and CNS membrane levels of polyunsaturated fatty acids observed in schizophrenia.48 There are other disorders outside of schizophrenia in which peripheral inflammation appears to impact brain function. Inflammation is a risk factor for Alzheimer’s disease and mild cognitive impairment,49 rheumatoid arthritis is a risk factor for dementia,50 and “sickness behavior” is induced by peripheral cytokines.51,52 Depression is also associated with increased inflammation.53 The effects in depressed patients of an antibody against the cytokine TNF-alpha54 support the concept that brain function is impacted by peripheral cytokines. There are other mechanisms by which peripheral inflammation might cause or reflect brain dysfunction in schizophrenia. Cytokines may directly modulate dopaminergic neurotransmission55–57 or indirectly modulate glutamatergic neurotransmission through tryptophan metabolism.58–61 There is also some movement of peripheral leukocytes into the brain parenchyma, and the interaction of cytokines with the vagus nerve influences brain function.62 Blood cytokines induce cytokine production in the cells that form the BBB, and cytokines may move into the brain via the circumventricular organs, which lack a BBB.62 Inflammation may also disrupt the BBB, resulting in abnormal trafficking of cells and inflammatory molecules between blood and brain. Some have suggested that the increase in blood concentrations of the protein S100-beta in schizophrenia63 is consistent with abnormal function of the BBB in people with schizophrenia, resulting in abnormal trafficking of cells and inflammatory molecules between blood and brain. However, circulating S100-beta has sources other than the brain.64,65 Several potentially confounding variables are important to consider in studies of inflammation. Antipsychotics increase the risk of weight gain and diabetes, which are associated with inflammation. However, there is evidence from meta-analyses of abnormal inflammatory parameters in FEP,8,9,22,46 suggesting that the association between schizophrenia and inflammation is not solely due to antipsychotics. Antipsychotic-naïve relatives of people with schizophrenia also have increased inflammation compared with controls.66–68 Other potentially confounding variables include body mass index, age, gender, smoking, alcohol and illicit drug use, and whether patients are fasting at the time of sampling.69 The proportion of studies that either matched patients and controls, or statistically controlled for many of these potential confounders, has been low.8,9,22,46 Inflammation is comorbid with other physiological abnormalities, including hypertension, impaired glucose tolerance (fasting blood glucose [FBG] 100–126mg/dl), diabetes (FBG > 126, or a random blood glucose >200mg/dl), and increased oxidative stress. The associations with these other conditions also support the plausibility of increased inflammation in schizophrenia. However, the comorbidity of these physiological measures in schizophrenia complicates the interpretation of adjunctive treatment trials: what is the best therapeutic target? Another complicating issue is the relationship of inflammation to neurotropic viruses. One study found that treatment of patients with antibodies to herpes simplex 1 virus with a herpes-specific antiviral drug improved cognition with impressive effect sizes, suggesting the presence of an ongoing problem related to the virus.70 The association of other infectious agents with schizophrenia also raises the question of what relationship might exist between inflammation and either chronic infections or the expression of genes derived from an infectious agent and integrated into human DNA. The background presented above can be used to guide future research. Attempts to replicate current findings in well-matched patients and controls would be helpful. Cytokine levels in subjects with prodromal psychosis have not been investigated. We would hypothesize that these subjects should have abnormal trait markers compared with controls; within prodromal subjects, those who develop clinical psychosis should have abnormal state markers compared with high-risk subjects who do not. The effects of fish oil in preventing conversion to psychosis in high-risk subjects should be investigated in relationship to its effects on inflammation. The therapeutic anti-inflammatory agents that have been studied to date, such as aspirin, celecoxib, and fish oil, have multiple actions. Specific antibodies against individual cytokines are used in the treatment of rheumatoid arthritis and have been studied in depression.54 A change in symptoms or cognition in response to these antibodies would directly implicate inflammation in the pathophysiology of schizophrenia. More longitudinal studies with serial measurement of inflammatory parameters across the clinical course of illness are needed. It would be useful to test the hypothesis that patients with treatment-resistant schizophrenia have a different inflammatory profile than other patients with schizophrenia.7 Although it seems likely that there is increased inflammation in the brain when there are cytokine increases in the peripheral blood, the response might not be exactly the same in these two compartments. For instance, the inflammatory cytokines with altered levels in the brain might not be the same as those that change in the blood. More studies of markers of inflammation in the CNS—including CSF, postmortem analyses, and imaging studies—are needed. Two strategies may increase the signal-to-noise ratio for adjunctive trials of anti-inflammatory agents. First, inflammation may play a role in some patients with schizophrenia but not others. Patients with evidence of inflammation in the peripheral blood may be more likely to respond to an anti-inflammatory treatment strategy than those without inflammation and should be the ones included in treatment studies. Second, acutely ill and stable patients should be studied in separate trials and considered separately in meta-analyses. Furthermore, baseline-to-end-point analyses may not appropriate for studies of relapsed patients because there may be faster improvement with the use of adjunctive anti-inflammatories but not a greater total improvement by the end of the study. Studies of inflammation in schizophrenia should assess possible relationships of inflammatory cells and molecules to symptoms and cognition. To date, few studies have considered these measures.8,9,22,46 The comorbidity of inflammation, oxidative stress, hypertension, and abnormal glucose concentrations raise the issue what is the most appropriate treatment target in schizophrenia. As a first step in understanding this issue, it would be helpful to investigate relationships between inflammation, oxidative stress, hypertension, and glucose intolerance on the one hand, and clinical variables on the other. Several studies found that first-degree relatives of people with schizophrenia have increased inflammation and oxidative stress.66–68 It would advance the field to test the hypothesis that relatives have abnormal concentrations of the trait markers for schizophrenia but not of the state markers associated with relapse. Inflammatory molecules do not work in isolation but have complex interactions among themselves and with other systems. Most previous studies have measured only a small number of molecules. Concurrent measurement of cytokines, leukocytes, oxidative stress, and related parameters would increase the ability to make broader inferences regarding inflammation. Furthermore, if groups or clusters of covarying molecules—ie, molecules that change simultaneously—could be defined within schizophrenia, investigation of these groups is likely to yield better signal-to-noise ratios than individual molecules and should have more biological validity. Does increased inflammation due to infections or physical trauma increase the risk of relapse? If so, do preventive measures (eg, antibiotic prophylaxis for recurrent urinary tract infections)23 decrease that risk? What is the relationship between inflammation and the presence of antibodies to herpes viruses, toxoplasmosis, etc? Although the evidence on inflammation in schizophrenia is provocative, the number of studies in some areas is small, and increased methodological rigor is needed. Nonetheless, the evidence from FEP and first-degree relatives of patients with schizophrenia supports the idea that increased inflammation is truly associated with schizophrenia. This research raises the possibility that further study of inflammation will lead to greater understanding of the etiology and pathophysiology of schizophrenia. Dr B.K. is a member of Advisory Boards for Genentech and Roche. In the past 3 years, Dr B.J.M has received grant support from the National Institute of Mental Health (K23MH098014), the Georgia Regents University (GRU) Intramural Scientist Training Program, the GRU Brain & Behavior and Immunotherapy Discovery Institutes, the University of Oulu (Finland), the Thule Institute of the University of Oulu, and Oy H. Lundbeck Ab; research support from the National Institutes of Health Clinical Loan Repayment Program; consultancy fees for surveys from Medefied Europe and Plaza Research, on behalf of Genetech/Roche; speaker fees for grand rounds lectures from the Maryland Psychiatric Research Center and the Texas A&M University and Scott and White Hospital Department of Psychiatry; and payment for a survey from e-Rewards Medical Market Research.
Schizophrenia Bulletin · review · 315 citationsread the source →
Developmental Coordination Disorder
For the last 100 years, poor motor coordination in children has been recognized as a developmental problem.1 As early as 1937, these children were classified as “clumsy.”1 Since then, other terms such as “motorically awkward,” “motor impaired,” and “physically awkward” have been used to describe these children, and the terms “developmental apraxia” and “perceptual motor difficulties” have been used to characterize this developmental problem.2,3 Since the 1994 International Consensus Conference on Children and Clumsiness, the term “developmental coordination disorder” (DCD) has been used to describe the condition of children with motor incoordination.1,4 The purpose of this article is to provide the following information about DCD: (1) definition, (2) prevalence, (3) etiology, (4) discussion regarding the difficulties in classifying these children, (5) common characteristics, (6) long-term prognosis, and (7) brief review of treatment approaches. Developmental coordination disorder, a chronic and usually permanent condition found in children, is characterized by motor impairment that interferes with the child's activities of daily living and academic achievement.3,5 In order for a child to be diagnosed with DCD, these motor impairments must negatively affect some other aspect of his or her life.6 Impairment alone, however, does not qualify a child for the diagnosis of DCD; the motor impairment must not be caused by or have the symptoms of an identifiable neurological problem.2,5 That is, the child must not have any disturbances of muscle tone (ataxia or spasticity), sensory loss, or involuntary movements. If mental retardation is present, the testable IQ of the child must be greater than 70 and the motor impairments must be greater than what would normally be expected for children with mental retardation.5 Finally, a child diagnosed with DCD must not meet the criteria for a diagnosis of pervasive developmental disorder.6 Developmental coordination disorder appears to be a fairly common disorder of childhood and is usually identified in children between 6 and 12 years of age. Ten years ago, researchers7,8 estimated that DCD occurred in 10% to 19% of school-aged children. With a more precise definition of DCD, the current prevalence is estimated to be between 5% and 8% of all school-aged children,5,9–11 with more boys than girls (2:1) being diagnosed with DCD.12 This difference may reflect higher referral rates for boys, because the behavior of boys with motor incoordination may be more difficult to manage at home and in the classroom.8 In addition, a higher incidence of DCD may be found among children with a history of prenatal or perinatal difficulties.3 Due to the heterogeneity of DCD, finding its cause has been difficult.3 Several theories speculate that the etiology of DCD is part of the continuum of cerebral palsy5,13; is secondary to prenatal, perinatal, or neonatal insult3; or is secondary to neuronal damage at the cellular level in the neurotransmitter or receptor systems.14 Hadders-Algra14 based her view that DCD is a result of damage at the cellular level on evidence that cerebral palsy is often caused by prenatal damage that cannot be identified by current diagnostic techniques. Developmental coordination disorder, a chronic and usually permanent condition found in children, is characterized by motor impairment that interferes with the child’s activities of daily living. Although both standard and nonstandard functional tests are available to identify the specific disabilities experienced by a child with DCD, relating the observed disabilities to the primary impairment(s) or any possible neuropathology is not easily accomplished. The problems experienced by children with DCD are believed to emanate from abnormalities in neurotransmitter or receptor systems rather than from damage to specific groups of neurons or brain regions.15 Children's difficulties with coordination can result from a combination of one or more impairments in proprioception, motor programming, timing, or sequencing of muscle activity. A number of theories have evolved in an attempt to shed light on the specific neuronal processing deficits that contribute to DCD. Current models used to explain the neural regulation of posture and movement during development can serve as a basis for the examination and management of individuals with DCD. Using these models, many of the deficits of motor control observed in these children can be described. A variety of theoretical models exist to explain the role of the nervous system in motor development. Forty years ago, the primitive reflex model was a generally accepted theory used to explain how the brain regulates early motor behavior.16 As development proceeded, the higher centers exerted increasing control over the lower reflexes.16 These earlier models were based on a hierarchy of motor control in which higher centers were capable of planning and executing a motor plan without external or internal feedback from lower centers of the central nervous system (CNS). The more recently proposed systems model suggests a more complex interaction among various levels of the CNS. In the systems model, sensory feedback is interpreted by the CNS, and the appropriate movement strategy is selected based on current experience, the state of the internal and external environment, and memory of similar movements. Edelman's neuronal group selection theory includes aspects of both of these models and proposes that functional groups of neurons exist at all levels of the CNS.17 These neuronal groups are determined by evolution, but their functional integrity is dependent on afferent information produced by movement and experience.17 In this regard, these genetically determined collections of interconnected neurons (neuronal groups) in both cortical and subcortical structures serve as an early repertoire for motor behavior or receipt of specific sensory information.14,17,18 According to neuronal group selection theory, motor development proceeds in 2 phases.15 The first, the phase of primary variability, is characterized by crude and erratic motor activity that does not require sensory information for its initiation or guidance. These self-generated movements give rise to afferent (visual, kinesthetic) inputs that reinforce more specific synaptic connections within each group. An intermediate period in which effective patterns are selected is followed by the secondary variability phase. In this phase, sensory and motor factors interact to establish the intercellular connections that produce the specific and complex muscle contraction patterns that characterize coordinated, goal-directed movement. Reciprocal connections between groups subserving movements in various body parts and representing different parts of visual space are reinforced with each repetition of a particular function. As the more efficient movement patterns are practiced, the appropriate synaptic circuits are reinforced and subsequently established.14,17,19,20 The literature includes a wide variation in terminology and criteria to describe DCD. This variation has made studying the causes of DCD and developing treatment approaches for the child with DCD difficult. In their analysis of clinical trial data, Macnab et al21 identified 5 different subtype profiles of DCD. The first subtype included children with better gross motor than fine motor skills, although both were still below normal while standing balance and visual-perceptual skills were both within normal ranges. Compared with children of the same age with DCD, children in the second subtype scored high on measures of upper-limb speed and dexterity, visuomotor integration, and visual-perception skills, but they demonstrated poor performance on measures of kinesthetic ability (accuracy in discriminating movement and position of the upper limbs) and balance. Children in subtype 3 demonstrated the greatest overall motor involvement and were the only subtype to have difficulty with both kinesthetic and visual skills. Compared with their peers with DCD, children in subtype 4 performed well on kinesthetic tasks but demonstrated poor performance on tasks requiring visual and dexterity skills. Children in subtype 5 demonstrated poor performance on measurements of running speed and agility compared with their peers with DCD; however, they performed well relative to their peers with DCD in the tasks involving visual-perception skills. The development of different classification systems for DCD may have been influenced by the design of motor tests.21 For example, items testing one motor skill may be influenced by a related motor skill (eg, ball-throwing skills cannot be separated from visuomotor skills). In addition, a test may have an over-representation of one skill that could unduly influence the child's performance on the test. For example, having a greater number of items testing gross motor rather than fine motor skills could either positively or negatively influence a child's score, depending on the child's specific strengths and weaknesses. Another difficulty in interpreting the literature on DCD is the lack of inclusion criteria. Geuze et al22 reviewed 164 publications on the study of DCD and found that only 60% of the studies had objective inclusion criteria. Because of this lack of inclusion criteria, Geuze et al recommended that a child scoring below the 15th percentile on standardized tests of motor skills and having an IQ score above 69 would qualify for a diagnosis of DCD. The inconsistency among standardized motor tests used to identify children with DCD is another problem. In one study,5 the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP) and the Movement Assessment Battery for Children (M-ABC) were administered to 157 children with DCD and 155 children with no motor difficulties; the test results were in agreement 82% (kappa=.62) of the time in distinguishing children who had DCD from children who did not have DCD. This is considered a substantial level of agreement.23 In a study of 202 children (101 with DCD and 101 without DCD), the BOTMP and M-ABC agreed only 67% of the time (kappa=.41), which was considered a moderate level of agreement.24 Because the BOTMP and the M-ABC are 2 of the most commonly used tests for identifying children with DCD, the potential lack of agreement by these tests in identifying children who have DCD is a concern. Two primary factors may explain the difference in outcomes between the BOTMP and M-ABC when used to identify children with DCD.24 First, the BOTMP allows the tester to verbally prompt and correct the child during the testing procedure, allowing the child who is dependent on more external controls to do better on the BOTMP. The BOTMP tends to under-identify children with DCD. Second, the M-ABC requires more careful instruction on the part of the examiner and allows more opportunities for the examinee to practice, but does not allow any verbal or physical prompting by the examiner. Children with attention problems may have more difficulty with the careful instructions for the M-ABC. Another difficulty in classifying children with DCD is the overlap with other disorders. Approximately 41% of children with attention-deficit/hyperactivity disorder (ADHD) and 56% of children with learning disabilities also have DCD.5,21 Further confusing the classification scheme is that the terms “developmental coordination disorder,” for which no identifiable organic brain damage is present, and “apraxia,” which is caused by identifiable brain damage, have been used interchangeably.3 Children with DCD may have a wide range of dysfunctions. These dysfunctions can be grouped into 3 areas: gross motor, fine motor, and psychosocial. Many children with DCD have neurological soft signs such as hypotonia, persistence of primitive reflexes, and immature balance reactions that interfere with gross motor development.5,25 These children also may demonstrate an awkward running pattern, fall frequently, drop items, and have difficulty imitating body positions and following 2- to 3-step motor commands.8 Because of their gross motor problems, children with DCD also perform poorly in sporting events,2 possibly due, in part, to their slow reaction and movement times.7 Their decreased participation in sports may result in decreased muscle force.8 Difficulty with handwriting or drawing often is the first identifiable sign of a fine motor problem and is the most frequently mentioned motor problem experienced by children with DCD. Children with DCD frequently have difficulty planning and executing other fine motor skills such as gripping and dressing.26–29 Unfortunately, children with DCD may experience problems not limited to fine or gross motor areas. These children also may experience psychosocial problems at school. Children with DCD may have learning disabilities or reading problems and may be at increased risk for lower intelligence.5,8 They may act out in class more than other children,13 may be the class clown, and may exhibit less socially desirable means of gaining recognition and friends.8 Adolescents with DCD have been found to have fewer friends, and they have more feelings of low self-worth and more anxiety than peers without DCD and younger children with DCD.30 Historically, parents have been told not to worry about their child's clumsiness because the child will outgrow the problem.31 However, current researchers in the area of DCD report that the children do not outgrow clumsiness and that, without intervention, they will not improve.1,8,12,27,31 Losse et al31 tested 17 children aged 6 years and retested them at age 16 years. The children with motor difficulties at 6 years of age continued to exhibit problems at 16 years of age. In another study,32 818 children with DCD were tested for reading comprehension at age 7 years and then again at age 10 years. A positive correlation in poor reading comprehension existed for children with DCD at 7 and 10 years of age. A follow-up study was conducted on 22-year-old individuals (N=55) who at age 7 years had either DCD or attention-deficit/hyperactivity disorder (ADHD), or both.33 The children with DCD and those with both DCD and ADHD had poorer outcomes than their similarly aged peers without DCD and children with ADHD only. The children with DCD and those with both DCD and ADHD were found to have had more criminal offenses, more incidences of substance abuse and other psychiatric disorders, and lower levels of schooling. Treatment approaches used by occupational therapists and physical therapists can be broadly categorized into either bottom-up or top-down approaches (Tab. 1).10,12,34–36 Bottom-up approaches are based on hierarchical theories of motor control. These theories tend to explain the remediation of motor dysfunction through activation of higher levels of neuronal functioning in a child. The bottom-up approaches frequently used in managing children with DCD are sensory integration, the process-oriented treatment approach, and perceptual motor training.34 Summary of Bottom-Up Versus Top-Down Approaches Summary of Bottom-Up Versus Top-Down Approaches In sensory integration therapy, the child is provided sensory stimulation designed to promote motor development and higher cortical learning. A child undergoing sensory integration therapy may show some gains in motor development, but these gains often do not generalize to functional skills.34 Kinesthesia (the perception of one's own body parts, weight, and movement) is integral to the acquisition of motor skills in process-oriented treatment approaches. Therapeutic intervention with process-oriented treatment is based on specifically designed kinesthetic training activities. As described by Laszlo and Bairstow,37 this approach has an inherent reward system built into it through its use of positive reinforcement, presentation of desirable activities within the capabilities of the child, and judicious progression of the level of difficulty. The usefulness of the process-oriented treatment approach has been the subject of considerable study.9,10,37,38 Sims and colleagues35 suggested that much of the success of this approach can be attributed to a strong motivation effect, fostered by positive feedback and a sense of self-competence. Perceptual motor training, an eclectic approach, offers the child with DCD a wide range of motor experiences along with ample opportunities to practice these skills. Often, in outcome studies, children who receive perceptual motor training are compared with children who receive either sensory integration therapy or process-oriented treatment. Children perceptual motor training have been found to demonstrate motor to or greater than those of children either sensory integration therapy or process-oriented perceptual motor training, process-oriented may promote learning through positive feedback and reinforcement, these do not and to the that top-down approaches approaches use a approach to motor skill development and have been influenced by the systems approach to motor learning and control. This approach suggests that motor skills from an interaction of many both internal and external to the approaches also the in which motor behavior intervention and approaches or are the 2 most commonly intervention on of a The theoretical for intervention in a child's motor performance is the result of learning on a specific Motor tasks are into with each and then to the Children with this approach have demonstrated gains in motor skills.34 approaches to motor development problem The approach strategy the to to the and perform the well did plan The child verbal to the to motor learning. In this approach, the as a by the child out how to his or her motor performance on various motor intervention, the results of studies of approaches are In one 10 children with DCD who were with a approach to motor development were compared with 10 children who were with a bottom-up The children were for and groups on various standardized motor tests 10 treatment However, children in the approach group motor skill and to better than children who were the bottom-up and the approach both provide repetition and practice of specific motor skills, and the approach has the of problem The greater success of top-down when compared with bottom-up be a result of the top-down inclusion of both and motor learning with for attention to and memory as the child in activities. The results of these studies, in to outcome measures of the different approaches in children with DCD, would that approaches that systems theory on sensory information being only part of the and motor learning theory be most effective for these 2 a brief of clinical the of various treatment approaches used with children with of Treatment Approaches for Children With Developmental approach to daily occupational performance treatment approach treatment group integration, perceptual motor, gross and fine motor integration Assessment Battery for Test of Motor Test of for of Motor and of of Treatment Approaches for Children With Developmental approach to daily occupational performance treatment approach treatment group integration, perceptual motor, gross and fine motor integration Assessment Battery for Test of Motor Test of for of Motor and of The neuronal group selection theory can provide a for interpreting the in outcomes among the various approaches. children with moderate to cerebral palsy have a limited repertoire of primary neuronal which children with DCD are believed to experience difficulty at the level of secondary variability, that is, in and the most efficient and effective for a normal development, experience a primary role in the neuronal group selection that the for and According to the neuronal group selection theory, this of motor skill during the of secondary variability as a result of of neuronal selection of specific neurons within each repetition of synaptic within and among neuronal and sensory synaptic which act in and cortical and subcortical and following to a variety of motor of these connections is dependent on sensory Bottom-up approaches such as sensory integration, process-oriented and perceptual motor training sensory experience, with less on processing and motor Although an intervention based on information processing may provide the experience to the most effective neuronal bottom-up approaches may not provide for motor practice of and goal-directed tasks in order to reinforce and establish these approaches less on the specific impairments to decreased coordination and more on the of that is, the among a number of structures and systems and the within which the is Treatment based on a top-down approach that provide the child the to in problem while afferent subcortical structures the feedback and to identify and the most efficient movement for the Because integration, internal of motor and appropriate motor at the level of secondary the on sensory rather than factors by the bottom-up approaches in part, be for the observed in outcomes following treatment. A number of motor learning theories have been proposed in an attempt to explain the through which are into more complex According to the motor control and learning theory proposed by and motor circuits that the and following long-term these and functioning neuronal circuits through practice, the child is to motor into more complex movements. and proposed 2 to such the first of which on sensory to neuronal is during the second that the to the specific motor tasks through the and involving the and in the first of learning requires attention and The motor then in the of learning through repetition and top-down approaches meet both of these bottom-up approaches information processing only. the and of the neural in children with DCD is a not Motor control are complex and on functioning of and motor only are children with DCD a group in terms of functional disabilities the specific of the problems observed can from one child to the Because of these an approach to the management of children with DCD is Developmental coordination disorder is a complex disorder 5% to of school-aged children. intervention, these children will to exhibit poor motor skills and show deficits in other as for may (1) the most appropriate level of intervention (2) which produce results that generalize to the and provide long-term in motor (3) what have on the child's motor and (4) motor skills to the that to the
Physical Therapy · review · 472 citationsread the source →
Harald M. Stauss (2003)MEDLINE-indexed journal, not yet read by usAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology · review Heart rate variability
IN FOCUSHeart rate variabilityHarald M. StaussHarald M. StaussDepartment of Exercise Science, University of Iowa, Iowa City, Iowa 52242Published Online:01 Nov 2003https://doi.org/10.1152/ajpregu.00452.2003MoreSectionsPDF (59 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations the rhythm of the heart has not only fascinated cardiologists but also inspired poets and musicians. Indeed, the periodic beat of the heart was used to define the speed of music. In music notation, the traditional Italian term "moderato" originally referred to one beat of the measure per walking pace (76-80 paces/min) or heartbeat (∼72 beats/min). The use of the heartbeat to define the speed of music may imply that the periodicity of the beat of the heart is very constant. However, this is not necessarily the case. In fact, loss of heart rate variability can indicate severe cardiovascular diseases and reliably predict poor outcome of such conditions (18, 22, 27, 47a). This In Focus article reviews sources of heart rate variability, its role as a prognostic marker for cardiovascular diseases, and its application in estimation of cardiac autonomic nervous system activity. All of these topics have been addressed intensely in articles published in the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology during the last two years. In healthy subjects, the sinoatrial node located at the posterior wall of the right atrium initiates each beat of the heart. Due to the unstable membrane potential of the myocytes located in this region, action potentials are generated periodically at a fairly constant frequency. This relatively constant frequency generated by the autorhythmicity of the sinoatrial node is modulated by many factors that add variability to the heart rate signal at different frequencies. According to the Task Force of The European Society of Cardiology and The North American Society of Pacing and Electrophysiology (47a) these frequencies are classified into 1) ultra-low frequencies (ULF; >5-h cycle length) that include the circadian rhythm (6, 9, 34, 54); 2) very low frequencies (VLF; >25-s cycle length) that are supposed to be affected by temperature regulation (1, 7, 34, 52, 54) and humoral systems (9, 36); 3) low frequencies (LF; >6-s cycle length in humans) that are sensitive to changes in cardiac sympathetic (and presumably parasympathetic) nerve activity (27, 30); and 4) high frequencies (HF; 2.5- to 6.0-s cycle length in humans) that are synchronized to the respiratory rhythm (5) and are primarily modulated by cardiac parasympathetic innervation (38).The most prominent oscillation in the ULF band of the heart rate spectrum is the circadian rhythm. The autonomic nervous system contributes significantly to circadian heart rate variability. Using long-term recordings in conscious rabbits, Barrett et al. (6) demonstrated a strong circadian rhythm in heart rate, mean arterial blood pressure, renal blood flow, and renal sympathetic nerve activity. The importance of this study is that it clearly demonstrates that sympathetic nerve discharges exhibit a strong circadian rhythmicity. The paraventricular nucleus of the hypothalamus (PVN) appears to play a central role in mediating the circadian rhythm of autonomic nervous system activity. First, GABAergic and glutamatergic neurons project from the suprachiasmatic nuclei of the hypothalamus (SCN) to spinal-projecting neurons of the PVN (12). The SCN is the major central oscillator that triggers the day/night cycle. It receives photic input from the retina (47) and drives many neuroendocrine, metabolic, autonomic, and behavioral circadian rhythms (14, 16, 21, 31, 35, 44, 46, 50). In addition, microinjections of the inhibitory neurotransmitter GABA into the PVN of anesthetized rats elicit dose-dependent decreases in renal sympathetic nerve activity, whereas bicuculline (a GABA antagonist) increases renal sympathetic nerve activity (56). Second, from the PVN, neurons project to the nucleus of the solitary tract (that integrates inputs from the baroreceptors), the nucleus ambiguus (origin of preganglionic parasympathetic neurons to the heart), the rostroventrolateral medulla (location of sympathetic premotor neurons), and the intermediolateral cell column of the thoracolumbar spinal cord (location of preganglionic sympathetic neurons). Thus PVN neurons can modulate autonomic nervous system activity by sending inputs to major sites of autonomic nervous system regulation. As an example, a pivotal role of the PVN for sympathoexcitation during parturition was recently demonstrated in sheep. The increase in sympathetic nerve activity that accompanies birth in maternal animals was prevented by stereotactic lesioning of the PVN (43). Taken together, a major component of the circadian heart rate variability is elicited by diurnal fluctuations in autonomic nervous system activity, generated by corresponding fluctuations of neuronal activity within the PVN, which depend on circadian inputs originating from the SCN.It has been suggested that thermoregulation affects VLF heart rate variability (10, 26). Cooling the heart causes bradycardia, a mechanism used in heart surgeries. Conversely, fever is known to increase heart rate. Raising body core temperature from 36.0 to 36.6°C caused an increase in heart rate by almost 40 beats/min in male subjects (1), whereas acutely reducing ambient temperature from thermoneutral conditions (35°C) to 29, 23, and 17°C, reduced heart rate from 400 to 250 beats/min in 8-day-old rats (7). In addition, lowering temperature in the isolated working rat heart from 37 to 31°C reduced heart rate from 332 to 215 beats/min and markedly increased heart rate variability (28), indicating that parts of the temperature effects on heart rate and heart rate variability are independent from the autonomic nervous system. In contrast to the tachycardia that accompanies acute elevations in temperature, chronically raising ambient temperature in adult rodents from a standard housing temperature of 21-23°C to thermoneutral conditions (29-30°C) reduced heart rate by roughly 50 beats/min in rats (34) and by 200-300 beats/min in mice (54). The authors of these articles (34, 54) suggested that standard housing temperatures are associated with cold stress that causes parallel activation of brown adipose tissue, cardiac, and vasomotor sympathetic drives that elicits nonshivering thermogenesis and tonically elevates heart rate and arterial blood pressure. These and other studies indicate that both direct effects of temperature on pacemaker activity of the sinus node (28) and indirect effects mediated via the autonomic nervous system (11, 25, 51, 55) mediate temperature effects on heart rate and heart rate variability. Thus fluctuation in temperature is an important source of heart rate variability that should not be underestimated. In a more recent study, this was taken into account by core body temperature correction of heart rate variability (3).Endocrine factors affecting heart rate variability include thyroxine, reproductive hormones, the renin-angiotensin system, steroids, and others. Chronic subcutaneous infusion of angiotensin II in rats markedly increased blood pressure and heart rate variability, expressed as standard deviation (9). In contrast, chronic corticosterone treatment is likely to reduce baroreflex-mediated heart rate variability, because baroreceptor-heart rate (39) and baroreceptor-renal sympathetic nerve activity reflex sensitivity (41) were blunted in chronically corticosterone-treated rats. Furthermore, an interaction between angiotensin II and glucocorticoids was recently described. Intracerebro-ventricular microinjections of angiotensin II AT1 receptor antagonists caused marked decreases in mean blood pressure and heart rate in rats chronically treated with corticosterone but not in control animals (40). This interaction is likely to take place in the central nervous system, because peripheral angiotensin II AT1 receptor blockade did not alter the effects of betamethasone treatment on blood pressure, heart rate, and baroreceptor-heart rate reflex sensitivity in newborn lambs (42).Adenosine is a substance less known to affect heart rate variability. It is produced locally in the heart (53) and binds to A1-adenosinergic receptors, which are among the earliest expressed G protein-coupled receptors in the heart (36). The A1-adenosinergic agonist N6-cyclopentyladenosine dose dependently reduced heart rate in murine embryos, whereas 1,3-dipropyl-8-cyclopentylxanthine, an A1-adenosinergic antagonist, increased heart rate (36). Adenosine also exerts central nervous system effects in various brain areas (15, 20). Microinjections of adenosine into the nucleus of the solitary tract of awake rats caused dose-dependent changes in heart rate: low doses (0.01 nmol) produced a bradycardic response, whereas high doses (2.5-5.0 nmol) elicited a tachycardic response (15). Thus adenosine may indeed be involved in the regulation of heart rate and modulate heart rate variability via local cardiac and central nervous system effects. It has been proposed that the intrinsic cardiac nervous system plays an active role in regulating cardiac function (4, 37, 45, 57). This nervous system consists of sympathetic and parasympathetic neurons and interconnecting local circuits (37). Neurons in the canine right atrial ganglionated plexus (RAGP) spontaneously generate activity even after chronic cardiac autonomic denervation (45). Right atrial neurons in patients undergoing coronary artery bypass surgery generated spontaneous activity that was unrelated to the cardiac cycle but sensitive to changes in systemic arterial pressure, indicating that these neurons receive pressure-sensitive sensory inputs (4). In addition, it has been suggested that substance P acts as a neuromodulator and neurotransmitter in intracardiac ganglia of the guinea pig, modulates the response to vagal inputs, and triggers action potentials at the site of parasympathetic ganglia independent of acetylcholine (57). Furthermore, the right atrial (RAGP) and the posterior atrial ganglionated plexus (PAGP) appear to have different functions. Ablation of the PAGP reduced vagally mediated bradycardia by 26%, whereas RAGP ablation completely abolished this response. Inhibition of sympathetically mediated tachycardia by vagal stimulation was attenuated by ablation of either plexus (37). Thus parasympathetic efferent neurons are primarily located in the RAGP, whereas prejunctional parasympathetic-sympathetic interactions also involve neurons within the PAGP (37). The spontaneous activity of neurons in the intrinsic cardiac nervous system, even after cardiac denervation (45), suggests an active role of this system in regulating heart rate. However, the impact of the intrinsic cardiac nervous system on heart rate variability remains to be elucidated. The importance of the autonomic nervous system for heart rate variability in humans becomes apparent in patients following cardiac transplantation, in whom heart rate variability is markedly reduced (49). Although reinnervation is possible after months and years, initially transplanted hearts can be considered to be denervated. Thus the reduced heart rate variability in cardiac transplanted patients (49) underlines the importance of an intact autonomic innervation for spontaneously occurring heart rate variability. A major component of the chronotropic effect of the autonomic nervous system is linked to cAMP. Intracellular cAMP increases the inward current of Na+ (funny current, If), which determines the rate of the slow diastolic depolarization that precedes each action potential. The activity of adenylate cyclase and thus intracellular cAMP levels are increased by stimulation of sympathetic β1-adrenergic receptors and decreased (via a Gi protein) by stimulation of parasympathetic muscarinic receptors. Thus cardiac sympathetic innervation increases the rate of the slow diastolic depolarization and accelerates heart rate, while cardiac parasympathetic innervation elicits opposite effects. Interestingly, parasympathetic-mediated changes in heart rate occur much faster than sympathetic-mediated effects on heart rate (27, 30, 47a). As a result, cardiac sympathetic nervous system activity can only affect LF components of heart rate variability, whereas the parasympathetic nervous system can also modulate HF components. A hitherto unsolved question in this context is if the rapid heart rate response to parasympathetic stimulation compared with the slow effect of sympathetic inputs is due to 1) different kinetics of β1-adrenergic vs. muscarinic receptors, 2) different kinetics of adenylate cyclase vs. phosphodiesterase, the enzyme that cleaves cAMP, or 3) fast parasympathetic-mediated opening of KACh channels (via muscarinic receptors and a GK protein). Support for the latter possibility comes from experiments in the rabbit sinoatrial node that demonstrated that activation of KACh channels contributes to the initial slowing of heart rate as a result of vagal stimulation (8).On the basis of the different frequency response characteristics of sympathetic and parasympathetic modulation of heart rate, frequency analysis of heart rate variability is often used as a tool to determine "autonomic balance" or sympathetic and parasympathetic nervous system activity (27, 47a). As an example, the wavelet transform was recently used to determine cardiac autonomic responses to reperfusion in patients with thrombolysis after coronary thrombosis. Depending on the location of the infarct, marked alterations in LF or HF spectral power of heart rate or in the LF/HF ratio was observed in all successful reperfusions (48).The HF component corresponds to the frequency of respiration and is driven by the vagus as indicated by the strong respiratory pattern of cardiac vagal motoneurons in the nucleus ambiguus (38). The LF component has been ascribed to sympathetic modulation of cardiac pacemaker activity, because a variety of studies demonstrated that acute interventions that increase sympathetic nervous system activity, such as orthostatic perturbations (17, 19, 33), mental stress (32), or handgrip exercise (13, 24) increases LF spectral power of heart rate (27, 30). In addition to acute perturbations of cardiac sympathetic nerve activity, feedback oscillations generated by the baroreceptor reflex also appear to contribute to LF spectral power of heart rate as it was demonstrated that sinoaortic denervation markedly reduces the LF component (27, 30). Despite the strong modulation of heart rate by the autonomic nervous system, the LF and HF spectral components of heart rate variability may not always be very reliable markers for cardiac sympathetic and parasympathetic "tone" (30). In a recent study, muscle sympathetic nerve activity was recorded together with heart rate variability during application of lower body negative pressure that is known to increase muscle sympathetic nerve activity (17, 33). At higher levels of lower body negative pressure (-15 mmHg), both muscle sympathetic nerve activity and relative LF spectral power of heart rate increased significantly, whereas HF spectral power decreased (17). These findings suggest that LF spectral power reflects cardiac sympathetic "tone." However, no correlation within subjects was found between changes in LF/HF ratio and muscle sympathetic nerve activity (17). Thus heart rate variability does not reliably reflect the sympathetic response to orthostatic stress. Respiration-related fluctuation of heart rate (respiratory sinus arrhythmia) is probably the most often investigated component of heart rate variability, as it is believed that this component reflects respiration-driven vagal modulation of sinus arrhythmia (27). In a recent study, Rentero et al. (38) recorded the electrical activity from cardiac vagal motoneurons in the nucleus ambiguus. Firing of these neurons was modulated by the central respiratory cycle. This and other studies support the view that respiratory sinus arrhythmia is generated by central coupling of the respiratory oscillator with autonomic centers in the brain stem. However, a mechanical cardiopulmonary coupling as a source of respiration-related heart rate variability has also been suggested (5). The Bainbridge reflex causes a tachycardia in response to hypervolemia. This reflex is initiated by atrial mechanoreceptors and uses efferent sympathetic and parasympathetic pathways to modulate heart rate in response to changes in central venous pressure (23). Thus respiratory changes in central blood volume cause corresponding respiratory fluctuations in cardiac autonomic nervous system activity via the Bainbridge reflex. Only the parasympathetic component of the efferent pathway of the reflex can contribute to respiratory sinus arrhythmia, because sympathetic actions on heart rate are too damped to follow the respiratory frequency. The gain and phase of the transfer function between respiratory changes in lung volume and R-R intervals of the ECG were calculated in human subjects during graded changes in central blood volume (5). At the respiratory frequency, the phase was -180 degree, indicating that an inspiratory increase in central blood volume was associated with a decrease in R-R interval (increase in heart rate). Furthermore, the gain of the transfer function at the respiratory frequency steadily increased with increasing central volumes (except at the highest volume). Both of these findings confirm the presence of the Bainbridge reflex in humans (5). Thus, in addition to the central coupling of respiratory oscillators with cardiovascular centers, the Bainbridge reflex may contribute to respiration-related heart rate variability by mechanical cardiopulmonary coupling. There is general agreement that low heart rate variability is an unfavorable prognostic marker for cardiovascular diseases, such as diabetic autonomic neuropathy, hypertension, myocardial infarction, and heart failure (18, 22, 27, 29, 47a). Heart rate variability (variance of R-R intervals) was reduced in patients with mild hypertension (29) compared with normal values (1,134 ± 202 vs. 3,466 ± 1,018 ms2) provided by the Task Force (47a). In the rat model of myocardial infarction-induced congestive heart failure, Francis and colleagues (18) reported loss of spontaneous heart rate variability 6 wk after coronary artery ligation. Interestingly, reduced heart rate variability was also observed in a rat model of depression that is based on chronic (4 wk) mild stress application (22). Because depression is an independent risk factor for coronary artery disease, this finding may realistically model a human disease process. The reduction in heart rate variability was abolished by β-adrenergic receptor blockade, indicating that the reduced heart rate variability in this model of depression is related to elevated cardiac sympathetic tone (22).In summary, heart rate variability is generated by multiple factors not exclusively limited to the autonomic nervous system. Specific frequency components of heart rate variability mirror acute perturbations of the autonomic nervous system but do not always reflect autonomic nervous system activity. Simple statistics of heart rate variability, such as the standard deviation of R-R intervals in the ECG, can reliably predict the prognosis of cardiovascular diseases.I thank Dr. R. McAllen for critically reviewing the manuscript. References 1 Aoki K, Stephens DP, and Johnson JM. Diurnal variation in cutaneous vasodilator and vasoconstrictor systems during heat stress. Am J Physiol Regul Integr Comp Physiol 281: R591-R595, 2001.Link | ISI | Google Scholar3 Aoyagi N, Ohashi K, and Yamamoto Y. Frequency characteristics of long-term heart rate variability during constant-routine protocol. Am J Physiol Regul Integr Comp Physiol 285: R171-R176, 2003.Link | ISI | Google Scholar4 Arora RC, Hirsch GM, Johnson Hirsch K, Hancock Friesen C, and Armour JA. Function of human intrinsic cardiac neurons in situ. Am J Physiol Regul Integr Comp Physiol 280: R1736-R1740, 2001.Link | ISI | Google Scholar5 Barbieri R, Triedman JK, and Saul JP. Heart rate control and mechanical cardiopulmonary coupling to assess central volume: a systems analysis. Am J Physiol Regul Integr Comp Physiol 283: R1210-R1220, 2002.Link | ISI | Google Scholar6 Barrett CJ, Navakatikyan MA, and Malpas SC. Long-term control of renal blood flow: what is the role of the renal nerves? Am J Physiol Regul Integr Comp Physiol 280: R1534-R1545, 2001.Link | ISI | Google Scholar7 Blumberg MS, Knoot TG, and Kirby RF. Neural and hormonal control of arterial pressure during cold exposure in un-anesthetized week-old rats. Am J Physiol Regul Integr Comp Physiol 281: R1514-R1521, 2001.Link | ISI | Google Scholar8 Boyett MR, Kodama I, Honjo H, Arai A, Suzuki R, and Toyama J. Ionic basis of the chronotropic effect of acetylcholine on the rabbit sinoatrial node. Cardiovasc Res 29: 867-878, 1995.Crossref | PubMed | ISI | Google Scholar9 Braga and of on fluctuations and changes in blood pressure. Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google and elicited of heart rate variability. J Physiol | ISI | Google and modulation of sympathetic nerve activity to muscle in Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google and and GABA mediate suprachiasmatic nucleus inputs to spinal-projecting paraventricular Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and is not associated with of the exercise reflex in Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google C, and Y. The effect of on the circadian control of human core body temperature is Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and of adenosine receptors in the does not affect the in awake rats. Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google JK, A, and circadian and during two Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and sympathetic nerve and heart rate spectral effects of lower body negative pressure. Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google Francis Johnson and of heart failure after myocardial in the Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google A, and of lower body pressure on muscle sympathetic nerve activity response to Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and Adenosine initial depression of in the rat in Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google R, and and circadian phase in a diurnal the Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and Johnson alterations and autonomic in an model of Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google MA, and The interaction of the Bainbridge and in the conscious Res | ISI | Google A, and handgrip exercise arterial control of sympathetic in Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and nerve regulation to is in rats. Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and in heart rate variability. J Physiol | ISI | Google and function and cardiovascular interactions and Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and interval variability in isolated working rat hearts at various conditions and Res | PubMed | Google A, A, and and autonomic of in patients with mild Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google Malpas SC. Neural on cardiovascular and Am J Physiol Heart Physiol 2002.Link | ISI | Google and thermoregulation in and rats in a Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and effects on reflex responses to mental stress in Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and reflex during orthostatic in Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and and responses to and are in rats. Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and and in a by cycle. Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and of humoral heart rate regulation in the Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google Armour and within the intrinsic cardiac nervous system contribute to chronotropic regulation. Am J Physiol Regul Integr Comp Physiol 285: 2003.Link | ISI | Google Rentero N, A, and McAllen of cardiac vagal motoneurons in rat nucleus ambiguus. Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and modulate control of heart rate in conscious rats. Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google and central actions of angiotensin to increase arterial pressure. Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and modulate control of renal sympathetic nerve activity. Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and modulation of cardiovascular and autonomic function in role of Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and Inhibition of sympathetic responses at birth in by of the paraventricular Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and JP. pattern of during acute and chronic in conscious adult rats. Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google Armour and of chronic cardiac on of canine intracardiac neurons in Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and levels and circadian rhythm of activity in the a model of Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and nerve response of suprachiasmatic nucleus and Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · review · 309 citationsread the source →
Assessing treatment effects in clinical trials with the discan metric of the Sheehan Disability Scale.
The Sheehan Disability Scale (SDS) is a patient-rated, discretized analog measure of functional disability in work, social, and family life. Its increasing use in clinical trials in psychiatry suggests a need to assess its responsiveness and interpretability. In this paper we identify and review studies in which the SDS was used as a treatment outcome measure. Our objectives are (i) to evaluate the sensitivity of the SDS to treatment effects and (ii) to examine potential thresholds or cutoff scores for remission and response. Studies for the review were retrieved from the National Library of Medicine's PubMed database (1966 to 21 March 2007) and other sources. All studies had to use the SDS, be double-blind, controlled or large open-label trials in English. Studies assessing nonpharmacological treatments, long-term trials (>12 weeks), small n trials (less than 20 patients per treatment arm) and trials for conditions other than one of the anxiety disorders, depression, or premenstrual dysphoric disorder were excluded. Extracted data included the diagnostic target of treatment, n, study design, and method of analysis. Initial, endpoint and/or mean change scores were extracted from tables, text, or extrapolated from figures. In all, 37 studies meeting the inclusion criteria were retrieved and reviewed. All of the studies treated the SDS as a numeric scale and analyzed mean change or endpoint differences with parametric statistics. Three provided additional outcome data using nonparametric response or remission criteria. Overall, the SDS performed well in discriminating between active and inactive treatments. The results indicate that the SDS is sensitive to treatment effects. To establish reliable and valid cutoff scores for remission and response, there is a need to supplement parametric analyses using mean change and endpoint differences with nonparametric analyses showing the percentage meeting specified response and remission criteria. In addition, the percentages with endpoint scores of zero should be reported.
International clinical psychopharmacology · review · 328 citationsread the source →
Trends and Thematic Clusters in Moral Injury Research: A Bibliometric Analysis.
Moral injury (MI) spans biological, psychological, social, and spiritual domains, yet systematic bibliometric evaluation remains scarce. A bibliometric analysis of Scopus-indexed publications containing "moral injury" (1992-2025) was conducted using three search strategies (i) Title-Abstract-Keywords (TAK), (ii) Abstract-only (AO), and (iii) Title-only (TO). Publication types, annual trends, and the performance of authors, institutions, countries, sponsors, and journals were examined. A total of 2,081 documents were identified, including articles (1,491), reviews (164), book chapters (193), and editorials (75). TAK yielded 1,655 records, AO 1,400 records, and TO 879 records, demonstrating notable variation in dataset size. Output remained limited until 2017, followed by rapid growth from 2018, peaking in 2025. The USA led global production, followed by the UK, Canada, and Australia. TAK analysis identified the most prolific authors in this review by country: in the USA, Maguen, S. (36) and Koenig, H.G. (34); in the UK, Greenberg, N. (37) and Murphy, D. (36); in Canada, McKinnon, M.C. (23) and Nazarov, A. (21); and in Australia, Carey, L.B. (13) and Nickerson, A. (10). Other top contributors by country are also identified. Within this study, prolific institutions included VA Medical Center, King's College London, Western University, McMaster University, Duke University Medical Center, and the Boston University Chobanian and Avedisian School of Medicine. Prominent journals were 'Psychological Trauma: Theory, Research, Practice, and Policy', the 'European Journal of Psychotraumatology', 'Traumatology', 'Frontiers in Psychiatry', and the 'Journal of Religion and Health'. Title-based co-word analysis (AO and TO datasets) identified ten thematic clusters covering psychological outcomes, military and healthcare contexts, ethics, assessment, and interventions. Analysis of the top 100 most cited papers highlighted five foundational themes in conceptualization, measurement, mental health outcomes, and treatment approaches. MI research expanded rapidly after 2018, emphasizing the need for methodological transparency through a bibliometric study across multidisciplinary fields. While not all authors/coauthors or their respective institutions and nations have been acknowledged within this analysis of MI research, nevertheless the significant leaders have been identified, as have a number of key research and clinical themes. Search strategy selection however, substantially determines dataset size, contributor visibility, and thematic representation, hence a number of limitations regarding this analysis are noted.
Journal of religion and health · 1 citationsread the source →
The pleasure of art as a matter of fact
You have accessMoreSectionsView PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail Cite this article Nadal Marcos and Skov Martin 2018The pleasure of art as a matter of factProc. R. Soc. B.2852017225220172252http://doi.org/10.1098/rspb.2017.2252SectionYou have accessCommentThe pleasure of art as a matter of fact Marcos Nadal Marcos Nadal http://orcid.org/0000-0002-9341-4688 Department of Psychology, University of the Balearic Islands, Palma de Mallorca 07122, Spain [email protected] Google Scholar Find this author on PubMed Search for more papers by this author and Martin Skov Martin Skov Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Copenhagen 2650, Denmark Center for Decision Neuroscience, Copenhagen Business School, Copenhagen 2000, Denmark Google Scholar Find this author on PubMed Search for more papers by this author Marcos Nadal Marcos Nadal http://orcid.org/0000-0002-9341-4688 Department of Psychology, University of the Balearic Islands, Palma de Mallorca 07122, Spain [email protected] Google Scholar Find this author on PubMed and Martin Skov Martin Skov Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Copenhagen 2650, Denmark Center for Decision Neuroscience, Copenhagen Business School, Copenhagen 2000, Denmark Google Scholar Find this author on PubMed Published:21 March 2018https://doi.org/10.1098/rspb.2017.2252All other forms of perception divide a man, because they are exclusively based either on the sensuous or on the intellectual part of his being; only the perception of the Beautiful makes something whole of him, because both his natures must accord with it.— Schiller, 1793–1795, Letters on the Aesthetic Education of Man, p. 138, Letter 27Can art make us better people? Better members of society? In her recent article, 'Pleasure junkies all around! Why it matters and why "the arts" might be the answer: a biopsychological perspective', Christensen [1] claims that engaging with art can promote healthy choices, choices that balance short-term pleasure goals with long-term general well-being. She suggests that many modern life conveniences, such as social media, computer games or online shopping, have the potential to turn us into 'pleasure junkies' because they maximize short-term pleasures. But art, Christensen argues, is a safe choice and a means to remedy this unhealthy addiction to pleasure. Christensen's argument is grounded on three claims about the sort of pleasure we get from art. First, in contrast to low-level pleasure, which Christensen conceives as 'a mere perceptual stimulation leading to a rewarding sensation (food, sex, etc.)' ([1], p. 2), pleasure from art is presented as a kind of higher-order pleasure that engages 'broader neural networks implied in the attribution of meaning' (p. 2), presumably leading to 'long-term maintenance of healthy bodily function' (p. 2). Second, 'the arts do not induce states of craving without fulfilment—as do activities with reinforcement schedules which are prone to create habits and addictions such as intermittent variable ratio or interval reinforcement schedules (e.g. social media, gambling, football, extreme sports, drugs' (p. 4). Third, 'the arts do not search for a perceptual "Bliss point" […]. They do not just repeat over and over again a sensory stimulus that excites the senses and induces craving for more of a "pleasurable itch" (e.g. sugar, sexualized body displays, certain musical lyrics, tones; i.e. a perceptual "bliss point")' (p. 4).The claim, in a nutshell, is that the pleasure induced by art is different to the pleasure induced by food, sex, sports or drugs, because it is related to the balanced activation of brain systems related to short-term pleasure and long-term wellbeing goals, because it does not induce craving, and because it is not aimed at a perceptual 'bliss point'. This distinct sort of pleasure, according to Christensen, makes it possible for the arts to thwart the pernicious effects that the unhealthy urges and cravings licensed by 'today's mainstream acceptance of pleasure-seeking behaviour' (p. 5) have on individuals' lives and on societies. Such sweeping statements about art, food, sex, sports and society as a whole merit close examination. Christensen's primary claim that the pleasure induced by art is of a special kind, different to the pleasure induced by other activities is not supported by current understanding of what pleasure is. It is, moreover, contradicted by abundant empirical evidence. This evidence shows that pleasures, whatever their source, owe to activity in the same mesocorticolimbic circuit [2] and are encoded as a common neural currency [3]. As Kent Berridge and Morten Kringelbach put it: 'the brain mechanisms involved in fundamental pleasures (food and sexual pleasures) overlap with those for higher-order pleasures (e.g. monetary, artistic, musical, altruistic and transcendent pleasures) […] From sensory pleasures and drugs of abuse […] to monetary, aesthetic and musical delights, all pleasures seem to involve the same hedonic brain systems' ([4], p. 481). Thus, there is no evidence for specific brain regions or neural circuits related to the pleasure from art. Rather, the appreciation of art relies on brain mechanisms that evolved to appraise the value of biologically relevant objects in relation to internal homeostatic states [5]: 'Emotional reactions to music, further, activate the same cortical, subcortical and autonomic circuits, which are considered as the essential survival circuits of biological organisms in general' ([6], p. 6). In sum, the evidence shows that pleasure elicited by music and other art forms is no different in genesis and function to the pleasure induced by food, drugs and sex [7,8]. This is a matter of fact, not opinion. What supports Christensen's argument if not empirical evidence? In our view, her argument for the distinctness of art-induced pleasure seems based upon an oversimplified and devaluing conception of the pleasures of sex, food and sports, and a very narrow notion of art and its function. Christensen presents food, sex and sports as meaningless low-level sources of pleasure, and the arts as privileged vehicles for meaningful experiences. It is the personal and meaningful engagement with art—Christensen suggests—that fosters a balanced activation of brain systems related to short-term pleasure and long-term well-being goals. However, rarely—if ever—are food, sex and sports meaningless rewarding sensations. Contrary to Christensen's definition on page 2 of her article, pleasure—even sensory pleasure—is not simply reward, and never simply a sensation [4]. Indulging in food, sex or sports are meaningful and personally significant experiences that are not a matter of mere physical sensation. The experience of pleasure from food and sex is shaped by context, knowledge, expectations, anticipations, attitudes and beliefs that bring meaning to them [9–11]. Sex can be meaningful because it signifies physical connection with one's loved one, because it is cheating on someone, or deemed a sin. Likewise, eating is not about obtaining low-level pleasure. What we eat, the way we eat, what we believe about what we eat, where and whom we eat with, imbue eating with individual and social meaning, and shape the actual pleasure of eating [12]. On the other hand, encounters with art are not necessarily meaningful [13,14]. Actually, there is nothing intrinsically meaningful about engaging with art. Many laypeople lack the knowledge schemata required to engage meaningfully with abstract, cubist or contemporary art [15,16]. There are plenty of artworks people do not find meaningful or pleasant. Meaning making is not a special feature of art; it is a general feature of our species's cognition [17,18]. We can endow virtually any aspect of reality with meaning: sex, food, sports, a urinal, the shape of a cloud, an averted glance, someone's absence. Christensen's argument also rests on a historically and culturally narrow conception of art and its function. Art is presented as a circumscribed category of activities that elicit a unique sort of pleasant experiences: — The arts are set of activities of a special kind that share certain defining features distinguishing them from other activities: 'the arts push boundaries, surprise, reveal and excite both artist and spectator' ([1], p. 4).— Art encounters are positive, leading to 'pleasurable chills' and pleasurable experiences of understanding: 'The moment of meaning-assignation, also called "mastering" or "understanding" an artwork, is therefore a pleasurable experience' ([1], p. 4).— The pleasure elicited by art is special, because it does not involve craving for intense peaks: 'The arts do not search for a perceptual "bliss point" […] They do not just repeat over and over a sensory stimulus that excites the senses and induces craving for more of a "pleasurable itch"' ([1], p. 4).This characterization of the arts substantially overlaps with the notion of 'fine arts'. The core features of this characterization were instituted in the eighteenth century, after European intellectuals grouped certain activities into a distinct and autonomous collection, labelled 'fine arts'. To make sense of and promote this grouping, it became imperative to identify a common essence setting art apart from other activities [19,20,21]. One of the most popular proposals was that only art could produce a special sort of pleasure, sophisticated and polite [19,21]—a conception stemming not from any understanding of physiology, but from mere speculation. This limited historical and cultural scope renders this conception of the arts unfit for behavioural or neuroscientific research [19]. The category 'the arts' should not be mistaken for a natural kind. It is a historical convention, and has no direct biological correspondence. Moreover, this conception of art that Christensen espouses does not apply to art as practised in non-Western societies [19,22]. It does not even apply to Western art before the eighteenth century or after the nineteenth century [19,20,21]. First, art does not necessarily evoke pleasurable experiences. There are abundant artworks intended to arouse negative emotions [19,23], and to portray physical and moral ugliness [24]. Understanding art is not necessarily a pleasant experience: it can be an angering, disgusting or upsetting one [25]. Second, many artworks actually exploit repetition, bliss points and craving [26]. Repetition is a fundamental design feature of music and other performance arts [27]: In Relation in Space (1976) Marina Abramovic and Ulay ran into each other repeatedly for an hour; Ravel's Bolero is a 17 min-long instance of melodic and rhythmic repetitiveness. Anticipation and craving for bliss points are also essential to music [28]. In fact, the enjoyment of music is linked to intense feelings of anticipation and expectation caused by dopamine activity in the caudate nucleus (also involved in the rewarding aspect of food) [29,30], and peak pleasure states (bliss points) [31], caused by the release of dopamine and opioids in the brain's reward system (also involved in cocaine induced euphoria) [29,30]. Given the available evidence, therefore, there is no reason to believe that the pleasure from art is special or unique [32].In sum, Christensen's claim for the distinctiveness of pleasure from art is contradicted by empirical evidence, and her argument for the beneficial effects of art rests upon disputed foundations. Art's capacity to promote healthier choices and make us better people that can contribute to a better society remains as unconfirmed today as it was when Schiller speculated on art's power to harmonize human's conflicting sensuous and formal impulses. Christensen's argument is problematic even if intended to highlight hypothetical possibilities. Arguments about hypothetical possibilities should still rely on valid premises, and scientific hypotheses should be grounded on evidence, or at least in line with it. Otherwise, they are merely unfounded speculations. Scientific aesthetics is only just finding its footing and its place within cognitive neuroscience [33,34]. If evidence is ignored or rejected because it does not fit preconceived notions about art and its function, scientific aesthetics will become only an arena to promote and legitimize personally appealing notions of art by applying a scientific gloss over them. A proper scientific study of art needs to be grounded on empirical evidence and strong arguments that follow from solid premises [35,36]. Only then can scientific aesthetics provide reliable explanations for artistic and aesthetic behaviour, and thus make a significant contribution to the understanding of our human nature. Data accessibilityThis article has no additional data. Authors' contributionsBoth authors have contributed to conceiving, developing and writing the research presented in this paper, and approved it for publication. Competing interestsWe declare we have no competing interests. FundingThis research was supported by grant PSI2016-77327-P (MINECO/AEI/ERDF, EU).Footnotes© 2018 The Author(s)Published by the Royal Society. All rights reserved. References1Christensen JF. 2017Pleasure junkies all around! Why it matters and why 'the arts' might be the answer: a biopsychological perspective. Proc. R. Soc. B 284, 20162837. (doi:10.1098/rspb.2016.2837) Link, ISI, Google Scholar2Berridge CW, Kringelbach ML. 2013Neuroscience of affect: brain mechanisms of pleasure and displeasure. Curr. Opin. Neurobiol. 23, 294–303. (doi:10.1016/j.conb.2013.01.017) Crossref, PubMed, ISI, Google Scholar3Levy DJ, Glimcher PW. 2012The root of all value: a neural common currency for choice. Curr. Opin. Neurobiol. 22, 1027–1038. (doi:10.1016/j.conb.2012.06.001) Crossref, PubMed, ISI, Google Scholar4Kringelbach ML, Berridge KC. 2009Towards a functional neuroanatomy of pleasure and happiness. Trends Cogn. Sci. 13, 479–487. (doi:10.1016/j.tics.2009.08.006) Crossref, PubMed, ISI, Google Scholar5Brown S, Gao X, Tisdelle L, Eickhoff LM. 2011Naturalizing aesthetics: brain areas for aesthetic appraisal across sensory modalities. Neuroimage 58, 250–258. (doi:10.1016/j.neuroimage.2011.06.012) Crossref, PubMed, ISI, Google Scholar6Reybrouck M, Eerola T. 2017Music and its inductive power: a psychobiological and evolutionary approach to musical emotions. Front. Psychol. 8, 494. (doi:10.3389/fpsyg.2017.00494) Crossref, PubMed, ISI, Google Scholar7Blood AJ, Zatorre RJ. 2001Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion. Proc. Natl Acad. Sci. USA 98, 11 818–11 823. (doi:10.1073/pnas.191355898) Crossref, ISI, Google Scholar8Mallik A, Chandra ML, Levitin DJ. 2017Anhedonia to music and mu-opioids: evidence from the administration of naltrexone. Sci. Rep. 7, 41952. (doi:10.1038/srep41952) Crossref, PubMed, ISI, Google Scholar9Barrett LF. 2015How emotions are made: the secret life of the brain. London, UK: Macmillan. Google Scholar10Bloom P. 2010How pleasure works: the new science of why we like what we like. New York, NY: Norton. Google Scholar11Chatterjee A. 2014The aesthetic brain: how we evolved to desire beauty and enjoy art. New York, NY: Oxford University Press. Google Scholar12Spence C. 2017Gastrophysics: the new science of eating. London, UK: Penguin. Google Scholar13Leder H, Belke B, Oeberst A, Augustin D. 2004A model of aesthetic appreciation and aesthetic judgments. Br. J. Psychol. 95, 489–508. (doi:10.1348/0007126042369811) Crossref, PubMed, ISI, Google Scholar14Vessel EA, Rubin N. 2010Beauty and the beholder: highly individual taste for abstract, but not real-world images. J. Vis. 10, 1–14. (doi:10.1167/10.2.18) Crossref, PubMed, ISI, Google Scholar15Minissale G. 2013The psychology of contemporary art. Cambridge, UK: Cambridge University Press. Crossref, Google Scholar16Muth C, Pepperell R, Carbon C-C. 2013Give me Gestalt! Preference for cubist artworks revealing high detectability of objects. Leonardo 46, 488–489. (doi:10.1162/LEON_a_00649) Crossref, ISI, Google Scholar17Deacon TW. 1997The symbolic species: the co-evolution of language and the brain. New York, NY: Norton. Google Scholar18Henshilwood CS, d'Errico F. 2011Homo symbolicus: the dawn of language, imagination and spirituality. Amsterdam, The Netherlands: John Benjamins Publishing Co. Crossref, Google Scholar19Carroll N. 2008Aesthetic experience, art and artists. In Aesthetic experience (eds Shusterman R, Tomlin A), pp. 145–165. New York, NY: Routledge. Google Scholar20Kivy P. 2012What really happened in the eighteenth century: the 'Modern System' re-examined (again). Br. J. Aesthetics 52, 61–74. (doi:10.1093/aesthj/ayr046) Crossref, ISI, Google Scholar21Shiner L. 2001The invention of art: a cultural history. Chicago, IL: University of Chicago Press. Crossref, Google Scholar22Anderson RL. 1989Art in small-scale societies. 2nd edn. Englewood Cliffs, NJ: Prentice Hall. Google Scholar23Silvia PJ. 2009Looking past pleasure: anger, confusion, disgust, pride, surprise, and other unusual aesthetic emotions. Psychol. Aesthetics Creat. Arts 3, 48–51. (doi:10.1037/a0014632) Crossref, ISI, Google Scholar24Eco U. 2007On ugliness. London, UK: Harvill Secker. Google Scholar25Silvia PJ, Brown EM. 2007Anger, disgust, and the negative aesthetic emotions: expanding an appraisal model of aesthetic experience. Psychol. Aesthetics Creat. Arts 1, 100–106. (doi:10.1037/1931-3896.1.2.100) Crossref, Google Scholar26Huron D. 2006Sweet anticipation: music and the psychology of expectation. Cambridge, MA: MIT Press. Crossref, Google Scholar27Fitch W. 2006The biology and evolution of music: a comparative perspective. Cognition 100, 173–215. (doi:10.1016/j.cognition.2005.11.009) Crossref, PubMed, ISI, Google Scholar28Trainor LJ, Zatorre RJ. 2009The neurobiological basis of musical expectations. In The Oxford handbook of music psychology (eds Hallam S, Cross I, Thaut M), pp. 171–183. Oxford, UK: Oxford University Press. Google Scholar29Salimpoor VN, Benovoy M, Larcher K, Dagher A, Zatorre RJ. 2011Anatomically distinct dopamine release during anticipation and experience of peak emotion to music. Nat. Neurosci. 14, 257–262. (doi:10.1038/nn.2726) Crossref, PubMed, ISI, Google Scholar30Salimpoor VN, Zatorre RJ. 2013Neural interactions that give rise to musical pleasure. Psychol. Aesthetics Creat. Arts 7, 62–75. (doi:10.1037/a0031819) Crossref, ISI, Google Scholar31Whaley J, Sloboda J, Gabrielsson A. 2009Peak experiences in music. In The Oxford handbook of music psychology (eds Hallam S, Cross I, Thaut M), pp. 452–461. Oxford, UK: Oxford University Press. Google Scholar32Skov M, Nadal M.In press. Art is not special: an assault on the last lines of defense against the naturalization of the human mind. Rev. Neurosci. (doi:10.1515/revneuro-2017-0085) ISI, Google Scholar33Chatterjee A. 2011Neuroaesthetics: a coming of age story. J. Cogn. Neurosci. 23, 53–62. (doi:10.1162/jocn.2010.21457) Crossref, PubMed, ISI, Google Scholar34Pearce MT, Zaidel DW, Vartanian O, Skov M, Leder H, Chatterjee A, Nadal M. 2016Neuroaesthetics: the cognitive neuroscience of aesthetic experience. Perspect. Psychol. Sci. 11, 265–279. (doi:10.1177/1745691615621274) Crossref, PubMed, ISI, Google Scholar35Nadal M, Vartanian O, Skov M. 2017Psychological models of art reception must be empirically grounded. Behav. Brain Sci. 40, 36–37. (doi:10.1017/S0140525X17001790) Crossref, ISI, Google Scholar36Nadal M, Skov M. 2017Top–down and bottom–up: front to back: comment on 'Move me, astonish me… delight my eyes and brain: the Vienna integrated model of top–down and bottom–up processes in Art Perception (VIMAP) and corresponding affective, evaluative, and neurophysiological correlates' by Matthew Pelowski et al. Phys. Life Rev. 21, 148–149. (doi:10.1016/j.plrev.2017.06.013) PubMed, ISI, Google Scholar Previous ArticleNext Article VIEW FULL TEXT DOWNLOAD PDF FiguresRelatedReferencesDetailsCited by Clemente A, Pearce M, Skov M and Nadal M (2021) Evaluative judgment across domains: Liking balance, contour, symmetry and complexity in melodies and visual designs, Brain and Cognition, 10.1016/j.bandc.2021.105729, 151, (105729), Online publication date: 1-Jul-2021. Chuan-Peng H, Huang Y, Eickhoff S, Peng K and Sui J (2020) Seeking the "Beauty Center" in the Brain: A Meta-Analysis of fMRI Studies of Beautiful Human Faces and Visual Art, Cognitive, Affective, & Behavioral Neuroscience, 10.3758/s13415-020-00827-z, 20:6, (1200-1215), Online publication date: 1-Dec-2020. Skov M and Nadal M (2020) A Farewell to Art: Aesthetics as a Topic in Psychology and Neuroscience, Perspectives on Psychological Science, 10.1177/1745691619897963, 15:3, (630-642), Online publication date: 1-May-2020. Kalpokas I (2019) Making the Theory Political A Political Theory of Post-Truth, 10.1007/978-3-319-97713-3_4, (87-121), . Kalpokas I (2019) Affective Encounters of the Algorithmic Kind: Post-Truth and Posthuman Pleasure, Social Media + Society, 10.1177/2056305119845678, 5:2, (205630511984567), Online publication date: 1-Apr-2019. Skov M (2019) Aesthetic Appreciation: The View From Neuroimaging, Empirical Studies of the Arts, 10.1177/0276237419839257, 37:2, Online publication date: H, I and (2020) A for We Aesthetic in Human Neuroscience, A and in A New for Arts, This March Article in 2018 The Author(s)Published by the Royal Society. All rights Citations and are available with
Proceedings of the Royal Society B Biological Sciences · editorial or comment · 24 citationsread the source →
Autism spectrum symptomatology in children: the impact of family and peer relationships.
This study examines the potential impact of family conflict and cohesion, and peer support/bullying on children with autism spectrum disorder (ASD). While such impacts have been established for a range of non-ASD childhood disorders, these findings may not generalize to children with ASD because of unique problems in perspective-taking, understanding others' emotion, cognitive rigidity, and social reasoning. A structural model-building approach was used to test the extent to which family and peer variables directly or indirectly affected ASD via child anxiety/depression. The sample (N = 322) consisted of parents of children with ASD referred to two specialist clinics. The sample contained parents of children with Autistic Disorder (n = 76), Asperger Disorder (n = 188), Pervasive Disorder Not Otherwise Specified (n = 21), and children with a non-ASD or no diagnosis (n = 37). Parents completed questionnaires on-line via a secure website. The key findings were that anxiety/depression and ASD symptomatology were significantly related, and family conflict was more predictive of ASD symptomatology than positive family/peer influences. The results point to the utility of expanding interventions to include conflict management for couples, even when conflict and family distress is low. Further research is needed on the potentially different meanings of family cohesion and conflict for children with ASD relative to children without ASD.
Journal of abnormal child psychology · 58 citationsread the source →
Davis KAS, Coleman JRI, Adams M, Allen N, Breen G, Cullen B, Dickens C, Fox E, Graham N, Holliday J, Howard LM, John A, Lee W, McCabe R, McIntosh A, Pearsall R, Smith DJ, Sudlow C, Ward J, Zammit S, Hotopf M. (2020)MEDLINE-indexed journal, not yet read by usBJPsych open Mental health in UK Biobank - development, implementation and results from an online questionnaire completed by 157 366 participants: a reanalysis.
Background: UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Aims: Describe the development, implementation and results of this questionnaire.
Method: An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
Results: A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45-82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
Conclusions: The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
BJPsych open · 312 citationsread the source →
When emotions remain unnamed: alexithymia and rejection sensitivity fuel aggression via anger rumination.
Aggressive behavior has been consistently associated with difficulties in emotion regulation, yet the mechanisms through which interpersonal vulnerability and impaired emotional awareness contribute to aggression remain insufficiently specified. Rejection sensitivity (RS) and alexithymia are established cognitive-affective risk factors, but their joint pathways to aggression warrant clarification. The present study aimed to test a theoretically grounded structural model in which anger rumination functions as a proximal cognitive-affective mechanism linking RS and alexithymia to aggressive behavior. In a community sample of women (n = 666; M = 34.62, SD = 8.35), we tested a structural equation model (SEM) in which anger rumination was specified as a mediator linking RS and alexithymia to aggression. Participants completed validated self-report measures of RS, alexithymia (PAQ), anger rumination (ARS), and aggression (AQ). Measurement models were supported via CFA. SEM with robust maximum likelihood estimation was conducted, controlling for age and education. Indirect effects were evaluated using bias-corrected bootstrapping. The model demonstrated a good fit. RS (β = .34, p < .001) and alexithymia (β = .21, p < .001) were significantly associated with anger rumination, which, in turn, was linked to aggression (β = .37, p < .001). Both RS (β = .14, 95% CI [.08, .20]) and alexithymia (β = .07, 95% CI [.01, .12]) showed significant indirect effects on aggression via anger rumination. Anger rumination emerges as a key cognitive-affective pathway linking interpersonal hypersensitivity and emotional unawareness to aggression. Targeting rumination and emotional clarity may enhance interventions for aggression in rejection-sensitive individuals.
Psychology, health & medicineread the source →
de Vocht F, McQuire C, Brennan A, Egan M, Angus C, Kaner E, Beard E, Brown J, De Angelis D, Carter N, Murray B, Dukes R, Greenwood E, Holden S, Jago R, Hickman M. (2020)MEDLINE-indexed journal, not yet read by usAddiction (Abingdon, England) Evaluating the causal impact of individual alcohol licensing decisions on local health and crime using natural experiments with synthetic controls.
Background and aims: Given the costs of alcohol to society, it is important to evaluate whether local alcohol licensing decisions can mitigate the effects of alcohol misuse. Robust natural experiment evaluations of the impact of individual licensing decisions could potentially inform and improve local decision-making. We aimed to assess whether alcohol licensing decisions could be evaluated at small spatial scale by using a causal inference framework.
Design: Three natural experiments.
Setting and participants: Three English local areas of 1000-15 000 people each.
Intervention and comparator: The case study interventions were (i) the closure of a nightclub following reviews; (ii) closure of a restaurant/nightclub following reviews and (iii) implementation of new local licensing guidance (LLG). Trends in outcomes were compared with synthetic counterfactuals created using Bayesian structural time-series.
Measurements: Time-series data were obtained on emergency department admissions, ambulance call-outs and alcohol-related crime at the Lower or Middle Super Output geographical aggregation level.
Findings: Closure of the nightclub led to temporary 4-month reductions in antisocial behaviour (-18%; 95% credible interval - 37%, -4%), with no change in other outcomes. Closure of the restaurant/nightclub did not lead to measurable changes in outcomes. The new licensing guidance led to small reductions in drunk and disorderly behaviour (nine of a predicted 21 events averted), and the unplanned end of the LLG coincided with an increase in domestic violence of two incidents per month.
Conclusions: The impact of local alcohol policy, even at the level of individual premises, can be evaluated using a causal inference framework. Local government actions such as closure or restriction of alcohol venues and alcohol licensing may have a positive impact on health and crime in the immediate surrounding area.
Addiction (Abingdon, England) · 22 citationsread the source →
Domestic violence in pregnancy: prevalence and characteristics of the pregnant woman.
Aims and objectives: To determine the prevalence of domestic violence (physical, psychological or sexual) during pregnancy and to characterise these women.
Background: Pregnant women are not immune to domestic violence and therefore may be subject to any form of physical, psychological or sexual violence by partners. Health professionals' knowledge and awareness are important in the identification and intervention of pregnant women who experience domestic violence.
Methods: Quantitative, descriptive, correlational study, using a nonprobabilistic convenience sample consisting of a total of 852 postpartum women, of whom 370 were experiencing domestic violence according to the criteria adopted through the modified scale of prevalence, applied between February-June 2012 in two Portuguese public health institutions. Authorisation was given by the Ethics Committees/Administration Councils of both institutions involved and the National Committee of Data Protection.
Results: The prevalence of DV during pregnancy was 43·4% (physical violence - 21·9%; psychological violence - 43·2%; and sexual violence - 19·6%). These women had the following profile: immigrant (OR = 5·70; IC95% 3·32-9·78), non-Caucasian (OR = 6·27; IC95% 3·76-10·46), single/divorced/widowed (OR = 2·28; IC95% 1·70-3·05), academic qualifications up to year 9 (OR = 4·94; IC95% 3·31-7·37); between 10-12 years of schooling (OR = 2·36; IC95% 1·70-3·29); unemployed (OR = 2·01; IC95% 1·50-2·69); and with a monthly income <1000 euros (OR = 1·90; IC95% 1·44-2·50). Through logistic regression, the following protective factors have been identified: nationality (Portuguese), race (Caucasian) and place of residence (city).
Conclusions: Almost half of the sample had experienced some form of domestic violence. This is associated with certain sociodemographic factors identified in the study. Psychological violence was the most prevalent during pregnancy.
Relevance to clinical practice: Knowledge of the prevalence and characteristics of pregnant women who experience domestic violence is of paramount importance in planning appropriate strategies for their needs during pregnancy. Results indicate the need for nurses to intervene when warning signs of domestic violence against pregnant women are detected.
Journal of clinical nursing · 30 citationsread the source →
Programmatic approaches to achieving equity for women in anesthesiology
Key points Women anesthesiologists can experience barriers and bias in the workplace, which varies in nature across their career and can negatively hinder professional development. Mitigation of these barriers and discrimination can be achieved through: (1) addressing individual bias, (2) closing the knowledge gap on the scope of bias, (3) deliberate representation, (4) strengthening professional networks, and (5) organized efforts to create policies that address gender inequity in the workplace. Women in anesthesiology is one example of several organized initiatives and programs that promote gender equity for women anesthesiologists of all identities. Introduction Women have long fought for equity in medicine and to be treated respectfully and professionally as physicians. One hundred seventy-five years ago, Elizabeth Blackwell was admitted to medical school as a joke, and since then, the viewpoint that medicine is emotionally undesirable, intellectually taxing, and physically draining for women has persisted. Pioneering women anesthesiologists, including Isabella Herb and Virginia Apgar, were discouraged from training as surgeons and pushed into the lower paying and “lower status” specialty of anesthesiology. Despite 50 years since the passage of Title IV, a Federal civil rights law that prohibits discrimination on the basis of sex in any educational program or activity that receives federal funding, and the fact that half of the medical students are women, there is still major attrition of women as they advance in anesthesiology residencies, careers, and leadership.1,2 Recent studies have attempted to examine the reasons for this inequity and bring awareness of the widespread discrimination and systemic bias affecting women anesthesiologists and their departure from medicine.1,3–8 Identifying as a woman in anesthesiology is multifaceted and nuanced. Women can be at different points in their professional careers and personal lives. This may be associated with a broad spectrum of identities, including but not limited to clinicians, academicians, activists, or advocates, as well as mothers, children, siblings, or partners. These identities also intersect with sexuality, race, ethnicity, culture, spirituality, and community. This diversity of lived experiences is why blanket assumptions about women anesthesiologists should be avoided. However, despite these varied identities, all women anesthesiologists are subject to institutional and cultural norms regarding gender. Therefore, the development of multiple initiatives and programs to promote gender equity for women anesthesiologists of all identities is paramount. In this article, we will review the scope of the gender problem in our specialty, discuss proposed strategies to enhance equity, and examine 1 organization’s approach to advocating for gender equity in anesthesiology. Scope of the problem Overworked, undervalued, harassed, and silenced. These are the sentiments of many women in anesthesiology. Many of the challenges encountered are synergized by a climate and culture that enable and fail to adequately address these issues.9 Gender disparities within anesthesiology exist because of systemic barriers and biases, limited number of women in anesthesiology leadership, and limited mentorship.5 The proportion of women physicians in anesthesiology ranks in the lower third among all medical specialties.10 Despite significant advances in the number of women entering medicine over the last few decades, anesthesiology programs have yet to achieve gender parity.7 Among anesthesiology residents, 33% are women. Women represent 25% of the overall anesthesiology workforce and 37% of the academic anesthesiology workforce, and these numbers remain relatively static.1,6,8 Meanwhile, other surgical and procedural subspecialties have doubled and tripled the percentage of women in their field and surpassed anesthesiology. Women anesthesiologists also are underrepresented in various positions of leadership or influence, and as authors and editors.4 They are paid significantly less than their male counterparts for equitable work, with an annual pay gap of 8%, or $32,000 a year, and are overall more likely to be in a lower salary range.5 Over a 30-year career span, this translates to roughly $1,000,000 in lost earnings.5 Even after adjusting for age, work experience, hours worked, academic productivity, and rank, the gap in gender pay remained and in fact, widened over the course of an anesthesiologist’s career.5 There are several systemic issues that hinder the recruitment, retention, and success of women in anesthesiology. Women physicians, relative to men, encounter additional hurdles to performing their jobs, especially at the early stages of their careers.11 Women physicians are more frequently asked about their age and experience compared with their men counterparts. A study found when treatment advice was given by an inexperienced physician, and participants reported relying significantly more on the advice of a man versus a woman.11 This suggests that some of the hurdles that women physicians face are rooted in the psychological biases of others rather than objective features of cases or treatment settings.11 The results of the few studies examining the effects of gender on daily practice in the specialty of anesthesiology are discouraging. A recent survey study assessing gender disparities perceived by women anesthesiologists found that majority (90%) of the respondents felt that women in medicine need to work harder than men to achieve the same career goals, and sexual harassment was experienced by 55%.12 Similarly, in a survey of women cardiothoracic anesthesiologists, 24% of respondents reported experiencing unwanted physical or sexual advances, and 45% reported experiencing verbal harassment.13 The majority of respondents also reported experiencing intimidation or derogatory language in the workplace.13 As well stated by the authors: “lack of psychological safety and respect in working environments increases the risk of communication failures, and intimidation in the setting of managing surgical patients increases stress and risk for burnout”.13 The original “pipeline theory” proposed that sex-based discrimination in academic medicine would diminish once women achieved a critical mass of > 30% of the academic workforce.14 Interestingly, “women who examine trends in sex disparities in the workplace are often ridiculed, labeled as whining, or determined to be less capable in their ability to lead.”15 Paired with that, women physicians are less likely to be addressed as “doctor,” they are more likely to be interrupted (at times in the middle of their preoperative assessment), and more likely to be labeled as “bossy” when asserting information.16 The culture of medicine is unlikely to change without improving formal reporting mechanisms of sex-based discrimination and sexual harassment.14 Unfortunately, the prevalence of sexist microaggressions against women anesthesiologists is still high, and this ongoing workplace mistreatment can cause chronic and severe distress.17 Sex equity is an issue of urgency in the practice of anesthesiology. Those in leadership positions have the additional responsibility of leveraging their power to influence the broader institutional culture.15 Having women at the top of organizations has been shown to improve organizational performance.18 Women represent approximately half of students entering medical school and ~41% of full-time academic faculty,19 yet women constitute a minority of leaders.20 Sex disparities continue to exist at the upper levels of leadership in academic anesthesiology.1 Only 18% of women are professors, and the percentage of women anesthesiology department chairs remains unchanged from 2006 to 2016 (12.7% vs. 14%).21 As of this writing, neither Anesthesia & Analgesia nor Anesthesiology has had a woman Editor-in-Chief. On that note, men and women have significant differences in measures of publication productivity, a recent study demonstrating that male anesthesiologists had a higher h-index, number of publications, and number of citations.22 Women have also been underrepresented in national meetings with fewer speaker opportunities.8 Overall, the extremely limited proportion of women professors and chairs in anesthesiology, presidents of professional societies, and senior editors of specialty journals speak for itself when it comes to a lack of visibility at the highest level of the specialty.9 Despite the many barriers that women experience, they are just as eager as men to assume leadership positions.23 The “glass ceiling” still exists within the culture of anesthesiology, benefiting the “masculine” attitudes in the competition for academic positions.24 We need to change this outdated culture and climate in anesthesiology and create and help elevate more women into a pathway of equity. Anesthesiologists and pregnancy Pregnancy and motherhood have a tremendous impact on sex discrimination in anesthesiology. A woman’s peak fertility often coincides with residency training and early career, a time when one’s career trajectory becomes established. This is also the time when the sex gap in academic promotion and productivity widens. Having children at that time is a challenge, and it is known that work demands adversely affect women anesthesiologists’ desired number of children and the desired age of childbearing. Anesthesiologists have the highest rate of maternal discrimination among all medical specialties.25 Sixty percent of anesthesiology residents reported a negative stigma around being pregnant and having children during training, and about half of trainees reported feeling discouraged from becoming pregnant or breastfeeding during training.7,26,27 Difficulties faced by women who are pregnant during training include inadequate maternity leave, insufficient access to lactation facilities at work, and negative culture surrounding pregnancy during training.26 Because of obstacles pertaining to motherhood, 1 in 10 female anesthesiologists would counsel a student against a career in anesthesiology.7 However, 86.2% of women anesthesiologists indicated that if given a choice again, they would still have their child during training despite these obstacles.26 Given the negative stigma associated with pregnancy in residency training, many women delay pregnancy until their early career, which typically occurs in the early 30s, leading to a higher likelihood of infertility.28 Approximately one-fourth of American female physicians are diagnosed with infertility at almost 34 years old, with a third of those due to diminished ovarian reserve, and this rate is significantly higher than the general population and other professionals that pursued higher education and careers.28,29 Contributing factors to the high rate of infertility among women in medicine may include stressors intrinsic to training, long hours, and night shifts.29 Infertility can lead to substantial depression, anxiety, burnout, and family planning regrets.28,29 Compounding the physical and emotional challenges of infertility is the exorbitant financial burden of treatment.29 In the United States, in vitro fertilization (IVF) costs ~$15,000 per round of treatment, not including the cost of medication.29 Unfortunately, fertility coverage for the majority of health professionals is lacking, and many medical institutions provide limited fertility coverage that will cover ~1 to 2 IVF cycles.29 In comparison, companies in the business, technology, and social media sector are recognizing the growing need for fertility coverage and are offering more comprehensive fertility, adoption, and surrogacy coverage, which has promoted physical and emotional well-being, job satisfaction, and enhanced employee recruitment and retention.29,30 In addition to cost, time is an additional barrier for seeking fertility treatment for anesthesiologists, and schedule modifications are often necessary. IVF typically requires the patient to present for multiple in-person monitoring appointments over a 2-week period during ovarian stimulation. On the basis of the outcome of the monitoring, an egg retrieval may be scheduled imminently, with little room for flexibility in timing. Without accommodation, women may need to take a vacation, paid or unpaid time off to undergo treatment, worsening the financial strain of infertility. Women anesthesiologists are also more likely to have pregnancy complications and miscarriages than the general population.31 Data suggests that women who work in the operating room have a higher incidence of first-trimester spontaneous abortions or a higher risk of birth defects.31 Women anesthesiologists report a higher rate of pregnancy complications [premature labor (8.8%), bedrest (7.8%), preeclampsia (6.5%), and a Neonatal Intensive Care Unit (NICU) stay for the baby (5.7%)], negative stigma for taking time off for pregnancy complications, and guilt in burdening colleagues with increased shifts and calls.26 Many attending anesthesiologists do not receive a modified work schedule during pregnancy.27 In some practice models, time off for pregnancy complications may not be paid and may decrease time for parental leave. Parental leave is an essential component to achieving postpartum physical and mental health and is crucial for infant bonding. trainees in parental leave was reported as and a of training programs not have a formal maternity leave trainees a of and for Approximately of anesthesiology residents felt their maternity leave was felt discouraged from taking more time and felt of with on However, of trainees also their programs as in of maternity leave In the American of Anesthesiologists a on which paid parental leave for after birth or of a In the American of Anesthesiology from the which residents to for an additional of leave without In the American of and a parental leave which for all to of parental leave, of for parental leave, without who as attending anesthesiologists report an parental leave time of and a of on the practice maternity leave may be of a of and leave This is in to other as and that have significant in paid parental leave, with companies offering to of paid other women anesthesiologists work postpartum to the to work and face the of lactation in the breastfeeding at a higher rate than the general they have a lower rate by infant age of the report the desired breastfeeding and having lactation In time and lack of can it to there are that are becoming more they may not work for all women. the has a on Among Anesthesia in to lactation in the of with the demands of work, women anesthesiologists face the burden of of of or motherhood, women physicians an of more hours per on are more likely to be the for children or the and are less likely to have a In addition to the women the and mental in labor about the of and labor on the emotional about in and managing is the of and emotional labor and is to as the in the of the The these to the by the to the culture of medicine and in the United In the stages of the some anesthesiologists were on unpaid leave of others work hours because of increased at A survey from the of Anesthesiologists at the time that women anesthesiologists were or given more often than those women who continue working on the they an and as there was about the of the They were to the and the to their from the and the of their children as As a more women anesthesiologists, work hours, to work, and medicine In with school and a on many women their time to on and an of more hours per than on and in a 33% in hours and academic productivity as compared with The percentage of with women as authors during the early stages of the despite the of in the sex gap in academic crucial for academic were also for women physicians as and there was time for because of personal or institutional the provide the flexibility to from the prevalence of and also Overall, the an increased burden on women anesthesiologists to the family and with and the sex gap in academic productivity and strategies to enhance gender equity in anesthesiology strategies to achieve gender equity in our we to gender equity in and policies and in and medical The in all that the to achieving sex equity in our is and is more than women with and leadership However, we that systemic change can be achieved by which were present in all the we (1) addressing individual bias, (2) closing the knowledge gap on the scope of bias, (3) deliberate representation, (4) strengthening professional networks, and (5) organized efforts to create policies that address gender inequity in the workplace. individual bias to create a culture of in a or and training in equity, and is to address individual equity, and training and education can cover a of systemic to as bias, and and can be in a of from individual to There are organizations that provide training, and as and are efforts lead to the of policies and leadership that women in the workplace, should gender equity to be a of the and should in the of sex equity into organizational and the knowledge gap on the scope of bias should be and reported to the of women anesthesiologists, barriers to their and systemic Data include performing of and professional need to be about professional is and among and should be and to and should be There to be deliberate and of women in recruitment, retention, promotion and in including women and their in any or policies are that affect work culture is should be or than that if more than 1 woman is there is a higher likelihood that a woman will achieve a has been in diversity by the of and which to the of women. additional strategies to enhance should by the job of an and should equity rather than flexibility and choice is leave policies with job and for workplace of for and other and policies should be to enhance the of women anesthesiologists at all There should be for and sex-based professional has been on the of women, but there are other that are as including and and help to women and their are and They can and promote women, their and their experience, the woman’s is for the of and media has increased the visibility of women anesthesiologists and has without the to in-person and However, deliberate formal or are also known development and leadership training for women that on and visibility can with efforts to create policies that address sex inequity in the workplace is to that there are challenges to a sex and the gender that are in workplace Women are known as and the of of a is for lactation and by the workplace that is and enhance is to the workplace a more for women to women are not on the promotion and should be In organized efforts to provide professional leadership training, and for women anesthesiologists at the and national levels are This not to enhance the of women but also to help women and address the systemic issues they encounter in a of an example organizations have been that are to improving equity for women These include national organizations in and of the anesthesiology organizations of Anesthesiologists on Women of Women in American of Anesthesia and Women in Anesthesia and and for Care Women in Care and leadership development and for Anesthesiology and Women of in Anesthesiology Women of Anesthesiology A of programs that there is and to provide professional development to discuss the organizational approach to gender equity in anesthesiology, we will on 1 Women in Anesthesiology is a in by to the professional and personal development of women also the recruitment, retention, and job of women in anesthesiology and a culture of and faced challenges residency and early career as a without the of a from the for and after other women of Women Women in the was to provide a addressing systemic were on addressing (1) lack of professional respect in with male (2) personal and professional and (3) of and to promote women to leadership efforts the of social media to women across and to provide education and to the affecting women efforts were by women in early and who were experiencing the of work for in leadership across societies, and institutions was pursued regarding enhanced and of women for and education regarding the of having women in leadership As a not associated with a efforts are in systemic change in other anesthesiology work, social media and in the of for and at efforts by of the of have national leave of and lactation in the and the on and the on were by who in The nature of also for on social and health issues to anesthesiologists, including and on these issues by and for to more in efforts that are to In addition to professional development for women and men an and a women anesthesiologists as national and to as the a and the operating have on to or In a social and on the provide on to women The of are these and annual including the and and on levels are by and a in-person the However, as a of full-time working women physicians, their careers and personal 1 of the has been the and to a and for our there have been many associated with the and development of 1 of the is the recent of a is well known that anesthesiology has remained other in the recruitment of women to the it would anesthesiologists that women medical students are more likely to a surgical than anesthesiology as a The a recent from the on to a program at students to about anesthesiology, address the challenges that women anesthesiologists and provide a national for from in medical the student are women of and their for and will help to improve the diversity of our has on the initiatives include a for all practice a professional and an in-person medical education In will continue to in medical students and physicians by programs and a The has for women in but that there is still work to be is in the of the to be of all and to improve for identities. In of our work has in for change in but culture change is by at the and institutional The by and other organizations at sex equity a of to into and to a systemic approach to of Despite numbers there is still major attrition of women in anesthesiology as they advance in their Sex disparities within anesthesiology exist because of systemic barriers and biases, with in cultural norms to which results in many women anesthesiologists feeling and discrimination from their women anesthesiologists with and leadership training is inadequate to address this and studies the need for systemic change to address inequity as enhanced representation, and as Women in Anesthesiology and other to equity for women anesthesiologists of all identities are paramount. of The authors that they have to
International Anesthesiology Clinics · 8 citationsread the source →
Susan Carr (2015)MEDLINE-indexed journal, not yet read by usInternational Journal of Gynecology & Obstetrics Psychosexual health in gynecological cancer
The literature surrounding psychosexual health and cancer patients has primarily considered the functional aspects of the disease and its treatment at the major expense of the emotional sequelae. Sexual health is defined by WHO as: "a state of physical, emotional, mental, and social well-being in relation to sexuality; it is not merely the absence of disease, dysfunction or infirmity. Sexual health requires a positive and respectful approach to sexuality and sexual relationships, as well as the possibility of having pleasurable and safe sexual experiences, free of coercion, discrimination and violence" [1]. A principle goal of WHO is to assist its member states in achieving the highest attainable standard of health care for all, including sexual and reproductive health [2]. Global statistics show that the world's female population is carrying an overwhelming burden of need in this area. Over 200 million women cannot access modern contraception, and millions of women suffer rape, domestic violence, and sexual abuse, not only in the context of wars and criminal activities, but also in their own homes [2]. Although the physical sequelae of these disasters can be treated, such as treatment for sexually transmitted infections, the emotional impact can frequently be hidden, ignored, or may not reveal its impact until many years after the event. Any illness or traumatic life event, past or present, can lead to sexual problems in the lifetime of a woman, and gynecological cancer is no exception. It is the root cause or trigger for sexual difficulties in at least 50% of women affected [3]. In 2012, the estimated number of women living with gynecological cancers was over three million, which means that potentially 1.5 million gynecological cancer survivors could be affected by an associated sexual difficulty [4]. Within the context of gynecological cancer, many of these problems can be alleviated if recognized and acknowledged early in the cancer journey, therefore contributing dramatic improvements to a woman's overall well-being. It is now estimated that half of the population of either sex will develop cancer at some time in their life. Globally, 40% − 45% of women will have a sexual problem at some stage, with the prevalence increasing with age [5]. Between 10% and 90% of women with any cancer will have sexual problems [6] and over 50% of women with gynecological cancer will have either temporary or persistent sexual difficulties [3]. As diagnosis and treatments improve, the number of women surviving cancer will increase, and survivorship issues including quality of life have become increasingly important. Sexuality is a key component of most subjective measurable quality of life indicators [7]. Sexual function and enjoyment are important components of survivorship and should not be ignored. The most common sexual problems can be divided into two groups: problems of function and/or problems of desire. There is, however, a complex interplay of organic disorders with emotional and psychosocial issues, and these divisions are merely artificial. Formal definitions of female sexual dysfunction have been adopted, including the US classifications in the Diagnostic and Statistical Manual of Mental Disorders [8], although having a sexual difficulty does not constitute having a mental health disorder. Basson et al. [9] published a useful classification of the problems. Such classifications are useful for research purposes, but may often be less helpful when treating women. The predominant functional female sexual problem is pain on sexual intercourse, or dyspareunia. Deep dyspareunia describes intracoital pelvic pain, and superficial dyspareunia is pain on vaginal entry. Either could signify organic disease, and should be appropriately investigated. If no pathology is demonstrated, and the pain persists, then an emotional cause must be considered and pursued. Vaginismus, or involuntary spasm of the pubococcygeal and related musculature, can prevent sexual intercourse taking place. Good history taking can clarify whether there has been any penetration of the vagina, not only penile, but by fingers, sex toys, or tampons. If not, this is diagnostic of primary vaginismus, and apart from close inspection of the vulva and offer of gentle digital vaginal examination to determine the extent of the vaginismus, no further clinical investigation is warranted. Women with gynecological cancer are more likely to have secondary vaginismus caused by pain experienced from the disease or its treatment, and fear of the pain occurring during sex [10]. Loss of libido or loss of sexual interest on the other hand is a problem of desire. There are no physiological markers for loss of desire when its origins are psychogenic, with psychosocial contributions, past and present relationships, traumas, and emotional factors all inhibiting the woman's wish to be sexual. One of the key ways to determine the origins of the sexual difficulty is to ask about the sexual and emotional relationship between the woman and her partner before the cancer diagnosis. It should not be assumed that problems are all due to the cancer, as long-standing relationship problems may be disclosed, and need to be incorporated into any counselling. The exception to this is the woman who suddenly becomes menopausal following cancer treatment, who had no problems with sex or desire prior to her cancer therapy. Appropriate standard therapy for her menopausal symptoms should be considered; however, the impact of a cancer diagnosis will be life changing, and drug treatment of hormonal deprivation symptoms may not be sufficient without some psychological or counselling support, or may be contraindicated as in the case of breast and endometrial cancer [11]. A diagnosis of gynecological cancer is overwhelming. While the instinctive professional response from clinicians is to ensure long-term survival, sexual issues are important for quality of life and should be considered in the decision-making process [12]. Sexual dysfunction is one of the most common and distressing consequences of cancer treatment [13]. Many treatments are shown to have sexual impacts, both positive and negative, and should be discussed fully with the woman pre-treatment so that she can make an autonomous decision about her care. Early offer of discussion of sexual issues in the cancer journey can lead to better sexual outcomes. Cervical cancer is the most common gynecological cancer worldwide. Cervical cancer survivors are at risk of sexual pain disorders, no matter which modality of treatment is used. A small study of patients who underwent radical vaginal trachelectomy for early stage cervical cancer showed sexual dysfunction, including loss of libido, for up to one year following treatment; however, by 12 months, sexual activity had reached that of healthy women [14]. Following radical hysterectomy for locally advanced cervical cancer, there was no significant difference in sexual activity and enjoyment between women with benign or malignant disease; however, the cancer group had worse problems than healthy controls with body image and vaginal functioning [15]. In women with advanced cervical cancer given chemoradiotherapy, pain during intercourse was in fact reduced after treatment [16]. This may have been a result of the resolution of bleeding, discharge, and pelvic pain. However, the anxiety surrounding cancer remains for many women. Women surviving up to 15 years following cervical cancer treatment showed poorer quality of life than healthy controls, and those who had received radiotherapy were significantly more affected by sexual dysfunction than those who had surgery alone [17]. Despite this however, orgasm may be unimpaired following radiation [18]. Many additional needs were expressed by women with cervical cancer; however, sexuality and intimacy came to the fore as a predominant issue for survivorship [19]. It has been known for some time that the physical and emotional impact of ovarian cancer can be devastating, leading to sexual as well as global quality of life issues [20]. One study has shown a prevalence of 63% for sexual difficulties among women with a diagnosis of ovarian cancer [3]. The effects of chemotherapy and surgery, combined with the anxiety about survival can have a dramatic negative effect on the woman's libido, and even women who undertake risk-reducing salpingo-oophorectomy can suffer sexual dysfunction [21]. Many of these women are totally unprepared for the devastating effects of sudden menopause, with hot flushes, vaginal dryness, and loss of libido replacing a previously healthy sex life. This could be helped by more realistic counselling before the procedure, and increased postoperative emotional support. One study has shown that women who had surgery for endometrial cancer had no differences in their own sexual experience postoperatively, but compared with healthy controls, they had more sexual difficulties overall [22]. Women with Lynch syndrome who opt for preventive surgery tend to be happy overall with the surgery, but are often unprepared for the physical adverse effects of menopause [23]. In contrast, Moldovan et al. [24] has reported that, despite sometimes debilitating menopausal symptoms, there were no significant sexual difficulties associated with the procedure. Vulvectomy is a common treatment for vulvar malignancy. This is increasingly affecting younger women, who are HIV positive. Women with vulvar cancer can have many years of difficulties with sex due to often distressing vulvar symptoms and bleeding. Following treatment they still suffer severe dyspareunia and body image distortion due to the effects of treatment. Although a recent study showed no differences in psychosocial and sexual functioning before and after vulvectomy, it was acknowledged that women with vulvar malignancy have a high risk for sexual problems compared with healthy controls [25]. Factors associated with postoperative sexual difficulties are increased age, poor overall physical and mental health well-being, and extent of the surgical excision [25]. This often elderly group of patients is usually neglected from the psychosexual point of view. The majority of the literature related to sexuality and cancer stems from high-resource countries. Although most of these studies encompass all women, there is a lack of good published evidence on the treatment of the sexual sequelae of cancer in relation to ethnic minority groups, within a majority culture [26]. Furthermore, data from low- and middle-income countries are scant. Much of the literature focuses on sexual distress and activity in relation to HIV and AIDS which, of course, is a global priority; however, this focus on infection transmission should not take away from the emotional needs of the woman who suffers from gynecological cancer. Sexuality research around the globe must be perceived and researched in terms of cultural, spiritual, ethnic, and religious contexts. Sexual problems in women with gynecological cancer may be associated with adverse effects of surgical, hormonal, and chemical treatments, as well as by the cancer itself. Fortunately, emotional, sexual, and quality of life outcomes improve as less morbid, more minimally invasive surgical treatments for gynecological cancers develop [12]. Chemotherapy-induced ovarian failure in cancer patients is associated with all the possible symptoms of a sudden menopause, combined with the emotional impact not only of the cancer, but loss of physical well-being and fertility all at the same time. Vaginal dryness can be a major problem to those women who wish to have sex [27], and appropriate vaginal moisturizers and lubricants can help. The issue of vaginal estrogen is still debated, but should be discussed with the patient, weighing up the risk − benefit ratio for each individual. Vaginal estrogen will, in most cases, alleviate the dryness, but there may be concerns about using hormones, especially in relation to breast cancer where the evidence is unclear. The scientific data, however, support the safety of low dose vaginal estrogen therapy [28]. It is not well understood that following a few weeks of vaginal estrogen, the vagina thickens and cornifies and estrogen is not absorbed as a result. Newer treatments such as selective estrogen receptor modulators have been used in place of vaginal estrogen in women without cancer [29], and may prove good alternatives in the future [30]. There are non-hormonal vaginal moisturizers and lubricants to make sexual intercourse more comfortable. Unfortunately, some commercial sexual lubricants can be hyperosmolar and could cause epithelial disruption, facilitating HIV transmission [31]. Simple lubricants such as olive oil or liquid glycerin have been used successfully in interventions to alleviate pain on intercourse due to vaginal dryness, combining their use with physiotherapy and psychosexual counselling. Treatments with pelvic external beam radiotherapy and/or with brachytherapy may cause vaginal shortening, tightening, and lack of pliability. The use of vaginal dilators to overcome these complications is widespread, despite lack of conclusive evidence, either for or against, either with or without a coating of estrogen cream [32]. Unsurprisingly, the intrusion of inserting a plastic (or sometimes glass) tube into a tender vagina after treatment is a task that may carry a deep psychological and emotional impact [33], and will have resultant poor compliance. Radiation oncologists agree that information about dilator use should be given before treatment [34], and that sufficient patient information and support are essential to improve compliance. Sensitivity to emotions and women's views and personal values in relation to sexuality are essential supports to encouraging dilator use [35]. Any of the above problems cannot fail to have an emotional impact on the woman and on her partner. Many sexual difficulties are automatically blamed on the organic disruption caused by cancer and its treatments; however, once any clearly indicated treatments have been given, in a sizable proportion of cases, the sexual difficulty will remain unresolved. Many sexual difficulties are psychogenic, and no amount of skilled clinical treatments will help if not linked closely to appropriate counselling, psychological, or psychosexual therapy. This form of intervention will enable the woman to expose and reflect on her sexual difficulties, in the context of her life and relationship not only since the cancer, but beforehand. This is often a time when past problems, such as childhood abuse, or problems with her current partner will surface. Some partners are disgusted by the physical impacts of cancer, and the relationship will suffer. On the other hand, some partners become more supportive and the cancer leads to stronger relationships [36]. Classic psychosexual therapy, using brief, focused psychotherapeutic techniques is the mainstay of treatment. It can be used with an individual or a couple, of any sexual orientation or cultural or religious background. This is a way of listening reflectively to the patient, so that they can gain their own insights into their sexual problem. The issue of genital examination is considered if relevant, as it enables the woman to connect with her genital area, and may trigger deep-seated thoughts or anxieties that the woman had blocked emotionally. This, of course, is a technique used only by clinicians who are qualified to examine the patient [37]. Clinical psychologists and counsellors trained in psychosexual work also treat women with sexual problems. Globally, because the availability of trained personnel differs, many simple innovative treatment interventions have been tried. A brief intervention using a well-accepted treatment, cognitive behavioral therapy (CBT), combined with sexual health education had positive results on patients who had risk-reducing salpingo-oophorectomy [21]. Psychosexual interventions work [38], and like all psychodynamic interventions only require a trained counsellor and a means of allowing access to the patient. The internet has enabled access to health care for many people around the world who are not able to travel long and difficult land journeys to direct provision of health care. An online intervention with a professional moderator has proven acceptable to gynecological cancer patients with a sexual difficulty [39], and another internet-based sexual difficulties intervention with counselling sessions proved more successful in improving sexuality issues than without a counsellor; however, there was no difference between the two groups in relation to emotional distress and quality of life [40]. Elsewhere, telephone interventions are being used, also with some success; however, it is clear that the knowledge, skills, and training of the health professional providing the intervention are relevant to the patient outcome. Multidisciplinary care should form the backbone of treatment of sexual difficulties in women with gynecological cancer, incorporating physical, psychoeducational, and psychosexual input. Team discussions, including clinicians, psychosexual therapists, and physiotherapists are well within the capabilities of many cancer centers, remembering that the patient and her partner are the focal point and should always be consulted. It is impossible to diagnose and treat a sexual problem if one does not acknowledge that it exists. Many studies in the past have identified lack of willingness of doctors and nurses to discuss sex, but sadly recent research has shown that not much has changed. For instance, in a cohort sample of 1154 US obstetrician − gynecologists, 60% did not ask patients about sexual problems [41]. Too often clinicians make value judgements about their patients including whether sexuality is an important part of their lives. Such assumptions may include biases about age, appearance, sexual preferences, and marital status of people who have sex. People with cancer and their partners have unmet sexual information and support needs [42], often due to the unwillingness of healthcare professionals to discuss sexual issues, even though they recognize it may be important to the patient. There are many barriers to talking about sex, affecting both the patient and the clinician, such as cultural background, and age and gender discrepancies between doctor and patient. There may be simple barriers, such as lack of privacy in a consultation, as often cancer patients are accompanied by family or close friends. Patients often state that they feel it is trivial to take up the doctor's time with non-life-threatening issues such as sex. Clinicians often cite lack of training as a reason that they are uncomfortable talking about sex and poor provision of this training has been noted [13]. Different models of communication skills training have been used and those undertaking the training have shown greater empathy and were more inclined to use open questions [43]. This technique of speaking to the patient in an open rather than interrogative manner can easily facilitate discussion of intimate issues. An even greater challenge in communication is the recognition that individuals are sexual beings up to the end of life. To some women in the palliative phase, sexual touch and closeness to their partner is of vital importance. Sadly this is rarely recognized and addressed by palliative care physicians [44]. It is important to remember that a minority of the female population identifies as lesbian, and that about 8% of the population is bisexual. While this should make no difference to the quality of sexual health care they receive, lesbians and bisexuals find it difficult to disclose their sexuality to clinicians, often inhibited by their cultural or religious background, and fears of facing discrimination [45]. If the clinician asks the patient at the outset if they have a sexual partner, and whether the partner is male or female, it will greatly enhance the quality of the doctor − patient interaction. Lesbian partners in particular can be very supportive during the cancer journey, and should be given the opportunity to be present if the patient wishes. Despite the recognized need for treatment of sexual problems in menopause and gynecological cancer, there is poor provision of specialist training to ensure that this important area of service provision is met [46]. Undergraduate teaching is important, but it is only by recognizing psychosexual medicine in formal gynecology or oncology training, as a compulsory requirement of the course, that this situation will begin to be addressed. Innovative online programs [47] can make a major impact on global training opportunities and give trainees around the world an opportunity to gain some skills and insight into treating sexual difficulties in a nonjudgmental way. Owing to the global prevalence of sexual problems associated with gynecological cancer, it should be within every gynecologist's or oncologist's duty of care to the patient to be aware of and have some understanding of how to diagnose and facilitate treatment for sexual problems in a nonjudgmental manner. This is true holistic medicine, recognizing not only the cancer, but the woman behind the symptoms, and requires awareness of the emotional, social, and relationship aspects of the patient's life. The ability of any person to enjoy a sexual life free of coercion, shame, disease, or pain in a consensual manner is a fundamental element of the human rights of women, and should be an unequivocally accepted as part of her gynecological cancer care. To make a difference, even in the absence of expensive and sophisticated cancer treatments, just acknowledging, listening, and offering support to the woman with sexual difficulties related to cancer will ultimately have a major benefit to her quality of life. The author has no conflict of interest. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
International Journal of Gynecology & Obstetrics · 17 citationsread the source →
Conrad N, Misra S, Verbakel JY, Verbeke G, Molenberghs G, Taylor PN, Mason J, Sattar N, McMurray JJV, McInnes IB, Khunti K, Cambridge G. (2023)MEDLINE-indexed journal, not yet read by usLancet (London, England) Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK.
Background: A rise in the incidence of some autoimmune disorders has been described. However, contemporary estimates of the overall incidence of autoimmune diseases and trends over time are scarce and inconsistent. We aimed to investigate the incidence and prevalence of 19 of the most common autoimmune diseases in the UK, assess trends over time, and by sex, age, socioeconomic status, season, and region, and we examine rates of co-occurrence among autoimmune diseases.
Methods: In this UK population-based study, we used linked primary and secondary electronic health records from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex and ethnicity. Eligible participants were men and women (no age restriction) with acceptable records, approved for Hospital Episodes Statistics and Office of National Statistics linkage, and registered with their general practice for at least 12 months during the study period. We calculated age and sex standardised incidence and prevalence of 19 autoimmune disorders from 2000 to 2019 and used negative binomial regression models to investigate temporal trends and variation by age, sex, socioeconomic status, season of onset, and geographical region in England. To characterise co-occurrence of autoimmune diseases, we calculated incidence rate ratios (IRRs), comparing incidence rates of comorbid autoimmune disease among individuals with a first (index) autoimmune disease with incidence rates in the general population, using negative binomial regression models, adjusted for age and sex.
Findings: Among the 22 009 375 individuals included in the study, 978 872 had a new diagnosis of at least one autoimmune disease between Jan 1, 2000, and June 30, 2019 (mean age 54·0 years [SD 21·4]). 625 879 (63·9%) of these diagnosed individuals were female and 352 993 (36·1%) were male. Over the study period, age and sex standardised incidence rates of any autoimmune diseases increased (IRR 2017-19 vs 2000-02 1·04 [95% CI 1·00-1·09]). The largest increases were seen in coeliac disease (2·19 [2·05-2·35]), Sjogren's syndrome (2·09 [1·84-2·37]), and Graves' disease (2·07 [1·92-2·22]); pernicious anaemia (0·79 [0·72-0·86]) and Hashimoto's thyroiditis (0·81 [0·75-0·86]) significantly decreased in incidence. Together, the 19 autoimmune disorders examined affected 10·2% of the population over the study period (1 912 200 [13·1%] women and 668 264 [7·4%] men). A socioeconomic gradient was evident across several diseases, including pernicious anaemia (most vs least deprived area IRR 1·72 [1·64-1·81]), rheumatoid arthritis (1·52 [1·45-1·59]), Graves' disease (1·36 [1·30-1·43]), and systemic lupus erythematosus (1·35 [1·25-1·46]). Seasonal variations were observed for childhood-onset type 1 diabetes (more commonly diagnosed in winter) and vitiligo (more commonly diagnosed in summer), and regional variations were observed for a range of conditions. Autoimmune disorders were commonly associated with each other, particularly Sjögren's syndrome, systemic lupus erythematosus, and systemic sclerosis. Individuals with childhood-onset type 1 diabetes also had significantly higher rates of Addison's disease (IRR 26·5 [95% CI 17·3-40·7]), coeliac disease (28·4 [25·2-32·0]), and thyroid disease (Hashimoto's thyroiditis 13·3 [11·8-14·9] and Graves' disease 6·7 [5·1-8·5]), and multiple sclerosis had a particularly low rate of co-occurrence with other autoimmune diseases.
Interpretation: Autoimmune diseases affect approximately one in ten individuals, and their burden continues to increase over time at varying rates across individual diseases. The socioeconomic, seasonal, and regional disparities observed among several autoimmune disorders in our study suggest environmental factors in disease pathogenesis. The inter-relations between autoimmune diseases are commensurate with shared pathogenetic mechanisms or predisposing factors, particularly among connective tissue diseases and among endocrine diseases.
Funding: Research Foundation Flanders.
Lancet (London, England) · 508 citationsread the source →
Zhang X, Tulloch JSP, Knott S, Allison R, Parvulescu P, Buchan IE, Garcia-Finana M, Piroddi R, Green MA, Baird S, Barr B. (2023)MEDLINE-indexed journal, not yet read by usBMJ open Evaluating the impact of using mobile vaccination units to increase COVID-19 vaccination uptake in Cheshire and Merseyside, UK: a synthetic control analysis.
Objective: To evaluate the impact of mobile vaccination units on COVID-19 vaccine uptake of the first dose, the percentage of vaccinated people among the total eligible population. We further investigate whether such an effect differed by deprivation, ethnicity and age.
Design: Synthetic control analysis.
Setting: The population registered with general practices (GPs) in nine local authority areas in Cheshire and Merseyside in Northwest England, UK.
Intervention: Mobile vaccination units that visited 37 sites on 54 occasions between 12 April 2021 and 28 June 2021. We defined intervention neighbourhoods as having their population weighted centroid located within 1 km of mobile vaccination sites (338 006 individuals). A weighted combination of neighbourhoods that had not received the intervention (1 495 582 individuals) was used to construct a synthetic control group.
Outcome: The weekly number of first-dose vaccines received among people aged 18 years and over as a proportion of the population.
Results: The introduction of a mobile vaccination unit into a neighbourhood increased the number of first vaccinations conducted in the neighbourhood by 25% (95% CI 21% to 28%) within 3 weeks after the first visit to a neighbourhood, compared with the synthetic control group. Interaction analyses showed smaller or no effect among older age groups, Asian and black ethnic groups, and the most socioeconomically deprived populations.
Conclusions: Mobile vaccination units are effective interventions for increasing vaccination uptake, at least in the short term. While mobile units can be geographically targeted to reduce inequalities, we found evidence that they may increase inequalities in vaccine uptake within targeted areas, as the intervention was less effective among groups that tended to have lower vaccination uptake. Mobile vaccination units should be used in combination with activities to maximise outreach with black and Asian communities and socioeconomically disadvantaged groups.
BMJ open · 17 citationsread the source →
Goodridge D, Reis N, Neiser J, Haubrich T, Westberg B, Erickson-Lumb L, Storozinski J, Gonzales C, Michael J, Cammer A, Osgood N. (2021)MEDLINE-indexed journal, not yet read by usJMIR aging An App-Based Mindfulness-Based Self-compassion Program to Support Caregivers of People With Dementia: Participatory Feasibility Study.
Background: The number of persons with dementia is steadily growing, as is the number of individuals supporting persons with dementia. Primary caregivers of persons with dementia are most often family members or spouses of the persons with dementia, and they are more likely to experience increased stress and other negative effects than individuals who are not primary caregivers. Although in-person support groups have been shown to help buffer the negative impacts of caregiving, some caregivers live in isolated or rural communities and are unable to make the burdensome commitment of traveling to cities. Using an interdisciplinary approach, we developed a mobile smartphone support app designed for primary caregivers of persons with dementia, with the goal of reducing caregiver burden and easing stress. The app features a 12-week intervention, largely rooted in mindfulness-based self-compassion (MBSC), because MBSC has been linked to minimizing stress, depression, and anxiety.
Objective: The primary objectives of our program are twofold: to explore the feasibility of a 12-week mobile support program and to conduct an initial efficacy evaluation of changes in perceived caregiver burden, coping styles, and emotional well-being of caregivers before and after the program.
Methods: Our feasibility study used a 2-phase participatory pretest and posttest design, focusing on acceptability, demand, practicality, implementation, and efficacy. At phase I, we recruited 57 primary caregivers of persons with dementia (mean age 76.3, SD 12.9 years), comprising spouses (21/57, 37%), children (21/57, 37%), and friends or relatives (15/57, 26%) of persons with dementia, of whom 29 (51%) completed all measures at both pre- and postprogram. The content of the program featured a series of MBSC podcasts. Our primary outcome measure was caregiver burden, with secondary outcome measures including coping styles and emotional well-being. Daily ecological momentary assessments enabled us to ask participants, "How are you feeling today?" Phase II of our study involved semistructured follow-up interviews with most participants (n=21) who completed phase I.
Results: Our findings suggest that our app or program meets the feasibility criteria examined. Notably, participants generally accepted the program and believed it could be a useful resource. Emotional well-being increased significantly (P=.04), and emotion-based coping significantly decreased (P=.01). Participants generally considered the app or program to be a helpful resource.
Conclusions: Although there were no significant changes in caregiver burden, we were encouraged by the increased emotional well-being of our participants following the completion of our program. We also conclude that our app or program demonstrated feasibility (ie, acceptability, practicality, implementation, and efficacy) and can provide a much-needed resource for primary caregivers of persons with dementia. In the subsequent version of the program, we will respond to participant feedback by incorporating web-based weekly sessions and incorporating an outcome measure of self-compassion.
JMIR aging · 25 citationsread the source →
Charting the Future of Cancer Health Disparities Research: A Position Statement from the American Association for Cancer Research, the American Cancer Society, the American Society of Clinical Oncology, and the National Cancer Institute
The academic field of cancer health disparities was stimulated by the U.S. civil rights movement. Concerns about civil rights led to concerns about equality in health care. The first publications to make the observation that black Americans have higher rates of death as a result of certain cancers compared with white Americans were published by the early 1970s (1, 2). The discipline concerned with these differences was first called “minority health research” and later “special populations health” or “special populations research.” The National Cancer Institute (NCI) defines cancer health disparities as adverse differences in cancer incidence, cancer prevalence, cancer mortality, cancer survivorship, and burden of cancer or related health conditions that exist among specific population groups in the United States (3). However, with greater and renewed acknowledgment of health disparities as rooted within the context of historical and contextual inequities in the United States, many health disparities are considered health inequities (4).The National Cancer Act of 1971 created the Surveillance, Epidemiology, and End Results (SEER) program within the NCI. This program began collecting incidence, mortality, and survival data by race in the early 1970s from a number of population-based registries around the United States. The SEER program improved documentation of differences in outcomes and analyzed them through its black–white studies (5). These studies especially demonstrated differences in treatment patterns, with a higher proportion of blacks receiving inappropriate cancer care compared with whites. The discipline grew from a focus on black–white differences to encompass differences in outcomes for a number of racial and ethnic groups, as well as for cohorts defined by age, sex, socioeconomic status (SES), and other social determinants of health. There is now even greater appreciation for disparities among communities, whether rural versus urban or even by state or region. The definition of health outcomes also broadened beyond death rates. The field of health disparities was once simply a description of population differences and a call for cultural competence among health care providers. Today, the field is transdisciplinary, integrating basic science, clinical science, policy, epidemiology, and the social sciences. It involves people trained in diverse nonmedical fields, such as education, economics, sociology, religion, geography, and anthropology. The field is also dynamic. It changes as better and more granular statistics, greater understanding of causes of health disparities, and new challenges to mitigate these underlying causes have emerged. As an example, in the 1970s, the breast cancer death rate for black and white American women was the same. Today, the death rate is substantially higher for blacks compared with whites (6). Policy changes have also created opportunities and challenges. The Affordable Care Act has allowed for Medicaid expansion in each state. Expansion has been adopted by 32 states and the District of Columbia. This will create a new challenge, because poor residents of some states have expanded access to care and residents of other states do not. It is essential that any future policy changes should be carefully designed to increase, rather than decrease, equitable access to care throughout the cancer continuum. Population categorizations also are being redefined. The Asian category includes Korean Americans and Pakistani Americans. The Pacific Islander category, often merged with the Asian category, includes native Hawaiians and Samoans. These populations are incredibly heterogeneous and have dramatically different cancer statistics. In 2015, representatives from four leading cancer organizations, the American Association for Cancer Research, the American Cancer Society, the American Society of Clinical Oncology (ASCO), and the NCI, began to meet to discuss the state of health disparities in the United States. These discussions involved the state of cancer health disparities research and what could be done to move it forward. The discussions were purposely not meant as a comprehensive review of cancer health disparities research. Rather, the meeting and the resulting document aimed to identify issues in health disparities research and make specific recommendations to improve the way disparities research is conducted and disseminated. This statement presents a unified strategy among four of the leading cancer organizations in the United States to promote cooperation among investigators in all areas of the cancer health disparities research community, to ensure that cancer research benefits all populations and patients regardless of race, ethnicity, age, gender identity, sexual orientation, SES, or the communities in which they live. Disparities in outcomes across the cancer continuum have been identified in numerous medically underserved populations, including racial and ethnic minorities and patients of lower SES. In addition to individual social status, social contextual and community factors, such as neighborhood safety, social cohesion, availability of healthy foods, and residential segregation, play an important role in health of both individuals and populations. All of these factors can intersect to generate larger disparities (7, 8).To understand and fully address cancer health disparities, complete, consistent, and accurate collection of patient, community, and structural factors that put people at risk for disparate outcomes is essential. Unfortunately, cancer health disparities research has often been fraught with missing, inaccurate, or overly simplified patient-level data, and most research has failed to consider the community-level factors described above (9–11).For the most part, the manner in which data are collected and integrated in disparities research is suboptimal. The literature is characterized by variable methodology for collection of the factors that put patients and communities at risk for disparate care and outcomes. For example, although race and ethnicity are distinct constructs, they are often conflated such that a person is identified as Hispanic without identification of his or her race. Many studies that investigate cancer care or outcomes according to socioeconomic position have only area-level data on socioeconomic position, whereas others use only composite measures. While valuable in many cases in identifying disparities, such measures fall short in providing the richness of data needed to understand an individual's socioeconomic position. Health literacy and numeracy are rarely assessed in practice and are not available in administrative and research databases. Finally, methods for uniform data collection of information on sexual orientation and gender identity are in their infancy, despite calls for such data collection from the Institute of Medicine, among others (12).Disparities in cancer incidence are pronounced and longstanding. Drivers of these disparities are multifactorial and multilevel, and they include sociodemographic factors, access to health care, risk factor profiles and lifestyle/health habits, cultural perceptions, biologic differences, and genetic predisposition. Disparities in cancers for which single etiologic factors account for a substantial proportion of disease (e.g., human papillomavirus and cervical cancer, or Helicobacter pylori and stomach cancer) can be reasonably understood and explained, but disparities for many of the common etiologically heterogeneous cancers, such as breast, prostate, and colorectal cancers, remain much less well understood. Multilevel approaches are needed to advance knowledge relevant to addressing disparities in cancer incidence rates. One approach is to design and implement observational studies focused on a population in which disparities exist to advance knowledge about etiology and to inform novel prevention strategies. A successful example of such an effort is the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium, a multicenter consortium that has combined data and biospecimens from 7,500 African American patients with breast cancer and 17,000 healthy controls, representing the largest study of breast cancer in African American women in the United States (14). It has yielded a number of insights on multilevel risk factors specific to the major molecular subtypes of breast cancer among African American women (15–17).There is also a need for studies focused on identifying the genetic contributors to cancer health disparities. Recent work has focused on the prioritization of candidate variants relevant to prostate cancer risk within the context of genetic ancestry (based on ancestry informative markers) across those with European, African, Japanese, or Latino ancestry (18). Furthermore, the African Ancestry Prostate Cancer Genome-Wide Association Studies (GWAS) Consortium has reported on susceptibility loci for aggressive prostate cancer specific to men of African ancestry (19).Although some cancer risk factors are well established, the biologic mechanisms through which their impact on cancer risk varies across different populations remain incompletely understood. For example, variations in diet are hypothesized to be the primary driver of the dramatic variations in colorectal cancer incidence rates observed across populations. Recent research has evaluated the impact that different diets have on microbiota composition and function, which in turn affects the production of metabolites that either promote mucosal health or are proinflammatory/neoplastic in the gut. A study that compared Americans with African ancestry (who have a relatively high incidence of colorectal cancer) with rural South Africans (who have a comparatively very low colorectal cancer incidence rate) demonstrated that a typical U.S. diet with high meat and fat intake increases mucosal proliferation rates (a marker of cancer risk) when fed to both populations, whereas typical high-fiber South African diets were associated with low proliferation rates when fed to both groups. This demonstrates that diet can have a profound and fairly immediate impact on the gut microbiome that can either promote or suppress tumors (20).Cancer outcome disparities are well documented for racial and ethnic minorities, and presentation at more advanced stages of cancer explains much of this difference. However, even when controlling for the stage of cancer at diagnosis, the survival disparities persist. What is most concerning is that rather than improving over time, for cancers such as colon cancer, the stage-specific disparities are actually worsening (21). The reason for this growing disparity is not completely clear but involves socioeconomic issues such as education status and the level of insurance and access to medical care. Even in studies that normalize socioeconomic issues (with the limitations cited in the Defining Measures section), disparities that disproportionally affect U.S. minority populations can still be demonstrated for several cancers and may highlight the not-so-well-understood interplay between genetic predisposition and environmental exposure, such as lifestyle and diet, that modifies cancer risk (22, 23). Ultimately, growing postdiagnosis survival disparities are caused by the interplay of system, social, biologic, and environmental factors. Documenting and addressing each of these and their interactions are key to eliminating these disparities. The role of system-level and social determinants in explaining cancer health disparities is best demonstrated by recognizing that disparities vary widely across the United States; some states show almost no disparities, whereas others show striking ones (24). We also know that disparities in treatment of cancer differ and that when treatment differences are accounted for, either through the use of standardized therapies on a clinical trial or through multivariable modeling, cancer-specific survival disparities often disappear. We also have clear examples of successful system-level reform (21, 25, 26). We know, therefore, this is a solvable problem. The key step toward improving care and reducing cancer health disparities requires accurate measurement of meaningful variables, fed back in real time to key stakeholders in the system, followed by meaningful action and continued monitoring to ensure that the action was successful. Determining meaningful measurement across the cancer spectrum may vary by sociocultural factors and require patient and stakeholder input. These system-based practices formed the core of a recent Institute of Medicine report, “Systems Practices for the Care of Socially At-Risk Populations” (27). Systems can be thought of at a macro level, such as state, county, or city governments, all the way down to the individual practice or physician level. Implementation science can inform the best approaches to ensure delivery of high-quality cancer care. Cancers can start as a result of chronic inflammation, and inflammation can modify the behavior of cancer. Biomarkers, such as elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) that can be detected from inflammation-laden cancers, are associated with worse patient outcome and increased metastasis and appear to be more common among African Americans. Microsatellite-unstable (MSI) cancers, which have an overall good prognosis, may be half as common among African Americans compared with whites (28). Both EMAST and MSI have implications for (1) chemotherapeutic response and (2) immunotherapeutic response. In terms of race, these aspects have not been studied. Furthermore, there is much evidence that the microbiome can influence (1) inflammation, (2) response to chemotherapy, and (3) cancer or precancerous lesion formation; also, the microbiome itself can be determined by diet and other factors. These aspects have not been examined with race in mind. Additionally, driver genes may be different within the same type of cancer from patients with different genetic backgrounds, which have implications for correct, definitive therapeutic approaches (29).Most studies that use human specimens to study aspects of cancer and race or ethnicity come from limited individual collections with sparse clinical–epidemiologic information, with rare exception. The exceptions tend to be NCI-funded projects, such as the North Carolina Colon Cancer Study, in which peer review and thoughtful input about how the collection was made with controls, surveys, and linked information to make the collection more meaningful, comprehensive in information, potentially useful for other future studies, and possessed of longevity. However, these types of collections or biorepositories, which include tumor and nontumor specimens, have not been created from diverse samples representative of the U.S. Census population. Current models of health care delivery are highly focused on the use of technology and innovation to improve patient outcomes across disease processes, as demonstrated by the focus on precision medicine in cancer treatment (32–36). Although oncology attempts to embrace this approach, the impact of innovative treatments has been hampered by poor translation of innovation into health care systems and patients from diverse community settings (37, 38). As precision medicine in cancer is accelerated as part of the Beau Biden Cancer Moonshot and other initiatives, the importance of community engagement to ensure that all patients benefit from these advances cannot be overlooked. Cancer health disparities must be taken into consideration in the design, execution, and evaluation of all such programs. Community-engaged research (CER) has been documented as an effective, beneficial method for engaging communities and formulating research that has relevance and impact for both researchers and affected communities (39–42). Involving relevant community stakeholders in research at the planning stages allows for a deeper understanding of community needs, allows researchers to have an iterative method for evaluating research questions in an active realistic milieu, and simultaneously creates a valuable vehicle for active dissemination of the research findings into the communities they are intended to serve. CER offers the potential to improve processes and outcomes in several areas, including care delivery, continuity of care, managing comorbidities, and supportive care (42).Unfortunately, there is a dearth of support for oncology health professionals who choose to work in CER, given its necessity for infrastructure and relationship building, the complex personal interactions with communities and community organizations, and the need to establish long-term benefits to the community after the research project is completed. Importantly, CER requires not only a broad range of expertise across multiple disciplines, but also investigators skilled in a team science approach (43). The benefit of this type of team science has been touted across disciplines; however, its implementation has been limited (44).A lack of workforce diversity has been identified as a barrier to improving access to care for underserved minority groups as well as to advancing research on health disparities (45, 46). Organizations, including ASCO and the American Society of Hematology, have sought to increase workforce diversity in oncology through awards and mentoring programs that expose minorities to in oncology at the medical and In the to Cancer Health Disparities and the American Association for Cancer several programs aimed at the of researchers in cancer and cancer health disparities research. of these types are needed to an oncology workforce that the diversity of the patients it CER not often with most and will require on of the research in both and such an it will remain to create a between CER and the that in cancer are the most important and available to evidence for care and of patients with cancer and individuals at risk for cancer that advanced new approaches from clinical care and diverse oncology the of clinical is to evidence that is both and future must include research questions that consider the multifactorial and multilevel that populations with the cancer This to advance disparities research within the cancer clinical within a new of for in cancer clinical and common for providing trial information have been to for rural patients and patients with lower SES, limited low health and The high and of chronic and of risk factors for chronic such as and must inform to these populations fully in cancer As an example, African Americans a burden of the that from studies, and it is to which could be reasonably as or could be or within the study In addition to those from cancer prevention and treatment also has that populations often are later in the and do not support and rates are key that influence the outcome of clinical cancer studies, those in which minorities have higher disease such as breast, prostate, and cancers In and treatment and rates lower rates exist for those patients who from to and Many such as and to the However, community engagement is to address the and challenges that the clinical CER has been demonstrated to promote building, and the and dissemination of information needed for and long-term As an example, the evaluated the of community health to promote and in and rural populations and that community health can be trained to as research and can be for of and cancer clinical trial and require an of often to be collected at multiple time thought should be given to how best to the of and the study (e.g., and needed to support collection and of specimens from and that to field of cancer health disparities has into a complex science and an field of cancer research. Unfortunately, the to this research has not been and the infrastructure needed to it to the level, can be is The of this which has been by from these four organizations, is to the of advances in this is that this statement will be by both and organizations to inform specific made to improve cancer health disparities eliminating identified disparities in cancer incidence, of care, and recommendations for action have a new in cancer health disparities that has the potential to benefit from across and the in cancer incidence and disparities that affects minorities and the medically it is that in this of cancer research when are being there will be opportunities to this new knowledge to all populations, and cancer health disparities for and future has in a or role for and and as a of the for has research from and has other from the has in a or role for and has research his from and and has and from and has from has in a or role for the and and has research from or other in and has from and has and from for both and an immediate or other in and and has research her from potential of were by the other and and of and of for all aspects of the the of and the for their of this to and
Cancer Research · 84 citationsread the source →
Atypical Antipsychotics: CATIE Study, Drug-Induced Movement Disorder and Resulting Iatrogenic Psychiatric-Like Symptoms, Supersensitivity Rebound Psychosis and Withdrawal Discontinuation Syndromes
Chronic illness can result in chronicity of clinical practice. As we have moved away from prescribing classical antipsychotics and tricyclic antidepressants, issues remain with the use of atypical antipsychotics and second-generation antidepressants that need to be addressed, namely, iatrogenic discontinuation syndromes and supersensitivity psychiatric symptoms. An optimal maintenance drug treatment consists of regular attempts to reduce the dose by finding a minimal therapeutic dose, regularly asking the question of when to reduce or withdraw treatment and for which patients, and moreover, why it is difficult to decrease a given drug treatment. Recently, Falloon [1] proposed that maintenance pharmacotherapy in schizophrenia will depend on finally finding minimally effective doses through ‘extensive training in stress management’. In the long-term treatment of major depression, Fava [2] has hypothesized that antidepressants can aggravate the course of depressive illness. Lambert [3] recently suggested that ‘antipsychotic-switching syndromes’, which include discontinuation syndromes, are a ‘major barrier’ to adjusting antipsychotic treatment. In this paper, we propose that to achieve optimal maintenance treatment with antipsychotics, and to reduce or withdraw antipsychotics effectively, we must distinguish syndromes associated with discontinuing antipsychotics, such as supersensitivity psychosis, from true relapse. While the prevalence and incidence of drug-induced movement disorder(s) (DIMD) has continuously decreased with atypical antipsychotics, DIMD persist as do psychiatric and psychiatric-like symptoms associated with DIMD, and these must also be identified and evaluated. Persistent DIMD have been found to be a predictor of the later emergence of tardive dyskinesia (TD) and supersensitivity psychosis [4]. At present, we need to determine the relative risk of iatrogenic discontinuation syndromes, DIMD and DIMD psychiatric symptoms resulting from atypical antipsychotics. Although atypical antipsychotics are now most commonly prescribed, a debate has emerged on the differences between classical and atypical antipsychotics following the results of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study [5]. The question that comes to the forefront is why recent studies are no longer finding well-established differences between these two generations in terms of efficacy and DIMD. Reasons to explain why recent schizophrenia studies have found reduced drug and placebo differences were examined at the International Society for CNS Clinical Trials and Methodology Annual Mid-Year Conference [6]. While the fact must be considered that patients included in recent studies have less severe illness with symptoms that are better controlled than in past studies (likely due to earlier treatment), the issue that psychiatric symptoms specific to schizophrenia are not being adequately measured nor differentiated from psychiatric and psychiatric-like symptoms associated with DIMD is crucial to answering this question. For example, it is hard to believe that in a recent review of psychomotor slowing in schizophrenia, the authors, when evaluating its effect on measurement and treatment research to improve cognition in schizophrenia (MATRICS), nearly completely ignored the influence of akinesia and DIMD on neuropsychological tests in schizophrenia and the importance of accurate DIMD measurements [7]. As we pursue this ongoing discussion, we recommend the discontinuation of all classical antipsychotics due to their neurotoxic association with a high prevalence of DIMD and increases in basal ganglia volumes [8], and now address how to prescribe atypical antipsychotics most effectively, by taking into account DIMD-associated psychiatric symptoms and iatrogenic discontinuation syndromes. The first widely prescribed atypical antipsychotic, risperidone, was first approved in Canada in 1993 following the publication of the Canadian Multicenter Risperidone Study, which reported clear advantages of risperidone over haloperidol and the placebo, and significantly less appearance of DIMD with risperidone than haloperidol [9]. DIMD includes the 4 types of movement disorders induced by antipsychotics: parkinsonism, dystonia, dyskinesia and akathisia [10]. These findings were confirmed by the American Risperidone Study [11] and several other studies reporting greater efficacy of risperidone over classical antipsychotics in terms of cost-efficiency [12] and the clinical management of patients with schizophrenia [13,14,15,16,17]. However, the CATIE study [5] challenged these results. The CATIE study found that of the 4 atypical antipsychotics studied, olanzapine was the only atypical to be more efficacious than the classical antipsychotic perphenazine, and to be highly superior to risperidone for discontinuation of treatment, due to lack of efficacy [5]. Olanzapine is known to produce less DIMD compared to risperidone, therefore one would expect psychiatric symptoms caused by DIMD to be less frequent with olanzapine than risperidone. The expected higher rate of DIMD-induced emergent psychiatric symptoms associated with risperidone would explain the CATIE results, showing risperidone to be significantly less efficacious than olanzapine [5], despite risperidone being known to be at least as efficacious as olanzapine for true schizophrenic symptoms. Furthermore, the rating scales used to measure DIMD did not find the well-established differences between the 5 antipsychotics for DIMD rates [5]. Thus, we propose that DIMD and DIMD-induced psychiatric symptoms were confounded with true schizophrenic symptoms in the CATIE study. DIMD-associated psychiatric symptoms could be classified into 3 types: (1) emergent psychiatric symptoms caused by DIMD, such as akinesia inducing depression, akathisia inducing anxiety; (2) iatrogenic psychiatric-like symptoms resulting from confounding DIMD with psychiatric symptoms, such as akinesia confounded with psychomotor retardation, akathisia with agitation; (3) supersensitivity psychosis symptoms associated with DIMD. In the CATIE study, quetiapine (mean dose = 543.4 mg/day), which shares a low rate of DIMD with olanzapine, was also found to be significantly less efficacious compared to olanzapine, but in contrast to risperidone, this lack of efficacy could be due to psychiatric symptoms related to supersensitivity psychosis explained by quetiapine’s loose binding properties at the D2 receptor [18]. Patients taking quetiapine had a completion rate of 18% out of 329 patients, whereas in our 3-year prospective study of quetiapine monotherapy with a lower mean dose of 487 mg/day (thus less likely to develop therapeutic tolerance), the completion rate was 21.7% out of 23 patients; 6 of 7 patients who relapsed, after a minimum 3 months of stabilized quetiapine treatment, met the criteria for supersensitivity psychosis [19]. Without distinguishing these DIMD-associated psychiatric symptoms from symptoms due to the original illness, the major impact of atypical antipsychotics is on the reduction of DIMD and TD [10, 20,] and their beneficial effects on psychosis are masked by DIMD emergent psychiatric symptoms, including supersensitivity psychosis. We will review 4 multicenter trials, which include a total of 14,497 patients, to illustrate how psychiatric and schizophrenic symptoms are confounded with DIMD-associated psychiatric symptoms.TD epidemiology has changed significantly since the introduction of atypical antipsychotics, with a constant decline in its prevalence [10]. TD, classified as a DIMD, is a hyperkinetic, involuntary and purposeless movement disorder [10, 20]. Considered as the most significant side effect of classical antipsychotics, TD has been associated with antipsychotics and gastrointestinal neuroleptics, and usually occurs after several years of treatment. Persistent TD can also occur after short-term exposure to classical antipsychotics and gastrointestinal neuroleptics even at low doses and for as few as 2 months [8,21,22,23], while reversible and withdrawal dyskinesias share properties with levodopa-induced dyskinesia [24]. We conducted several epidemiological studies of TD [4,25,26,27] and in 1975, using the National Institute of Mental Health (NIMH) psychopharmacology criteria, we found a 31% prevalence of TD in 261 outpatients with schizophrenia [25]. We also evaluated these patients according to the Schooler and Kane research diagnostic criteria and found a 22% prevalence of TD. This variability of findings related to defining criteria complicates comparisons across studies [10]. In a 5-year follow-up study of 169 of the same patients [4, 25], 45% met the research diagnostic criteria for TD. In 1975, 131 of the 261 patients did not meet the research diagnostic for TD, and in 1980 treatment-emergent TD was found in 46 of the patients who did not have it in 1975, for a 5-year cumulative incidence rate of 35% and a mean annual incidence rate of 8.4%. When corrected for remissions, the mean annual incidence rate decreased to 2.9%. This incidence rate, which includes both patients who developed and remitted from TD over time, is similar to results found by other studies during the same time period [28, 29]. The cumulative incidence of treatment-emergent TD in the study by Kane et al. [29] was 12% after 4 years and 40% after 8 years of neuroleptic exposure, which is similar to our finding of an annual incidence rate (corrected for remissions) of 3% for classical antipsychotics. In a study carried out in 130 lithium-treated affective disorder patients previously, but less, exposed to antipsychotics, we found a TD prevalence of 9.2% [26], which was a quarter of the incidence reported in our previous studies on patients with schizophrenia who had greater exposure to antipsychotics. In this time period of classical antipsychotics, 2 meta-analyses (including mostly patients with schizophrenia) reported mean TD prevalences of 23% [30] and 20% [31]. In view of the fact that 58% of patients treated with classical antipsychotics will develop treatment-emergent TD after 10–15 years of treatment [4], and the known beneficial neuroprotective effects of atypical antipsychotics on TD [32] and on increased basal ganglia volumes induced by classical antipsychotics [8], we recommend the discontinuation of all classical antipsychotics due to their neurotoxic effects. In the time period of both classical and atypical antipsychotics, the following multicenter studies (n = 3,753) evaluated the incidence and prevalence of TD, using the same definitions, Extrapyramidal Symptom Rating Scale [20] and training videotapes as in the previous time period. In the first study, an annual TD incidence of 0.68% was reported prospectively in 725 patients with schizophrenia, treated with the long-acting injectable atypical antipsychotic risperidone [27, 33]. Treatment-emergent TD was found in 12 of 587 patients without dyskinesia at the baseline [33]; however, expert case assessment determined 7 cases (1.19%) of withdrawal dyskinesia (3 cases resolved, 4 cases unchanged), 1 case (0.17%) of reversible dyskinesia and 4 cases (0.68%) of persistent treatment-emergent TD. Of the patients with baseline dyskinesia, 28.4% improved, no longer met TD criteria and maintained this response [33]. This annual treatment-emergent TD incidence of 0.68% with atypical antipsychotics is only 22% of the annual incidence of 3% reported with classical antipsychotics [4]. In the second study, the Schizophrenia International Suicide Prevention Trial (67 centers in 11 countries) [34], 980 patients with schizophrenia, or schizoaffective disorders, taking an atypical alone (25.6%), a classical alone (31.5%) or both a classical and an atypical antipsychotic (42.9%) were included from March 19, 1998, to February 14, 1999, and TD was found at the baseline in 115 (12%) patients [27, 35]. Thus, after 10 years in the time period of both classical and atypical antipsychotics, the overall prevalence of TD decreased by at least twofold compared to our previous 1979–1988 studies with classical antipsychotics [4, 25], using the same definitions, Extrapyramidal Symptom Rating Scale and training videotapes. In the third study (baseline data from three Ris-Consta multicenter studies) [27, 36] carried out 1 year later, 2,048 patients were included from March 21, 1999, to December 15, 2000, and TD was found at the baseline in 209 patients (10.2%), using the same methodology. This study showed a further decrease in the prevalence of TD after an additional year of atypical use. This changing epidemiology of TD with atypical antipsychotics is confirmed by Correll et al. [37] in a systematic review of 1-year prospective studies with atypical antipsychotics, and by Jeste et al. [38] in a 1-year study of elderly patients treated with risperidone. In conclusion, following the introduction of atypical antipsychotics, the prevalence and incidence of TD have significantly decreased. However, the risk for TD still exists with both atypical and classical antipsychotics, and there is a need for continued surveillance of emerging cases of TD in patients taking antipsychotics [39], especially as the current debate continues on the differences in efficacy between these two generations of antipsychotics following results from studies such as the CATIE [5, 39]. Furthermore, Kane [39] has pointed out that newly trained clinicians using mostly atypical antipsychotics may not have had the same exposure to TD as previously trained clinicians.A high prevalence of all 4 types of DIMD (parkinsonism, dystonia, dyskinesia and akathisia) remains. In the Schizophrenia International Suicide Prevention Trial (n = 980), a prevalence of 57.5% of DIMD (n = 551 patients) was found [27, 35]. In the Ris-Consta studies (n = 2,048) [27, 36], 970 patients (47.4%) had DIMD at the baseline, which consisted of 778 patients with parkinsonism (38.0%), 285 patients with akathisia (14%) and 209 patients with TD (10.2%). Thus, nearly 1 patient out of 2 had a definite DIMD in this time period of classical and atypical antipsychotics. In addition, DIMD have been consistently associated with significant psychiatric symptoms as measured by the positive and negative syndrome scale (PANSS) [40, 41]. In the InterSept study (n = 980), which included patients with schizophrenia and schizoaffective disorder who were at risk of suicide, suicidality was associated at baseline with DIMD, parkinsonism, TD and akathisia, and depression was associated with TD and akathisia [27, 35]. Based on these results, we recommend routinely assessing DIMD in patients with schizophrenia with suicidal and depressive symptoms. In the Ris-Consta studies (n = 2,048), baseline DIMD were also significantly associated with the PANSS total score, positive, negative and anxiety/depression symptoms [27, 36]. Greater anxiety and depression were seen in patients with severer DIMD, akathisia and parkinsonism. Higher PANSS negative symptom rating was associated with parkinsonism and higher PANSS total scores were associated with akathisia. In this time period, these last two studies (n = 3,028) show that DIMD persists with atypical antipsychotics, and that patients with DIMD have significantly higher PANSS scores compared to patients without DIMD.These results are in agreement with findings from 2 other multicenter studies: the American CATIE study [5] and the European Schizophrenia Outpatient Health Outcomes (SOHO) study [42]. In the CATIE baseline data, patients with TD (n = 212) were found to have significantly more psychopathology than patients without TD (n = 1,098) as measured by the PANSS total score and PANSS general psychopathology subscale [43]. In the 3-year prospective SOHO study, emergent cases of TD were associated with greater overall psychopathology. An increase in clinical global impression overall symptom severity was longitudinally associated with cases of TD in patients without TD at the baseline (n = The SOHO and the CATIE studies have also examined other for TD. the CATIE and SOHO studies found that other DIMD were associated with TD the CATIE study showed that patients with TD had more parkinsonism akathisia while the SOHO study found that baseline symptoms TD our findings in a prospective study of TD [4]. In to reporting that the incidence of TD was lower in patients taking atypical compared to classical antipsychotics after 6 months the SOHO study showed that the incidence of TD was associated with the incidence of of drug-induced in is crucial to that there is a of DIMD with atypical antipsychotics, which are not and confounded with psychiatric symptoms rating scales used routinely in clinical to DIMD do not DIMD from psychiatric symptoms from the 4 multicenter (n = 14,497 patients) into this the CATIE the [27, the Ris-Consta [27, 36] and the SOHO studies have all confirmed the association of DIMD with psychiatric symptoms. most of the studies included in this measure psychiatric symptoms according to the we propose the following of PANSS psychiatric symptoms associated with emergent psychiatric symptoms caused by DIMD, such as depression and suicidality example, akinesia is known to produce depression, psychomotor and suicidal while akathisia psychomotor and suicidal and TD is also associated with suicidal iatrogenic psychiatric-like symptoms resulting from confounding and DIMD with psychiatric symptoms, such as confounding and with and retardation, akathisia with anxiety and and and dyskinesias with and schizophrenic psychiatric schizophrenic symptoms associated with DIMD caused by supersensitivity psychosis, which we are now to first reported drug-induced associated with TD a in and increased receptor after long-term treatment with classical antipsychotics, and we this supersensitivity psychosis. We that TD and supersensitivity psychosis with the decrease or withdrawal of an antipsychotic, given risk not and at the same The debate continues on how to most withdraw antipsychotic [1] and and psychiatric syndromes associated with types of syndromes have been with the discontinuation of (1) withdrawal syndromes and major (2) syndromes anxiety and which have been reported with and (3) supersensitivity syndromes such as TD and supersensitivity psychosis These discontinuation syndromes all produce psychiatric symptoms that can be confounded with true of the original illness. In a recent review of the on psychosis the importance of between antipsychotic withdrawal effects related to the course of the original illness and drug-induced effects such as supersensitivity psychosis. due to the discontinuation of a drug can be differentiated from the course of original illness and more long-term maintenance treatment could be reduced and in patients The long-term maintenance with second-generation antidepressants and of a major depressive disorder is of the in and during long-term maintenance treatment. The has also recently been to produce a persistent disorder following withdrawal to be related to supersensitivity When discontinuing antipsychotics and antidepressants, the of supersensitivity syndromes and other iatrogenic discontinuation syndromes must be to high doses or of outpatients and with schizophrenia treated with a classical antipsychotic treatment also included 1 but no antidepressants, no and no showed a prevalence of 22% for supersensitivity psychosis The prevalence of TD using Schooler and Kane criteria, was that found for supersensitivity psychosis. cases of supersensitivity psychosis increased the prevalence of supersensitivity psychosis to psychosis was associated with a higher maintenance dose of classical antipsychotics, high and schizophrenia with a The higher antipsychotic dose and higher associated with supersensitivity psychosis to the of supersensitivity and these results that lower doses of antipsychotics could the appearance of supersensitivity psychosis. In this study, there was no found between TD and supersensitivity psychosis, due to TD being associated with schizophrenia and supersensitivity psychosis with higher antipsychotic dose was not to be a risk for TD, whereas increased was associated with TD but not associated with supersensitivity psychosis. is that most patients in this study were treated with which has a high for the D2 which could to both a high incidence of supersensitivity psychosis and DIMD as the drug is known to produce a high incidence of symptoms psychosis, in its masked and withdrawal is known to occur 6 following the decrease or withdrawal of an antipsychotic or 3 months for a long-acting injectable We have proposed that TD and supersensitivity psychosis can result from the of in the caused by following in D2 with high for The of supersensitivity psychosis and TD share can both occur after long-term use of antipsychotics and can and difficult to with of the antipsychotic stress both TD and supersensitivity psychosis and both can be by and by and TD was to be the predictor of supersensitivity psychosis in our and follow-up study of supersensitivity psychosis [4, TD and supersensitivity psychosis may or may not occur in the same time but TD is associated with supersensitivity psychosis when it occurs during withdrawal of antipsychotics These two supersensitivity syndromes have been difficult to study due to the fact that antipsychotics can their appearance further with supersensitivity psychosis is that symptoms the original illness and true however, supersensitivity psychosis can be as it more after of the antipsychotic than true occurs with high doses of antipsychotics and not with antipsychotic treatment and therapeutic to antipsychotic treatment after drug response time, as therapeutic there is further of supersensitivity and further syndromes, TD, can (1) or (2) persistent or (3) reversible or symptoms can persist for several months or years and can still be reversible or When persistent and supersensitivity symptoms symptoms, being severer than the original symptoms, but these supersensitivity symptoms persist in contrast to symptoms and may include symptoms atypical antipsychotics, it has been proposed that supersensitivity psychosis occurs more with antipsychotics with from the D2 receptor The 2 atypical antipsychotics most associated with supersensitivity psychosis are quetiapine and which both have loose binding properties at the D2 receptor An additional which and severe in the withdrawal of is its effect as an receptor Thus, for the withdrawal would be by the receptor following of at this drug in the of the a and psychosis results cases of supersensitivity psychosis have also been reported with olanzapine psychosis was found to be associated with quetiapine in our 3-year study of quetiapine in 23 outpatients with schizophrenia and schizoaffective disorder who had previously been treated with classical antipsychotics risperidone, and had symptoms and of side effects [19]. As in our of the CATIE study, 7 patients after a minimum of 3 months of stabilized treatment and 6 of these patients met the criteria for supersensitivity psychosis [19]. the 11 of patients with baseline TD relapsed, the that TD to supersensitivity psychosis and have been to be efficacious in of patients with supersensitivity psychosis We also recommend the use of in supersensitivity and anxiety disorder induced by the discontinuation of the An can be used in with an antipsychotic or an in to more decrease or withdraw these and find the minimal therapeutic dose for patients who still need long-term treatment. a minimal therapeutic dose with an has an additional for a drug olanzapine, as the dose will significant side In in the of Mental Health psychiatric 35% of patients with a of schizophrenia and For severe cases of schizophrenia, the use of or is in to drug to antipsychotic While is less than or it is superior to for anxiety and the of optimal minimal maintenance drug treatment. proposed the beneficial results of treatment in schizophrenia is their effect We have also related their beneficial effects to an of a We recommend treatment as a first for from treatment, can also be prescribed as with as it has a In a and that and had than other in addition, emerging that may improve DIMD has also been to be effective as an to antipsychotic monotherapy in patients with schizophrenia who treatment We that of cases of schizophrenia can be related to supersensitivity psychosis. In patients for maintenance treatment is a minimal therapeutic dose can be with the use of an that will patients from antipsychotic or conclusion, DIMD-induced psychiatric symptoms and supersensitivity syndromes will to to results such as found in the CATIE study which show that olanzapine is the only atypical antipsychotic more efficacious than a classical The proposed for psychiatric and psychiatric-like symptoms associated with DIMD may to the of all classical antipsychotics and the use of higher doses and longer than of atypical antipsychotics. research is in to develop to distinguish between true and iatrogenic discontinuation syndromes and to to more withdraw antipsychotics and antidepressants by and supersensitivity syndromes, for the antipsychotics and quetiapine and for the may to further of DIMD, TD and supersensitivity psychosis as we to more differences in the of As most of antipsychotics and second-generation antidepressants are not routinely or for more differences in drug will also to prescribe minimal therapeutic doses of antipsychotics and antidepressants for greater efficacy and better in the maintenance has and the last 3 years from and
Psychotherapy and Psychosomatics · editorial or comment · 168 citationsread the source →
The impact of end-stage kidney disease (ESKD) on close persons: a literature review
Kidney disease is defined as end-stage when a patient's glomerular filtration rate has fallen to <15 ml/min/ 1.73 m2 [1]. Mortality associated with end-stage kidney disease (ESKD) is high [2]. The incidence of treated ESKD is rising in the western world, with a corresponding increase in the incidence of diabetes and cardiovascular disease, especially in ethnic minority groups. Survival on dialysis has been shown to be poorer in the older age group, especially in patients with increased comorbidity and in those whose functional status at the start of dialysis is poor [3]. Whilst renal transplant rates vary between different countries [4], the liberalization in the acceptance of older people into renal replacement therapy (RRT) programmes, together with changes in population demographics and the fact that kidney transplantation is less suitable for this group of older patients, means that dialysis may be the only treatment option available for an increasing number of patients aged 65 years and over [5]. Recent health policy changes in the OECD countries [6,7] acknowledge that end of life care may be more appropriate for some of these people, and maximum conservative management programmes (where residual renal function is supported, haemoglobin levels maintained and symptoms relieved) have been introduced into many renal units, particularly in the United Kingdom [6]. The onset of ESKD and subsequent recommendation of dialysis as a treatment option involves a change in lifestyle for both patients and close persons [8]. Even before end-stage disease is reached, as renal function deteriorates, patients frequently require additional support, and it is often family members who provide this [9]. In the UK it is estimated that 9 out of 10 carers of patients with either physical or neurological disabilities will be close relatives. In particular when home haemodialysis is undertaken, family members have been involved in supporting patients [10,11]. Studies have shown that good family support is associated with successful adaptation to dialysis and compliance with dietary restrictions [12,13]. Conversely, one of the main factors associated with patients discontinuing dialysis is patients’ perception that they have become a ‘burden’ to close family members [14]. There is therefore a need for health professionals to be aware of the important contribution that close persons make to the care of renal patients, to communicate effectively with them and to provide bereavement support for this group when appropriate [15]. The literature on close persons of patients with renal disease has identified two main areas of impact. Firstly, both haemodialysis and peritoneal dialysis may have a disruptive influence on family members’ social lives [16] and the structure of the week may be geared towards dialysis sessions. Secondly, some patients become frail and lose functional independence, leaving family members to provide greater physical support. Family members may have health and social care needs of their own that need to be addressed [16,17]. Qyinan [18] reported that close persons commonly felt overwhelmed and stressed, although this review was limited to an evidence base of four articles and considered home dialysis only. Campbell [19] used findings from the general carer literature to illustrate demands of ageing partners with ESKD. In other chronic illnesses such as stroke [20] or in palliative care for cancer and mental health [21], interventions aimed at providing family members with training to support patients with their rehabilitation, or to address unmet needs as a result of the patient's illness, have been developed and evaluated. Results have been mixed. In the case of stroke, carers in the intervention group experienced less depression and anxiety and better quality of life [20], whilst in the palliative care study, no statistically significant differences were found between the intervention and control group on carers’ psychological outcomes [21]. However, before such interventions can be developed in ESKD, it is important to understand better the emotional and physical needs of close persons. This review aims to identify all studies involving close persons caring for ESKD patients, to describe the main findings and critique the methodology. Specific attention has been paid to (a) studies exploring the impact of ESKD on close persons, in particular for those close persons where the patients are either withdrawing from dialysis or being provided with end of life care and (b) studies looking at the provision of health care for close persons. A literature search for relevant articles was conducted in five databases: Medline (1950–2006), Embase (1991–2006), CINAHL (1982–2006), PsycINFO (1970–2006) and AMED (1985–2006), employing the following key words: carers, caregivers, end-stage kidney disease, end-stage renal disease, haemodialysis, peritoneal dialysis and renal replacement therapy. These keywords were used both in word search options and exploded as thesaurus terms to obtain the maximum number of articles. The abstracts for each article were read to check for inclusion into the main review, using the following criteria: Published in peer-reviewed journals. Research studies with an introduction, a methodology and results section and a conclusion. Involve close persons, defined as either a family member or the person identified by the patient as an informal carer. By an informal carer, we mean a person who provides the majority of a patient's physical and emotional care needs and who is neither a volunteer nor in the employment of statutory services. Use a sample of close persons caring for adult ESKD patients (over 18 years). Non-English language articles were considered if the English translation of the abstract met the above criteria. Using these criteria, 334 articles were identified from the five databases (139 in Medline, 121 in Embase, 80 in CINAHL, 8 in AMED and 34 in PsycINFO). J.L. went through the abstracts of each of the 382 articles, of which 37 initially met the inclusion criteria. One was later excluded on closer inspection, as it was specifically a validation study of a fatigue severity scale. Of the remaining 36 studies, 16 exclusively looked at family members, 12 specifically at the patient-family dyad and 3 at the family-health professional dyad. Whilst the latter two types of studies did not concentrate solely on family concerns, we decided to include them in the analysis, because these findings further contribute to the limited number of studies in this field. Thirty-six studies were included in the review. Both J.L. and G.S. first went through the remaining 36 studies independently and extracted the following information for each study: the number of carers in the study sample, the RRT population they were caring for, authors’ definition of a carer, demographic details of the sample, patients’ dialysis history, caring history, study design, outcome measures used and main findings. J.L. and G.S. then met together to discuss these findings and obtain an initial consensus before meeting with A.B. and L.J. to obtain a final consensus. We undertook an exploration of the aims of these studies, their study design, the sample of participants and the outcome measures highlighted in the quantitative studies. The three main themes explored were (a) the impact of caring for a patient with ESKD on dialysis on close persons, in particular quality of life, psychological morbidity, close person responsibilities—which authors often referred to as ‘burden’ or ‘carer burden’—and their life situation; (b) the coping strategies employed by these close persons and (c) factors that influence psychological morbidity. No studies of health provision for close persons of patients with ESKD were identified. Four studies looking at end of life issues explored the following themes for close persons: (a) their perceptions of patients’ terminal symptoms; (b) their reasons for why patients decided to stop dialysis; (c) the long-term impact of patient death following dialysis cessation and (d) their perceptions of advance directives. End of life care may be provided by the renal multi-disciplinary team alone, or it may involve referral for specialist palliative care advice. Such advice is likely to include symptom control, attention to spiritual and psychological issues for patients and, where possible, involvement of their families in decision-making. Whilst most studies were interested in the direct impact on close persons only, one triangulated close person data with patient data. The majority of studies reviewed used a cross-sectional design; there was only one longitudinal study. Whilst most were quantitative (24/36), there were some qualitative studies (11/36) and one used a mixed methods approach. The total sample was predominantly female, with mean ages ranging from 41 to 68 years (analysis possible in only 18 studies). Sample sizes also tended to be small, with a median sample of 55 participants for the quantitative and 15 participants for the qualitative studies. Most of the sample was recruited in studies where associated patients were undergoing haemodialysis or peritoneal dialysis. Three studies also involved kidney transplant patients. Only five studies looked at close persons dealing with end of life issues or with patients withdrawing from dialysis. Many studies did not focus on close persons in their potential role as ‘informal carers’. Thirteen studies actively sought close persons who also considered themselves to be informal carers, of which eight provided full definitions of what they meant by this term. All studies included spouses as part of their sample, of which eight specifically concentrated on this group alone. Adult children were included in seven of these studies and parents in five. A wide variety of outcome measures were used to rate health-related quality of life, anxiety, depression, coping strategies and patient disease severity. Some studies used standardized outcome measures; others used simple self-rated tools. The most commonly used standardized measures were the Zarit Burden Interview [22] to evaluate the sense of carer responsibility (3/8), the Beck Depression Scale [23] to evaluate depression (2/5), SF-36 [24] to evaluate health-related quality of life (3/8), Jalowiec Coping Scale [25] to evaluate close persons’ use of coping strategies (3/3) and End-Stage Renal Disease Severity Index [26] to evaluate patients’ disease severity (2/4). A breakdown of the country of origin for each study showed that over half originated from either the USA (11/36) or Canada (7/36), with five originating from Australia and only seven from the European Union, of which only one was conducted in the UK. The remaining six studies came from the following countries: Japan (2/36), Brazil (2/36), China (1/36) and Turkey (1/36). The 36 studies have shown mixed results. They have mainly explored the following areas associated with caring for an ESKD patient: the impact on close persons and their social life and the factors affecting close persons’ psychological health. There have been very few studies looking at palliative care issues and these have primarily concentrated on dealing with end of life issues rather than the provision of supportive care in the pre-terminal phase. In only one study, close persons rated their quality of life as excellent and reported few pressures resulting from their carer responsibilities [27], whilst in all others, ESKD and dialysis were shown to increase the close person's sense of responsibility and lead to a poorer quality of life when compared with age-matched controls [28]. Close persons found living with an ESKD patient on dialysis stressful [29] and experienced increased fatigue [30]. The dominating effect of caring for an ESKD patient often led close persons to neglect their own health. For those who took time to have a break from their carer responsibilities, there were health benefits [31]. Other issues that close persons reported included isolation through the loss of social activity [30–36], life restrictions [36–38], increased workload, negative economic consequences [39,40], changed relationship with the patient [30,34] and sexual problems for spouses [41]. Impact on family life (quantitative and mixed methods studies) CAPD = Continuous Ambulatory Peritoneal Dialysis; CBI = Caregivers Burden Interview; FES = Family Environment Scale; HD = Haemodialysis; IIRS = Illness Intrusiveness Ratings Scale; MAES = Marital Attitudes Evaluation Scale; NGQ = Norris & Groves Questionnaire; PAF = Physicians’ Assessment Form; PAIS = Psychosocial Adjustment to Illness Scale; SF-36 = Short-Form 36; SwQoL = Swedish Health-Related Quality of Life Survey; VAS = Visual Analogue Scale; ZBI = Zarit Burden Interview. Impact on family life (quantitative and mixed methods studies) CAPD = Continuous Ambulatory Peritoneal Dialysis; CBI = Caregivers Burden Interview; FES = Family Environment Scale; HD = Haemodialysis; IIRS = Illness Intrusiveness Ratings Scale; MAES = Marital Attitudes Evaluation Scale; NGQ = Norris & Groves Questionnaire; PAF = Physicians’ Assessment Form; PAIS = Psychosocial Adjustment to Illness Scale; SF-36 = Short-Form 36; SwQoL = Swedish Health-Related Quality of Life Survey; VAS = Visual Analogue Scale; ZBI = Zarit Burden Interview. Impact on family life (qualitative studies) CAPD = continuous ambulatory peritoneal dialysis; HD = haemodialysis; PD = peritoneal dialysis. Impact on family life (qualitative studies) CAPD = continuous ambulatory peritoneal dialysis; HD = haemodialysis; PD = peritoneal dialysis. The treatment modality may also have an impact on family members. Studies have highlighted that spouses of transplant patients were more assertive, self-sufficient and able to handle the physical, social and existential aspects of the illness better than dialysis spouses [33,42]. Despite these pressures, close persons recognized that they play a positive role in promoting patients’ well-being [11,43]. They recognized that health care professionals were important in providing support to discuss their problems [39] and would like to have more information about the care being provided to patients [44]. However, they also reported poor communication with professionals, felt that their needs were not always addressed [30,39,45] and felt themselves uneducated and poorly equipped to deal with the regimented lifestyle associated with the dialysis regimen [14]. Whilst some studies have shown that close persons display few signs of psychological distress [40,46–49], others have identified the following: Caring and psychological health ABS = Affect Balance Scale; BDI = Beck Depression Inventory; BI = Barthel Index; CAPD = Continuous Ambulatory Peritoneal Dialysis; CAS = Clinical Anxiety Scale; CBI = Caregivers Burden Interview; CBS = Caregiver Burden Scale; CES-D = Center for Epidemiologic Studies Depression Scale; CID = Cognitive Index of Depression; DAS = Adjustment Scale; = = Anxiety and Scale; = Questionnaire; = Depression Questionnaire; = Questionnaire; = End-Stage Renal Disease Severity Index; = End-Stage Renal Disease Severity = Family Questionnaire; = Scale; = = Index; HD = haemodialysis; = Scale; = Impact on Family Scale; = Jalowiec Coping Scale; = Scale; = of control of = Marital Adjustment = Marital Questionnaire; = Scale of = Psychosocial Adjustment to Illness PD = peritoneal dialysis; = Scale; = for and Family Scale; = Quality of Life Index; = Scale; = Inventory; SF-36 = Short-Form 36; = = Anxiety Inventory; = with Life Scale; = ZBI = Zarit Burden Interview. Caring and psychological health ABS = Affect Balance Scale; BDI = Beck Depression Inventory; BI = Barthel Index; CAPD = Continuous Ambulatory Peritoneal Dialysis; CAS = Clinical Anxiety Scale; CBI = Caregivers Burden Interview; CBS = Caregiver Burden Scale; CES-D = Center for Epidemiologic Studies Depression Scale; CID = Cognitive Index of Depression; DAS = Adjustment Scale; = = Anxiety and Scale; = Questionnaire; = Depression Questionnaire; = Questionnaire; = End-Stage Renal Disease Severity Index; = End-Stage Renal Disease Severity = Family Questionnaire; = Scale; = = Index; HD = haemodialysis; = Scale; = Impact on Family Scale; = Jalowiec Coping Scale; = Scale; = of control of = Marital Adjustment = Marital Questionnaire; = Scale of = Psychosocial Adjustment to Illness PD = peritoneal dialysis; = Scale; = for and Family Scale; = Quality of Life Index; = Scale; = Inventory; SF-36 = Short-Form 36; = = Anxiety Inventory; = with Life Scale; = ZBI = Zarit Burden Interview. A negative between close persons’ psychological health and their sense of carer responsibility their use of coping strategies strategies that the symptoms of the of the the close person's age and the social and changes as a result of ESKD A positive between good mental health and the following a of of dialysis the of dialysis patients are on of social support and sense of carer responsibility The sense of carer responsibilities are if patients are in of living have less or comorbidity This was further in studies in patients home haemodialysis or transplant where close persons not anxiety or depression felt less by their carer responsibility and a quality of life to the age-matched population were found between levels of responsibility and other outcomes such as quality of life and The use of coping was found to have a negative with a positive with the number of years on dialysis Close persons were more likely to have negative towards patients if they no of the dialysis and a high of involvement with the caring whilst living in a We identified five studies that explored end of life only one specifically on close persons. This study the long-term impact of death on families when dialysis was found that most families felt that patients a good death as at and with close people and most family members showed only levels of However, carers and those with levels of caring responsibility for the did End of life care HD = End of life care HD = The remaining four studies on patient outcomes such as reasons for withdrawing from dialysis the quality of death the of close persons in ESKD patients’ to and care and use of advance as a in advance by patients, which the of treatment to be by health care a patient is to provide to that person's of These studies found that close persons that whilst most patients a many patients were to be in and from fatigue care family members in that patients’ were and most recognized the of living which they felt were health care professional Close persons were poorly for caring for a dialysis and patients did not to be a on their families [14]. They were also poor at both patients’ and for or dialysis No studies were identified for carers of patients with supportive care those on maximum conservative management The main of most studies included in this review is the of and of the demographic over half of the studies demographic details of close persons’ ages and or details of their relationship to patients of other relevant demographic such as employment status or social is and only seven studies the time that close persons as Whilst all studies the of dialysis half reported the of time a patient has been on with very few patients’ functional although carer studies in other that this has an impact on carers’ quality of life In only 18 9 qualitative and mixed methods study details of their sample of the quantitative studies included in the used cross-sectional and were predominantly Such studies are in exploring between are limited as they not to be only five studies provide the full details of sample it is therefore not possible to rates or the sample The sample sizes were with a median of 55 and details of were reported in only one study. the of the used to the different outcomes it to between the different studies. We identified that most studies poor of their methods and a of of their data Most used of family members with five studies using only one details of their studies with their studies with their one a of their their approach. One study no details of their the studies were poorly that the was and authors were as to to use qualitative data with the and of the qualitative data demographic of data and poor use of supporting This study reviewed the literature exploring the of close persons of patients with ESKD, from which can be the quality of and for the of in this Firstly, studies exploring end of life issues are with only four identified. these four studies are they that health are the time for informal carers to discuss patients’ about end of life care and, long-term distress of close persons resulting from the patients’ However, about such end of life issues close persons, and we studies in this Secondly, definitions of close persons were there were some differences identified between the different groups. the literature the that most close persons are to patients, the in to patients who were and those with family and relationship were not not all close persons to on the role of the informal carer, and the of this role can be a as illness review did not identify differences between informal carers and family carers in the outcome measures used included both the of differences may in their with ‘informal carers’ a more members’ may be as being more this needs further issues that need to be addressed the use of methodology were identified in the Most quantitative studies were and with no intervention studies being identified. Studies of demographic details and rates and all were cross-sectional with sample sizes that used standardized Whilst the use of standardized measures the of the the findings from cross-sectional studies are limited in that they can only between We the use of longitudinal methods in that would that between key be explored in more This would also into the long-term of close persons. In those studies using qualitative most used with poor and of demographic and social and Many authors used the ‘burden’ or ‘carer such terms may influence of the relationship between close person and was not they were by close persons to use the ‘burden’ or it was a by the authors to describe the responsibilities of Such and the of study findings the half of the studies originated from either the USA (11/36) or Canada This it to the results of these studies their to in the of health care provision in other there is evidence that the psychological health of close persons them to to care which in can the mental health of patients, we to identify studies in review that looked specifically at health close persons of patients with ESKD. review has identified in the literature that need to be is therefore to the relationship between health and close persons in to We would like to acknowledge for this review and for support in this of
Clinical Kidney Journal · editorial or comment · 83 citationsread the source →
Gregor Hasler (2010)MEDLINE-indexed journal, not yet read by usWorld Psychiatry · editorial or comment PATHOPHYSIOLOGY OF DEPRESSION: DO WE HAVE ANY SOLID EVIDENCE OF INTEREST TO CLINICIANS?
Major depressive disorder (MDD) is a common and costly disorder which is usually associated with severe and persistent symptoms leading to important social role impairment and increased mortality 1,2. It is one of the most important causes of disability worldwide 3. The high rate of inadequate treatment of the disorder remains a serious concern 1. This review is aimed at summarizing the solid evidence on the etiology and pathophysiology of MDD that is likely relevant for clinical psychiatry. Neurobiological findings are regarded as solid when they are consistent and convergent, i.e., they have been confirmed by several studies using the same method and fit into results from studies using different methodological approaches. Family, twin, and adoption studies provide very solid and consistent evidence that MDD is a familial disorder and that this familiality is mostly or entirely due to genetic factors 4. This important finding suggests that parental social behavior and other familial environmental risk factors are not as important in the pathogenesis of MDD as previously assumed and should not be the major focus of the treatment of the disorder. The above-mentioned studies consistently show that the influence of genetic factors is around 30–40% 4. Non-genetic factors, explaining the remaining 60–70% of the variance in susceptibility to MDD, are individual-specific environmental effects (including measurement error effects and gene-environment interactions). These effects are mostly adverse events in childhood and ongoing or recent stress due to interpersonal adversities, including childhood sexual abuse, other lifetime trauma, low social support, marital problems, and divorce 5,6. These results suggest that there is a huge potential in the prevention of MDD by means of psychosocial interventions (e.g., in schools, at workplace). In addition, these results mirror the clinical practice of empirically validated psychotherapies to treat depression 7,8,9, including interpersonal, psychodynamic and cognitive behavioral psychotherapies and cognitive behavioural analysis system of psychotherapy, which all focus directly or indirectly on interpersonal difficulties and skills. This does not exclude the fact that unidentified non-genetic, non-psychosocial risk factors may also play important roles in some patients (e.g., climatic change, medical conditions). Stress sensitivity in depression is partly gender-specific. While men and women are, in general, equally sensitive to the depressogenic effects of stressful life events, their responses vary depending upon the type of stressor. Specifically, men are more likely to have depressive episodes following divorce, separation, and work difficulties, whereas women are more sensitive to events in their proximal social network, such as difficulty getting along with an individual, serious illness, or death 10. These findings point to the importance of gender-sensitive psychosocial approaches in the prevention and treatment of MDD. In contrast to the very solid evidence from epidemiological studies on broad risk factor domains, there is no solid evidence for specific genes and specific gene-by-environment interactions in the pathogenesis of MDD. Genome-wide association studies have indicated that many genes with small effects are involved in complex diseases, increasing the difficulty in identifying such genes 11. While there has been progress in the search for risk genes for several complex diseases despite this methodological problem 12, psychiatric conditions have turned out to be very resistant to robust gene identification. For example, based on a community-based prospective study, it has been proposed that a specific genetic variation in the promoter region of the serotonin transporter (a target of antidepressant drugs) interacts with stressful life events in the pathogenesis of depression 13. Although there is high clinical and neurobiological plausibility of this interaction, a recent meta-analysis yielded no evidence that the serotonin transporter gene alone or in interaction with psychological stress was associated with the risk of depression 14. The limited success of genetic studies of depression has been related to use of current classification schemas including ICD-10 and DSM-IV. These diagnostic manuals are based on clusters of symptoms and characteristics of clinical course that do not necessarily describe homogenous disorders but instead reflect common final pathways of different pathophysiolgical processes 15,16. The clinician should be aware that family history will continue to be the most solid source of information to estimate the genetic risk of MDD. Corticotropin-releasing hormone (CRH) is released from the hypothalamus in response to the perception of psychological stress by cortical brain regions. This hormone induces the secretion of pituitary corticotropin, which stimulates the adrenal gland to release cortisol into the plasma. The physiologic response to stress is partly gender-specific: women show generally greater stress responsiveness than men, which is consistent with the greater incidence of major depression in women 17. Moreover, men show greater cortisol responses to achievement challenges, whereas women show greater cortisol responses to social rejection challenges 18. Although MDD is considered as a stress disorder, most subjects treated for MDD have no evidence of dysfunctions of the hypothalamic-pituitary-adrenal axis (HPA) 19. However, some subjects with MDD do show abnormalities of that axis and of the extrahypothalamic CRH system 20. Altered stress hormone secretion appeared to be most prominent in depressed subjects with a history of childhood trauma 21. Elevated cortisol may act as a mediator between major depression and its physical long-term consequences such as coronary heart disease, type II diabetes, and osteoporosis 22. The importance of HPA axis dysfunction for the efficacy of antidepressants is a matter of debate 23. This axis is regulated through a dual system of mineralocorticoid (MR) and glucocorticoid (GR) receptors. Decreased limbic GR receptor function 24,25 and increased functional activity of the MR system 26 suggest an imbalance in the MR/GR ratio in stress-related conditions such as MDD. Epigenetic regulation of the glucocorticoid receptors has been associated with childhood abuse 27. Such environmental programming of gene expression may represent one possible mechanism that links early life stress to abnormal HPA axis function and increased risk of MDD in adults. While the CRH stimulation test (dex/CRH test) 28 is a sensitive measure of the HPA axis dysfunction in depression, the specificity of this test for MDD is low. However, non-suppression in the dex/CRH test has consistently predicted increased risk for depressive relapse during clinical remission 23. Additionally, the measurement of waking salivary cortisol concentration has been shown to be a simple and sensitive test for HPA axis hyperactivity in depression 29. Hypercortisolemia is almost exclusively found in subjects with severe and psychotic depression, in whom glucocorticoid antagonists may have some therapeutic effect 30. There is convergent evidence for CRH to play a major role in the pathogenesis of certain types of depression. Levels of CRH in the cerebrospinal fluid are elevated in some depressed subjects 31. Post-mortem studies reported an increased number of CRH secreting neurons in limbic brain regions in depression 32, likely reflecting a compensatory response to increased CRH concentrations 33. In addition, CRH produces a number of physiological and behavioral alterations that resemble the symptoms of major depression, including decreased appetite, disrupted sleep, decreased libido, and psychomotor alterations 34. There is also preliminary evidence that CRH1 receptor antagonists reduce symptoms of depression and anxiety 35. “Sickness behavior” as a result of an activation of the inflammatory response system shares many symptoms with depression, including fatigue, anhedonia, psychomotor retardation, and cognitive impairment. Sickness is mediated by pro-inflammatory cytokines such as interleukin-1α, tumor necrosis factor-α, and interleukin-6, which activate the HPA axis and impair the central serotonin system 36. The prevalence of depression as an unwanted effect of recombinant interferons is around 30% 37. In animals, blocking pro-inflammatory cytokine-mediated signaling produces antidepressant-like effects 38. Clinical data suggest that cytokines may play a role in the pathophysiology of a subgroup of depressed subjects, particularly those with comorbid physical conditions 36. The antidepressant enhancing effect of acetylsalicylic acid 39 points to the possible clinical relevance of psychoneuroimmunology in clinical depression research. Taken together, the laboratory tests with the highest potential to be clinically useful in the care of depressed individuals are based on abnormalities of the neuroendocrine and neuroimmune systems. Despite the large amount of basic science data suggesting that the HPA axis is importantly involved in the pathophysiology of depression, the effect of pharmacological modulation of this neuroendocrine system as antidepressant therapy has been disappointing. The link between childhood trauma and a permanently altered physiologic stress system points to the use of specific psychotherapies in the treatment of depressed patients with a history of early life trauma 40. Most of the serotonergic, noradrenergic and dopaminergic neurons are located in midbrain and brainstem nuclei and project to large areas of the entire brain. This anatomy suggests that monoaminergic systems are involved in the regulation of a broad range of brain functions, including mood, attention, reward processing, sleep, appetite, and cognition. Almost every compound that inhibits monoamine reuptake, leading to an increased concentration of monoamines in the synaptic cleft, has been proven to be a clinically effective antidepressant 19. Inhibiting the enzyme monoamine oxidase, which induces an increased availability of monoamines in presynaptic neurons, also has antidepressant effects. These observations led to the pharmacologically most relevant theory of depression, referred to as the monoamine-deficiency hypothesis. The monoamine-deficiency theory posits that the underlying pathophysiological basis of depression is a depletion of the neurotransmitters serotonin, norepinephrine or dopamine in the central nervous system. Serotonin is the most extensively studied neurotransmitter in depression. The most direct evidence for an abnormally reduced function of central serotonergic system comes from studies using tryptophan depletion, which reduces central serotonin synthesis. Such a reduction leads to the development of depressive symptoms in subjects at increased risk of depression (subjects with MDD in full remission, healthy subjects with a family history of depression) 41,42, possibly mediated by increased brain metabolism in the ventromedial prefrontal cortex and subcortical brain regions 42. Experimentally reduced central serotonin has been associated with mood congruent memory bias, altered reward-related behaviors, and disruption of inhibitory affective processing 16, all of which add to the clinical plausibility of the serotonin deficiency hypothesis. There is also evidence for abnormalities of serotonin receptors in depression, with the most solid evidence pointing to the serotonin-1A receptor, which regulates serotonin function. Decreased availability of this receptor has been found in multiple brain areas of patients with MDD 43, although this abnormality is not highly specific for MDD and has been found in patients with panic disorder 44 and temporal lobe epilepsy 45, possibly contributing to the considerable comorbidity among these conditions. However, there is no explanation for the mechanism of serotonin loss in depressed patients, and studies of serotonin metabolites in plasma, urine and cerebrospinal fluid, as well as post-mortem research on the serotonergic system in depression, have yielded inconsistent results. There is preliminary evidence that an increased availability of the brain monoamine oxidase, which metabolizes serotonin, may cause serotonin deficiency 46. In addition, loss-of-function mutations in the gene coding for the brain-specific enzyme tryptophan hydroxylase-2 may explain the loss of serotonin production as a rare risk factor for depression 47. Dysfunction of the central noradrenergic system has been hypothesized to play a role in the pathophysiology of MDD, based upon evidence of decreased norepinephrine metabolism, increased activity of tyrosine hydroxylase, and decreased density of norepinephrine transporter in the locus coeruleus in depressed patients 48. In addition, decreased neuronal counts in the locus coeruleus, increased alpha-2 adrenergic receptor density, and decreased alpha-1 adrenergic receptor density have been found in the brains of depressed suicide victims post-mortem 49. Since there is no method to selectively deplete central norepinephrine and no imaging tool to study the central norepinephrine system, solid evidence for abnormalities of this system in depression is lacking. While the classical theories of the neurobiology of depression mainly focused on serotonin and norepinephrine, there is increasing interest in the role of dopamine 50. Dopamine reuptake inhibitors (e.g., nomifensine) and dopamine receptor agonists (e.g., pramipexole) had antidepressant effects in placebo-controlled studies of MDD 51. In the cerebrospinal fluid and jugular vein plasma, levels of dopamine metabolites were consistently reduced in depression, suggesting decreased dopamine turnover 52. Striatal dopamine transporter binding and dopamine uptake were reduced in MDD, consistent with a reduction in dopamine neurotransmission 53. Degeneration of dopamine projections to the striatum in Parkinson's disease was associated with a major depressive syndrome in about one half of cases, which usually preceded the appearance of motor signs 54. Experimentally reduced dopaminergic transmission into the accumbens has been associated with anhedonic symptoms and performance deficits on a reward processing task in subjects at increased risk of depression 55,56. These findings are consistent with the clinical observation that depressed patients have a blunted reaction to positive reinforcers and an abnormal response to negative feedback 57. Almost all established antidepressants target the monoamine systems 58. However, full and partial resistance to these drugs and their delayed onset of action suggest that dysfunctions of monoaminergic neurotransmitter systems found in MDD represent the downstream effects of other, more primary abnormalities. Despite this limitation, the monoamine-deficiency hypothesis has proved to be the most clinically relevant neurobiological theory of depression. New findings on the role of dopamine in depression emphasize the scientific potential of this theory, and promising reports of antidepressant effects of drugs that modulate the dopaminergic system (e.g., pramipexole, modafinil) in difficult-to-treat depression underline its clinical relevance 51,59. Although many historical attempts to localize mental functions have failed, they have considerably contributed to a modern neuroscientific understanding of mental disorders 60. The development of neuroimaging techniques has opened up the potential to investigate structural and functional abnormalities in living depressed patients. Unfortunately, the diversity of imaging techniques used, the relatively small and heterogeneous study samples studied, and the limited overlap of results across imaging paradigms 61 make it difficult to reliably identify neuronal regions or networks with consistently abnormal structure or function in MDD. Functional imaging studies have provided the most limited overlap of findings. This may be due to methodological limitations and/or the complexity of neurocircuitry involved in MDD. A recent meta-analytic study found the best evidence for abnormal brain activity in MDD in lateral frontal and temporal cortices, insula, and cerebellum. In these brain regions activity was decreased at rest, they showed a relative lack of activation during induction of negative emotions, and an increase in activity following treatment with serotonin reuptake inhibitors. Opposite changes may exist in ventromedial frontal areas, striatum and possibly other subcortical brain regions 61. More solid evidence has been provided by structural imaging and post-mortem studies. A recent meta-analytic study on brain volume abnormalities in MDD revealed relatively large volume reductions in the ventromedial prefrontal cortex, particularly in the left anterior cingulate and in the orbitofrontal cortex. Moderate volume reductions were found in the lateral prefrontal cortex, hippocampus and striatum 62. Post-mortem studies consistently identified a reduction in glia cell density in dorsal, orbital and subgenual prefrontal cortices, as well as in the amygdala 63,64. Overall, functional, structural and post-mortem studies suggest that structural and functional abnormalities in the left subgenual cingulate cortex are the most solid neuroanatomical finding in MDD. Volume reduction in this region was found early in illness and in young adults at high familial risk for MDD 65, suggesting a primary neurobiological abnormality associated with the etiology of the illness. Humans with lesions that include the subgenual prefrontal cortex showed abnormal autonomic responses to social stimuli 66, and rats with left-sided lesions in this region had increased sympathetic arousal and corticosterone responses to restraint stress 67. Most importantly, chronic deep brain stimulation to reduce the potentially elevated activity in the subgenual cingulated cortex produced clinical benefits in patients with treatment-resistant depression 68. In summary, despite the considerable heterogeneity of findings from neuroimaging studies, there is convergent evidence for the presence of abnormalities in the subgenual prefrontal cortex in some patients with MDD. Neuroanatomical research in depression is of great clinical interest, since novel antidepressant treatments such as deep brain stimulation can target specific brain regions. In addition, there are promising leads for neuroimaging findings to predict the likelihood of responses to specific treatments 69. Risk factors for depressive episodes change during the course of the illness. The first depressive episode is usually “reactive”, i.e., triggered by important psychosocial stressors, while subsequent episodes become increasingly “endogenous”, i.e., triggered by minor stressors or occurring spontaneously 70. There is consistent evidence that the volume loss of the hippocampus and other brain regions is related to the duration of depression 71, suggesting that untreated depression leads to hippocampal volume loss, possibly resulting in increased stress sensitivity 72 and increased risk of recurrence 73. Glucocorticoid neurotoxicity, glutamatergic toxicity, decreased neurotrophic factors, and decreased neurogenesis have been proposed as possible mechanisms explaining brain volume loss in depression. There is no solid evidence on of these since there are no imaging to directly and neurotrophic processes in neurotrophic factor has considerable Specifically, studies have shown between and in hippocampal as well as expression of following antidepressant treatment The clinician should be aware of the potentially effect of depression and treat depressed patients as early and as A of studies consistently showed reductions in acid concentrations in the prefrontal and cortex in depression This may reflect stress since psychological stress to presynaptic of prefrontal neurotransmission low concentration may reflect reduction in the density and of In addition, chronic stress may reduce receptor possibly through changes in evidence of the hypothesis of depression the lack of effects of drugs on depressive symptoms and prefrontal concentration in subjects with MDD of evidence suggest a dysfunction of the neurotransmitter system in a of the receptor produced and large antidepressant effects in patients with treatment-resistant MDD inhibitors of release (e.g., antidepressant abnormal levels were found in depressed subjects as by and there is evidence for abnormal signaling in post-mortem Since is the major neurotransmitter involved in almost every brain the of the specific role of in depression (e.g., there are promising leads that the receptor is involved in MDD and are diagnostic for MDD, suggesting regulation in depressed patients. In addition, some depressive symptoms may show psychomotor of of positive and negative and a subgroup of patients with MDD may have a disorder In healthy young subjects, changes in the of the had specific effects on subsequent mood In depressed patients, of can have antidepressant on these abnormalities have been hypothesized to be associated with MDD The association between of the and in cortisol in some subjects with and the effect of antidepressants on of and to the of this hypothesis Despite of the many promising the and genetic of this hypothesis are It remains to be antidepressant effects of such as directly to of on these abnormalities have been hypothesized to be associated with MDD The association between of the and in cortisol in some subjects with and the effect of antidepressants on of and to the of this hypothesis Despite of the many promising the and genetic of this hypothesis are It remains to be antidepressant effects of such as directly to of The and of the neurobiological of depression are in 1. The many theories of depression and the relatively low response rate of all antidepressant treatments a hypothesis of and suggest that depression is a clinically and heterogeneous disorder. This research on of the response to therapeutic interventions using such as neuroimaging and neuroendocrine tests in with for with to stress sensitivity and antidepressant The of of therapeutic will for the development of that has the potential to interventions and to up pathways in the of novel therapeutic approaches.
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Bullying and Suicide: A Public Health Approach
Several recent studies have found an association between bullying and depression [[1]Wang J. Iannotti R.J. Luk J.W. Nansel T.R. Co-occurrence of victimization from five subtypes of bullying: Physical, verbal, social exclusion, spreading rumors, and cyber.J Pediatr Psychol. 2010; 35: 1103-1112Crossref PubMed Scopus (223) Google Scholar] or bullying and suicide-related behaviors [[2]Kim Y.S. Leventhal B. Suicide and bullying. A review. Int J Adolesc Med Health. 2008; 20: 133-154Crossref PubMed Scopus (324) Google Scholar], and one study found evidence consistent with a causal link, at least for girls [3Klomek A.B. Sourander A. Niemela S. et al. Childhood bullying behaviors as a risk for suicide attempts and completed suicides: A population-based birth cohort study.J Am Acad Child Adolesc Psychiatry. 2009; 48: 254-261Abstract Full Text Full Text PDF PubMed Scopus (324) Google Scholar, 4Klomek A.B. Sourander A. Gould A. The association of suicide and bullying in childhood to young adulthood: A review of cross-sectional and longitudinal research findings. Can J Psychiatry. 2010; 55: 282-288PubMed Google Scholar]. These studies, in conjunction with extensive media coverage of the deaths by suicide of several young people who were victims of bullying, led the Centers for Disease Control and Prevention (CDC) to convene an expert panel focusing on the relationship between bullying involvement and suicide-related behaviors. The purpose of the panel, held in September 2010, was to synthesize the latest research about the relationship between youth involvement in bullying (youth who bully, youth who are bullied, and those who bully and are bullied) and suicide-related behaviors (attempts, fatalities, and risk factors associated with suicide, such as depression). Experts on the topics of bullying and suicide presented their research about the relationship between these two behaviors; their work is contained in this supplement. The panel and this special issue provide clarity around the complicated issues of bullying and suicide among youth. Three key themes emerged: (1) bullying among youth is a significant public health problem; it is prevalent and frequently has detrimental effects; (2) there is a strong association between bullying and suicide-related behaviors, but this relationship is often mediated by other factors, including depression and delinquency; and (3) there are public health strategies that can be applied to the prevention of bullying and suicide. Bullying is a significant public health problem because it is prevalent and harmful. Between 20% and 56% of young people are involved in bullying annually [5Centers for Disease Control and Prevention. Youth risk behavior surveillance—United States, 2011. MMWR, Surveillance Summaries 2012;61(no. SS-4). Available at: www.cdc.gov/mmwr/pdf/ss/ss6104.pdf. Google Scholar, 6Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 7Kowalski R.M. Limber S.P. Psychological, physical, and academic correlates of cyberbullying and traditional bullying.J Adolesc Health. 2013; 53: S13-S20Abstract Full Text Full Text PDF PubMed Scopus (768) Google Scholar]. Thus, in a classroom of 30 students, between 6 and 17 students are involved in bullying as a victim, perpetrator, or both (bully-victim). The specific rate of bullying victimization and perpetration varies according to age, type of bullying, time period over which bullying behaviors are assessed, and by subgroup. Younger (middle school-aged) children are more likely to be involved in bullying than high school-aged children [[8]Robers S. Zhang J. Truman J. Indicators of school crime and safety: 2011 (NCES 2012-002/NCJ 236021). National Center for Education Statistics, U.S. Department of Education, and Bureau of Justice Statistics, Office of Justice Programs, U.S. Department of Justice, Washington, DC2012Google Scholar]. Verbal bullying is generally more prevalent than physical or cyber-bullying and bullying is more likely to occur over a longer time period—“ever” or over the “past year” as opposed to “the past few months” [[9]David-Ferdon C. Hertz M.F. Electronic media and youth violence: A CDC issue brief for researchers. Centers for Disease Control, Atlanta, GA2009Google Scholar]. Specific subgroups are more likely to be victimized. For example, bullying victimization is more prevalent upon lesbian and gay youth—60% report victimization during the past 30 days prior to the survey compared with 28.8% of heterosexual youth [[10]Hatzenbuehler M.L. Keyes K.M. Inclusive anti-bullying policies and reduced risk of suicide attempts in lesbian and gay youth.J Adolesc Health. 2013; 53: S21-S26Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar]. For young people involved in bullying in any capacity—youth who bully others, who are bullied, or who both bully and are bullied, this involvement is correlated with poor mental and physical health and engagement in other risk behaviors. Youth who are bullied are more likely to be depressed or anxious [[11]Fekkes M. Pijpers F. Fredriks A.M. et al. Do bullied children get ill, or do ill children get bullied? A prospective cohort study on the relationship between bullying and health-related symptoms. Pediatrics. 2006; 117: 1568-1574Crossref PubMed Scopus (426) Google Scholar], have lower academic achievement, report feeling like they do not belong at school [[12]Glew G.M. Fan M. Katon W. et al. Bullying, psychosocial adjustment, and academic performance in elementary school. Arch Pediatr Adolesc Med. 2005; 159: 1026-1031Crossref PubMed Scopus (384) Google Scholar], have poorer social and emotional adjustment, greater difficulty making friends, poorer relationships with classmates, and greater loneliness [[13]Nansel T.R. Overpeck M. Pilla M. et al. Bullying behavior among U.S. youth: Prevalence and association with psychosocial adjustment.JAMA. 2001; 285: 2094-2100Crossref PubMed Scopus (2743) Google Scholar]. Bully-victims are more likely than those who bully, those who are bullied, or their uninvolved peers to report being physically hurt by a family member, to witness family violence, and exhibit suicide-related behaviors [[14]McKenna M. Hawk E. Mullen J. Hertz M. The association between bullying behavior and health risks among middle school and high school students in Massachusetts, 2009.Morbidity and Mortality Weekly Review. 2011; 60: 465-471PubMed Google Scholar]. Those who bully others are more likely to drink alcohol and use cigarettes, to have poorer academic achievement and poorer perceived school climate, but to also report greater ease of making friends [[13]Nansel T.R. Overpeck M. Pilla M. et al. Bullying behavior among U.S. youth: Prevalence and association with psychosocial adjustment.JAMA. 2001; 285: 2094-2100Crossref PubMed Scopus (2743) Google Scholar]. Involvement in bullying can also have long-lasting, detrimental effects months or even years after the bullying occurs. Young people who are bullied are more likely than uninvolved youth to develop depression and anxiety and report abdominal pain and feeling tense over the course of a school year [[11]Fekkes M. Pijpers F. Fredriks A.M. et al. Do bullied children get ill, or do ill children get bullied? A prospective cohort study on the relationship between bullying and health-related symptoms. Pediatrics. 2006; 117: 1568-1574Crossref PubMed Scopus (426) Google Scholar]. One study examining the impact of bullying victimization of those who were between 9, 11, and 13 years of age when they were victimized found, that over a 7-year period, youth who were bullied were more likely to develop generalized anxiety and panic disorder as adults while bully-victims were more likely to subsequently suffer from depression, panic disorder, and suicidality [[15]Copeland W.E. Wolke D. Angold A. Costello E.J. Adult psychiatric outcomes of bullying and being bullied by peers in childhood and adolescence.JAMA Psychiatry. 2013; 70: 419-426Crossref PubMed Scopus (746) Google Scholar]. Another longitudinal study found that those who were perpetrators of bullying at age 14 were more likely to receive a diagnosis of antisocial personality disorder, to have low job status at age 18 years, and to use drugs at ages 27–32 years [[16]Farrington D.P. Ttofi M.M. Bullying as a predictor of offending, violence and later life outcomes. Crim Behav Ment Health. 2011; 21: 90-98Crossref PubMed Scopus (169) Google Scholar]. The articles in this special issue generally show a strong association between involvement in bullying behaviors and suicide-related behaviors. In Espelage and Holt's work with middle school students, suicidal ideation and attempts were significantly more prevalent among victims, bully-victims and perpetrators, with rates of ideation and attempts among those involved as a victim, perpetrator, or bully-victims three to five times higher than the rate of uninvolved youth [[17]Espelage D.L. Holt M.K. Suicidal ideation and school bullying experiences after controlling for depression and delinquency.J Adolesc Health. 2013; 53: S27-S31Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar]. Likewise, in Borowsky's study of 6th, 9th, and 12th graders, 1.2% of uninvolved youth made a suicide attempt, compared with 5% for those who frequently bullied others verbally or socially; 6.5% for those who were frequent victims of verbal/social bullying; and 11.1% for those who were frequent bully-victims of verbal/social bullying [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. In Kowalski and Limber's paper, depression, anxiety, self-esteem, self-reported health problems, absences from school, leaving school because of illness, and grades were, with only one exception, significantly related to students' involvement in cyber-bullying others, being cyber-bullied, bullying others through traditional means, and being bullied through traditional means [[7]Kowalski R.M. Limber S.P. Psychological, physical, and academic correlates of cyberbullying and traditional bullying.J Adolesc Health. 2013; 53: S13-S20Abstract Full Text Full Text PDF PubMed Scopus (768) Google Scholar]. Those who witness bullying but are not directly involved are also at increased risk. Rivers and Noret [[18]Rivers I. Noret N. Potential suicide ideation and its association with observing bullying at school.J Adolesc Health. 2013; 53: S32-S36Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar] report that students who observed bullying behavior were significantly more likely than those uninvolved in bullying to report symptoms of interpersonal sensitivity (feelings of being hurt and feelings of inferiority) and greater helplessness. However, the papers in this issue also convey the complexity of the relationship between bullying and suicide-related behaviors. In Espelage and Holt's work [[17]Espelage D.L. Holt M.K. Suicidal ideation and school bullying experiences after controlling for depression and delinquency.J Adolesc Health. 2013; 53: S27-S31Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar], after controlling for delinquency and depression there was no increased risk of suicide-related behaviors for perpetrators; the increased risk did remain for victims. Klomek's [[19]Klomek A.B. Kleinman M. Altschuler E. et al. Suicidal adolescents' experiences with bullying perpetration and victimization during high school as risk factors for later depression and suicidality.J Adolesc Health. 2013; 53: S37-S42Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar] comparison of young people with bullying involvement and psychiatric symptoms (depression, suicidality, or substance use) at an initial screen to those with psychiatric symptoms but no bullying involvement found, at 2-year follow-up, that only perpetrators of bullying were significantly more likely to be functionally impaired than bullying-uninvolved students. In King's study of hospitalized suicidal youth, those who reported perpetrating bullying were more likely than uninvolved youth to have severe suicidal thoughts and psychosocial impairment, and to abuse substances. However, at 12-month follow-up, only the difference in psychosocial impairment remained. Interestingly, over the course of 1-year treatment for the suicidality, the rate of bullying perpetration declined [[20]King C.A. Horwitz A. Berona J. Jiang Q. Acutely suicidal adolescents who engage in bullying behavior: 1-year trajectories.J Adolesc Health. 2013; 53: S43-S50Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar]. In Karch's analysis of suicide fatalities among youth, bullying involvement was one of a myriad of factors precipitating a death by suicide. A quarter of young suicide victims had school problems, but only 12.4% of these school problems were attributed to bullying [[21]Karch D.L. Logan J. McDaniel D.D. et al. Precipitating circumstances of suicide among youth aged 10–17 years by sex: Data from the National Violent Death Reporting System, 16 States, 2005–2008.J Adolesc Health. 2013; 53: S51-S53Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar]. Other salient circumstances included depressed mood and/or other current mental health problems (37%); intimate partner problems (25%); history of suicide attempts (18%); and substance abuse problems (16%). Suicide attempts and substance use were risk factors that co-occurred with suicide ideation in Borowsky et al. as well [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. Across all groups (victims, perpetrators, and bully-victims) a history of self-harm within the prior year and greater emotional distress (feelings of sadness, hopelessness, worry, stress, or pressure) drastically increased risk for suicide. For victims and bully-victims, a history of sexual abuse, a mental health problem, or running away from home in the past year increased the likelihood of suicidal thinking or behavior [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. More than half of the youth who were bully-victims and who expressed suicidal ideation or reported making an attempt also witnessed family violence, had a history of physical abuse, smoked cigarettes, used marijuana, skipped school because of safety concerns, or carried a weapon at school. Youth who were involved in bullying and reported suicide-related thoughts or behaviors also had higher mean scores for distractibility/impulsivity and lower mean scores for parent connectedness, connectedness to other adults, perceived caring by teachers, perceived caring by friends, liking school, academic achievement, physical activity, perceived school safety, and perceived neighborhood safety [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. Across all three bullying-involved groups, parent connectedness (feeling like you can talk to mom/dad about problems; that mom/dad care about you) was protective for suicidal ideation and attempts. Other protective factors for victims included stronger connections to nonparental adults, stronger perceived caring by friends, and liking school. For bully-victims, greater perceived caring by friends was also protective [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. That there is a relationship between bullying and depression and that this relationship may help to explain the relationship between bullying and suicide is fairly consistent across papers. However, the direction of this relationship is unclear. Do youth who are bullied become depressed or are depressed youth more likely to be bullied? A study from the Netherlands suggests the answer may be “both.” Researchers found that victims of bullying had significantly higher chances of developing new psychosomatic and psychosocial problems over the course of a school year compared with children who were not bullied. However, children with preexisting depressive symptoms or anxiety were also significantly more likely to be newly victimized over the course of the school year [[11]Fekkes M. Pijpers F. Fredriks A.M. et al. Do bullied children get ill, or do ill children get bullied? A prospective cohort study on the relationship between bullying and health-related symptoms. Pediatrics. 2006; 117: 1568-1574Crossref PubMed Scopus (426) Google Scholar]. Despite the complexity of the relationship between bullying and suicide, there is no doubt that bullying involvement can have detrimental effects and prevention of bullying could improve health and mental health outcomes for many youth. The findings in these articles underscore the complexity of the relationship between bullying and suicide. A critical difference distinguishes an association between bullying and suicide from a causal relationship, with significant implications for prevention. Conveying that bullying alone causes suicide at best minimizes, and at worst ignores, the other factors that may contribute to death by suicide. This neglect may result in too narrow a focus of preventive action. We echo the call made by others for an integrated approach to preventing suicide and youth violence by focusing on shared risk and protective factors including individual coping skills, family and school social support, and supportive school environments [[22]Lubell K.M. Vetter J.B. Suicide and youth violence prevention: The promise of an integrated approach. Aggression and Violent Behavior. 2006; 11: 167-175Crossref Scopus (71) Google Scholar]. Strengthening social connectedness and ensuring access to supportive adults may pay dividends in impacting both bullying and suicide behaviors. Supportive home and school environments where young people feel connected are just one overlapping protective factor. Borowksy's findings regarding connection to parents, other adults, school, and friends reflect the need for multiple strategies that focus on both the school and home environments and that move beyond the individual skill-building level to foster supportive environments [[6]Borowsky I.W. Taliaferro L.A. McMorris B.J. Suicidal thinking and behavior among youth involved in verbal and social bullying: Risk and protective factors.J Adolesc Health. 2013; 53: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar]. The case for a supportive environment on bullying and suicide prevention is supported by Hatzenbuehler's work. In the paper contained in this special issue, he reports findings that lesbian and gay youths living in counties with fewer school districts with antibullying policies that specifically mentioned sexual orientation as a protected group were nearly two times more likely to have attempted suicide in the past year compared with those living in counties where more districts had these policies [[10]Hatzenbuehler M.L. Keyes K.M. Inclusive anti-bullying policies and reduced risk of suicide attempts in lesbian and gay youth.J Adolesc Health. 2013; 53: S21-S26Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar]. Williams and Guerra reported that youth who describe their school climate as being trusting, fair, and pleasant have lower involvement in verbal, physical, and Internet bullying perpetration [[23]Williams K.R. Guerra N.G. Prevalence and predictors of internet bullying.J Adolesc Health. 2007; 41: S14-S21Abstract Full Text Full Text PDF PubMed Scopus (669) Google Scholar]. As reflected in CDC's strategic direction on suicide [[24]Centers for Disease Control and Prevention (CDC). Connectedness as a strategic direction for the prevention of suicidal behavior. Available at: http://www.cdc.gov/violenceprevention/pdf/suicide_strategic_direction-one-pager-a.pdf. Google Scholar], approaches intended to build connections between youth and school and home environments, as well as communities, are essential to suicide prevention. Sources of Strength is a school-based suicide-prevention program that trains youth opinion leaders to change the norms and behaviors of their peers by conducting well-defined messaging activities with adult mentoring, as well as increasing perceptions of adult support for suicidal youths and the acceptability of seeking help M. et of the Sources of Strength suicide prevention program by leaders in high J Health. 2010; PubMed Scopus Google Scholar]. work also the of connections to support prevention. As an example, the youth suicide prevention found that who reported a stronger connection to youth in their program were as likely to suicidal youth. the research also that the bullying prevention are A of school bullying strategies that school approaches that included multiple and at of school more often reduced victimization and bullying than the that only included or social groups A review of school-based to Pediatr Adolesc Med. 2007; PubMed Scopus Google Scholar]. there is about the prevention of bullying and suicide, there is also do not studies over the past two have the of bullying prevention However, studies have in the States, these have not A review of school-based to Pediatr Adolesc Med. 2007; PubMed Scopus Google Scholar]. is evidence that youth violence prevention that for such as and also rates of bullying The impact of and on bullying and A Pediatr Adolesc Med. PubMed Scopus Google Scholar]. More work is to strategies that bullying from among youth in the In that depression is a significant risk for bullying and suicide as well as a of other behaviors. We need to to mental among young people and their and to do in and However, the and impact of bullying, it is to move while these strategies are being We can by and strategies that have at increasing protective factors and risk factors associated with both bullying and suicide. is not that bullying in is it that bullying occur in the in and health their focus beyond just to those who are involved in bullying or suicide-related behaviors, but also in strategies to bullying and suicidal behavior from in the
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