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Workers' health and productivity under occupational heat strain: a systematic review and meta-analysis.

Background: Occupational heat strain (ie, the effect of environmental heat stress on the body) directly threatens workers' ability to live healthy and productive lives. We estimated the effects of occupational heat strain on workers' health and productivity outcomes. Methods: Following PRISMA guidelines for this systematic review and meta-analysis, we searched PubMed and Embase from database inception to Feb 5, 2018, for relevant studies in any labour environment and at any level of occupational heat strain. No restrictions on language, workers' health status, or study design were applied. Occupational heat strain was defined using international health and safety guidelines and standards. We excluded studies that calculated effects using simulations or statistical models instead of actual measurements, and any grey literature. Risk of bias, data extraction, and sensitivity analysis were performed by two independent investigators. Six random-effects meta-analyses estimated the prevalence of occupational heat strain, kidney disease or acute kidney injury, productivity loss, core temperature, change in urine specific gravity, and odds of occupational heat strain occurring during or at the end of a work shift in heat stress conditions. The review protocol is available on PROSPERO, registration number CRD42017083271. Findings: Of 958 reports identified through our systematic search, 111 studies done in 30 countries, including 447 million workers from more than 40 different occupations, were eligible for analysis. Our meta-analyses showed that individuals working a single work shift under heat stress (defined as wet-bulb globe temperature beyond 22·0 or 24·8°C depending on work intensity) were 4·01 times (95% CI 2·45-6·58; nine studies with 11 582 workers) more likely to experience occupational heat strain than an individual working in thermoneutral conditions, while their core temperature was increased by 0·7°C (0·4-1·0; 17 studies with 1090 workers) and their urine specific gravity was increased by 14·5% (0·0031, 0·0014-0·0048; 14 studies with 691 workers). During or at the end of a work shift under heat stress, 35% (31-39; 33 studies with 13 088 workers) of workers experienced occupational heat strain, while 30% (21-39; 11 studies with 8076 workers) reported productivity losses. Finally, 15% (11-19; ten studies with 21 721 workers) of individuals who typically or frequently worked under heat stress (minimum of 6 h per day, 5 days per week, for 2 months of the year) experienced kidney disease or acute kidney injury. Overall, this analysis include a variety of populations, exposures, and occupations to comply with a wider adoption of evidence synthesis, but resulted in large heterogeneity in our meta-analyses. Grading of Recommendations, Assessment, Development and Evaluation analysis revealed moderate confidence for most results and very low confidence in two cases (average core temperature and change in urine specific gravity) due to studies being funded by industry. Interpretation: Occupational heat strain has important health and productivity outcomes and should be recognised as a public health problem. Concerted international action is needed to mitigate its effects in light of climate change and the anticipated rise in heat stress. Funding: EU Horizon 2020 research and innovation programme.

The Lancet. Planetary health · meta-analysis · 253 citationsread the source →

Populations and Interventions for Palliative and End-of-Life Care: A Systematic Review.

Importance: Evidence supports palliative care effectiveness. Given workforce constraints and the costs of new services, payers and providers need help to prioritize their investments. They need to know which patients to target, which personnel to hire, and which services best improve outcomes. Objective: To inform how payers and providers should identify patients with "advanced illness" and the specific interventions they should implement, we reviewed the evidence to identify (1) individuals appropriate for palliative care and (2) elements of health service interventions (personnel involved, use of multidisciplinary teams, and settings of care) effective in achieving better outcomes for patients, caregivers, and the healthcare system. Evidence review: Systematic searches of MEDLINE, EMBASE, PsycINFO, Web of Science, and Cochrane Database of Systematic Reviews databases (1/1/2001-1/8/2015). Results: Randomized controlled trials (124) met inclusion criteria. The majority of studies in cancer (49%, 38 of 77 studies) demonstrated statistically significant patient or caregiver outcomes (e.g., p < 0.05), as did those in congestive heart failure (CHF) (62%, 13 of 21), chronic obstructive pulmonary disease (COPD; 58%, 11 of 19), and dementia (60%, 15 of 25). Most prognostic criteria used clinicians' judgment (73%, 22 of 30). Most interventions included a nurse (70%, 69 of 98), and many were nurse-only (39%, 27 of 69). Social workers were well represented, and home-based approaches were common (56%, 70 of 124). Home interventions with visits were more effective than those without (64%, 28 of 44; vs. 46%, 12 of 26). Interventions improved communication and care planning (70%, 12 of 18), psychosocial health (36%, 12 of 33, for depressive symptoms; 41%, 9 of 22, for anxiety), and patient (40%, 8 of 20) and caregiver experiences (63%, 5 of 8). Many interventions reduced hospital use (65%, 11 of 17), but most other economic outcomes, including costs, were poorly characterized. Palliative care teams did not reliably lower healthcare costs (20%, 2 of 10). Conclusions: Palliative care improves cancer, CHF, COPD, and dementia outcomes. Effective models include nurses, social workers, and home-based components, and a focus on communication, psychosocial support, and the patient or caregiver experience. High-quality research on intervention costs and cost outcomes in palliative care is limited.

Journal of palliative medicine · systematic review · 135 citationsread the source →

Psychotherapy for depression in older veterans via telemedicine: a randomised, open-label, non-inferiority trial.

Background: Many older adults with major depression, particularly veterans, do not have access to evidence-based psychotherapy. Telemedicine could increase access to best-practice care for older adults facing barriers of mobility, stigma, and geographical isolation. We aimed to establish non-inferiority of behavioural activation therapy for major depression delivered via telemedicine to same-room care in largely male, older adult veterans. Methods: In this randomised, controlled, open-label, non-inferiority trial, we recruited veterans (aged ≥58 years) meeting DSM-IV criteria for major depressive disorder from the Ralph H Johnson Veterans Affairs Medical Center and four associated community outpatient-based clinics in the USA. We excluded actively psychotic or demented people, those with both suicidal ideation and clear intent, and those with substance dependence. The study coordinator randomly assigned participants (1:1; block size 2-6; stratified by race; computer-generated randomisation sequence by RGK) to eight sessions of behavioural activation for depression either via telemedicine or in the same room. The primary outcome was treatment response according to the Geriatric Depression Scale (GDS) and Beck Depression Inventory (BDI; defined as a 50% reduction in symptoms from baseline at 12 months), and Structured Clinical Interview for DSM-IV, clinician version (defined as no longer being diagnosed with major depressive disorder at 12 months follow-up), in the per-protocol population (those who completed at least four treatment sessions and for whom all outcome measurements were done). Those assessing outcomes were masked. The non-inferiority margin was 15%. This trial is registered with ClinicalTrials.gov, number NCT00324701. Findings: Between April 1, 2007, and July 31, 2011, we screened 780 patients, and the study coordinator randomly assigned participants to either telemedicine (120 [50%]) or same-room treatment (121 [50%]). We included 100 (83%) patients in the per-protocol analysis in the telemedicine group and 104 (86%) in the same-room group. Treatment response according to GDS did not differ significantly between the telemedicine (22 [22·45%, 90% CI 15·52-29·38] patients) and same-room (21 [20·39%, 90% CI 13·86-26·92]) groups, with an absolute difference of 2·06% (90% CI -7·46 to 11·58). Response according to BDI also did not differ significantly (telemedicine 19 [24·05%, 90% CI 16·14-31·96] patients; same room 19 [23·17%, 90% CI 15·51-30·83]), with an absolute difference of 0·88% (90% CI -10·13 to 11·89). Response on the Structured Clinical Interview for DSM-IV, clinician version, also did not differ significantly (39 [43·33%, 90% CI 34·74-51·93] patients in the telemedicine group and 46 [48·42%, 90% CI 39·99-56·85] in the same-room group), with a difference of -5·09% (-17·13 to 6·95; p=0·487). Results from the intention-to-treat population were similar. MEM analyses showed that no significant differences existed between treatment trajectories over time for BDI and GDS. The criteria for non-inferiority were met. We did not note any adverse events. Interpretation: Telemedicine-delivered psychotherapy for older adults with major depression is not inferior to same-room treatment. This finding shows that evidence-based psychotherapy can be delivered, without modification, via home-based telemedicine, and that this method can be used to overcome barriers to care associated with distance from and difficulty with attendance at in-person sessions in older adults. Funding: US Department of Veterans Affairs.

The lancet. Psychiatry · randomised controlled trial · 123 citationsread the source →

Mental health care for unaccompanied young refugees in Germany through a stepped care approach versus enhanced usual care: a cluster-randomised hybrid effectiveness-implementation trial.

Background: Unaccompanied young refugees are a vulnerable group with high rates of post-traumatic stress symptoms (PTSS). Stepped care approaches are recommended as a potential treatment framework, but research on the effectiveness of these models remains scarce. We aimed to compare a stepped care approach for unaccompanied young refugees with enhanced usual care under real-world conditions. Methods: In this cluster-randomised controlled type I hybrid implementation-effectiveness trial, we compared two active conditions, BETTER CARE and enhanced usual care, for unaccompanied young refugees in child and youth welfare service (CYWS) facilities across seven states in Germany. Eligibility criteria included age 12-20 years; arrival in Germany as unaccompanied minors; asylum application or intention; in CYWS facility care at baseline; and at least one traumatic event reported. Masking of participants was not possible due to each CYWS facility being randomly assigned to a specific treatment arm. Additionally, although study personnel were not masked to the condition, all data were self-reported and study personnel remained masked to data entry. BETTER CARE was a stepped care approach consisting of screening, prevention (via the Mein Weg [My Way] group intervention), and trauma-focused cognitive behavioural therapy (TF-CBT). Enhanced usual care included screening and a corresponding treatment recommendation. Clusters comprised one CYWS facility and were stratified and randomly assigned (1:1) using permuted blocks. Self-report questionnaires were used to assess PTSS, depressive symptoms, anxiety symptoms, and quality of life at baseline, 6 months, and 12 months. The primary outcome was a reduction in PTSS, analysed with the Child and Adolescent Trauma Screen (CATS-2) score in the intention-to-treat sample (all randomly assigned participants). The study was preregistered in the German Clinical Trials Register (DRKS00017453). Findings: The study was conducted between Oct 14, 2019, and July 27, 2023. 58 (11%) of 525 eligible facilities, including 627 unaccompanied young refugees originating from 40 countries, decided to participate and were randomly assigned. The mean age of the participants was 16·7 years (SD 1·3), with 569 (91%) identifying as male, 53 (8%) as female, and five (1%) as gender diverse. Participants reported a mean of six traumatic events (SD 3·3). 270 (43%) unaccompanied young refugees had clinically elevated levels of PTSS, and 357 (57%) were below the clinical threshold for PTSS (based on CATS-2 scores). 12 months after random assignment, there was a significant between-groups change over time effect size for PTSS in favour of BETTER CARE in the intention-to-treat sample (d=-0·17 [95% CI -0·34 to -0·004]). The dropout rate at 12 months was 38% (n=124) in BETTER CARE and 43% (n=131) in enhanced usual care. Service use and retention were low within the 12-month study period. Interpretation: This study shows the effectiveness of a stepped care model including screening, prevention, and evidence-based interventions for unaccompanied young refugees in a high-income country. The potential benefit of screening and structured care recommendations was highlighted further by improvements in the enhanced usual care condition. Dropout rates were high but similar to those in previous studies with young refugees. Future studies should address demand-side barriers to improve service use and retention. Funding: German Federal Ministry of Education and Research.

The Lancet. Global health · randomised controlled trial · 1 citationsread the source →

Relapse prevention interventions for smoking cessation.

Background: A number of treatments can help smokers make a successful quit attempt, but many initially successful quitters relapse over time. Several interventions have been proposed to help prevent relapse. Objectives: To assess whether specific interventions for relapse prevention reduce the proportion of recent quitters who return to smoking. Search methods: We searched the Cochrane Tobacco Addiction Group trials register, clinicaltrials.gov, and the ICTRP in May 2019 for studies mentioning relapse prevention or maintenance in their title, abstracts, or keywords. Selection criteria: Randomised or quasi-randomised controlled trials of relapse prevention interventions with a minimum follow-up of six months. We included smokers who quit on their own, were undergoing enforced abstinence, or were participating in treatment programmes. We included studies that compared relapse prevention interventions with a no intervention control, or that compared a cessation programme with additional relapse prevention components with a cessation programme alone. Data collection and analysis: We used standard methodological procedures expected by Cochrane. Main results: We included 81 studies (69,094 participants), five of which are new to this update. We judged 22 studies to be at high risk of bias, 53 to be at unclear risk of bias, and six studies to be at low risk of bias. Fifty studies included abstainers, and 30 studies helped people to quit and then tested treatments to prevent relapse. Twenty-eight studies focused on special populations who were abstinent because of pregnancy (19 studies), hospital admission (six studies), or military service (three studies). Most studies used behavioural interventions that tried to teach people skills to cope with the urge to smoke, or followed up with additional support. Some studies tested extended pharmacotherapy. We focused on results from those studies that randomised abstainers, as these are the best test of relapse prevention interventions. Of the 12 analyses we conducted in abstainers, three pharmacotherapy analyses showed benefits of the intervention: extended varenicline in assisted abstainers (2 studies, n = 1297, risk ratio (RR) 1.23, 95% confidence interval (CI) 1.08 to 1.41, I2 = 82%; moderate-certainty evidence), rimonabant in assisted abstainers (1 study, RR 1.29, 95% CI 1.08 to 1.55), and nicotine replacement therapy (NRT) in unaided abstainers (2 studies, n = 2261, RR 1.24, 95% Cl 1.04 to 1.47, I2 = 56%). The remainder of analyses of pharmacotherapies in abstainers had wide confidence intervals consistent with both no effect and a statistically significant effect in favour of the intervention. These included NRT in hospital inpatients (2 studies, n = 1078, RR 1.23, 95% CI 0.94 to 1.60, I2 = 0%), NRT in assisted abstainers (2 studies, n = 553, RR 1.04, 95% CI 0.77 to 1.40, I2 = 0%; low-certainty evidence), extended bupropion in assisted abstainers (6 studies, n = 1697, RR 1.15, 95% CI 0.98 to 1.35, I2 = 0%; moderate-certainty evidence), and bupropion plus NRT (2 studies, n = 243, RR 1.18, 95% CI 0.75 to 1.87, I2 = 66%; low-certainty evidence). Analyses of behavioural interventions in abstainers did not detect an effect. These included studies in abstinent pregnant and postpartum women at the end of pregnancy (8 studies, n = 1523, RR 1.05, 95% CI 0.99 to 1.11, I2 = 0%) and at postpartum follow-up (15 studies, n = 4606, RR 1.02, 95% CI 0.94 to 1.09, I2 = 3%), studies in hospital inpatients (5 studies, n = 1385, RR 1.10, 95% CI 0.82 to 1.47, I2 = 58%), and studies in assisted abstainers (11 studies, n = 5523, RR 0.98, 95% CI 0.87 to 1.11, I2 = 52%; moderate-certainty evidence) and unaided abstainers (5 studies, n = 3561, RR 1.06, 95% CI 0.96 to 1.16, I2 = 1%) from the general population. Authors' conclusions: Behavioural interventions that teach people to recognise situations that are high risk for relapse along with strategies to cope with them provided no worthwhile benefit in preventing relapse in assisted abstainers, although unexplained statistical heterogeneity means we are only moderately certain of this. In people who have successfully quit smoking using pharmacotherapy, there were mixed results regarding extending pharmacotherapy for longer than is standard. Extended treatment with varenicline helped to prevent relapse; evidence for the effect estimate was of moderate certainty, limited by unexplained statistical heterogeneity. Moderate-certainty evidence, limited by imprecision, did not detect a benefit from extended treatment with bupropion, though confidence intervals mean we could not rule out a clinically important benefit at this stage. Low-certainty evidence, limited by imprecision, did not show a benefit of extended treatment with nicotine replacement therapy in preventing relapse in assisted abstainers. More research is needed in this area, especially as the evidence for extended nicotine replacement therapy in unassisted abstainers did suggest a benefit.

The Cochrane database of systematic reviews · meta-analysis · 37 citationsread the source →

The Self-Directed Biological Transformation Initiative and Well-Being.

Objective: To examine the effects of a comprehensive residential mind-body program on well-being. Design: The Self-Directed Biological Transformation Initiative was a quasi-randomized trial comparing the effects of participation in a 6-day Ayurvedic system of medicine-based comprehensive residential program with a 6-day residential vacation at the same retreat location. Setting: Retreat setting. Participants: 69 healthy women (n = 58) and men (n = 11) (mean age ± standard deviation, 53.6 ± 12 years). Intervention: The Ayurvedic intervention addressed physical and emotional well-being through group meditation and yoga, massage, diet, adaptogenic herbs, lectures, and journaling. Outcome measures: A battery of standardized questionnaires. Results: Participants in the Ayurvedic program showed significant and sustained increases in ratings of spirituality (p < 0.01) and gratitude (p < 0.05) compared with the vacation group, which showed no change. The Ayurvedic participants also showed increased ratings for self-compassion (p < 0.01) as well as less anxiety at the 1-month follow-up (p < 0.05). Conclusions: Findings suggest that a short-term intensive program providing holistic instruction and experience in mind-body healing practices can lead to significant and sustained increases in perceived well-being and that relaxation alone is not enough to improve certain aspects of well-being.

Journal of alternative and complementary medicine (New York, N.Y.) · randomised controlled trial · 13 citationsread the source →

Acceptance and Commitment Therapy versus Cognitive Behavior Therapy for Children With Anxiety: Outcomes of a Randomized Controlled Trial.

Acceptance and Commitment Therapy (ACT) has a growing empirical base in the treatment of anxiety among adults and children with other concerns. This study reports on the main outcomes of a randomized controlled trial of ACT and traditional cognitive behavioral therapy (CBT) in children with a Diagnostic and Statistical Manual of Mental Disorders (4th ed.) anxiety disorder. Participants were 193 children from urban Sydney, Australia, who were block-randomized to a 10-week group-based program of ACT or CBT or a 10-week waitlist control (WLC). Completers included 157 children (ACT = 54, CBT = 57, WLC = 46; M = 11 years, SD = 2.76; 78% Caucasian, 58% female). Pretreatment, posttreatment, and 3 months posttreatment assessments included clinician/self/parent-reported measures of anxiety, quality of life (QOL; anxiety interference, psychosocial and physical health-related QOL), and acceptance/defusion outcomes. Completer and intention-to-treat analyses revealed that ACT and CBT were both superior to WLC across outcomes, reflecting statistically and clinically significant differences, with gains maintained at 3 months posttreatment. Both completer and intention-to-treat analyses found ACT and CBT to produce similar outcomes. There was some support for ACT having greater effect sizes for QOL outcomes but not for avoidance/fusion. Although this study does not suggest that ACT is equivalent to CBT or should be adopted in its place, it does provide evidence that ACT might be another empirically supported treatment option for anxious youth. Further research is needed to replicate these findings.

Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53 · randomised controlled trial · 42 citationsread the source →

Body composition and appetite: fat-free mass (but not fat mass or BMI) is positively associated with self-determined meal size and daily energy intake in humans.

The idea of body weight regulation implies that a biological mechanism exerts control over energy expenditure and food intake. This is a central tenet of energy homeostasis. However, the source and identity of the controlling mechanism have not been identified, although it is often presumed to be some long-acting signal related to body fat, such as leptin. Using a comprehensive experimental platform, we have investigated the relationship between biological and behavioural variables in two separate studies over a 12-week intervention period in obese adults (total n 92). All variables have been measured objectively and with a similar degree of scientific control and precision, including anthropometric factors, body composition, RMR and accumulative energy consumed at individual meals across the whole day. Results showed that meal size and daily energy intake (EI) were significantly correlated with fat-free mass (FFM, P values < 0·02-0·05) but not with fat mass (FM) or BMI (P values 0·11-0·45) (study 1, n 58). In study 2 (n 34), FFM (but not FM or BMI) predicted meal size and daily EI under two distinct dietary conditions (high-fat and low-fat). These data appear to indicate that, under these circumstances, some signal associated with lean mass (but not FM) exerts a determining effect over self-selected food consumption. This signal may be postulated to interact with a separate class of signals generated by FM. This finding may have implications for investigations of the molecular control of food intake and body weight and for the management of obesity.

The British journal of nutrition · randomised controlled trial · 151 citationsread the source →

Resident Burnout and Well-being in Otolaryngology and Other Surgical Specialties: Strategies for Change.

Objective: To perform a literature review on burnout prevalence, factors that affect burnout and well-being, and solutions to address burnout in otolaryngology-head and neck surgery (OTO-HNS) residents and residents in other surgical specialties. Data sources: Ovid Medline, Embase, and article reference lists. Review methods: A literature search was performed to identify articles on resident burnout, distress, wellness, well-being, and quality of life. Articles deemed outside the scope of the current work were excluded. Search was limited to the past 5 years. Conclusions: Moderate to high burnout has been reported in 35% to 86% of OTO-HNS residents. Among other surgical specialties, resident burnout ranges between 58% and 66% in plastics, 11% and 67% in neurosurgery, 38% and 68% in urology, and 31% and 56% in orthopedics. Highest burnout rates were seen in postgraduate year 2 residents. Factors significantly associated with burnout included hours worked (>80 h/wk), level of autonomy, exercise, and program support. Reported resident work hours have steadily increased: 8% of OTO-HNS residents in 2005 vs 26% in 2019 reported averaging >80 h/wk. Practical implications of resident burnout include decreased empathy, moral distress and injury, poor health, decreased quality of life, increased attrition, decreased desire to pursue fellowship, and increased likelihood of medical errors. Structured mentorship programs, wellness initiatives, and increased ancillary support have been associated with lower burnout rates and improvements in resident well-being across specialties. Implications for practice: Addressing burnout, which is prevalent in OTO-HNS residents, is critical to improving patient care and physician well-being. Surgical specialties can share strategies to effectively address resident burnout through institutional interventions, which can be essential quality improvement initiatives, to promote well-being.

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · review · 25 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 →

Cognitive and psychiatric symptom trajectories 2-3 years after hospital admission for COVID-19: a longitudinal, prospective cohort study in the UK.

Background: COVID-19 is known to be associated with increased risks of cognitive and psychiatric outcomes after the acute phase of disease. We aimed to assess whether these symptoms can emerge or persist more than 1 year after hospitalisation for COVID-19, to identify which early aspects of COVID-19 illness predict longer-term symptoms, and to establish how these symptoms relate to occupational functioning. Methods: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study of adults (aged ≥18 years) who were hospitalised with a clinical diagnosis of COVID-19 at participating National Health Service hospitals across the UK. In the C-Fog study, a subset of PHOSP-COVID participants who consented to be recontacted for other research were invited to complete a computerised cognitive assessment and clinical scales between 2 years and 3 years after hospital admission. Participants completed eight cognitive tasks, covering eight cognitive domains, from the Cognitron battery, in addition to the 9-item Patient Health Questionnaire for depression, the Generalised Anxiety Disorder 7-item scale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, and the 20-item Cognitive Change Index (CCI-20) questionnaire to assess subjective cognitive decline. We evaluated how the absolute risks of symptoms evolved between follow-ups at 6 months, 12 months, and 2-3 years, and whether symptoms at 2-3 years were predicted by earlier aspects of COVID-19 illness. Participants completed an occupation change questionnaire to establish whether their occupation or working status had changed and, if so, why. We assessed which symptoms at 2-3 years were associated with occupation change. People with lived experience were involved in the study. Findings: 2469 PHOSP-COVID participants were invited to participate in the C-Fog study, and 475 participants (191 [40·2%] females and 284 [59·8%] males; mean age 58·26 [SD 11·13] years) who were discharged from one of 83 hospitals provided data at the 2-3-year follow-up. Participants had worse cognitive scores than would be expected on the basis of their sociodemographic characteristics across all cognitive domains tested (average score 0·71 SD below the mean [IQR 0·16-1·04]; p<0·0001). Most participants reported at least mild depression (263 [74·5%] of 353), anxiety (189 [53·5%] of 353), fatigue (220 [62·3%] of 353), or subjective cognitive decline (184 [52·1%] of 353), and more than a fifth reported severe depression (79 [22·4%] of 353), fatigue (87 [24·6%] of 353), or subjective cognitive decline (88 [24·9%] of 353). Depression, anxiety, and fatigue were worse at 2-3 years than at 6 months or 12 months, with evidence of both worsening of existing symptoms and emergence of new symptoms. Symptoms at 2-3 years were not predicted by the severity of acute COVID-19 illness, but were strongly predicted by the degree of recovery at 6 months (explaining 35·0-48·8% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); by a biocognitive profile linking acutely raised D-dimer relative to C-reactive protein with subjective cognitive deficits at 6 months (explaining 7·0-17·2% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); and by anxiety, depression, fatigue, and subjective cognitive deficit at 6 months. Objective cognitive deficits at 2-3 years were not predicted by any of the factors tested, except for cognitive deficits at 6 months, explaining 10·6% of their variance. 95 of 353 participants (26·9% [95% CI 22·6-31·8]) reported occupational change, with poor health being the most common reason for this change. Occupation change was strongly and specifically associated with objective cognitive deficits (odds ratio [OR] 1·51 [95% CI 1·04-2·22] for every SD decrease in overall cognitive score) and subjective cognitive decline (OR 1·54 [1·21-1·98] for every point increase in CCI-20). Interpretation: Psychiatric and cognitive symptoms appear to increase over the first 2-3 years post-hospitalisation due to both worsening of symptoms already present at 6 months and emergence of new symptoms. New symptoms occur mostly in people with other symptoms already present at 6 months. Early identification and management of symptoms might therefore be an effective strategy to prevent later onset of a complex syndrome. Occupation change is common and associated mainly with objective and subjective cognitive deficits. Interventions to promote cognitive recovery or to prevent cognitive decline are therefore needed to limit the functional and economic impacts of COVID-19. Funding: National Institute for Health and Care Research Oxford Health Biomedical Research Centre, Wolfson Foundation, MQ Mental Health Research, MRC-UK Research and Innovation, and National Institute for Health and Care Research.

The lancet. Psychiatry · 46 citationsread the source →

Self-regulation mechanisms in health behavior change: a systematic meta-review of meta-analyses, 2006-2017.

Self-regulation is one primary mechanism in interventions for health behavior change and has been examined in numerous recent meta-analyses. This pre-registered meta-review (PROSPERO CRD42017074018) examined Mmeta-analyses of any intervention and health behavior/outcome were eligible if they quantitatively assessed self-regulation and appeared between January 2006 and August 2017. In total, 66 meta-analyses were ultimately eligible; 27% reported a protocol, 11% used GRADE; 58% focused on RCTs. Reviews satisfied only a moderate number of items on the AMSTAR 2 (M = 45.45%, SD = 29.57%). Only 6% of meta-analyses directly examined whether changes in self-regulation predicted the behavior change (i.e., self-efficacy and physical activity, l = 2; frequency of self-monitoring and goal attainment, l = 1; cognitive bias modification and addiction, l = 1). Meta-analyses more routinely assessed self-regulation by comparing the efficacy of intervention components (97%), such as those from behavior change taxonomies. Meta-analyses that focused on intervention components identified several as successful, including personalized feedback, goal setting, and self-monitoring; however, none were consistently successful in that each worked only for some health behaviors and with particular populations. Some components had inconclusive evidence, given that they were only examined in low- quality reviews. Future reviewers should utilize advanced methods to assess mechanisms, and study authors should report hypothesized mechanisms to facilitate synthesis.

Health psychology review · 112 citationsread the source →

The prevalence and risk factors of mental problems in medical students during COVID-19 pandemic: A systematic review and meta-analysis.

Background: This meta-analysis and systematic review aimed to evaluate the global prevalence and risk factors of mental problems (i.e., depression, anxiety, stress, sleep disorder, posttraumatic stress disorder (PTSD), burnout, psychological distress, and suicidal ideation) among medical students during the COVID-19 pandemic. Method: We searched PubMed, Embase, Web of Science, psycARTICLES, PsycINFO, CNKI, and Wan Fang for studies on the prevalence of mental problems among medical students from January 1, 2020, to April 1, 2022. The pooled prevalence was calculated by random-effect models. We performed a narrative review to identify the risk factors. Results: The meta-analysis included 201 studies (N = 198,000). The prevalence of depression (41 %, 95 % CI, 37-45 %,), anxiety (38 %,95 % CI, 34 %-42 %), stress (34 %, 95 % CI, 27 %-42 %), sleep disorder (52 %, 95 % CI, 44 %-60 %), psychological distress (58 %, 95 % CI, 51 %-65 %), PTSD (34 %, 95 % CI, 22 %-46 %), suicidal ideation (15 %, 95 % CI, 11 %-18 %) and burnout (38 %, 95 % CI, 25 %-50 %) was high. The major risk factors were being female, being junior or preclinical students, exposure to COVID-19, academic stress, psychiatric or physical disorders history, economic trouble, fear of education impairment, online learning trouble, fear of infection, loneliness, low physical activity, low social support, problematic internet or smartphone use, and young age. Limitations: Most studies were cross-sectional. Few studies provided a reasonable response rate, suggesting potential selection bias. Conclusions: The study demonstrated a high prevalence and risk factors for mental problems during COVID-19, calling for mental health services. Our findings are valuable for college and health authorities to identify high-risk students and provide targeted intervention.

Journal of affective disorders · meta-analysis · 154 citationsread the source →

Mindfulness, Compassion, and Self-Compassion Among Health Care Professionals: What's New? A Systematic Review.

Health care professionals (HCPs) are a population at risk for high levels of burnout and compassion fatigue. The aim of the present systematic review was to give an overview on recent literature about mindfulness and compassion characteristics of HCPs, while exploring the effectiveness of techniques, involving the two aspects, such as MBSR or mindfulness intervention and compassion fatigue-related programs. A search of databases, including PubMed and PsycINFO, was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and the methodological quality for this systematic review was appraised using AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews-2). The number of articles that met the inclusion criteria was 58 (4 RCTs, 24 studies with pre-post measurements, 12 cross-sectional studies, 11 cohort studies and 7 qualitative studies). MBSR intervention was effective at improving, and maintaining, mindfulness and self-compassion levels and to improve burnout, depression, anxiety, stress. The most frequently employed interventional strategies were mindfulness-related trainings that were effective at improving mindfulness and self-compassion, but not compassion fatigue, levels. Compassion-related interventions have been shown to improve self-compassion, mindfulness and interpersonal conflict levels. Mindfulness was effective at improving negative affect and compassion fatigue, while compassion satisfaction may be related to cultivation of positive affect. This systematic review summarized the evidence regarding mindfulness- and compassion-related qualities of HCPs as well as potential effects of MBSR, mindfulness-related and compassion-related interventions on professionals' psychological variables like mindfulness, self-compassion and quality of life. Combining structured mindfulness and compassion cultivation trainings may enhance the effects of interventions, limit the variability of intervention protocols and improve data comparability of future research.

Frontiers in psychology · systematic review · 129 citationsread the source →

Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies.

Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11-34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7-16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9-25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14-29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15-23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17-48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20-41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20-34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20-33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21-46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.

Molecular psychiatry · meta-analysis · 2420 citationsread the source →

Therapist-supported Internet cognitive behavioural therapy for anxiety disorders in adults.

Background: Cognitive behavioural therapy (CBT) is an evidence-based treatment for anxiety disorders. Many people have difficulty accessing treatment, due to a variety of obstacles. Researchers have therefore explored the possibility of using the Internet to deliver CBT; it is important to ensure the decision to promote such treatment is grounded in high quality evidence. Objectives: To assess the effects of therapist-supported Internet CBT (ICBT) on remission of anxiety disorder diagnosis and reduction of anxiety symptoms in adults as compared to waiting list control, unguided CBT, or face-to-face CBT. Effects of treatment on quality of life and patient satisfaction with the intervention were also assessed. Search methods: We searched the Cochrane Depression, Anxiety and Neurosis Review Group Specialised Register (CCDANCTR) to 16 March 2015. The CCDANCTR includes relevant randomised controlled trials from MEDLINE, EMBASE, PsycINFO and CENTRAL. We also searched online clinical trial registries and reference lists of included studies. We contacted authors to locate additional trials. Selection criteria: Each identified study was independently assessed for inclusion by two authors. To be included, studies had to be randomised controlled trials of therapist-supported ICBT compared to a waiting list, attention, information, or online discussion group; unguided CBT (that is, self-help); or face-to-face CBT. We included studies that treated adults with an anxiety disorder (panic disorder, agoraphobia, social phobia, post-traumatic stress disorder, acute stress disorder, generalized anxiety disorder, obsessive compulsive disorder, and specific phobia) defined according to the Diagnostic and Statistical Manual of Mental Disorders III, III-R, IV, IV-TR or the International Classification of Disesases 9 or 10. Data collection and analysis: Two authors independently assessed the risk of bias of included studies and judged overall study quality. We used data from intention-to-treat analyses wherever possible. We assessed treatment effect for the dichotomous outcome of clinically important improvement in anxiety using a risk ratio (RR) with 95% confidence interval (CI). For disorder-specific and general anxiety symptom measures and quality of life we assessed continuous scores using standardized mean differences (SMD). We examined statistical heterogeneity using the I(2) statistic. Main results: We screened 1736 citations and selected 38 studies (3214 participants) for inclusion. The studies examined social phobia (11 trials), panic disorder with or without agoraphobia (8 trials), generalized anxiety disorder (5 trials), post-traumatic stress disorder (2 trials), obsessive compulsive disorder (2 trials), and specific phobia (2 trials). Eight remaining studies included a range of anxiety disorder diagnoses. Studies were conducted in Sweden (18 trials), Australia (14 trials), Switzerland (3 trials), the Netherlands (2 trials), and the USA (1 trial) and investigated a variety of ICBT protocols. Three primary comparisons were identified, therapist-supported ICBT versus waiting list control, therapist-supported versus unguided ICBT, and therapist-supported ICBT versus face-to-face CBT.Low quality evidence from 11 studies (866 participants) contributed to a pooled risk ratio (RR) of 3.75 (95% CI 2.51 to 5.60; I(2) = 50%) for clinically important improvement in anxiety at post-treatment, favouring therapist-supported ICBT over a waiting list, attention, information, or online discussion group only. The SMD for disorder-specific symptoms at post-treatment (28 studies, 2147 participants; SMD -1.06, 95% CI -1.29 to -0.82; I(2) = 83%) and general anxiety symptoms at post-treatment (19 studies, 1496 participants; SMD -0.75, 95% CI -0.98 to -0.52; I(2) = 78%) favoured therapist-supported ICBT; the quality of the evidence for both outcomes was low. One study compared unguided CBT to therapist-supported ICBT for clinically important improvement in anxiety at post-treatment, showing no difference in outcome between treatments (54 participants; very low quality evidence). At post-treatment there were no clear differences between unguided CBT and therapist-supported ICBT for disorder-specific anxiety symptoms (5 studies, 312 participants; SMD -0.22, 95% CI -0.56 to 0.13; I(2) = 58%; very low quality evidence) or general anxiety symptoms (2 studies, 138 participants; SMD 0.28, 95% CI -2.21 to 2.78; I(2) = 0%; very low quality evidence).Compared to face-to-face CBT, therapist-supported ICBT showed no significant differences in clinically important improvement in anxiety at post-treatment (4 studies, 365 participants; RR 1.09, 95% CI 0.89 to 1.34; I(2) = 0%; low quality evidence). There were also no clear differences between face-to-face and therapist supported ICBT for disorder-specific anxiety symptoms at post-treatment (7 studies, 450 participants; SMD 0.06, 95% CI -0.25 to 0.37; I(2) = 60%; low quality evidence) or general anxiety symptoms at post-treatment (5 studies, 317 participants; SMD 0.17, 95% CI -0.35 to 0.69; I(2) = 78%; low quality evidence).Overall, risk of bias in included studies was low or unclear for most domains. However, due to the nature of psychosocial intervention trials, blinding of participants and personnel, and outcome assessment tended to have a high risk of bias. Heterogeneity across a number of the meta-analyses was substantial, some was explained by type of anxiety disorder or may be meta-analytic measurement artefact due to combining many assessment measures. Adverse events were rarely reported. Authors' conclusions: Therapist-supported ICBT appears to be an efficacious treatment for anxiety in adults. The evidence comparing therapist-supported ICBT to waiting list, attention, information, or online discussion group only control was low to moderate quality, the evidence comparing therapist-supported ICBT to unguided ICBT was very low quality, and comparisons of therapist-supported ICBT to face-to-face CBT were low quality. Further research is needed to better define and measure any potential harms resulting from treatment. These findings suggest that therapist-supported ICBT is more efficacious than a waiting list, attention, information, or online discussion group only control, and that there may not be a significant difference in outcome between unguided CBT and therapist-supported ICBT; however, this latter finding must be interpreted with caution due to imprecision. The evidence suggests that therapist-supported ICBT may not be significantly different from face-to-face CBT in reducing anxiety. Future research should explore heterogeneity among studies which is reducing the quality of the evidence body, involve equivalence trials comparing ICBT and face-to-face CBT, examine the importance of the role of the therapist in ICBT, and include effectiveness trials of ICBT in real-world settings. A timely update to this review is needed given the fast pace of this area of research.

The Cochrane database of systematic reviews · meta-analysis · 158 citationsread the source →

Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.

Background: Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19. Methods: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I2 statistics, and assessment of study quality. Findings: 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27·9%; 95% CI 20·5-36·0] of 129 patients), depressed mood (42 [32·6%; 24·7-40·9] of 129), anxiety (46 [35·7%; 27·6-44·2] of 129), impaired memory (44 [34·1%; 26·2-42·5] of 129), and insomnia (54 [41·9%; 22·5-50·5] of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10·5%; 95% CI 7·5-14·1] of 332 patients), insomnia (34 [12·1%; 8·6-16·3] of 280), anxiety (21 [12·3%; 7·7-17·7] of 171), irritability (28 [12·8%; 8·7-17·6] of 218), memory impairment (44 [18·9%; 14·1-24·2] of 233), fatigue (61 [19·3%; 15·1-23·9] of 316), and in one study traumatic memories (55 [30·4%; 23·9-37·3] of 181) and sleep disorder (14 [100·0%; 88·0-100·0] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7-42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1-18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1-19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1-84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality. Interpretation: If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term. Funding: Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.

The lancet. Psychiatry · meta-analysis · 1531 citationsread the source →

Adverse childhood experiences and related outcomes among adults experiencing homelessness: a systematic review and meta-analysis.

Background: Adverse childhood experiences (ACEs) are strong risk factors for homelessness and poor health and functioning. We aimed to evaluate the lifetime prevalence of ACEs and their associations with health-related and functioning-related outcomes among homeless adults. Methods: In this systematic review and meta-analysis, we searched from database inception to Nov 11, 2020, for original and peer-reviewed studies in English that documented lifetime prevalence of ACEs or associations between ACEs and health-related or functioning-related outcomes. We selected studies if they included a definable group of homeless adults and measured at least four ACE categories. We calculated pooled estimates of lifetime prevalence of one or more ACEs and four or more ACEs with random-effects models. We used the leave-one-out method in sensitivity analyses and studied meta-regressions to explore potential moderators of ACE prevalence. We also did a narrative summary of associations between ACEs and health-related and functioning-related outcomes, as there were too few studies on each outcome for quantitative meta-analysis. This study is registered with PROSPERO, CRD42020218741. Findings: We identified 2129 studies through systematic search, of which 29 studies (16 942 individuals) were included in the systematic review, 20 studies (10 034 individuals) were included in the meta-analysis for one or more ACEs, and 15 studies (5693 individuals) were included in the meta-analysis for four or more ACEs. Studies included samples of adults experiencing homelessness in the USA, Canada, and the UK; participants in the included studies were predominantly male (65·2%) and mean ages ranged between 18·3 and 58·1 years, but many studies did not report race, ethnicity, and sexual and gender minority data. Lifetime prevalence of one or more ACEs among homeless adults was 89·8% (95% CI 83·7-93·7) and the lifetime prevalence of four or more ACEs was 53·9% (45·9-61·7). Considerable heterogeneity was identified in both meta-analyses (I2>95%). Of the potential moderators analysed, the ACE measurement tool significantly moderated the estimated lifetime prevalence of one or more ACEs and four or more ACEs, and age also significantly moderated the estimated lifetime prevalence of four or more ACEs. In the narrative synthesis, ACEs were consistently positively associated with high suicidality (two studies), suicide attempt (three studies), major depressive disorder (two studies), substance misuse (two studies), and adult victimisation (two studies). Interpretation: The lifetime prevalence of ACEs is substantially higher among homeless adults than among the general population, and ACE exposure might be associated with prevalence of mental illness, substance misuse, and victimisation. Policy efforts and evidence-based interventions are urgently needed to prevent ACEs and address associated poor outcomes among this population. Funding: Rhodes Trust and Canadian Institutes of Health Research.

The Lancet. Public health · meta-analysis · 70 citationsread the source →

Efficacy of psychological interventions for mental health and pregnancy rates among individuals with infertility: a systematic review and meta-analysis.

Background: Depression and anxiety are highly prevalent among individuals struggling with infertility. Thus, numerous psychological interventions have been adapted to infertility, with the aim of relieving distress as well as increasing pregnancy rates. Objective and rationale: This systematic review and meta-analysis aimed to identify all randomized controlled trials (RCTs) evaluating the effect of psychological interventions on infertility-related distress and pregnancy rates among individuals and/or couples with infertility and to analyse their overall effect. It also sought to examine potential treatment moderators, including intervention length, format and therapeutic approach. Search methods: An electronic search of 11 databases, including MEDLINE, EMBASE, PsycINFO and Cochrane Central Register of Controlled Trials, was performed for studies published until January 2022. The inclusion criteria were RCTs conducted on humans and published in English. Psychological outcomes of interest included anxiety, depression, infertility-related distress, wellbeing and marital satisfaction. The Cochrane Risk of Bias tool was used to assess study quality, and the Grading of Recommendations Assessment, Development and Evaluation was used to assess the overall quality of the research evidence. Outcomes: There were 58 RCTs in total, including 54 which included psychological outcomes and 21 which assessed pregnancy rates. Studies originated from all regions of the world, but nearly half of the studies were from the Middle East. Although a beneficial effect on combined psychological outcomes was found (Hedge's g = 0.82, P < 0.0001), it was moderated by region (P < 0.00001) such that studies from the Middle East exhibited large effects (g = 1.40, P < 0.0001), while the effects were small among studies conducted elsewhere (g = 0.23, P < 0.0001). Statistically adjusting for study region in a meta-regression, neither intervention length, therapeutic approach, therapy format, nor participant gender (P > 0.05) moderated the effect of treatment. A beneficial treatment effect on pregnancy (RR (95% CI) = 1.25 (1.07-1.47), P = 0.005) was not moderated by region, treatment length, approach or format (P > 0.05). Largely due to the lack of high quality RCTs, the quality of the available evidence was rated as low to moderate. Wider implications: This is the first meta-analysis of RCTs testing the effect of psychological interventions on infertility-related distress and pregnancy rates. These findings suggest that in most regions of the world, psychological interventions are associated with small reductions in distress and modest effects on conception, suggesting the need for more effective interventions. These findings must be considered in light of the fact that the majority of the included RCTs were deemed to be at high risk of bias. Rigorously conducted trials are needed.

Human reproduction update · meta-analysis · 42 citationsread the source →

Impact of the Baby-friendly Hospital Initiative on breastfeeding and child health outcomes: a systematic review.

The Baby-friendly Hospital Initiative (BFHI) is a key component of the World Health Organization/United Nations Children's Fund Global Strategy for Infant and Young Child Feeding. The primary aim of this narrative systematic review was to examine the impact of BFHI implementation on breastfeeding and child health outcomes worldwide and in the United States. Experimental, quasi-experimental and observational studies were considered eligible for this review if they assessed breastfeeding outcomes and/or infant health outcomes for healthy, term infants born in a hospital or birthing center with full or partial implementation of BFHI steps. Of the 58 reports included in the systematic review, nine of them were published based on three randomized controlled trials, 19 followed quasi-experimental designs, 11 were prospective and 19 were cross-sectional or retrospective. Studies were conducted in 19 different countries located in South America, North America, Western Europe, Eastern Europe, South Asia, Eurasia and Sub-Saharan Africa. Adherence to the BFHI Ten Steps has a positive impact on short-term, medium-term and long-term breastfeeding (BF) outcomes. There is a dose-response relationship between the number of BFHI steps women are exposed to and the likelihood of improved BF outcomes (early BF initiation, exclusive breastfeeding (EBF) at hospital discharge, any BF and EBF duration). Community support (step 10) appears to be essential for sustaining breastfeeding impacts of BFHI in the longer term.

Maternal & child nutrition · systematic review · 383 citationsread the source →

School Closures During Social Lockdown and Mental Health, Health Behaviors, and Well-being Among Children and Adolescents During the First COVID-19 Wave: A Systematic Review.

Importance: School closures as part of broader social lockdown measures during the COVID-19 pandemic may be associated with the health and well-being of children and adolescents. Objective: To review published reports on the association of school closures during broader social lockdown with mental health, health behaviors, and well-being in children and adolescents aged 0 to 19 years, excluding associations with transmission of infection. Evidence review: Eleven databases were searched from inception to September 2020, and machine learning was applied for screening articles. A total of 16 817 records were screened, 151 were reviewed in full text, and 36 studies were included. Quality assessment was tailored to study type. A narrative synthesis of results was undertaken because data did not allow meta-analysis. Findings: A total of 36 studies from 11 countries were identified, involving a total of 79 781 children and adolescents and 18 028 parents, which occurred during the first wave of the COVID-19 pandemic (February to July 2020). All evaluated school closure as part of broader social lockdown during the first COVID-19 wave, and the duration of school closure ranged from 1 week to 3 months. Of those, 9 (25%) were longitudinal pre-post studies, 5 (14%) were cohort, 21 (58%) were cross-sectional, and 1 (3%) was a modeling study. Thirteen studies (36%) were high quality, 17 (47%) were medium quality, and 6 (17%) were low quality. Twenty-three studies (64%) were published, 8 (22%) were online reports, and 5 (14%) were preprints. Twenty-five studies (69%) concerning mental health identified associations across emotional, behavioral, and restlessness/inattention problems; 18% to 60% of children and adolescents scored above risk thresholds for distress, particularly anxiety and depressive symptoms, and 2 studies reported no significant association with suicide. Three studies reported that child protection referrals were lower than expected number of referrals originating in schools. Three studies suggested higher screen time usage, 2 studies reported greater social media use, and 6 studies reported lower physical activity. Studies on sleep (10 studies) and diet (5 studies) provided inconclusive evidence on harms. Conclusions and relevance: In this narrative synthesis of reports from the first wave of the COVID-19 pandemic, studies of short-term school closures as part of social lockdown measures reported adverse mental health symptoms and health behaviors among children and adolescents. Associations between school closure and health outcomes and behaviors could not be separated from broader lockdown measures.

JAMA pediatrics · systematic review · 426 citationsread the source →

Frenotomy for tongue-tie in newborn infants.

Background: Tongue-tie, or ankyloglossia, is a condition whereby the lingual frenulum attaches near the tip of the tongue and may be short, tight and thick. Tongue-tie is present in 4% to 11% of newborns. Tongue-tie has been cited as a cause of poor breastfeeding and maternal nipple pain. Frenotomy, which is commonly performed, may correct the restriction to tongue movement and allow more effective breastfeeding with less maternal nipple pain. Objectives: To determine whether frenotomy is safe and effective in improving ability to feed orally among infants younger than three months of age with tongue-tie (and problems feeding).Also, to perform subgroup analysis to determine the following.• Severity of tongue-tie before frenotomy as measured by a validated tool (e.g. Hazelbaker Assessment Tool for Lingual Frenulum Function (ATLFF) scores < 11; scores ≥ 11) (Hazelbaker 1993).• Gestational age at birth (< 37 weeks' gestation; 37 weeks' gestation and above).• Method of feeding (breast or bottle).• Age at frenotomy (≤ 10 days of age; > 10 days to three months of age).• Severity of feeding difficulty (infants with feeding difficulty affecting weight gain (as assessed by infant's not regaining birth weight by day 14 or falling off centiles); infants with symptomatic feeding difficulty but thriving (greater than birth weight by day 14 and tracking centiles). Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and CINAHL up to January 2017, as well as previous reviews including cross-references, expert informants and journal handsearching. We searched clinical trials databases for ongoing and recently completed trials. We applied no language restrictions. Selection criteria: Randomised, quasi-randomised controlled trials or cluster-randomised trials that compared frenotomy versus no frenotomy or frenotomy versus sham procedure in newborn infants. Data collection and analysis: Review authors extracted from the reports of clinical trials data regarding clinical outcomes including infant feeding, maternal nipple pain, duration of breastfeeding, cessation of breastfeeding, infant pain, excessive bleeding, infection at the site of frenotomy, ulceration at the site of frenotomy, damage to the tongue and/or submandibular ducts and recurrence of tongue-tie. We used the GRADE approach to assess the quality of evidence. Main results: Five randomised trials met our inclusion criteria (n = 302). Three studies objectively measured infant breastfeeding using standardised assessment tools. Pooled analysis of two studies (n = 155) showed no change on a 10-point feeding scale following frenotomy (mean difference (MD) -0.1, 95% confidence interval (CI) -0.6 to 0.5 units on a 10-point feeding scale). A third study (n = 58) showed objective improvement on a 12-point feeding scale (MD 3.5, 95% CI 3.1 to 4.0 units of a 12-point feeding scale). Four studies objectively assessed maternal pain. Pooled analysis of three studies (n = 212) based on a 10-point pain scale showed a reduction in maternal pain scores following frenotomy (MD -0.7, 95% CI -1.4 to -0.1 units on a 10-point pain scale). A fourth study (n = 58) also showed a reduction in pain scores on a 50-point pain scale (MD -8.6, 95% CI -9.4 to -7.8 units on a 50-point pain scale). All studies reported no adverse effects following frenotomy. These studies had serious methodological shortcomings. They included small sample sizes, and only two studies blinded both mothers and assessors; one did not attempt blinding for mothers nor for assessors. All studies offered frenotomy to controls, and most controls underwent the procedure, suggesting lack of equipoise. No study was able to report whether frenotomy led to long-term successful breastfeeding. Authors' conclusions: Frenotomy reduced breastfeeding mothers' nipple pain in the short term. Investigators did not find a consistent positive effect on infant breastfeeding. Researchers reported no serious complications, but the total number of infants studied was small. The small number of trials along with methodological shortcomings limits the certainty of these findings. Further randomised controlled trials of high methodological quality are necessary to determine the effects of frenotomy.

The Cochrane database of systematic reviews · systematic review · 61 citationsread the source →

The effects of improving sleep on mental health (OASIS): a randomised controlled trial with mediation analysis.

Background: Sleep difficulties might be a contributory causal factor in the occurrence of mental health problems. If this is true, improving sleep should benefit psychological health. We aimed to determine whether treating insomnia leads to a reduction in paranoia and hallucinations. Methods: We did this single-blind, randomised controlled trial (OASIS) at 26 UK universities. University students with insomnia were randomly assigned (1:1) with simple randomisation to receive digital cognitive behavioural therapy (CBT) for insomnia or usual care, and the research team were masked to the treatment. Online assessments took place at weeks 0, 3, 10 (end of therapy), and 22. The primary outcome measures were for insomnia, paranoia, and hallucinatory experiences. We did intention-to-treat analyses. The trial is registered with the ISRCTN registry, number ISRCTN61272251. Findings: Between March 5, 2015, and Feb 17, 2016, we randomly assigned 3755 participants to receive digital CBT for insomnia (n=1891) or usual practice (n=1864). Compared with usual practice, the sleep intervention at 10 weeks reduced insomnia (adjusted difference 4·78, 95% CI 4·29 to 5·26, Cohen's d=1·11; p<0·0001), paranoia (-2·22, -2·98 to -1·45, Cohen's d=0·19; p<0·0001), and hallucinations (-1·58, -1·98 to -1·18, Cohen's d=0·24; p<0·0001). Insomnia was a mediator of change in paranoia and hallucinations. No adverse events were reported. Interpretation: To our knowledge, this is the largest randomised controlled trial of a psychological intervention for a mental health problem. It provides strong evidence that insomnia is a causal factor in the occurrence of psychotic experiences and other mental health problems. Whether the results generalise beyond a student population requires testing. The treatment of disrupted sleep might require a higher priority in mental health provision. Funding: Wellcome Trust.

The lancet. Psychiatry · randomised controlled trial · 460 citationsread the source →

Clinical effectiveness and acceptability of structured group psychoeducation versus optimised unstructured peer support for patients with remitted bipolar disorder (PARADES): a pragmatic, multicentre, observer-blind, randomised controlled superiority trial.

Background: Group psychoeducation is a low-cost National Institute for Health and Care Excellence-recommended treatment for bipolar disorder. However, the clinical effectiveness and acceptability of this intervention are unclear compared with unstructured peer support matched for delivery and aim of treatment, and for previous bipolar history. We aimed to assess the clinical effectiveness and acceptability of structured group psychoeducation versus optimised unstructured peer support for patients with remitted bipolar disorder. Methods: We did this pragmatic, multicentre, parallel-group, observer-blind, randomised controlled superiority trial at eight community sites in two regions in England. Participants aged 18 years or older with bipolar disorder and no episode in the preceding 4 weeks were recruited via self-referral or secondary care referral. Participants were individually randomly assigned (1:1), via a computer-generated stochastic allocation sequence, to attend 21 2-h weekly sessions of either structured group psychoeducation or optimised unstructured peer support. Randomisation was minimised by number of previous episodes (one to seven, eight to 19, or ≥20) and stratified by clinical site. Outcome assessors were masked to group allocation. The primary outcome was time from randomisation to next bipolar episode, with planned moderator analysis of number of previous bipolar episodes and qualitative interview of participant experience. We did analysis by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN62761948. Findings: Between Sept 28, 2009, and Jan 9, 2012, we randomly assigned 304 participants to receive psychoeducation (n=153) or peer support (n=151); all (100%) participants had complete primary outcome data. Attendance at psychoeducation groups was higher than at peer-support groups (median 14 sessions [IQR three to 18] vs nine sessions [two to 17]; p=0·026). At 96 weeks, 89 (58%) participants in the psychoeducation group had experienced a next bipolar episode compared with 98 (65%) participants in the peer-support group; time to next bipolar episode did not differ between groups (hazard ratio [HR] 0·83, 95% CI 0·62-1·11; p=0·217). Planned moderator analysis showed that psychoeducation was most beneficial in participants with few (one to seven) previous bipolar episodes (χ2; HR 0·28, 95% CI 0·12-0·68; p=0·034). Four (1%) participants (one in the psychoeducation group and three in the peer-support group) died during follow-up; these deaths were deemed unrelated to the study interventions or procedures. Interpretation: Structured group psychoeducation was no more clinically effective than similarly intensive unstructured peer support, but was more acceptable and improved outcome in participants with fewer previous bipolar episodes. Optimum provision of structured psychological interventions, such as group psychoeducation, early in the course of bipolar disorder might have important benefits on the course of illness, and merits further research. Funding: National Institute for Health Research.

The lancet. Psychiatry · randomised controlled trial · 42 citationsread the source →

The EMPOWER blended digital intervention for relapse prevention in schizophrenia: a feasibility cluster randomised controlled trial in Scotland and Australia.

Background: Early warning signs monitoring by service users with schizophrenia has shown promise in preventing relapse but the quality of evidence is low. We aimed to establish the feasibility of undertaking a definitive randomised controlled trial to determine the effectiveness of a blended digital intervention for relapse prevention in schizophrenia. Methods: This multicentre, feasibility, cluster randomised controlled trial aimed to compare Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) with treatment as usual in community mental health services (CMHS) in Glasgow and Melbourne. CMHS were the unit of randomisation, selected on the basis of those that probably had five or more care coordinators willing to participate. Participants were eligible if they were older than 16 years, had a schizophrenia or related diagnosis confirmed via case records, were able to provide informed consent, had contact with CMHS, and had had a relapse within the previous 2 years. Participants were randomised within stratified clusters to EMPOWER or to continue their usual approach to care. EMPOWER blended a smartphone for active monitoring of early warning signs with peer support to promote self-management and clinical triage to promote access to relapse prevention. Main outcomes were feasibility, acceptability, usability, and safety, which was assessed through face-to-face interviews. App usage was assessed via the smartphone and self-report. Primary end point was 12 months. Participants, research assistants and other team members involved in delivering the intervention were not masked to treatment conditions. Assessment of relapse was done by an independent adjudication panel masked to randomisation group. The study is registered at ISRCTN (99559262). Findings: We identified and randomised eight CMHS (six in Glasgow and two in Melbourne) comprising 47 care coordinators. We recruited 86 service users between Jan 19 and Aug 8, 2018; 73 were randomised (42 [58%] to EMPOWER and 31 [42%] to treatment as usual). There were 37 (51%) men and 36 (49%) women. At 12 months, main outcomes were collected for 32 (76%) of service users in the EMPOWER group and 30 (97%) of service users in the treatment as usual group. Of those randomised to EMPOWER, 30 (71%) met our a priori criterion of more than 33% adherence to daily monitoring that assumed feasibility. Median time to discontinuation of these participants was 31·5 weeks (SD 14·5). There were 29 adverse events in the EMPOWER group and 25 adverse events in the treatment as usual group. There were 13 app-related adverse events, affecting 11 people, one of which was serious. Fear of relapse was lower in the EMPOWER group than in the treatment as usual group at 12 months (mean difference -7·53 (95% CI -14·45 to 0·60; Cohen's d -0·53). Interpretation: A trial of digital technology to monitor early warning signs blended with peer support and clinical triage to detect and prevent relapse appears to be feasible, safe, and acceptable. A further main trial is merited. Funding: UK National Institute for Health Research Health Technology Assessment programme and the Australian National Health and Medical Research Council.

The lancet. Psychiatry · randomised controlled trial · 50 citationsread the source →

Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial.

Importance: Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression. Objective: To investigate the effect of psilocybin therapy in patients with MDD. Design, setting, and participants: This randomized, waiting list-controlled clinical trial was conducted at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, Maryland. Adults aged 21 to 75 years with an MDD diagnosis, not currently using antidepressant medications, and without histories of psychotic disorder, serious suicide attempt, or hospitalization were eligible to participate. Enrollment occurred between August 2017 and April 2019, and the 4-week primary outcome assessments were completed in July 2019. A total of 27 participants were randomized to an immediate treatment condition group (n = 15) or delayed treatment condition group (waiting list control condition; n = 12). Data analysis was conducted from July 1, 2019, to July 31, 2020, and included participants who completed the intervention (evaluable population). Interventions: Two psilocybin sessions (session 1: 20 mg/70 kg; session 2: 30 mg/70 kg) were given (administered in opaque gelatin capsules with approximately 100 mL of water) in the context of supportive psychotherapy (approximately 11 hours). Participants were randomized to begin treatment immediately or after an 8-week delay. Main outcomes and measures: The primary outcome, depression severity was assessed with the GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at baseline (score of ≥17 required for enrollment) and weeks 5 and 8 after enrollment for the delayed treatment group, which corresponded to weeks 1 and 4 after the intervention for the immediate treatment group. Secondary outcomes included the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR). Results: Of the randomized participants, 24 of 27 (89%) completed the intervention and the week 1 and week 4 postsession assessments. This population had a mean (SD) age of 39.8 (12.2) years, was composed of 16 women (67%), and had a mean (SD) baseline GRID-HAMD score of 22.8 (3.9). The mean (SD) GRID-HAMD scores at weeks 1 and 4 (8.0 [7.1] and 8.5 [5.7]) in the immediate treatment group were statistically significantly lower than the scores at the comparable time points of weeks 5 and 8 (23.8 [5.4] and 23.5 [6.0]) in the delayed treatment group. The effect sizes were large at week 5 (Cohen d = 2.5; 95% CI, 1.4-3.5; P < .001) and week 8 (Cohen d = 2.6; 95% CI, 1.5-3.7; P < .001). The QIDS-SR documented a rapid decrease in mean (SD) depression score from baseline to day 1 after session 1 (16.7 [3.5] vs 6.3 [4.4]; Cohen d = 2.6; 95% CI, 1.8-3.5; P < .001), which remained statistically significantly reduced through the week 4 follow-up (6.0 [5.7]; Cohen d = 2.3; 95% CI, 1.5-3.0; P < .001). In the overall sample, 17 participants (71%) at week 1 and 17 (71%) at week 4 had a clinically significant response to the intervention (≥50% reduction in GRID-HAMD score), and 14 participants (58%) at week 1 and 13 participants (54%) at week 4 were in remission (≤7 GRID-HAMD score). Conclusions and relevance: Findings suggest that psilocybin with therapy is efficacious in treating MDD, thus extending the results of previous studies of this intervention in patients with cancer and depression and of a nonrandomized study in patients with treatment-resistant depression. Trial registration: ClinicalTrials.gov Identifier: NCT03181529.

JAMA psychiatry · randomised controlled trial · 900 citationsread the source →

Smoking cessation for people with severe mental illness (SCIMITAR+): a pragmatic randomised controlled trial.

Background: People with severe mental illnesses such as schizophrenia are three times more likely to smoke than the wider population, contributing to widening health inequalities. Smoking remains the largest modifiable risk factor for this health inequality, but people with severe mental illness have not historically engaged with smoking cessation services. We aimed to test the effectiveness of a combined behavioural and pharmacological smoking cessation intervention targeted specifically at people with severe mental illness. Methods: In the smoking cessation intervention for severe mental illness (SCIMITAR+) trial, a pragmatic, randomised controlled study, we recruited heavy smokers with bipolar disorder or schizophrenia from 16 primary care and 21 community-based mental health sites in the UK. Participants were eligible if they were aged 18 years or older, and smoked at least five cigarettes per day. Exclusion criteria included substantial comorbid drug or alcohol problems and people who lacked capacity to consent at the time of recruitment. Using computer-generated random numbers, participants were randomly assigned (1:1) to a bespoke smoking cessation intervention or to usual care. Participants, mental health specialists, and primary care physicians were unmasked to assignment. The bespoke smoking cessation intervention consisted of behavioural support from a mental health smoking cessation practitioner and pharmacological aids for smoking cessation, with adaptations for people with severe mental illness-such as, extended pre-quit sessions, cut down to quit, and home visits. Access to pharmacotherapy was via primary care after discussion with the smoking cessation specialist. Under usual care participants were offered access to local smoking cessation services not specifically designed for people with severe mental illnesses. The primary endpoint was smoking cessation at 12 months ascertained via carbon monoxide measurements below 10 parts per million and self-reported cessation for the past 7 days. Secondary endpoints were biologically verified smoking cessation at 6 months; number of cigarettes smoked per day, Fagerström Test for Nicotine Dependence (FTND) and Motivation to Quit (MTQ) questionnaire; general and mental health functioning determined via the Patient Health Questionnaire-9 (PHQ-9), the Generalised Anxiety Disorder-7 (GAD-7) questionnaire, and 12-Item Short Form Health Survey (SF-12); and body-mass index (BMI). This trial was registerd with the ISRCTN registry, number ISRCTN72955454, and is complete. Findings: Between Oct 7, 2015, and Dec 16, 2016, 526 eligible patients were randomly assigned to the bespoke smoking cessation intervention (n=265) or usual care (n=261). 309 (59%) participants were male, median age was 47·2 years (IQR 36·3-54·5), with high nicotine dependence (mean 24 cigarettes per day [SD 13·2]), and the most common severe mental disorders were schizophrenia or other psychotic illness (n=343 [65%]), bipolar disorder (n=115 [22%]), and schizoaffective disorder (n=66 [13%]). 234 (88%) of intervention participants engaged with the treatment programme and attended 6·4 (SD 3·5) quit smoking sessions, with an average duration of 39 min (SD 17; median 35 min, range 5-120). Verified quit data at 12 months were available for 219 (84%) of 261 usual care and 223 (84%) of 265 intervention participants. The proportion of participants who had quit at 12 months was higher in the intervention group than in the usual care group, but non-significantly (34 [15%] of 223 [13% of those assigned to group] vs 22 [10%] of 219 [8% of those assigned to group], risk difference 5·2%, 95% CI -1·0 to 11·4; odds ratio [OR] 1·6, 95% CI 0·9 to 2·9; p=0·10). The proportion of participants who quit at 6 months was significantly higher in the intervention group than in the usual care group (32 [14%] of 226 vs 14 [6%] of 217; risk difference 7·7%, 95% CI 2·1 to 13·3; OR 2·4, 95% CI 1·2 to 4·6; p=0·010). The incidence rate ratio for number of cigarettes smoked per day at 6 months was 0·90 (95% CI 0·80 to 1·01; p=0·079), and at 12 months was 1·00 (0·89 to 1·13; p=0·95). At both 6 months and 12 months, the intervention group was non-significantly favoured in the FTND (adjusted mean difference 6 months -0·18, 95% CI -0·53 to 0·17, p=0·32; and 12 months -0·01, -0·39 to 0·38, p=0·97) and MTQ questionnaire (adjusted mean difference 0·58, -0·01 to 1·17, p=0·056; and 12 months 0·64, 0·04 to 1·24, p=0·038). The PHQ-9 showed no difference between the groups (adjusted mean difference at 6 months 0·20, 95% CI -0·85 to 1·24 vs 12 months -0·12, -1·18 to 0·94). For the SF-12 survey, we saw evidence of improvement in physical health in the intervention group at 6 months (adjusted mean difference 1·75, 95% CI 0·21 to 3·28), but this difference was not evident at 12 months (0·59, -1·07 to 2·26); and we saw no difference in mental health between the groups at 6 or 12 months (adjusted mean difference at 6 months -0·73, 95% CI -2·82 to 1·36, and 12 months -0·41, -2·35 to 1·53). The GAD-7 questionnaire showed no difference between the groups (adjusted mean difference at 6 months -0·32 95% CI -1·26 to 0·62 vs 12 months -0·10, -1·05 to 0·86). No difference in BMI was seen between the groups (adjusted mean difference 6 months 0·16, 95% CI -0·54 to 0·85; 12 months 0·25, -0·62 to 1·13). Interpretation: This bespoke intervention is a candidate model of smoking cessation for clinicians and policy makers to address high prevalence of smoking. The incidence of quitting at 6 months shows that smoking cessation can be achieved, but the waning of this effect by 12 months means more effort is needed for sustained quitting. Funding: National Institute for Health Research Health Technology Assessment Programme.

The lancet. Psychiatry · randomised controlled trial · 134 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. In the and examined income and social as of STD and AIDS found social to be the of STD and AIDS In et al. examined one of social participation, as a for understanding community influences on HIV infection. found that in of and was in other social groups groups with high of social HIV risk. findings from these studies are and We identified categories of factors to HIV/AIDS epidemiology: structural and the and and Each is in the that highlights a of by often and forces that through as is more the the of p. is in patterns of on sexual and HIV A of how structural might influence HIV/AIDS risk is presented in 2. The and uses of race/ethnicity in epidemiologic research have been the of analysis and Social epidemiologists race/ethnicity as an of social forces than physical has that race/ethnicity is a for exposure to which may be defined as the and individual that and of p. The study of disease is of central importance in the study of HIV/AIDS In the for example, the of HIV HIV/AIDS and of also high HIV/AIDS with of behavioral risk factors at the individual have not observed HIV/AIDS or STD by race/ethnicity individual pathways by which HIV/AIDS in a group complex of economic and social patterns, of illicit and health Social epidemiology is and evidence as to what factors and these HIV/AIDS and found that sexual networks for in sexually transmitted infection in the National Health and Social et al. found that risk network structure in a of injection drug users in differences in HIV prevalence between and and structural factors key in shaping the patterns that to HIV/AIDS For example, the effects of sex from the of men may be relationships and sexual segregation by race/ethnicity also to shape social and risk networks in ways that to disease patterns. residential segregation was and associated with gonorrhea at the in the patterns might be observed for HIV/AIDS. is in the proportion of women among HIV/AIDS cases the for of HIV-positive in through and for of HIV-positive in HIV infections in women are at an and women are and more to HIV infection. theoretical for understanding in HIV/AIDS have been including and human beyond as a risk these approaches structural for in HIV/AIDS. focus has been on women in the of sex or transmission women HIV from their partner and reducing acquisition of HIV among men is key to reducing the spread of HIV to women the of and and than their male partners upon of HIV-positive in of of and HIV risks by women The effects of include individual to HIV and a of to HIV prevention The for and Prevention estimates that one of those with HIV not their HIV and have central in shaping to HIV/AIDS the effects of these social forces on the differential distribution of HIV/AIDS have not been well has been examined at the individual in studies of and and to of and in a that the of to p. et al. have defined as and that are at to have AIDS or HIV and at the and communities with which these are p. and have that a conceptual framework for understanding is our of and to as social that can be in relation to broader of and p. in et al. that HIV transmission and with AIDS the of or structural interventions change the in which and communities HIV infection The effective have been those in which communities have to and by increasing community of HIV Social interventions to and to affect community The for this is found in diffusion which on social networks, opinion and change these are by cultural through the in social networks within communities are essential for and behavior change to to HIV/AIDS structures refer to as well as to the and with their and et al. that laws can affect health in 1) may be a through which social determinants affect health direct and 2) may to social conditions associated with health outcomes indirect of direct effects of on HIV risk are on access to injection which have been associated with HIV incidence of an indirect of structures is the of laws on income which may social conditions that increase HIV vulnerability. key social determinants of HIV/AIDS, including poverty and income and community social change may affect HIV/AIDS patterns through population and and the and structures of Each of these factors may be as modifying between and persons in populations. the HIV infection than populations, of HIV prevalence in the or and may affect HIV transmission studies of have into 1) studies of the spread of HIV along and 2) studies of the that vulnerability to HIV/AIDS can the spread of HIV subtypes and to patterns of and evidence linking patterns and Beyrer et al. (14) found that distinct HIV subtypes were associated with different illicit drug trafficking routes in Southeast Asia. has to the spread of HIV in India, and In addition, studies have identified the importance of in the of for HIV/AIDS is a classic of an health have examined the role of in population HIV/AIDS patterns that might for the effects of on HIV/AIDS patterns include sexual and drug use patterns to in patterns, and of and persons, and on the health sex that men have also been associated with high HIV/AIDS prevalence at the This ecologic is to be by the effects of cultural at the local of the effects might have on and network patterns. the of resources in the public and and the environment a central role in the and of HIV/AIDS epidemics. of importance to HIV/AIDS include health social and illicit drug HIV/AIDS is a high on the health of and policies are to be contributing to increasing HIV/AIDS The complex and between policies and HIV/AIDS are to be policies affect health and by poverty in the distribution of and health have that structural designed to and in have a on the HIV/AIDS by increasing and and reducing in the health and social services as to how policies can be designed to to in HIV/AIDS Structural-level health policies and can to in HIV/AIDS HIV prevention have on individual behavior the of the HIV prevention is with of the for that the social and economic of HIV/AIDS The condom is an exemplary of an effective structural HIV prevention to the environment in which HIV risk behaviors the of may also affect in HIV/AIDS transmission by reducing among HIV-positive Social policies a critical role in the of those to HIV/AIDS, such as or Social policies such as and public affect access to resources and can also affect HIV transmission and access to quantitative research has social change to population health outcomes qualitative research has the importance of social in shaping risk In for example, et al. the effects of the and of which Social and Social 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Epidemiologic Reviews · meta-analysis · 394 citationsread the source →

Mediating Effects of Parental Stress on Harsh Parenting and Parent-Child Relationship during Coronavirus (COVID-19) Pandemic in Singapore.

Because of the Coronavirus (COVID-19) pandemic, "Circuit-breaker" safety distancing was implemented in Singapore from April to May 2020. Schools and workplaces were closed and parents had to balance telecommuting with parenting responsibilities. Coupled with the high degree of economic uncertainty and reduced social support, these circumstances are hypothesized to increase parenting stress. Based on the Parental Stress Model, this study aims to understand how parents' perceived impact of COVID-19 increased harsh parenting and reduced parent-child relationship closeness through the mediating effects of parenting stress. We collected data from 258 parents living in Singapore using online surveys disseminated through Facebook and community organizations. Our predictor was the perceived impact of COVID-19. Parental stress (mediator) was measured with the Parental Stress Scale. Two outcomes were used: parent-child relationship closeness and harsh parenting (spanking, yelling). Using mediation analysis in the SEM framework, we tested the indirect effects using bias-corrected bootstrap confidence intervals. Our results indicated that parenting stress was a significant mediator in the relationship between the perceived impact of COVID-19 and (a) parent-child closeness (indirect effect = -.30, Bootstrap 99% CI[-.59, -.11]) and (b) harsh parenting (indirect effect = .58, Bootstrap 99% CI[.25, .94]). The impact of COVID-19 and stay-home orders can increase parenting stress. This, in turn, has a negative impact on parenting by affecting parents' relationship with their children and increasing the use of harsh parenting. Given that these are risk factors for potential child abuse, supporting parents and mitigating the impact of COVID-19 are important.

Journal of family violence · 244 citationsread the source →

Evaluation of a classroom-based psychosocial intervention in conflict-affected Nepal: a cluster randomized controlled trial.

Background: In situations of ongoing violence, childhood psychosocial and mental health problems require care. However, resources and evidence for adequate interventions are scarce for children in low- and middle-income countries. This study evaluated a school-based psychosocial intervention in conflict-affected, rural Nepal. Methods: A cluster randomized controlled trial was used to evaluate changes on a range of indicators, including psychiatric symptoms (depression, anxiety, posttraumatic stress disorder), psychological difficulties, resilience indicators (hope, prosocial behavior) and function impairment. Children (n = 325) (mean age = 12.7, SD = 1.04, range 11-14 years) with elevated psychosocial distress were allocated to a treatment or waitlist group. Results: Comparisons of crude change scores showed significant between-group differences on several outcome indicators, with moderate effect sizes (Cohen d = .41 to .58). After correcting for nested variance within schools, no evidence for treatment effects was found on any outcome variable. Additional analyses showed gender effects for treatment on prosocial behavior (mean change difference: 2.70; 95% CI, .97 to 4.44), psychological difficulties (-2.19; 95% CI, -3.82 to -.56), and aggression (-4.42; 95% CI, -6.16 to -2.67). An age effect for treatment was found for hope (.90; 95% CI, -1.54 to -.26). Conclusions: A school-based psychosocial intervention demonstrated moderate short-term beneficial effects for improving social-behavioral and resilience indicators among subgroups of children exposed to armed conflict. The intervention reduced psychological difficulties and aggression among boys, increased prosocial behavior among girls, and increased hope for older children. The intervention did not result in reduction of psychiatric symptoms.

Journal of child psychology and psychiatry, and allied disciplines · randomised controlled trial · 131 citationsread the source →

Escitalopram for older adults with generalized anxiety disorder: a randomized controlled trial.

CONTEXT: Generalized anxiety disorder (GAD) is one of the most common psychiatric disorders in older adults; however, few data exist to guide clinicians in efficacious and safe treatment. Selective serotonin reuptake inhibitors (SSRIs) are efficacious for younger adults with GAD, but benefits and risks may be different in older adults. OBJECTIVE: To examine the efficacy, safety, and tolerability of the SSRI escitalopram in older adults with GAD. DESIGN, SETTING, AND PARTICIPANTS: A randomized controlled trial in primary care practices and related specialty clinics in Pittsburgh, Pennsylvania, of 177 participants aged 60 years or older with a principal diagnosis of GAD randomized to receive either escitalopram or placebo and conducted between January 2005 and January 2008. INTERVENTIONS: Twelve weeks of 10 to 20 mg/d of escitalopram (n = 85) or matching placebo (n = 92). MAIN OUTCOME MEASURES: Cumulative response defined by Clinical Global Impressions-Improvement score of much or very much improved; time to response; and anxiety and role functioning changes measured by the Clinical Global Impressions-Improvement scale, Hamilton Anxiety Rating Scale, Penn State Worry Questionnaire, Late-Life Function and Disability Instrument activity limitations subscale, and the role-emotional impairment and social function subscales of the Medical Outcome Survey 36-item Short Form. RESULTS: In the primary analytic strategy in which participants (n = 33) were censored at the time of dropout, mean cumulative response rate for escitalopram was 69% (95% confidence interval [CI], 58%-80%) vs 51% (95% CI, 40%-62%) for placebo (P = .03). A conservative intention-to-treat analysis showed no difference in mean cumulative response rate between escitalopram and placebo (57%; 95% CI, 46%-67%; vs 45%; 95% CI, 35%-55%; P = .11). Participants treated with escitalopram showed greater improvement than with placebo in anxiety symptoms and role functioning (Clinical Global Impressions-Improvement scale: effect size, 0.93; 95% CI, 0.50-1.36; P < .001; Penn State Worry Questionnaire: 0.30; 95% CI, 0.23-0.48; P = .01; activity limitations: 0.32; 95% CI, 0.01-0.63; P = .04; and the role-emotional impairment and social function: 0.96; 95% CI, 0.03-1.90; P = .04). Adverse effects of escitalopram (P < .05 vs placebo) were fatigue or somnolence (35 patients [41.1%]), sleep disturbance (12 [14.1%]), and urinary symptoms (8 [9.4%]). CONCLUSIONS: Older adults with GAD randomized to escitalopram had a higher cumulative response rate for improvement vs placebo over 12 weeks; however, response rates were not significantly different using an intention-to-treat analysis. Further study is required to assess efficacy and safety over longer treatment durations. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00105586.

PubMed · randomised controlled trial · 132 citationsread the source →

Comparing effects in regular practice of e-communication and Web-based self-management support among breast cancer patients: preliminary results from a randomized controlled trial.

Background: While Web-based interventions have been shown to assist a wide range of patients successfully in managing their illness, few studies have examined the relative contribution of different Web-based components to improve outcomes. Further efficacy trials are needed to test the effects of Web support when offered as a part of routine care. Objective: Our aim was to compare in regular care the effects of (1) an Internet-based patient provider communication service (IPPC), (2) WebChoice, a Web-based illness management system for breast cancer patients (IPPC included), and (3) usual care on symptom distress, anxiety, depression, (primary outcomes), and self-efficacy (secondary outcome). This study reports preliminary findings from 6 months' follow-up data in a 12-month trial. Methods: We recruited 167 patients recently diagnosed with breast cancer and undergoing treatment from three Norwegian hospitals. The nurse-administered IPPC allowed patients to send secure e-messages to and receive e-messages from health care personnel at the hospital where they were treated. In addition to the IPPC, WebChoice contains components for symptom monitoring, tailored information and self-management support, a diary, and communication with other patients. A total of 20 care providers (11 nurses, 6 physicians, and 3 social workers) were trained to answer questions from patients. Outcomes were measured with questionnaires at study entry and at study months 2, 4, and 6. Linear mixed models for repeated measures were fitted to compare effects on outcomes over time. Results: Patients were randomly assigned to the WebChoice group (n=64), the IPPC group (n=45), or the usual care group (n=58). Response rates to questionnaires were 73.7% (123/167) at 2 months, 65.9 (110/167) at 4 months, and 62.3% (104/167) at 6 months. Attrition was similar in all study groups. Among those with access to WebChoice, 64% (41/64) logged on more than once and 39% (25/64) sent e-messages to care providers. In the IPPC group, 40% (18/45) sent e-messages. Linear mixed models analyses revealed that the WebChoice group reported significantly lower symptom distress (mean difference 0.16, 95% CI 0.06-0.25, P=.001), anxiety (mean difference 0.79, 95% CI 0.09-1.49, P=.03), and depression (mean difference 0.79, 95% CI 0.09-1.49, P=.03) compared with the usual care group. The IPPC group reported significant lower depression scores compared with the usual care group (mean difference 0.69, 95% CI 0.05-1.32, P=.03), but no differences were observed for symptom distress or anxiety. No significant differences in self-efficacy were found among the study groups. Conclusions: In spite of practice variations and moderate use of the interventions, our results suggest that offering Web support as part of regular care can be a powerful tool to help patients manage their illness. Our finding that a nurse-administered IPPC alone can significantly reduce depression is particularly promising. However, the multicomponent intervention WebChoice had additional positive effects. Trial registration: Clinicaltrials.gov:NCT00971009; http://clinicaltrials.gov/show/NCT00971009 (Archived by WebCite at http://www.webcitation.org/6USKezP0Y).

Journal of medical Internet research · randomised controlled trial · 105 citationsread the source →

A brief dyadic group based psychoeducation program improves relapse rates in recently remitted bipolar disorder: a pilot randomised controlled trial.

Background: Various adjunctive psychotherapies assist in decreasing relapse and improving outcomes for people with bipolar disorder (BD). Psychoeducation programs involving patient-only or caregiver-only groups have demonstrated some efficacy. We tested in recently remitted BD if a combined group based psychoeducation program involving patient-companion dyads decreased relapse. Method: 58 recently remitted BD out-patients were randomised to receive either treatment as usual (TAU, n=31) or 12 x 90 minute psychoeducation sessions delivered weekly in a group program to the patient and companion (SIMSEP, n=27). After 12 weeks SIMSEP patients reverted to TAU and all patients were followed until week 60 or relapse. The primary outcome measure was relapse requiring hospital or intensive community intervention. Results: 45 patients completed the study. 29 patients remained well at week 60 (SIMSEP n=17, TAU n=12), whilst 16 had relapsed (SIMSEP n=3, TAU n=13). The SIMSEP group were less likely to relapse (Fisher's exact test p=0.013; OR=0.16; 95% CI 0.04-0.70) and had an 11 week longer time to relapse compared to the TAU group (chi-square (1)=8.48, p<0.01). At study completion SIMSEP compared to TAU patients had lower Young Mania Rating Scale scores (Mann-Whitney U=255, p<0.01). Limitations: The study was limited by a small sample size. Conclusion: A brief group psychoeducation program with recently remitted BD patients and their companions resulted in a decreased relapse rate, longer time to relapse, decreased manic symptoms and improved medication adherence suggesting utility in the adjunctive psychotherapeutic treatment of BD.

Journal of affective disorders · randomised controlled trial · 44 citationsread the source →

The use of exhaled nitric oxide to guide asthma management: a randomized controlled trial.

Rationale: Current asthma guidelines recommend adjusting antiinflammatory treatment on the basis of the results of lung function tests and symptom assessment, neither of which are closely associated with airway inflammation. Objectives: We tested the hypothesis that titrating corticosteroid dose using the concentration of exhaled nitric oxide in exhaled breath (Fe(NO)) results in fewer asthma exacerbations and more efficient use of corticosteroids, when compared with traditional management. Methods: One hundred eighteen participants with a primary care diagnosis of asthma were randomized to a single-blind trial of corticosteroid therapy based on either Fe(NO) measurements (n = 58) or British Thoracic Society guidelines (n = 60). Participants were assessed monthly for 4 months and then every 2 months for a further 8 months. The primary outcome was the number of severe asthma exacerbations. Analyses were by intention to treat. Measurements and main results: The estimated mean (SD) exacerbation frequency was 0.33 per patient per year (0.69) in the Fe(NO) group and 0.42 (0.79) in the control group (mean difference, -21%; 95% confidence interval [CI], -57 to 43%; p = 0.43). Overall the Fe(NO) group used 11% more inhaled corticosteroid (95% CI, -17 to 42%; p = 0.40), although the final daily dose of inhaled corticosteroid was lower in the Fe(NO) group (557 vs. 895 microg; mean difference, 338 microg; 95% CI, -640 to -37; p = 0.028). Conclusions: An asthma treatment strategy based on the measurement of exhaled nitric oxide did not result in a large reduction in asthma exacerbations or in the total amount of inhaled corticosteroid therapy used over 12 mo, when compared with current asthma guidelines. Clinical trial registered with www.controlled-trials.com (ISRCTN08067387).

American journal of respiratory and critical care medicine · randomised controlled trial · 229 citationsread the source →

Effect of screening and lifestyle counselling on incidence of ischaemic heart disease in general population: Inter99 randomised trial.

Objective: To investigate the effect of systematic screening for risk factors for ischaemic heart disease followed by repeated lifestyle counselling on the 10 year development of ischaemic heart disease at a population level. Design: Randomised controlled community based trial. Setting: Suburbs of Copenhagen, Denmark. Participants: 59,616 people aged 30-60 years randomised with different age and sex randomisation ratios to an intervention group (n = 11,629) and a control group (n = 47,987). Intervention: The intervention group was invited for screening, risk assessment, and lifestyle counselling up to four times over a five year period. All participants with an unhealthy lifestyle had individually tailored lifestyle counselling at all visits (at baseline and after one and three years); those at high risk of ischaemic heart disease, according to predefined criteria, were furthermore offered six sessions of group based lifestyle counselling on smoking cessation, diet, and physical activity. After five years all were invited for a final counselling session. Participants were referred to their general practitioner for medical treatment, if relevant. The control group was not invited for screening. Main outcome measures: The primary outcome measure was incidence of ischaemic heart disease in the intervention group compared with the control group. Secondary outcome measures were stroke, combined events (ischaemic heart disease, stroke, or both), and mortality. Results: 6091 (52.4%) people in the intervention group participated at baseline. Among 5978 people eligible at five year follow-up (59 died and 54 emigrated), 4028 (67.4%) attended. A total of 3163 people died in the 10 year follow-up period. Among 58,308 without a history of ischaemic heart disease at baseline, 2782 developed ischaemic heart disease. Among 58,940 without a history of stroke at baseline, 1726 developed stroke. No significant difference was seen between the intervention and control groups in the primary end point (hazard ratio for ischaemic heart disease 1.03, 95% confidence interval 0.94 to 1.13) or in the secondary endpoints (stroke 0.98, 0.87 to 1.11; combined endpoint 1.01, 0.93 to 1.09; total mortality 1.00, 0.91 to 1.09). Conclusion: A community based, individually tailored intervention programme with screening for risk of ischaemic heart disease and repeated lifestyle intervention over five years had no effect on ischaemic heart disease, stroke, or mortality at the population level after 10 years. Trial registration Clinical trials NCT00289237.

BMJ (Clinical research ed.) · randomised controlled trial · 174 citationsread the source →

An unheard voice: infection prevention professionals reflect on their experiences during the covid-19 pandemic.

Background: The COVID-19 pandemic required a shift away from the evidence-based practices known to infection prevention professionals' (IPP). Relaying these guidelines to beleaguered front line staff contributed to the experience of moral distress and burnout among IPPs. Methods: A mixed methods design was used to explore the experiences of IPPs during the COVID-19 pandemic. An electronic survey was sent to a convenience sample from the Wisconsin APIC membership. A subset of this sample completed additional semi-structured interviews. Results: A total of 61 IPPs responded to the survey, 18 agreed to interviews with 11 completions. Most respondents identified as female (n=58, 95.0%) and White (n=55, 90.1%). More than half of the respondents (n=39, 63.9 %) reported they experienced moral distress (MD). Themes from one-on-one interviews included: Feeling depleted, challenges to IPP role, validation of IPP expertise, value of peer support. Conclusions: We found that IPPs endured significant distress and exhaustion during the COVID-19 pandemic regardless of their practice setting. The long-term effects on the IPP profession must be examined. IPPs are susceptible to high levels of stress and anxiety similar to other frontline healthcare workers. IPPs deserve recognition for their service during the pandemic and should have access to resources that can support their well-being.

American journal of infection control · 5 citationsread the source →

Physical inactivity among older adults across Europe based on the SHARE database.

Background: Regular physical activity is one of the key components of a healthy lifestyle. It is associated with better physical and cognitive functioning in later life and with increased life expectancy. The purpose of this study was to evaluate the prevalence of, and factors related to, physical inactivity among older adults across Europe. Methods: In this cross-sectional analysis, we used data from participants aged 55 or older in Wave 4 of the Survey of Health, Ageing, and Retirement in Europe (SHARE) database, a multidisciplinary and cross-national panel database covering health, socioeconomic status, and social and family networks. Individuals included in this study were classified as physically active or physically inactive. Clinical, psychosocial and sociodemographic variables were evaluated for their association with physical inactivity. Results: From the total of 58,489 individuals in SHARE, we selected 19,298 people age 55 or older (mean age 67.8 ± 8.9 years; 11,430 (59.2%) female). The overall prevalence of inactivity among individuals age 55 or older in the 16 included countries was 12.5%. The prevalence of physical inactivity varied between countries, ranging from 4.9% (Sweden) to 29% (Portugal). Increasing age, depression, physical limitations, poor sense of meaning in life, social support and memory loss were significant variables associated with physical inactivity. Conclusions: Physical inactivity can be explained by physical, cognitive and psychological conditions. Interventions aimed at promoting physical activity among older people are needed to address this diversity of factors.

Age and ageing · cohort or longitudinal · 156 citationsread the source →

Perceptions of appropriateness of care among European and Israeli intensive care unit nurses and physicians.

Context: Clinicians in intensive care units (ICUs) who perceive the care they provide as inappropriate experience moral distress and are at risk for burnout. This situation may jeopardize patient quality of care and increase staff turnover. Objective: To determine the prevalence of perceived inappropriateness of care among ICU clinicians and to identify patient-related situations, personal characteristics, and work-related characteristics associated with perceived inappropriateness of care. Design, setting, and participants: Cross-sectional evaluation on May 11, 2010, of 82 adult ICUs in 9 European countries and Israel. Participants were 1953 ICU nurses and physicians providing bedside care. Main outcome measure: Perceived inappropriateness of care, defined as a specific patient-care situation in which the clinician acts in a manner contrary to his or her personal and professional beliefs, as assessed using a questionnaire designed for the study. Results: Of 1651 respondents (median response rate, 93% overall; interquartile range, 82%-100% [medians 93% among nurses and 100% among physicians]), perceived inappropriateness of care in at least 1 patient was reported by 439 clinicians overall (27%; 95% CI, 24%-29%), 300 of 1218 were nurses (25%), 132 of 407 were physicians (32%), and 26 had missing answers describing job title. Of these 439 individuals, 397 reported 445 situations associated with perceived inappropriateness of care. The most common reports were perceived disproportionate care (290 situations [65%; 95% CI, 58%-73%], of which "too much care" was reported in 89% of situations, followed by "other patients would benefit more" (168 situations [38%; 95% CI, 32%-43%]). Independently associated with perceived inappropriateness of care rates both among nurses and physicians were symptom control decisions directed by physicians only (odds ratio [OR], 1.73; 95% CI, 1.17-2.56; P = .006); involvement of nurses in end-of-life decision making (OR, 0.76; 95% CI, 0.60-0.96; P = .02); good collaboration between nurses and physicians (OR, 0.72; 95% CI, 0.56-0.92; P = .009); and freedom to decide how to perform work-related tasks (OR, 0.72; 95% CI, 0.59-0.89; P = .002); while a high perceived workload was significantly associated among nurses only (OR, 1.49; 95% CI, 1.07-2.06; P = .02). Perceived inappropriateness of care was independently associated with higher intent to leave a job (OR, 1.65; 95% CI, 1.04-2.63; P = .03). In the subset of 69 ICUs for which patient data could be linked, clinicians reported received inappropriateness of care in 207 patients, representing 23% (95% CI, 20%-27%) of 883 ICU beds. Conclusion: Among a group of European and Israeli ICU clinicians, perceptions of inappropriate care were frequently reported and were inversely associated with factors indicating good teamwork.

JAMA · cohort or longitudinal · 245 citationsread the source →

Omega‐3 fatty acids in colorectal cancer prevention

Colon cancer, which is the fourth most common cancer in the world, is one of the leading causes of cancer death in both men and women in the United States, Canada, Northern and Western Europe, Australia and New Zealand.1, 2 It is markedly less frequent in Asia, Africa and South America.1, 2 Therefore, it is a major public health problem. Migrant and temporal trend studies suggest that colon cancer is determined largely by environmental exposures, especially nutritional habits.1 Marked international differences in the incidence and mortality of colon cancer and increase of risk in populations migrating from low- to high-risk areas such as from Japan, China and the Philippines to the United States within 1 or 2 generations suggest that environmental factors, specifically dietary habits, rather than the genetic factors play an important role in the etiology of this cancer. This upward trend in incidences of colon cancer among Japanese immigrants in Hawaii and California compared to Japanese in Japan stimulated epidemiologists to investigate the reasons for this increase. Although the relationship between nutrition and cancer is complex and sometimes perplexing to nutritionists and to those who visualize carcinogenesis in terms of a specific carcinogen, it should be recognized that nutritional factors and diet may relate to cancer risk in several ways; first, food additives, contaminants, a particular dietary component, or products formed during food preparation may act as carcinogens, cocarcinogens and/or promoters; second, nutrient deficiencies and excesses may lead to biochemical/molecular alterations that may promote neoplastic processes; third, changes in the intake of selected macronutrients may induce metabolic, biochemical and molecular abnormalities that enhance cancer risk; and fourth, certain dietary constituents act as anticarcinogens or chemopreventives. During the last 3 decades, substantial progress has been made in understanding the relationship between dietary constituents and colon cancer risk. Fish oils are unique because they contain high levels of polyunsaturated omega-3 fatty acids (n-3 PUFAs) that are not present in vegetable oils or in saturated fats. Omega-3 fatty acids that are present in fish oil include docosahexaenoic acid (DHA; C22:6), eicosapentaenoic acid (EPA; C20:5) and docosapentaenoic acid (DPA; C22:5). Vegetable oils including corn oil and safflower oil contain high levels of linoleic acid (LA; C18:2). LA has the terminal double-bond 6 carbon atoms from the terminal (omega) methyl group of fatty acid, whereas DHA has the terminal double-bond 3 carbon atoms from the terminal (omega) methyl group of fatty acid (Fig. 1). Chemical structures of omega-3 and omega-6 fatty acids. Nutritional epidemiologic studies have provided evidence that dietary factors are important determinants of colorectal cancer in different populations worldwide. Cancer statistics in Japan for 2001 published by the Foundation for Promotion of Cancer Research indicate that there is an upward trend in age-adjusted mortality rates for colon cancer from 1955 to 1999.3 According to this report, the death rates due to colon cancer in Japanese men and women in 1955 were 2.9 and 3.0, respectively, whereas they increased to 14.7 and 9.8 in 1999. This upward trend in death rates due to colon cancer is mainly attributable to Westernization of Japanese food habits.3, 4 In addition, the report by the Foundation for Promotion of Cancer Research provided the data on the time trends in food consumption, which show increased dietary intakes of animal fat and meat and decreased consumption of whole grains from 1960 to 1999. For example, animal fat consumption in 1960 was about 25 g/day (per capita), whereas in 1999 it increased to about 58 g/day. Meat intake was increased from 19 to 78 g/day (per capita), whereas grain consumption decreased from 453 to 245 g/day during these years.3 The importance of types of dietary fat differing in fatty acid composition rather than total fat cannot be discounted because several preclinical studies using well-established colon cancer models strongly supported the notion that the colon tumor-promoting effect of dietary fat or lack of such effect depends on its fatty acid composition.5 A recent report by an expert panel assembled by the American Institute for Cancer Research/World Cancer Research Fund came to the scientific consensus that evidence for an association between the intake of saturated fat and/or animal fat and colon cancer risk is very strong.6 Continuing population studies revealed that diets particularly high in total fat, especially animal fat, are generally associated with increased risk of developing colon cancer, whereas high dietary fish oil or fish reduces this risk.7, 8 A recent ecologic study suggests that mortality data for colorectal cancer in 22 European countries, the United States and Canada correlate with the consumption of animal fat.7 That eating a diet rich in n-3 PUFAs may decrease the risk of colorectal cancer has been hypothesized in relation to fish and fish oil.7 Caygill and Hill et al.8 reported an inverse correlation between fish and fish oil consumption and colorectal cancer when expressed as a proportion of total or animal fat. This inverse relationship was significant for both male and female colorectal cancer, whether the intakes were in the current period or 10 years or 23 years before cancer mortality, It is noteworthy that these effects were only observed in countries with a high (> 85 g/caput/day) animal fat intake.8 Also, Mediterranean diet rich in olive oil and fish is associated with a low risk of colorectal cancer.9 On the basis of epidemiologic evidence, it is reasonable to suggest that diets high in saturated fats increase the risk of colorectal cancer, whereas diets high in fish and fish oil rich in n-3 PUFAs reduce the risk. Animal models have contributed significantly to understanding of the carcinogenesis process and to study the multiple environmental factors against the pathogenesis of colon cancer.10 Several studies have utilized these relevant animal models to investigate the modulation of colon carcinogenesis by nutritional and chemopreventive agents. These animal models include induction of colon tumors in rats by administration of aromatic amines such as 3,2′-dimethyl-4-aminobi-phenyl (DMBA); derivatives and analogs of cycacin, such as methylazoxymethanol (MAM), 1,2-dimethyl-hydrazine (DMH) and azoxymethane (AOM) in rats and mice of selected strains; direct-acting carcinogens of the type of alkylureas, such as methylnitrosourea (MNU) or N-methyl-N′-nitro-N-nitrosoguanidine (MNNG); and heterocyclic amines such as 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The spectrum of epithelial lesions induced in the colon by these agents is similar to various types of neoplastic lesions observed in the colorectum of humans. Azoxymethane (AOM), which is a potent inducer of carcinomas of the large intestine in various strains of male and female rats, has been used extensively by many investigators to induce colon tumors and to study the effects of nutritional factors and chemopreventive agents in colon carcinogenesis.10, 11, 12, 13, 14, 15, 16, 17 Colons of Fischer (F344) rats treated with AOM seem to have light and electron microscopic morphology as well as histochemical properties that are quite similar to that of humans and the biologic behavior of AOM-induced rat colon carcinomas is similar to that of human colon carcinomas.10, 18 Other characteristics of the human disease process reflected in the AOM rat model are the occurrence of both adenomas and adenocarcinomas.18 Also, aberrant crypt foci (ACF), which are recognized as early appearing preneoplastic lesions, develop in experimentally induced colon carcinogenesis in laboratory rodents as well as in the colonic mucosa of patients with colon cancer.19, 20 Recently, β-catenin-accumulated crypts were identified in the colonic mucosa at the early stages of AOM-induced colon carcinogenesis and are considered as early-appearing preneoplastic lesions.21 Therefore, ACF are now regarded as putative preneoplastic lesions for colon cancers and are used as biomarkers to evaluate potential chemopreventive agents against colon carcinogenesis.22 AOM treatment also induces oncogene mutations at codon 12 of K- and H-ras and increases in the expression of the ras family of protooncogenes have been causally associated with colon tumor development.23, 24 Enhanced ras oncogene expression has been observed in a variety of human colon tumors.25 AOM-induced colon tumors also demonstrate enhanced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression similar to human colon tumors.13, 26 Mutations in the tumor suppressor gene, APC, are known to be early events in the colon cancer process in humans and have been identified in patients with familial adenomatous polyposis, who have germline mutation in one of the APC alleles, and in sporadic colorectal cancer.27, 28 Evidence in humans thus implicates the APC suppressor gene as causal in large bowel carcinogenesis. Recent studies indicating the presence of APC mutation in AOM-induced colon tumors in rats strengthens the concept that these models are appropriate for human colon cancer studies.29 It has been increasingly apparent that β-catenin signaling pathway is closely associated with the development of colon cancer.30 Also, frequent mutations in the β-catenin gene are confirmed in AOM-induced colon tumors in rodent models.30 it has been that the expression of β-catenin is with the of colon of of of adenomas and ACF and several molecular between human colon tumors and AOM-induced colon it is that the AOM model and induced colon models to be appropriate colon cancer Recent progress in the of molecular carcinogenesis has identified multiple molecular for the and nutritional modulation of colon cancer. The multiple which a mutation codon of the APC gene from a to a is markedly different from that of patients with familial adenomatous in which adenomas are in the colon and whereas in adenomas are in the intestine and in the mice also develop at an early These are potential of and models for agents for potential chemopreventive properties against colon carcinogenesis. The development of for of colorectal cancer by dietary has been markedly by the of relevant laboratory animal including colon cancer the neoplastic process that in humans. and evidence from preclinical studies have provided evidence that not only the also types of dietary fat differing in fatty acid composition are important factors in effect of this nutrient in colon tumor in laboratory and those of have that diets high in and corn oil in the significantly increased induced colon carcinogenesis in and rats as compared to diets low in these studies in laboratory also demonstrate that male rats diets or corn oil rich in PUFAs were to colon carcinogenesis compared with those diets or corn et that dietary n-3 PUFAs methylazoxymethanol of areas of and colon whereas PUFAs enhance colon in In a recent et reported a effect of dietary fish oil against AOM-induced colon carcinogenesis in male dietary fish oil significantly colon tumors as compared to high corn oil In addition, colon tumor by fish oil diet was associated with levels of in the colon compared with corn oil These studies provided evidence in preclinical models that diets high of saturated fat of animal or PUFAs a colon effect than diets low in such fatty whereas diets high in n-3 PUFAs such effect studies in laboratory have the effects of high dietary corn oil and safflower oil rich in olive oil high in fatty acid acid, oil high in fatty acids such as acid and fish oil during the of AOM-induced colon carcinogenesis in male diets high corn oil or safflower oil a incidence of colon tumors than those diets low in fat diets high in olive oil or fish oil such colon The effects of different types of fat on colon carcinogenesis during suggest that fatty acid composition is one of the factors in colon tumor by a dietary fat and that the of types and of dietary fat is during the of In this it is to that in a 2 of patients with colonic dietary fish oil have in in the colonic progress has been made with to the relationship between dietary fat intake and colon cancer risk in that of the tumor-promoting effects of diets rich in PUFAs and saturated fatty acids and lack of such effects by n-3 it should be recognized that among the of dietary fat, animal fat with its fatty acid is by the most important to about to the Western dietary fat intake in the United States and Canada and Western countries, colon cancer rates are of a of and polyunsaturated A recent in mice that high dietary fat composition of the diet lesions in the colon of In of the of in colon cancer and because of potential properties of n-3 have a study to the effects of diets that contain rich in saturated fatty acids and to with the effects of fish oil during the different stages of colon carcinogenesis in male preneoplastic lesions, were in the diets for 23 and which are putative preneoplastic lesions in the were observed at high in the colonic mucosa of patients with colon and of rats and mice treated with colon ACF and are to be biomarkers of the effects of agents carcinogenesis in the ACF were observed in the of the diet a significantly of compared with those the corn oil or fish oil diet at time The incidence of aberrant foci was also in the diet group than in the or diet that administration of the diet significantly the and of preneoplastic lesions in the whereas the diet the of such Also, dietary significantly increased colon tumor incidence and when compared with the or rats the diet incidence of colonic compared with incidences of and in rats the and Also, the of was significantly in the diet as compared to those the the diet fat in the of fish induced tumors than diet the of total fat from This that both the type and the of fatty acids in the diet play a role in colon carcinogenesis. In evidence from preclinical studies is with the epidemiologic The of dietary n-3 PUFAs including DHA and against colon carcinogenesis has also been in rodent et reported that administration of of DHA a for 4 and 12 significantly AOM-induced ACF in the et also reported that administration of 1 of DHA a for significantly AOM-induced colon tumor specifically in the and colon in male et compared dietary at LA at or LA at against AOM-induced colon carcinogenesis in male The indicate that the rats a significantly colon tumor incidence and than those the LA of tumors that the rats on diet and than those on the LA Also, the of in the colon tumors of LA diet group was than that in the colon tumors of the diet These suggest that its effect the modulation of in colon Several potential have been for colon cancer of types of dietary fat. Several studies indicate that diets high in saturated fatty acids and and PUFAs oil or safflower increase the of colonic including acid and acid, whereas dietary fish oil high in n-3 PUFAs such epidemiologic studies that populations who are on Western diet and at high risk for colon cancer high levels of acids have been to in a similar to induce and a in and act as in colon these suggest that acids that are by types of dietary fat may be important for in relation to colon tumor in by et dietary PUFAs may and n-3 PUFAs may against colon carcinogenesis by and/or levels of AOM-induced were in fish rats as compared to those corn oil rich in et and et have also that fish oil an increase in in the colon compared with corn It is reasonable to that one of the by which n-3 PUFAs against colon carcinogenesis is in by the of and by the of colonic Also, of fish oil or n-3 fatty acid increased and DHA levels in the of at the of fatty It has been that of colon carcinogenesis by DHA is the of a of a large of n-3 PUFAs effects in the colon the of of the are factors that and are studies to indicate that inducible nitric oxide synthase which is at the is in human colon and in induced colon tumors of laboratory animal data also indicate that the of by is to carcinogenesis process and induces lesions, thus in and in the by family of also These data suggest a role for in tumor and in laboratory indicate that acid induces in with specific expression that one of the by which tumor including acids may an increase in expression of pathway that colon It is known that the fatty acid composition of is to in laboratory indicate that levels of dietary fish oil in rats increased the omega-3 fatty DHA and in the colonic at the of omega-6 PUFAs such as linoleic acid and acid, the that the DHA and of fish oil the of by acid and linoleic acid in the Therefore, the types of dietary fat the fatty acid composition of colonic It is well that acid and of its including play an important role in the signaling pathway associated with and gene increase promote and of which are in tumor The by which n-3 PUFAs colon carcinogenesis are in of an important role in colon and who have in the of of rat epithelial have that of lead to the of high intake of saturated fat and omega-6 PUFAs acid from and levels of have been observed in human colon tumors and induced colon tumors in rodent and human colon levels of that are by Northern Recent have a between the potential of APC mutations and by that of the gene reduces the of tumors in mice for an by than evidence a role for from which show a in colon tumors in rodents with Recent studies in laboratory have provided evidence that an diet AOM-induced expression of and from acid in colon tumors of rats, whereas the diet the levels of In this administration of the diet of in the colon significantly levels than the corn oil diet or the diet 28 indicating This suggests that of the modulation of may be important for the of n-3 PUFAs to colon Also, colon tumors of the diet a than was observed in the colon tumors of rats the The of these studies indicating that of in the tumors of the diet in to the diet and the tumor the that of lead to the of In colon the levels of may be to by and induction of and thus tumor A major that to be is which signaling are in of the These not only a between dietary fatty and of colon also molecular for colon cancer by which n-3 PUFAs colon carcinogenesis. The potential and molecular events by n-3 PUFAs against colon carcinogenesis. The of molecular events by n-3 PUFAs include including and specific and factors including that and dietary n-3 PUFAs by with the and of modulation of thus Recent studies from laboratory have that high dietary PUFAs enhance of including that have been or in colon tumor whereas diet n-3 PUFAs to the of these a gene family of that play in signaling events and are in and include several with unique to the from the et reported that chemopreventive of dietary fish oil is associated with the alterations in colonic a that is by PUFAs may the of the which a of It is that several have been to in The a of ras that is to the of in the of of are in the etiology of human colon It is also known that of from to is by a of closely including which is by It that of ras association of and neoplastic of in laboratory have provided data to indicate that high dietary PUFAs increases expression in colonic whereas high dietary n-3 PUFAs to by with and of the modulation of thus Several have against in both and laboratory animal in have the of in and of colon cancer. of is with the development of certain of has also been to induce an effect that with and have that expression of was in colon tumors of rats than in colon Colon tumors from rats the diet high levels of PUFAs very low levels of whereas the tumors from the diet high of n-3 PUFAs not of These correlate with colon tumor incidences by dietary n-3 and It that modulation of a significant role in n-3 colon tumor and studies in laboratory have that DHA of colon cancer in and induces also the effects of DHA on the genetic of human colon cancer at the using in gene expression due to DHA treatment was observed to be in the multiple signaling in the of and of DHA on and induction of were by an increase in the of several of family of and of such as and of several of these and factors the of the chemopreventive of DHA and important n-3 PUFAs present in fish oil and thus colon cancer. Also, of these and factors provided several expressed biologic many of which suggest as molecular for by chemopreventive including nutritional is a major of and mortality in patients with cancer, including colorectal cancer. Several studies have provided evidence for effects of fish oil administration in cancer during Omega-3 fatty acids have been to have effects on in cancer in patients with cancer is to and is associated with a time and of A fish nutritional has the potential to be a and of a fish oil preparation of and and a preparation in patients with 85 The of of the of which in the of of cancer patients and death from attributable to of of in cancer by and this may be one of the for of tumor Also, fish oil at a of during In on the basis of epidemiologic evidence from ecologic and it is reasonable to suggest that diets high in saturated fats increase the risk of colorectal cancer, whereas diets high in n-3 PUFAs not increase its risk. The studies both epidemiologic and evidence for the effects of diets rich in n-3 in the of colorectal cancer. Also, recent demonstrate effects of fish oil administration in cancer and during and studies have provided evidence that colon tumor-promoting effect of dietary fat depends on its fatty acid that the composition of dietary fatty acids is to colon cancer risk than is the total of fat. studies also demonstrate that a diet high in including saturated fats of animal as well as high dietary PUFAs a potential to promote colon than of a diet on of fat n-3 Although the by which diets high in saturated fats as those in Western and PUFAs promote colon carcinogenesis are not the studies thus indicate that increased levels of colonic modulation of the on and the expression of by the types of dietary fat, especially may play a role in colon carcinogenesis. studies are to the role of n-3 PUFAs on the modulation of that are in colon and types of cancer. The of is to decrease the and mortality from colorectal cancer. and those of suggest that nutritional has the potential to be a major of colorectal cancer especially in the are and in n-3 PUFAs be before they are for cancer Although there are data to indicate and n-3 PUFAs should be for of colorectal cancer, levels of dietary n-3 PUFAs should be with the on epidemiologic studies of disease as by several These studies suggest that fish or as as g/day of fish the risk of Although a dietary for n-3 PUFAs not there is a that consumption of of fish in on the epidemiologic studies may also reduce the risk of colorectal cancer. et has that the of PUFAs to n-3 PUFAs may be important for The risk for and several types of cancer among Mediterranean and Western European populations may at in be on the basis of to n-3 of and 10 in on preclinical and epidemiologic studies on and et for a in the intake of linoleic acid and increase in the intake of n-3 PUFAs that a of 2 be for of and that this is in Western countries for of and and This may well be for the of colorectal cancer in the consumption of and is also for those in Western countries to reduce the risk of colorectal cancer. In the of colorectal cancer in omega-3 fatty acids are in and of be It should be recognized that with nutritional and/or diet may not be for of colorectal cancer in patients such as those with and sporadic colon This to colon cancer is of importance as have not been in the high incidence or low of colorectal cancer. by diet as to the with chemopreventive agents that or the development of those which with and progress to and is an for of colon cancer in these high-risk This is important when chemopreventive agents demonstrate significant may effects at It is certain that colon cancer be a significant of and in high-risk by molecular that or the process of carcinogenesis. there is a to in patients with sporadic colon using the n-3 diets in with a chemopreventive to the of events leading to The for preparation of the and studies on n-3 PUFAs in colon cancer are supported by the Cancer Institute and

International Journal of Cancer · review · 65 citationsread the source →

Clinical Presentation of Left Atrial Cardiac Myxoma

Introduction Cardiac myxoma is the most frequent “benign” tumor of the heart and presents an important diagnostic challenge (4,43,47). Myxomas may resemble many cardiovascular or systemic diseases, and can arise in any of the cardiac chambers, although 75% occur in the left atrium. Most cases of atrial myxomas are now diagnosed in living patients, allowing successful surgical extirpation (1,3,30,44,53). Before the introduction of angiocardiography in 1951, cardiac myxoma diagnosis was made only at autopsy (22). The first successful surgical removal of an atrial myxoma was performed in 1954 (35,47). In 1959, the first M-mode echocardiogram of a left atrial myxoma was reported (16). Indeed, the introduction of echocardiography has provided an important noninvasive means of diagnosis for cardiac myxomas (55). Thus, the diagnosis of small myxomas (less than 5 cm in size and asymptomatic) is becoming easier. We report here the experience of a French cardiovascular center in the clinical presentation of left atrial myxomas. The large number of patients in this series allowed us to perform an analytic, clinicopathologic study. Patients and Methods We reviewed the 112 cases of left atrial myxoma seen at 1 institution (Hôpital Louis Pradel, Lyons, France) over a 40-year period (1959–1998). In all cases the diagnosis was established before surgical removal. The patients’ medical records were reviewed, and data concerning clinical presentation, diagnostic methods, and postoperative course were collected. Histopathologic slides were reviewed for all cases by the same pathologist (RL). Other locations where cardiac myxoma occurred during that time period were the right atrium (15 cases), left ventricle (2 cases), and right ventricle (1 case). Follow-up information was obtained by contacting either the patients or the attending physicians, and a standardized questionnaire was completed for each case. Statistical analysis A chi-square test, or the Fisher exact test when required, was performed for all qualitative variables, and odds ratios (OR) with 95% confidence intervals (95% CI) were computed. For ordinal variables a Wilcoxon rank sum test was used. Data analysis was performed using SAS (Statistical Analysis System, SAS Institute Inc., Cary, NC). The variables studied in the statistical analysis were 1) sex and age, period of diagnosis (before or after echocardiography was available), delay to diagnosis (delay between the first symptoms and diagnosis), possible systematic (serendipitous) discovery; 2) size of the tumor (> or < 5 cm), tumor surface appearance (smooth or villous); 3) the main symptoms: cardiac (cardiac failure, malaise or syncope, chest pain or palpitations), embolic (cerebral, coronary, or peripheral artery), systemic (fever, weight loss, or pseudo-connective tissue disease signs), or neurologic (stroke, vertigo, epilepsy, coma, or other signs); 4) cardiac auscultation modifications (pseudo-mitral signs, “tumor plop”, nonspecific other signs); 5) possible chest X-ray abnormalities (left cardiac failure signs, cardiomegaly, pleural effusion, left atrium enlargement, visible myxoma when calcified), electrocardiogram (ECG) alterations (arrhythmias or conduction disturbances, ST-segment and T-wave shifts, left atrial hypertrophy, and nonspecific signs), or serologic test abnormalities (elevated erythrocyte sedimentation rate [ESR], anemia). Results Patient characteristics The study group included 72 women, (64% of the whole sample; median age, 53 yr; range, 23–84 yr) and 40 men (36% of the sample; median age, 58 yr, range, 5–77 yr). Forty-six patients (41% of the sample, 31 women, 15 men) were less than 50 years old, 47 (42%, 31 women, 16 men) were between 50 and 70 years, and 19 (17%, 10 women, 9 men) were older than 70. Age distribution was homogenous in men, but most female patients were between 40 and 60 years old (Figure 1).Fig. 1: Age distribution of 112 patients with left atrial myxoma. The clinical and laboratory features of left atrial myxoma in our series are presented in Table 1. The different frequencies of clinical and laboratory signs according to sex and age are detailed in Table 2. Male patients were more at risk than females for embolic complications and for neurologic symptoms; females were more at risk than males to develop systemic symptoms such as fever; younger patients (age <50 yr) had more neurologic symptoms and cardiac auscultation abnormalities than older patients (age >50 yr).TABLE 1: Clinical and laboratory features of left atrial myxoma (112 cases)TABLE 2: Frequencies of clinical and laboratory signs by sex and age*We divided the patients into 2 groups according to the pre-and post-echocardiography periods: 1) between 1959 and 1977, when the only diagnostic methods were angiocardiography and cardiac cathe-terization, only 14 patients (12.5%) underwent surgery; 2) since 1977, with 2-dimensional echocardiography use (transthoracic, then transesophageal), about 5 patients per year have undergone surgery for left atrial myxoma (98 patients, 87.5%). The sex ratio and age ranges are similar in these 2 patient groups, but other differences can be identified (Table 3). Before 1977, most patients were diagnosed on the basis of serologic or blood test abnormalities (particularly elevated ESR) and radiologic abnormalities; chest X-ray evidence of cardiac failure or left atrium enlargement was particularly prevalent in patients diagnosed before 1977 compared with those diagnosed after 1977 (p = 0.006 and p = 0.02, respectively).TABLE 3: Symptoms by year of diagnosis*Delay before surgery In our series, the time interval between symptoms onset and diagnosis (surgical removal) varied from 0 to 126 months (median, 4 mo). The median delay before surgery was 5.5 months before 1977, and 3 months after 1977; the difference is not significant. The median delay to diagnosis increased significantly when cardiac symptoms were present; there was no significant difference for the other symptoms (Table 4).TABLE 4: Delay to diagnosis by year and by principal clinical symptoms*Initial symptoms ( Figure 2) For 11 patients, the left atrial myxoma diagnosis was a mere chance, or serendipitous, discovery (“systematic findings” in Figure 2). Among these patients, in 9 cases echocardiography (8 cases) or computed tomography (CT) (1 case) was performed for another indication and allowed a diagnosis of myxoma. For 2 patients, echocardiography had been systematically performed during follow-up for surgery on a right atrial myxoma. Fig. 2: Initial symptoms of left atrial myxoma (112 cases).The most common initial symptoms of left atrial myxoma in our series were related to mitral valve obstruction: dizziness and occasionally syncope, palpitations, dyspnea, cough, pulmonary edema, or congestive heart failure were observed in 58 patients. Eight patients showed atypical paroxysmal clinical manifestations: chest pain, hemoptysis, limb claudication, thoracic noise, shortness of breath, or syncope when reclining. Embolic manifestations suggested myxoma in 18 patients. Constitutional or general systemic signs appeared as initial manifestations for 17 patients: myalgia, muscle weakness, arthralgia, fever, weight loss, fatigue, and Raynaud syndrome. Clinical features at diagnosis All patients presented with at least 1 or more symptoms of the classic triad: 1) obstructive cardiac signs; 2) embolic signs; and 3) constitutional or systemic manifestations (See Table 1). 1) Intracardiac obstruction signs occurred in 75 patients. Pulmonary edema or progressive congestive cardiac failure (dyspnea, orthopnea) were the most common symptoms (n = 48). Malaise or syncope occurred in 16 cases. Two patients experienced cardiac arrest before surgery and fully recovered after resuscitation. Other nonspecific cardiac symptoms were present in 34 patients: cough, thoracic pain, palpi-tations, myocardial infarction due to coronary embolism. Malaise, palpitations, or thoracic pain could vary with body postural changes. 2) Signs of embolism were present in 33 patients, either with 1 (n = 25) or several (n = 8) locations. Embolic locations were the central nervous system (n = 24), in 1 case in the retinal artery, the upper and lower extremities (n = 15), and the coronary arteries (n = 4). 3) Thirty-eight patients presented with systemic or constitutional symptoms. These symptoms were obviously nonspecific, including fever (n = 22), weight loss or fatigue (n = 20), and immunologic diseases mimicking symptoms such as myalgia, muscle weakness, arthralgia, or Raynaud syndrome (n = 6). 4) Other clinical presentations 4.1) Twenty-nine patients had neurologic symptoms, particularly transient or permanent motor or sensory neurologic deficiencies (n = 23), when cerebral emboli were present (stroke). Three of these patients developed multiple cerebral aneurysms, induced by cerebral emboli. Three patients had epileptic fits, or multilocular sclerosis mimicking symptoms. Six patients also suffered from other neurologic manifestations, such as vertigo or coma. One patient with streptococcal meningitis underwent surgery for a supposed antibiotic-resistant endocarditis suggested by echocardiographic findings, but surgery uncovered an incidental noninfected myxoma. 4.2) One patient had fever and positive blood cultures for Streptococcus viridans. 4.3) Three patients were investigated for liver abnormalities connected in fact with right cardiac failure. 4.4) For 3 patients, the main symptoms were abdominal pain or hemoptysis. Physical examination (cardiac auscultation) On cardiac auscultation 72 patients (64%) had abnormal findings, 18 (16%) of them with postural changes or with time examination modifications. These murmurs looked like significant mitral stenosis findings: apical diastolic or presystolic murmur (n = 60, 53%). A tumor plop was heard in 17 patients (15%), all before 1989. Other auscultatory features were changes in preexisting murmurs, gallops, or modification of the first (split) or second heart sound (n = 12, 11%). A significant was observed between cardiac auscultation abnormalities and 1) systemic symptoms (fever, weight loss or and 2) cardiac symptoms and signs (cardiac failure, (Table no between auscultatory signs and embolic or neurologic symptoms was between clinical The most frequent laboratory was in patients Table 1). in men, in was observed in 15 patients. blood or was present in patients. The between these serologic abnormalities and systemic manifestations was significant Table there was no significant between serologic signs and or neurologic symptoms. abnormalities of the patients (n = had abnormal Table 1). atrial was the most frequent (n = or or conduction were Other were ST-segment abnormalities (n = or nonspecific abnormalities (n = hypertrophy, The of abnormalities with systemic manifestations and cardiac signs was significant Table was no significant with embolic or neurologic symptoms. were abnormal in patients Table 1). included pulmonary or congestive heart failure signs (n = and nonspecific (n = atrial enlargement (n = that made the tumor visible (n = and pleural were (n = The of radiologic abnormalities with systemic and cardiac manifestations was significant Table X-ray abnormalities were significantly less frequent in patients with embolic or neurologic methods Before 1977, all cases were diagnosed by angiocardiography with left heart (n = 1977, echocardiography was the diagnostic (n = only M-mode echocardiography was (Figure 3). 2-dimensional and particularly echocardiography the methods in many cases. For 2 patients the diagnosis was established by or 3: A myxoma is seen in the left The diagnosis of myxoma was obtained after surgical tumor for all cases. On the tumor from 1 cm to 15 The size was for was than 5 cm in and in cases had been during The weight of the from 15 to In our series of the myxomas were with a cm), and were the left atrial myxomas in our series, the and from the left atrial with only a other left and small mitral valve The myxoma surface was studied in was or in of these (n = and (Figure 4) in the other cases (n = The less common or (Figure 5) myxomas had a surface that of multiple or and with a to (Figure 4: left atrial myxoma after left atrial were on the of myxoma in an of an The myxoma had a or an and a were the The surface of the tumor was by a of was observed in of the cases. We with a myxoma from with a and or different of 1) (Figure with or by then by 2) (Figure with many or in the of the cases were left atrial of them with and with were myxomas with All were observed in patients with myxoma and atrial myxoma with with myxoma in atrial myxoma with or myxoma in significant could be between myxoma size or 5 and diagnosis or or of or serologic symptoms or signs (Table 6). a myxoma size cm was significantly with cardiac symptoms, auscultatory signs, and and chest X-ray of myxomas appeared to be more and the delay to diagnosis was for small than for large Table of clinical features to myxoma size was significantly with neurologic symptoms, embolic and cardiac auscultation there was no significant between and or X-ray signs or symptoms; discovery; or delay in diagnosis (Table of clinical features to myxoma surface course All patients had patients during the 1 patient in during a second surgical for a of myxoma years after the first surgical a on in with cardiac and on the second postoperative from a in from mitral by a mitral and a in from meningitis with the the incidental tumor had been 1 patient a mitral valve endocarditis was with the myxoma. The most frequent postoperative was transient or atrial in patients A permanent cardiac for was for only 2 patients. Follow-up the postoperative patients were to patients to and not our Among the other patients, 4 and were during the follow-up Patients presented with peripheral fully The follow-up for patients with multiple cerebral is 14 years a In the present series, were for a median of 3 years 1 yr). Six patients had a of myxoma. Three patients with myxoma in the left and 17 years Three other patients had One of them suffered 2 in the left 16 and months The other 2 patients with had an initial myxoma in the right for 1 of them the was in the left atrium 3 years and for the other the were multiple in the left atrium and years and then in the right atrium years We report here the series of patients with left atrial myxoma diagnosed in a to our The patients presented over a 40-year ratio is with other in this ratio from to Myxomas can occur in all but are most frequent between the and of occur in although there is no for this female due in to In our series, younger age is significantly with neurologic signs or cardiac auscultation and is with neurologic or embolic symptoms in men and systemic symptoms in Clinical features The clinical features of these are by and there are no signs and symptoms that the of a myxoma In a of there are no symptoms at all in our there is no significant between the size of the tumor or 5 and the of discovery or atrial myxomas when the mitral or systemic 1) symptoms occur in of patients in our cases as mitral valve in mitral atrial and of fever are only of patients had in our study. Cardiac obstruction can be by progressive congestive cardiac failure on or or by syncope, or to mitral valve obstruction by the myxoma or coronary arteries The of obstruction may vary with body and these postural changes are particularly of myxoma (35,47). Cardiac failure the most frequent in our In our the of cardiac signs increased the diagnosis to that clinical symptoms are by another more common disease due to 2) emboli are the second of the classic in of myxoma patients in our study. than of emboli to the central nervous system in our but any may be to a of symptoms and cases emboli in the upper and lower coronary and more emboli may to aneurysms, as of cardiac myxomas as in 3 patients in our was 12, yr, We that the of an or surface is significantly with cerebral and peripheral 3) Constitutional signs are the of the classic these symptoms are may occur in to of cases The is lower in our series studied a at a cardiovascular These signs and symptoms myalgia, muscle weakness, arthralgia, fever, weight loss, and are obviously nonspecific and may occur in a of or or immunologic diseases tissue manifestations have also been reported in myxoma patients Cardiac auscultation Cardiac auscultatory may vary between and may on body presystolic or diastolic murmurs, significant mitral may be heard in more than of the patients in our The auscultatory of myxoma is “tumor is a heart sound of heard after the second heart sound may be with a heart sound or a mitral The tumor plop is in only of patients in our We established a significant between cardiac auscultation abnormalities and cardiac or systemic symptoms. and are abnormal in only of the patients those with systemic symptoms significant was in our The main but nonspecific laboratory abnormalities are and elevated or is or may occur by on the has also been common are and that the and of a by the tumor may be for systemic and manifestations has been with of in patients with myxoma that to after surgical removal A between the size of the tumor and the of has also been suggested have also been in myxoma tissue myxoma tissue in cases by and are nonspecific but observed in our atrial in of patients, the alterations by the is (less than of cases) in to the in mitral valve We observed a significant between signs and the of cardiac or systemic symptoms. also nonspecific features in the patients and are not for when the tumor is in our a left atrium enlargement and signs of pulmonary may be In our series, chest X-ray abnormalities were significantly with cardiac or systemic symptoms, but there were radiologic signs when the myxoma was by embolic or neurologic In cardiac signs or symptoms are more prevalent with large and may that embolic becoming are diagnosed before the the size 5 that to cardiac and radiologic data a positive between small tumor size and embolic Table 6). methods is the and diagnostic of is and not any risk of tumor and and cardiac examination may be by the echocardiography is less with an to but echocardiography the for surgery is only on echocardiographic evidence of the in our series angiocardiography has not been since coronary in patients over 40 years old is in to coronary disease Other diagnostic methods and The of and over echocardiography is that of and thoracic are also more in tumor and tumor and size data that most left atrial myxomas arise from the atrial or the on the of and on the appearance is or with a or or is and the surface is either or and in our myxomas with constitutional symptoms, or In the such as and surface are seen in older that In our series, there was no significant between and The size and weight of myxomas but in our the of symptoms was in patients with on could or myxomas and or myxomas according to the of the that all occurred in patients with and myxomas. the of cardiac myxomas have been The of most is that myxomas are of is no that myxomas are myxomas may have a of that at first may be the of multiple surface or is not with or any of presentation, and is important not to an on the basis of these atypical are cardiac not be with myxomas The to the tumor are to be and analysis has that myxoma as tumor = and are and may be for and cases with is as is the showed that was by is also a for the that myxomas arise from the to A study that myxomas with a between tumor size and the of this a in Myxomas may to the but these not have any The myxoma tissue emboli may may the and may or may but any cerebral tissue years the may to Three patients in our series had embolic that into the with of multiple aneurysms, any or during and follow-up The of for myxomas is surgical removal the diagnosis is of the tumor is Embolic complications or are in patients: of patients in the time of our series, not due to cardiac but 2 patients had cardiac arrest in the before surgery with successful resuscitation. surgery is a as most are can be The may according to In our series, was 3 patients during the postoperative period before and another patient in of meningitis not to myxoma. The most frequent postoperative was transient or with an of Cardiac myxomas occur but or cases have been The reported rate ranges from to in the in our are reported from as as a months to as as years after of the myxoma in our The of is not but risk or of tumor of the a of tumor in the In most cases of of the to be the of Patients with abnormalities are at risk of and from 2 or more of the cardiac and myxomas or of the with and are as or The risk of for and myxomas is about and is only for In our series, 3 cases the cardiac myxoma the time of myxoma patients are younger than myxoma patients. myxomas of the 2 patient groups are not A to has been identified The is In the the rate is and after of myxomas ranges from 0 to in our may surgical removal in our A patients may permanent cardiac for conduction 2 patients in our In of the of a tumor that with mitral valve to in heart failure, the mitral valve is In our only 1 patient mitral valve for endocarditis with left atrial myxoma. the myxoma patients to be and cases. echocardiogram is over the period at diagnosis The mitral valve other and heart more common than and occur in patients with myocardial infarction or systemic symptoms are present (fever, weight loss, the diagnosis heart and tissue disease or The of embolic and constitutional symptoms is due more to but may also myxoma. The of or syndrome to the 2 diseases, as these are in myxoma. myxomas are occasionally the clinical of myxoma and endocarditis more of cardiac myxomas reported 40 cases with a presentation similar to is no clinical between and noninfected myxoma cardiac symptoms and the rate of systemic or cerebral constitutional symptoms significantly in patients with myxoma (fever, elevated and men are more than series of 112 cases of left atrial myxoma clinical that this tumor may a of clinical symptoms not only such as cardiac but also or neurologic is made only on clinical there are no signs or symptoms. but or cases have been that and of the by the tumor may be for or including the is the of for diagnosis and follow-up of this myxomas are be in the diagnosis of mitral valve disease and congestive heart failure, in patients with is also for any patient with embolic embolic in in the of signs or symptoms of endocarditis or to a of myxoma as the embolic The obtained by be are to the clinical features of in in myxoma or be studied for embolic myxomas with of could be performed to for the ratio and age We a series of 112 cases of left atrial myxoma diagnosed in a French and 40 age range, yr) over 40 years, from 1959 to Symptoms of mitral valve the first of the classic of myxoma presentation, were present in 75 patients with cardiac failure or Symptoms of the second frequent presentation in the classic were observed in 33 cases with 1 or several cerebral emboli with are at risk than females of embolic The of the classic of constitutional symptoms with fever, weight loss, or symptoms tissue due to and patients have more neurologic symptoms, and female patients have more systemic symptoms. patients (64%) had cardiac auscultation valve disease and more the tumor plop The most frequent was left atrial were The number of myxoma patients diagnosed after 1977 the introduction of echocardiography as a noninvasive diagnostic there was no significant in the time from onset of symptoms to between patients seen in the before and after The tumor from 1 to 15 cm with a weight of between 15 and The myxoma surface was or in of the and in the other cases. Myxomas in patients with embolism have a those in patients with cardiac symptoms, auscultation signs, tumor and electrocardiogram or radiologic signs of left atrium and are significantly the The is and only 4 occurred our 112 cases over a median follow-up of 3 The rate is but follow-up and echocardiography are for patients. The surgical were performed during the 40-year period by We are to for the

Medicine · review · 878 citationsread the source →

Barriers to Physical Activity in Children With Autism Spectrum Disorders: Relationship to Physical Activity and Screen Time.

Background: Individual, social, and community barriers to physical activity (PA) experienced by children with autism spectrum disorder (ASD) make PA participation more difficult and may contribute to increased screen time. Methods: We compared the prevalence of parent-reported barriers to PA among 58 typically developing (TD) children and 53 children with an ASD, 3 to 11 years, and assessed the association between barriers and PA participation and screen time among children with ASD. Results: Parents of children with ASD reported significantly more barriers than parents of TD children. Based on parent-report, 60% of children with ASD required too much supervision compared with no TD children (P < .001). Parents of children with ASD were more likely to report that adults lack skills needed to include their child (58%), that their child has few friends (45%), and that other children exclude their child (23%). The number of parent-reported barriers to PA was inversely correlated with the hours spent in PA per year (r = -0.27, P = .05) and positively related to total screen time (r = .32, P < .03). Conclusions: These findings underscore the need for community-based PA programs designed to meet the special requirements of this population and policies that compel schools and other government-supported organizations for inclusion and/or targeted programming.

Journal of physical activity & health · 110 citationsread the source →

Domain differentiated disclosure to mothers and siblings and associations with sibling relationship quality and youth emotional adjustment.

Disclosure, or revealing personal information to others, is important for the development and maintenance of close relationships (Jourard, 1971; Rotenberg, 1995). More recently within developmental psychology, however, the focus has been the study of adolescent disclosure to parents as a means of information management regarding their daily activities. This research assumes that a) disclosure between multiple adolescents and parents within the same family are similar, and b) only information transmitted from adolescents to parents is important for adolescent well-being. Thus, this article presents the findings of 2 within-family studies to investigate differences in the amount and social domain (Smetana, 2006; Turiel, 2002) of youth disclosure to mothers versus siblings, and the influence of disclosure to siblings on relationship quality and youth emotional adjustment. Study 1 utilized 101 sibling dyads with youth ranging in age from 11-21 years, but all siblings living together. Study 2 investigated a sample of 58 sibling dyads in which all first-borns were first-year college students and all second-borns were in high school. All participants completed questionnaire measures to assess study variables. Findings revealed that while youth disclosed more to mothers than siblings, this difference disappears by emerging adulthood, particularly depending on the domain of the issue. Additionally, while greater disclosure among siblings was positive for the quality of the relationship, sibling disclosure was differentially associated with emotional adjustment depending on whether youth were the disclosers or being disclosed to, the domain of the issues disclosed, and the gender composition of the dyad.

Developmental psychology · 14 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]. 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(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 →

Health of men, women, and children in post-trafficking services in Cambodia, Thailand, and Vietnam: an observational cross-sectional study.

Background: Trafficking is a crime of global proportions involving extreme forms of exploitation and abuse. Yet little research has been done of the health risks and morbidity patterns for men, women, and children trafficked for various forms of forced labour. Methods: We carried out face-to-face interviews with a consecutive sample of individuals entering 15 post-trafficking services in Cambodia, Thailand, and Vietnam. We asked participants about living and working conditions, experience of violence, and health outcomes. We measured symptoms of anxiety and depression with the Hopkins Symptoms Checklist and post-traumatic stress disorder with the Harvard Trauma Questionnaire, and used adjusted logistic regression models to estimate the effect of trafficking on these mental health outcomes, controlling for age, sector of exploitation, and time in trafficking. Findings: We interviewed 1102 people, of whom 1015 reached work destinations. Participants worked in various sectors including sex work (329 [32%]), fishing (275 [27%]), and factories (136 [13%]). 481 (48%) of 1015 experienced physical violence, sexual violence, or both, with 198 (35%) of 566 women and girls reporting sexual violence. 478 (47%) of 1015 participants were threatened and 198 (20%) were locked in a room. 685 (70%) of 985 who had data available worked 7 days per week and 296 (30%) of 989 worked at least 11 hours per day. 222 (22%) of 983 had a serious injury at work. 61·2% (95% CI 58·2-64·2) of participants reported symptom of depression, 42·8% (39·8-45·9) reported symptoms of anxiety, and 38·9% (36·0-42·0) reported symptoms of post-traumatic stress disorder. 5·2% (4·0-6·8) had attempted suicide in the past month. Participants who experienced extremely excessive overtime at work, restricted freedom, bad living conditions, threats, or severe violence were more likely to report symptoms of depression, anxiety, and post-traumatic stress disorder. Interpretation: This is the first health study of a large and diverse sample of men, women, and child survivors of trafficking for various forms of exploitation. Violence and unsafe working conditions were common and psychological morbidity was associated with severity of abuse. Survivors of trafficking need access to health care, especially mental health care. Funding: Anesvad Foundation and International Organization for Migration International Development Fund.

The Lancet. Global health · 87 citationsread the source →

Usability of Commercially Available Mobile Applications for Diverse Patients.

Background: Mobile applications or 'apps' intended to help people manage their health and chronic conditions are widespread and gaining in popularity. However, little is known about their acceptability and usability for low-income, racially/ethnically diverse populations who experience a disproportionate burden of chronic disease and its complications. Objective: The objective of this study was to investigate the usability of existing mobile health applications ("apps") for diabetes, depression, and caregiving, in order to facilitate development and tailoring of patient-facing apps for diverse populations. Design: Usability testing, a mixed-methods approach that includes interviewing and direct observation of participant technology use, was conducted with participants (n = 9 caregivers; n = 10 patients with depression; and n = 10 patients with diabetes) on a total of 11 of the most popular health apps (four diabetes apps, four depression apps, and three caregiver apps) on both iPad and Android tablets. Participants: The participants were diverse: 15 (58 %) African Americans, seven (27 %) Whites, two (8 %) Asians, two (8 %) Latinos with either diabetes, depression, or who were caregivers. Main measures: Participants were given condition-specific tasks, such as entering a blood glucose value into a diabetes app. Participant interviews were video recorded and were coded using standard methods to evaluate attempts and completions of tasks. We performed inductive coding of participant comments to identify emergent themes. Key results: Participants completed 79 of 185 (43 %) tasks across 11 apps without assistance. Three themes emerged from participant comments: lack of confidence with technology, frustration with design features and navigation, and interest in having technology to support their self-management. Conclusions: App developers should employ participatory design strategies in order to have an impact on chronic conditions such as diabetes and depression that disproportionately affect vulnerable populations. While patients express interest in using technologies for self-management, current tools are not consistently usable for diverse patients.

Journal of general internal medicine · 166 citationsread the source →

Roles of cyberbullying, sleep, and physical activity in mediating the effects of social media use on mental health and wellbeing among young people in England: a secondary analysis of longitudinal data.

Background: There is growing concern about the potential associations between social media use and mental health and wellbeing in young people. We explored associations between the frequency of social media use and later mental health and wellbeing in adolescents, and how these effects might be mediated. Methods: We did secondary analyses of publicly available data from the Our Futures study, a nationally representative, longitudinal study of 12 866 young people from age 13 years to 16 years in England. The exposure considered was the frequency of social media use (from weekly or less to very frequent [multiple times daily]) at wave 1 (participants aged 13-14 years) through wave 3 of the study (participants aged 15-16 years). Outcomes were mental health at wave 2 (with high 12-item General Health Questionnaire [GHQ12] scores [≥3] indicating psychological distress), and wellbeing at wave 3 (life satisfaction, feeling life is worthwhile, happiness, and anxiety, rated from 1 to 10 by participants). Analyses were adjusted for a minimal sufficient confounding structure, and were done separately for boys and girls. Cyberbullying, sleep adequacy, and physical activity were assessed as potential mediators of the effects. Findings: Very frequent use of social media increased from wave 1 to wave 3: from 34·4% (95% CI 32·4-36·4) to 61·9% (60·3-63·6) in boys, and 51·4% (49·5-53·3) to 75·4% (73·8-76·9) in girls. Very frequent social media use in wave 1 predicted a high GHQ12 score at wave 2 among girls (adjusted odds ratio [OR] 1·31 [95% CI 1·06-1·63], p=0·014; N=4429) and boys (1·67 [1·24-2·26], p=0·0009; N=4379). Persistent very frequent social media use across waves 1 and 2 predicted lower wellbeing among girls only (adjusted ORs 0·86 [0·74-0·99], N=3753, p=0·039 for life satisfaction; 0·80 [0·70-0·92], N=3831, p=0·0013 for happiness; 1·28 [1·11-1·48], N=3745, p=0·0007 for anxiety). Adjustment for cyberbullying, sleep, and physical activity attenuated the associations of social media use with GHQ12 high score (proportion mediated 58·2%), life satisfaction (80·1%), happiness (47·7%), and anxiety (32·4%) in girls, such that these associations (except for anxiety) were no longer significant; however, the association with GHQ12 high score among boys remained significant, being mediated only 12·1% by these factors. Interpretation: Mental health harms related to very frequent social media use in girls might be due to a combination of exposure to cyberbullying or displacement of sleep or physical activity, whereas other mechanisms appear to be operative in boys. Interventions to promote mental health should include efforts to prevent or increase resilience to cyberbullying and ensure adequate sleep and physical activity in young people. Funding: None.

The Lancet. Child & adolescent health · 131 citationsread the source →

Prevalence of post-traumatic stress disorder and common mental disorders in health-care workers in England during the COVID-19 pandemic: a two-phase cross-sectional study.

Background: Previous studies on the impact of the COVID-19 pandemic on the mental health of health-care workers have relied on self-reported screening measures to estimate the point prevalence of common mental disorders. Screening measures, which are designed to be sensitive, have low positive predictive value and often overestimate prevalence. We aimed to estimate prevalence of common mental disorders and post-traumatic stress disorder (PTSD) among health-care workers in England using diagnostic interviews. Methods: We did a two-phase, cross-sectional study comprising diagnostic interviews within a larger multisite longitudinal cohort of health-care workers (National Health Service [NHS] CHECK; n=23 462) during the COVID-19 pandemic. In the first phase, health-care workers across 18 NHS England Trusts were recruited. Baseline assessments were done using online surveys between April 24, 2020, and Jan 15, 2021. In the second phase, we selected a proportion of participants who had responded to the surveys and conducted diagnostic interviews to establish the prevalence of mental disorders. The recruitment period for the diagnostic interviews was between March 1, 2021 and Aug 27, 2021. Participants were screened with the 12-item General Health Questionnaire (GHQ-12) and assessed with the Clinical Interview Schedule-Revised (CIS-R) for common mental disorders or were screened with the 6-item Post-Traumatic Stress Disorder Checklist (PCL-6) and assessed with the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) for PTSD. Findings: The screening sample contained 23 462 participants: 2079 participants were excluded due to missing values on the GHQ-12 and 11 147 participants due to missing values on the PCL-6. 243 individuals participated in diagnostic interviews for common mental disorders (CIS-R; mean age 42 years [range 21-70]; 185 [76%] women and 58 [24%] men) and 94 individuals participated in diagnostic interviews for PTSD (CAPS-5; mean age 44 years [23-62]; 79 [84%] women and 15 [16%] men). 202 (83%) of 243 individuals in the common mental disorders sample and 83 (88%) of 94 individuals in the PTSD sample were White. GHQ-12 screening caseness for common mental disorders was 52·8% (95% CI 51·7-53·8). Using CIS-R diagnostic interviews, the estimated population prevalence of generalised anxiety disorder was 14·3% (10·4-19·2), population prevalence of depression was 13·7% (10·1-18·3), and combined population prevalence of generalised anxiety disorder and depression was 21·5% (16·9-26·8). PCL-6 screening caseness for PTSD was 25·4% (24·3-26·5). Using CAPS-5 diagnostic interviews, the estimated population prevalence of PTSD was 7·9% (4·0-15·1). Interpretation: The prevalence estimates of common mental disorders and PTSD in health-care workers were considerably lower when assessed using diagnostic interviews compared with screening tools. 21·5% of health-care workers met the threshold for diagnosable mental disorders, and thus might benefit from clinical intervention. Funding: UK Medical Research Council; UCL/Wellcome; Rosetrees Trust; NHS England and Improvement; Economic and Social Research Council; National Institute for Health and Care Research (NIHR) Biomedical Research Centre at the Maudsley and King's College London (KCL); NIHR Protection Research Unit in Emergency Preparedness and Response at KCL.

The lancet. Psychiatry · 57 citationsread the source →

Stressful life events, worry, and rumination predict depressive and anxiety symptoms in young adolescents.

Problem: Depression and anxiety are highly prevalent and frequently comorbid mental health disorders that often manifest during childhood and adolescence. The purpose of this study was to prospectively examine potential common underlying mechanisms predicting the development of depressive and anxiety symptoms to identify mutual underlying modifiable risk factors to target with mental health promotion and prevention interventions. Methods: A community-based sample of 11- to 15-year-old adolescents participated in a prospective, longitudinal pilot study with three waves of data collection over a 6-month period. Findings: At baseline, stressful life events, worry, and rumination accounted for 35% of the variance in anxiety scores (adjusted R(2) = 0.28) and 58% of the variance in depressive symptoms (adjusted R(2) = 0.53), while at Time 3 (T3; 6 months post baseline) these variables accounted for 63% of the variance in anxiety scores (adjusted R(2) = 0.59) and 45% of the variance in depressive symptoms (adjusted R(2) = 0.39). After controlling for baseline values, increases in stress, worry, and rumination were predictive of both depressive and anxiety symptoms at T3. Conclusions: Study findings point to the importance of prevention and early intervention programs including content addressing stress management, rumination, and worry.

Journal of child and adolescent psychiatric nursing : official publication of the Association of Child and Adolescent Psychiatric Nurses, Inc · 89 citationsread the source →

Correlation Between Financial Toxicity, Quality of Life, and Patient Satisfaction in an Insured Population of Breast Cancer Surgical Patients: A Single-Institution Retrospective Study.

Background: The relationship between treatment-related, cost-associated distress "financial toxicity" (FT) and quality-of life (QOL) in breast cancer patients remains poorly characterized. This study leverages validated patient-reported outcomes measures (PROMs) to analyze the association between FT and QOL and satisfaction among women undergoing ablative breast cancer surgery. Study design: This is a single-institution cross-sectional survey of all female breast cancer patients (>18 years old) who underwent lumpectomy or mastectomy between January 2018 and June 2019. FT was measured via the 11-item COmprehensive Score for financial Toxicity (COST) instrument. The BREAST-Q and SF-12 were used to asses condition-specific and global QOL, respectively. Responses were linked with demographic and clinical data. Pearson correlation coefficient and multivariable regression were used to examine associations. Results: Our analytical sample consisted of 532 patients; mean age 58, mostly white (76.7%), employed (63.7%), married/committed (73.7%), with 64.3% undergoing reconstruction. Median household income was $80,000 to $120,000/year, and mean COST score was 28.0. After multivariable adjustment, a positive relationship for all outcomes was noted; lower COST (greater cost-associated distress) was associated with lower BREAST-Q and SF-12 scores. This relationship was strongest for BREAST-Q psychosocial well-being, for which we observed a 0.89 (95% CI 0.76-1.03) change per unit change in COST score. Conclusions: Financial toxicity captured in this study correlates with statistically significant and clinically important differences in BREAST-Q psychosocial well-being, patient satisfaction with reconstructed breasts, and SF-12 global mental and physical quality of life. Treatment costs should be included in the shared decision-making for breast cancer surgery. Future prospective outcomes research should integrate COST.

Journal of the American College of Surgeons · 43 citationsread the source →

The Effect of Cyberbullying, Abuse, and Screen Time on Non-suicidal Self-Injury Among Adolescents During the Pandemic: A Perspective From the Mediating Role of Stress.

Adolescence is often a period of turmoil. The COVID-19 pandemic has increased adolescents' difficulty due to mental health consequences that may affect their developmental milestones. This study constructed and empirically tested a theoretical model of three predictive factors (cyberbullying, abuse, and screen time) and stress as the mediating factor in adolescent non-suicidal self-injury (NSSI). Structural equation model (SEM) analysis was applied to investigate stress as a mediating factor in the relationship between adolescent NSSI and cyberbullying, abuse, and screen time. This cross-sectional study used a "crowdsourcing" sample collection method to recruit 464 adolescents aged 11-17 years who were administered a questionnaire comprising scales on cyberbullying, abuse, screen time, stress, and NSSI. All scales had construct reliabilities ranging from 0.759 to 0.958. SEM statistical analysis was performed using Lisrel version 8.8 (Scientific Software International, USA) for Windows (Microsoft Corporation, Redmond, WA, USA). The mean (± SD) age of the cohort was 14.61 ± 1.65 years, and consisted of 66.7% females. Secondary high school was the highest educational background (58%). The study found that cyberbullying and abuse were direct positive predictors (critical t-value for the path > 1.96; p < 0.05) of adolescent NSSI; however, screen time did not have any direct relationship. Furthermore, stress was a significant full mediating factor of screen time and a partial mediating factor of cyberbullying and abuse in the relationship with adolescent NSSI (critical t-value of the path = 5.27; p < 0.05). Cyberbullying, screen time, and abuse with the mediating effect of stress could explain 48% of the variance in adolescent NSSI (R 2 = 0.48). Adolescent mental health prevention and promotion programs need to be redesigned during the current COVID-19 pandemic to manage their stress and minimize the mental health consequences of cyberbullying, abuse, and inappropriately increased screen time.

Frontiers in psychiatry · 19 citationsread the source →

Availability, use of, and satisfaction with green space, and children's mental wellbeing at age 4 years in a multicultural, deprived, urban area: results from the Born in Bradford cohort study.

Background: It is unknown whether the quantity or quality of green space is more important for mental wellbeing. We aimed to explore associations between availability of, satisfaction with, and use of green space and mental wellbeing among children aged 4 years in a multi-ethnic sample. Methods: We did a 4-year follow-up assessment of participants in the Born in Bradford longitudinal cohort study, which recruited children and mothers at the city's main maternity unit from 2007 to 2011. The primary outcome was parent-reported mental wellbeing for children aged 4 years, assessed with the standardised Strengths and Difficulties Questionnaire. Total, internalising, and externalising behavioural difficulties and prosocial behaviour scales were computed (with higher scores indicating greater difficulties or more prosocial behaviour). Residential green space around participants' home addresses and distance to major green spaces were computed with the normalised difference vegetation index (NDVI). A subsample of participants completed additional questionnaires on measures of satisfaction with, and use of, local green spaces. Multiple regressions examined associations between green space and children's mental wellbeing and explored moderation by ethnicity (white British vs south Asian) and socioeconomic status. Findings: Between Oct 1, 2012, and June 30, 2015, 2594 mothers attended a follow-up appointment during which they completed a detailed questionnaire assessing the health of their child. 1519 (58%) participants were of south Asian origin, 740 (29%) of white British origin, and 333 (13%) of another ethnicity. Data on ethnicity were missing for two participants. 832 (32%) of 2594 participants completed additional questionnaires. Ethnicity moderated associations between residential green space and mental wellbeing (p<0·05 for total and internalising difficulties). After adjusting for all relevant variables, more green space was associated with fewer internalising behavioural difficulties (mean NDVI 100 m: β -2·35 [95% CI -4·20 to -0·50]; 300 m: -3·15 [-5·18 to -1·13]; 500 m: -2·85 [-4·91 to -0·80]) and with fewer total behavioural difficulties (100 m: -4·27 [-7·65 to -0·90]; 300 m: -5·22 [-8·91 to -1·54]; 500 m: -4·82 [-8·57 to -1·07]) only for south Asian children across all three buffer zones. In the subsample of participants, the effect of NDVI on wellbeing was rendered non-significant after controlling for satisfaction with, and use of, green space. Among south Asian children, satisfaction with green space was significantly associated with fewer total behavioural difficulties across all three buffer zones (β -0·59 [95% CI -1·11 to -0·07]), fewer internalising behavioural difficulties within 100 m (-0·28 [95% CI -0·56 to -0·003]) and 300 m buffer zones (-0·28 [-0·56 to -0·002]), and greater prosocial behaviour across all three buffer zones (0·20 [0·02 to 0·38]); no such associations were observed among white British children. Interpretation: Positive effects of green space on wellbeing differ by ethnicity. Satisfaction with the quality of green space appears to be a more important predictor of wellbeing than does quantity of green space. Public health professionals and urban planners need to focus on both quality and quantity of urban green spaces to promote health, particularly among ethnic minority groups. Funding: European Community's Seventh Framework Programme.

The Lancet. Planetary health · 61 citationsread the source →

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.

World Psychiatry · editorial or comment · 607 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 →

Early childhood factors associated with the development of post-traumatic stress disorder: results from a longitudinal birth cohort.

Background: Childhood factors have been associated with increased risk of developing post-traumatic stress disorder (PTSD). Previous studies assessed only a limited number of childhood factors retrospectively. We examined the association between childhood neurodevelopmental, temperamental, behavioral and family environmental characteristics assessed before age 11 years and the development of PTSD up to age 32 years in a birth cohort. Method: Members of a 1972-73 New Zealand birth cohort (n=1037) who were assessed at ages 26 and 32 years for PTSD as defined by DSM-IV. Results: We identified two sets of childhood risk factors. The first set of risk factors was associated both with increased risk of trauma exposure and with PTSD assessed at age 26. These included childhood externalizing characteristics and family environmental stressors, specifically maternal distress and loss of a parent. The second set of risk factors affected risk for PTSD only and included low IQ and chronic environmental adversity. The effect of cumulative childhood factors on risk of PTSD at age 26 was substantial; over 58% of cohort members in the highest risk quartile for three developmental factors had PTSD as compared to only 25% of those not at high risk on any factors. Low IQ at age 5, antisocial behavior, and poverty before age 11 continued to predict PTSD related to traumatic events that occurred between the ages of 26 and 32. Conclusions: Developmental capacities and conditions of early childhood may increase both risk of trauma exposure and the risk that individuals will respond adversely to traumatic exposures. Rather than being solely a response to trauma, PTSD may have developmental origins.

Psychological medicine · 216 citationsread the source →

Taking a Spiritual History Allows Clinicians to Understand Patients More Fully

Journal of Palliative MedicineVol. 3, No. 1 Innovations in End-of-Life CareTaking a Spiritual History Allows Clinicians to Understand Patients More FullyDr. Christina Puchalski and Anna L. RomerDr. Christina Puchalski and Anna L. RomerPublished Online:19 Apr 2005https://doi.org/10.1089/jpm.2000.3.129AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byVerbalizing spiritual needs in palliative care: a qualitative interview study on verbal and non-verbal communication in two Danish hospices4 January 2022 | BMC Palliative Care, Vol. 21, No. 1Implementation of an Educational Toolkit to Increase Nurse Competence in Spirituality and Spiritual Care of Oncology Patients8 November 2022 | Journal of Holistic Nursing, Vol. 5Posicionamento sobre a Saúde Cardiovascular nas Mulheres – 2022Arquivos Brasileiros de Cardiologia, Vol. 119, No. 5Experiences of German health care professionals with spiritual history taking in primary care: a mixed-methods process evaluation of the HoPES3 intervention15 October 2022 | Family Practice, Vol. 29Religious and spiritual journeys of LGBT older adults in rural Southern Appalachia25 October 2021 | Journal of Religion, Spirituality & Aging, Vol. 34, No. 4The CASH assessment tool: A window into existential suffering19 May 2021 | Journal of Health Care Chaplaincy, Vol. 28, No. 4Integrating religion/spirituality into professional social work practice27 July 2022 | Journal of Religion & Spirituality in Social Work: Social Thought, Vol. 41, No. 4The Concept of Spirituality in the Health Sector: Contributions from the Study of Religion27 September 2022 | International Journal of Latin American Religions, Vol. 12Systematic review: The relationship between religion, spirituality and mental health in adolescents who identify as transgender13 September 2022 | Journal of Gay & Lesbian Mental Health, Vol. 26„Des Lebens Ruf an uns wird niemals enden“ – Sinnzentrierte Interventionen im Überblick30 August 2022 | Zeitschrift für Palliativmedizin, Vol. 23, No. 05Case discussion: The critically ill older adult in spiritual distressGeriatric Nursing, Vol. 47Australian Patient Preferences for the Introduction of Spirituality into their Healthcare Journey: A Mixed Methods Study3 August 2022 | Journal of Religion and Health, Vol. 27Religion, Spirituality, and Ethics in Psychiatric Practice30 March 2022 | Journal of Nervous & Mental Disease, Vol. 210, No. 8Spiritual distress in dialysis: A case report21 July 2022 | Progress in Palliative Care, Vol. 211Interprofessional communication training to address spiritual aspects of cancer care19 July 2022 | Journal of Health Care Chaplaincy, Vol. 29Spirituality in Serious Illness and HealthJAMA, Vol. 328, No. 2What is the role of spiritual care specialists in teaching generalist spiritual care? 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Psikoterapilerdeki Dini İzler15 December 2018 | Cumhuriyet İlahiyat Dergisi, Vol. 22, No. 3Women's Perceptions of Using Short Films to Integrate Spirituality in TherapyJournal of Systemic Therapies, Vol. 37, No. 4Content Validation of Advanced Illness Criteria of a Palliative Care Screening Tool Lauren C. 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September | Journal of Palliative Medicine, Vol. 20, No. in Patients with A Qualitative September | Journal of Research in Nursing and Vol. 14, No. theory on the and in an exploratory case study September | Vol. 69, No. of the of Spirituality and Palliative Care Research and of Pain and Symptom Management, Vol. No. of a spiritual care training program for staff on November | Palliative and Supportive Care, Vol. 15, No. 4Spiritual distress and spiritual care in advanced heart July | Reviews, Vol. and Spiritual Patient Simulation in Nursing, Vol. No. Vol. 42, No. 4The impact of a spiritual in patients with and and their support December | Vol. 26, No. 3The Importance of a Spiritual History in Healthcare Vol. No. About Substance Use DisordersJournal of Psychosocial Nursing and Mental Health Services, Vol. No. and Spiritual Beliefs of April | Journal of Religion and Health, Vol. No. Care Perceptions of and With of Hospice & Palliative Nursing, Vol. 19, No. in Substance Use What to Know to Practice30 November | in Mental Health Nursing, Vol. 38, No. End-of-Life Care to Religious and Vol. No. of Social Education, Vol. 53, No. Nursing Care and of Christian Nursing, Vol. 34, No. 1The of taking a religious and spiritual July | Psychiatry, Vol. 24, No. religion and spirituality in Vol. No. the role of religious in the at the of of Vol. No. care spiritual March | Supportive Care in Cancer, Vol. 24, No. Spiritual Care and the Role of An Review of Literature and April | Journal of Religion and Health, Vol. No. of the Spiritual Needs of of with Is in the June | Journal of Palliative Medicine, Vol. 19, No. Impact of a Tool for Comprehensive Assessment of Palliative Care on Assessment at and of Pain and Symptom Management, Vol. No. from Healthcare Students to Understand Spiritual Assessment in Clinical Practice29 October | Journal of Religion and Health, Vol. No. Spirituality in January | Journal of Religion and Health, Vol. No. 3Development and of to Assess Nurse Provision of Spiritual August 2014 | Journal of Holistic Nursing, Vol. 34, No. and Validation of the Practice Assessment September 2014 | Research on Social Practice, Vol. 26, No. and the Medical A of July | Journal of Health Care Chaplaincy, Vol. 22, No. history taking in palliative care: A controlled September | Palliative Medicine, Vol. 30, No. Is Is Using A and the Life With American in Spiritual March | Journal of in Mental Health, Vol. 11, No. and spiritual in September | International Journal of and Mental Health, Vol. No. 1The of Hospital to and Patients’ Spiritual A May | Journal for the Study of Spirituality, Vol. No. 1The and to March End-of-Life Spiritual March in Holistic Patient Journal of Nursing, Vol. No. of spiritual assessment for older September 2014 | and Vol. No. und der der Care, Vol. No. Spirituality and A for Holistic January | Journal of Religion and Health, Vol. No. and Belief, in Care spiritual history tool by C. M. Puchalski as an for an interdisciplinary in January | Journal for of and Social Vol. 21, No. the of Spiritual A Pain and Palliative Care Service Quality of Pain and Symptom Management, Vol. No. of Spiritual Assessment in September | Vol. No. the of Christian Nursing, Vol. 32, No. 4Spiritual care: is the assessment tool for palliative Journal of Palliative Nursing, Vol. 21, No. und Spiritualität in der September | Vol. 60, No. of September of spirituality assessment in palliative care patients in November 2014 | Progress in Palliative Care, Vol. 23, No. 4The for Spiritual A Mixed-Methods July | Oncology Nursing Vol. 42, No. 4The Integration of Religion and Spirituality in Social Practice: A May | Social Vol. 60, No. 3The and Educational of a Spiritual Life Review for Patients with and June 2014 | Journal of Cancer Education, Vol. 30, No. in Geriatric Palliative in Geriatric Medicine, Vol. No. An for Spiritual Well-Being May | Journal of Religion & Spirituality in Social Work: Social Thought, Vol. 34, No. Spiritual Assessment March | Journal of Health Care Chaplaincy, Vol. 21, No. American on Mental Health, and Help April | and Vol. 60, No. of Christian Nursing, Vol. 32, No. the Spiritual Needs and of Oncology Patients in Nursing Practice, Vol. 29, No. Care Training to Healthcare Professionals: A Systematic April | Journal of Pastoral Care & Counseling: Advancing theory and professional practice through scholarly and reflective publications, Vol. 69, No. analysis of spiritual

Journal of Palliative Medicine · 741 citationsread the source →

Female child sexual abuse within the family in a Hungarian County.

Background: The aim of the study was to analyze the characteristics of intrafamiliar female child sexual abuse and to explore common features that may be utilized as targets for possible methods of prevention. We also described the medical and legal approaches to handling child neglect. Methods: This was a descriptive, cross-sectional study on 52 sexually abused girls under the age of 18 at the Department of Obstetrics and Gynecology, Medical and Health Science Center of Debrecen. We prospectively recorded the data of all cases. Intrafamiliar events were defined if the victim and perpetrator belonged to the same family. Legal outcomes were also recorded. Results: During the 16-year period, 209 cases of sexual abuse were seen in our clinic, 52 of them had been involved in child sexual abuse within the family. This accounts for 25% of adolescent cases. Eighty-six percent of the victims were pupils, 50% of them were between 11 and 14 years of age. The perpetrator was the victim's father in 44%, and the stepfather in 40%. There was a slight difference between the type of abuse among the pre- and postpubertal group of victims, but statistically it was not significant. The abuse occurred on multiple occasions in 52%. The occurrence rate of assault was the highest in the summer season (58%), mostly in the afternoon (42%) and it took place almost exclusively at home (98%). The mother accompanied the victim in 38% of the cases and the police in 40%. Vaginal penetration was the type of abuse in 75%, and sexual perversion in 25%. Six victims were physically injured, the presence of sperm could be confirmed on vulvovaginal smears in 2 cases. One pregnancy conceived. Nine cases were reported to the police and as a result of legal proceedings, 5 perpetrators have been sentenced. Conclusion: The majority of crimes take place within the family and are disclosed after multiple episodes. The small proportion of reported sexual assaults is the consequence of the lack of harmony between the Hungarian conditions of emergency care and the criminal law. Prevention calls for attention at all levels of child education, observation at off-school times, early involvement of health professionals, applying standardized medical guidelines and the modification of jurisdiction.

Gynecologic and obstetric investigation · 7 citationsread the source →

Demoralization and depression in patients with advanced cancer: validation of the German version of the demoralization scale.

Context: The concept of demoralization has been widely used to describe states of existential distress and a self-perceived incapacity to deal effectively with a specific stressful situation. Objectives: To evaluate the psychometric properties of the German adaptation of the Demoralization Scale (DS) in patients with advanced cancer. Methods: Participants with heterogeneous tumor sites were recruited in several treatment and rehabilitation facilities. Concurrent and divergent validity of the DS was analyzed through associations with and group differences between measures of distress, depression, anxiety, and meaning-related life attitudes. Results: From a total sample of 1102 patients, 516 individuals (45%) with advanced cancer were enrolled (male 53%, median age 58 years [range 18-88], breast cancer 21%, prostate cancer 17%). The total mean score of the DS was 29.8 (SD=10.41). Four factors were extracted by exploratory factor analysis, which accounted for 59% of the variation (Cronbach α=0.84): loss of meaning and purpose (α=0.88), disheartenment (α=0.88), dysphoria (α=0.80), and sense of failure (α=0.76). DS dimensions shared between 12% and 62% of the variance. Demoralization was significantly associated with anxiety (r=0.71), depression (r=0.61), and distress (r=0.42). Fifty-seven percent of patients had high distress, 24% depression, and 11% high anxiety. According to different cutoff values, between 16% and 39% were seriously demoralized and 73% had moderate levels of demoralization. Between 5% and 20% of patients were seriously demoralized but not clinically depressed; 60% of patients with moderate levels of demoralization had no depression. Conclusion: Results provide further evidence that the DS is a valid and reliable instrument of high clinical relevance in patients with advanced cancer.

Journal of pain and symptom management · 104 citationsread the source →