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Peer-reviewed works with DOI and abstract, discovered from MEDLINE-indexed literature. Candidates: no tier, no stated finding, not yet read.
Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, Leucht S, Ruhe HG, Turner EH, Higgins JPT, Egger M, Takeshima N, Hayasaka Y, Imai H, Shinohara K, Tajika A, Ioannidis JPA, Geddes JR. (2018)MEDLINE-indexed journal, not yet read by usLancet (London, England) · systematic review Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.
Background: Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder.
Methods: We did a systematic review and network meta-analysis. We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016. We included placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults (≥18 years old and of both sexes) with major depressive disorder diagnosed according to standard operationalised criteria. We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; or patients with a serious concomitant medical illness. We extracted data following a predefined hierarchy. In network meta-analysis, we used group-level data. We assessed the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Primary outcomes were efficacy (response rate) and acceptability (treatment discontinuations due to any cause). We estimated summary odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO, number CRD42012002291.
Findings: We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89-2·41) for amitriptyline and 1·37 (1·16-1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72-0·97) and fluoxetine (0·88, 0·80-0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01-1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19-1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51-0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43-0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30-2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low.
Interpretation: All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants.
Funding: National Institute for Health Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science.
Lancet (London, England) · systematic review · 2220 citationsread the source →
Vitamin D deficiency, self-reported physical activity and health-related quality of life: the Comprehensive Dialysis Study.
Background: As research has identified a wide array of biological functions of vitamin D, the consequences of vitamin D deficiency in persons with chronic kidney disease has attracted increased attention. The objective of this study was to determine the extent of 25-hydroxyvitamin D (25-OH vitamin D) deficiency and its associations with self-reported physical activity and health-related quality of life (HRQoL) among participants of the Comprehensive Dialysis Study (CDS).
Methods: The nutrition substudy of the CDS enrolled patients new to dialysis from 68 dialysis units throughout the USA. Baseline 25-OH vitamin D concentration was measured using the Direct Enzyme Immunoassay (Immunodiagnostic Systems Inc.). Physical activity was measured with the Human Activity Profile (HAP); the Medical Outcomes Study Short Form-12 (SF-12) was employed to measure HRQoL.
Results: Mean age of the participants (n = 192) was 62 years. There were 124 participants (65%) with 25-OH vitamin D concentrations < 15 ng/mL, indicating deficiency, and 64 (33%) with 25-OH vitamin D ≥ 15 to <30 ng/mL, indicating insufficiency. After adjusting for age, sex, race/ethnicity, diabetes, season and center, lower 25-OH vitamin D concentrations were independently associated with lower scores on the HAP and on the Mental Component Summary of the SF-12 (P < 0.05 for both), but not with the Physical Component Summary of the SF-12.
Conclusion: In a well-characterized cohort of incident dialysis patients, lower 25-OH vitamin D concentrations were associated with lower self-reported physical activity and poorer self-reported mental health.
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 49 citationsread the source →
Volandes AE, Paasche-Orlow MK, Barry MJ, Gillick MR, Minaker KL, Chang Y, Cook EF, Abbo ED, El-Jawahri A, Mitchell SL. (2009)MEDLINE-indexed journal, not yet read by usBMJ (Clinical research ed.) · randomised controlled trial Video decision support tool for advance care planning in dementia: randomised controlled trial.
Objective: To evaluate the effect of a video decision support tool on the preferences for future medical care in older people if they develop advanced dementia, and the stability of those preferences after six weeks.
Design: Randomised controlled trial conducted between 1 September 2007 and 30 May 2008. Setting Four primary care clinics (two geriatric and two adult medicine) affiliated with three academic medical centres in Boston.
Participants: Convenience sample of 200 older people (>or=65 years) living in the community with previously scheduled appointments at one of the clinics. Mean age was 75 and 58% were women.
Intervention: Verbal narrative alone (n=106) or with a video decision support tool (n=94).
Main outcome measures: Preferred goal of care: life prolonging care (cardiopulmonary resuscitation, mechanical ventilation), limited care (admission to hospital, antibiotics, but not cardiopulmonary resuscitation), or comfort care (treatment only to relieve symptoms). Preferences after six weeks. The principal category for analysis was the difference in proportions of participants in each group who preferred comfort care.
Results: Among participants receiving the verbal narrative alone, 68 (64%) chose comfort care, 20 (19%) chose limited care, 15 (14%) chose life prolonging care, and three (3%) were uncertain. In the video group, 81 (86%) chose comfort care, eight (9%) chose limited care, four (4%) chose life prolonging care, and one (1%) was uncertain (chi(2)=13.0, df=3, P=0.003). Among all participants the factors associated with a greater likelihood of opting for comfort care were being a college graduate or higher, good or better health status, greater health literacy, white race, and randomisation to the video arm. In multivariable analysis, participants in the video group were more likely to prefer comfort care than those in the verbal group (adjusted odds ratio 3.9, 95% confidence interval 1.8 to 8.6). Participants were re-interviewed after six weeks. Among the 94/106 (89%) participants re-interviewed in the verbal group, 27 (29%) changed their preferences (kappa=0.35). Among the 84/94 (89%) participants re-interviewed in the video group, five (6%) changed their preferences (kappa=0.79) (P<0.001 for difference).
Conclusion: Older people who view a video depiction of a patient with advanced dementia after hearing a verbal description of the condition are more likely to opt for comfort as their goal of care compared with those who solely listen to a verbal description. They also have more stable preferences over time.
Trial registration: Clinicaltrials.gov NCT00704886.
BMJ (Clinical research ed.) · randomised controlled trial · 207 citationsread the source →
The Association between Prosocial Behaviour and Peer Relationships with Comorbid Externalizing Disorders and Quality of Life in Treatment-Naïve Children and Adolescents with Attention Deficit Hyperactivity Disorder.
Several recent studies confirmed that Attention Deficit Hyperactivity Disorder (ADHD) has a negative influence on peer relationship and quality of life in children. The aim of the current study is to investigate the association between prosocial behaviour, peer relationships and quality of life in treatment naïve ADHD samples. The samples included 79 children with ADHD (64 boys and 15 girls, mean age = 10.24 years, SD = 2.51) and 54 healthy control children (30 boys and 23 girls, mean age = 9.66 years, SD = 1.73). Measurements included: The "Mini International Neuropsychiatric Interview Kid; Strengths and Difficulties Questionnaire" and the "Inventar zur Erfassung der Lebensqualität bei Kindern und Jugendlichen". The ADHD group showed significantly lower levels of prosocial behaviour and more problems with peer relationships than the control group. Prosocial behaviour has a weak positive correlation with the rating of the child's quality of life by the parents, both in the ADHD group and in the control group. The rating of quality of life and peer relationship problems by the parents also showed a significant negative moderate association in both groups. The rating of quality of life by the child showed a significant negative weak relationship with peer relationships in the ADHD group, but no significant relationship was found in the control group. Children with ADHD and comorbid externalizing disorders showed more problems in peer relationships than ADHD without comorbid externalizing disorders. Based on these results, we conclude that therapy for ADHD focused on improvement of prosocial behaviour and peer relationships as well as comorbid externalizing disorders could have a favourable effect on the quality of life of these children.
Brain sciences · 14 citationsread the source →
The prevalence of mental illness in refugees and asylum seekers: A systematic review and meta-analysis.
Background: Globally, the number of refugees and asylum seekers has reached record highs. Past research in refugee mental health has reported wide variation in mental illness prevalence data, partially attributable to methodological limitations. This systematic review aims to summarise the current body of evidence for the prevalence of mental illness in global refugee populations and overcome methodological limitations of individual studies.
Methods and findings: A comprehensive search of electronic databases was undertaken from 1 January 2003 to 4 February 2020 (MEDLINE, MEDLINE In-Process, EBM Reviews, Embase, PsycINFO, CINAHL, PILOTS, Web of Science). Quantitative studies were included if diagnosis of mental illness involved a clinical interview and use of a validated assessment measure and reported at least 50 participants. Study quality was assessed using a descriptive approach based on a template according to study design (modified Newcastle-Ottawa Scale). Random-effects models, based on inverse variance weights, were conducted. Subgroup analyses were performed for sex, sample size, displacement duration, visa status, country of origin, current residence, type of interview (interpreter-assisted or native language), and diagnostic measure. The systematic review was registered with PROSPERO (CRD) 42016046349. The search yielded a result of 21,842 records. Twenty-six studies, which included one randomised controlled trial and 25 observational studies, provided results for 5,143 adult refugees and asylum seekers. Studies were undertaken across 15 countries: Australia (652 refugees), Austria (150), China (65), Germany (1,104), Italy (297), Lebanon (646), Nepal (574), Norway (64), South Korea (200), Sweden (86), Switzerland (164), Turkey (238), Uganda (77), United Kingdom (420), and the United States of America (406). The prevalence of posttraumatic stress disorder (PTSD) was 31.46% (95% CI 24.43-38.5), the prevalence of depression was 31.5% (95% CI 22.64-40.38), the prevalence of anxiety disorders was 11% (95% CI 6.75-15.43), and the prevalence of psychosis was 1.51% (95% CI 0.63-2.40). A limitation of the study is that substantial heterogeneity was present in the prevalence estimates of PTSD, depression, and anxiety, and limited covariates were reported in the included studies.
Conclusions: This comprehensive review generates current prevalence estimates for not only PTSD but also depression, anxiety, and psychosis. Refugees and asylum seekers have high and persistent rates of PTSD and depression, and the results of this review highlight the need for ongoing, long-term mental health care beyond the initial period of resettlement.
PLoS medicine · meta-analysis · 533 citationsread the source →
Risk-reducing mastectomy for the prevention of primary breast cancer.
Background: Recent progress in understanding the genetic basis of breast cancer and widely publicized reports of celebrities undergoing risk-reducing mastectomy (RRM) have increased interest in RRM as a method of preventing breast cancer. This is an update of a Cochrane Review first published in 2004 and previously updated in 2006 and 2010.
Objectives: (i) To determine whether risk-reducing mastectomy reduces death rates from any cause in women who have never had breast cancer and in women who have a history of breast cancer in one breast, and (ii) to examine the effect of risk-reducing mastectomy on other endpoints, including breast cancer incidence, breast cancer mortality, disease-free survival, physical morbidity, and psychosocial outcomes.
Search methods: For this Review update, we searched Cochrane Breast Cancer's Specialized Register, MEDLINE, Embase and the WHO International Clinical Trials Registry Platform (ICTRP) on 9 July 2016. We included studies in English.
Selection criteria: Participants included women at risk for breast cancer in at least one breast. Interventions included all types of mastectomy performed for the purpose of preventing breast cancer.
Data collection and analysis: At least two review authors independently abstracted data from each report. We summarized data descriptively; quantitative meta-analysis was not feasible due to heterogeneity of study designs and insufficient reporting. We analyzed data separately for bilateral risk-reducing mastectomy (BRRM) and contralateral risk-reducing mastectomy (CRRM). Four review authors assessed the methodological quality to determine whether or not the methods used sufficiently minimized selection bias, performance bias, detection bias, and attrition bias.
Main results: All 61 included studies were observational studies with some methodological limitations; randomized trials were absent. The studies presented data on 15,077 women with a wide range of risk factors for breast cancer, who underwent RRM.Twenty-one BRRM studies looking at the incidence of breast cancer or disease-specific mortality, or both, reported reductions after BRRM, particularly for those women with BRCA1/2 mutations. Twenty-six CRRM studies consistently reported reductions in incidence of contralateral breast cancer but were inconsistent about improvements in disease-specific survival. Seven studies attempted to control for multiple differences between intervention groups and showed no overall survival advantage for CRRM. Another study showed significantly improved survival following CRRM, but after adjusting for bilateral risk-reducing salpingo-oophorectomy (BRRSO), the CRRM effect on all-cause mortality was no longer significant. Twenty studies assessed psychosocial measures; most reported high levels of satisfaction with the decision to have RRM but greater variation in satisfaction with cosmetic results. Worry over breast cancer was significantly reduced after BRRM when compared both to baseline worry levels and to the groups who opted for surveillance rather than BRRM, but there was diminished satisfaction with body image and sexual feelings. Seventeen case series reporting on adverse events from RRM with or without reconstruction reported rates of unanticipated reoperations from 4% in those without reconstruction to 64% in participants with reconstruction. In women who have had cancer in one breast, removing the other breast may reduce the incidence of cancer in that other breast, but there is insufficient evidence that this improves survival because of the continuing risk of recurrence or metastases from the original cancer. Additionally, thought should be given to other options to reduce breast cancer risk, such as BRRSO and chemoprevention, when considering RRM.
Authors' conclusions: While published observational studies demonstrated that BRRM was effective in reducing both the incidence of, and death from, breast cancer, more rigorous prospective studies are suggested. BRRM should be considered only among those at high risk of disease, for example, BRCA1/2 carriers. CRRM was shown to reduce the incidence of contralateral breast cancer, but there is insufficient evidence that CRRM improves survival, and studies that control for multiple confounding variables are recommended. It is possible that selection bias in terms of healthier, younger women being recommended for or choosing CRRM produces better overall survival numbers for CRRM. Given the number of women who may be over-treated with BRRM/CRRM, it is critical that women and clinicians understand the true risk for each individual woman before considering surgery. Additionally, thought should be given to other options to reduce breast cancer risk, such as BRRSO and chemoprevention when considering RRM.
The Cochrane database of systematic reviews · meta-analysis · 149 citationsread the source →
Association of Oxytocin Receptor Gene (OXTR) rs53576 Polymorphism with Sociality: A Meta-Analysis.
A common variant in the oxytocin receptor gene (OXTR), rs53576, has been broadly linked to socially related personality traits and behaviors. However, the pattern of published results is inconsistent. Here, we performed a meta-analysis to comprehensively evaluate the association. The literature was searched for relevant studies and effect sizes between individuals homozygous for the G allele (GG) and individuals with A allele carriers (AA/AG). Specifically, two indices of sociality were evaluated independently: i) general sociality (24 samples, n = 4955), i.e., how an individual responds to other people in general; and ii) close relationships (15 samples, n = 5262), i.e., how an individual responds to individuals with closed connections (parent-child or romantic relationship). We found positive association between the rs53576 polymorphism and general sociality (Cohen's d = 0.11, p = .02); G allele homozygotes had higher general sociality than the A allele carriers. However, the meta-analyses did not detect significant genetic association between rs53576 and close relationships (Cohen's d = 0.01, p = .64). In conclusion, genetic variation in the rs53576 influences general sociality, which further implies that it is worthy to systematically examine whether the rs53576 is a valid genetic marker for socially related psychiatric disorders.
PloS one · meta-analysis · 89 citationsread the source →
Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder: a randomized clinical trial.
Importance: It is estimated that more than half of those with serious mental illness smoke tobacco regularly. Standard courses of pharmacotherapeutic cessation aids improve short-term abstinence, but most who attain abstinence relapse rapidly after discontinuation of pharmacotherapy.
Objective: To determine whether smokers diagnosed with schizophrenia and bipolar disease have higher rates of prolonged tobacco abstinence with maintenance pharmacotherapy than with standard treatment.
Design, setting, and participants: Randomized, double-blind, placebo-controlled, parallel-group, relapse-prevention clinical trial conducted in 10 community mental-health centers. Of 247 smokers with schizophrenia or bipolar disease recruited from March 2008-April 2012, 203 received 12-weeks' open-label varenicline and cognitive behavioral therapy and 87 met abstinence criteria to enter the relapse prevention intervention.
Interventions: Participants who had 2 weeks or more of continuous abstinence at week 12 of open treatment were randomly assigned to receive cognitive behavioral therapy and double-blind varenicline (1 mg, 2 per day) or placebo from weeks 12 to 52. Participants then discontinued study treatment and were followed up to week 76.
Main outcomes and measures: Seven-day rate of continuous abstinence at study week 52, the end of the relapse-prevention phase, confirmed by exhaled carbon monoxide. Secondary outcomes were continuous abstinence rates for weeks 12 through 64 based on biochemically verified abstinence and weeks 12 through 76, based on self-reported smoking behavior.
Results: Sixty-one participants completed the relapse-prevention phase; 26 discontinued participation (7 varenicline, 19 placebo) and were considered to have relapsed for the analyses; 18 of these had relapsed prior to dropout. At week 52, point-prevalence abstinence rates were 60% in the varenicline group (24 of 40) vs 19% (9 of 47) in the placebo group (odds ratio [OR], 6.2; 95% CI, 2.2-19.2; P < .001). From weeks 12 through 64, 45% (18 of 40) among those in the varenicline group vs 15% (7 of 47) in the placebo group were continuously abstinent (OR, 4.6; 95% CI, 1.5-15.7; P = .004), and from weeks 12 through 76, 30% (12 of 40) in the varenicline group vs 11% (5 of 47) in the placebo group were continuously abstinent (OR, 3.4; 95% CI, 1.02-13.6; P = .03). There were no significant treatment effects on psychiatric symptom ratings or psychiatric adverse events.
Conclusions and relevance: Among smokers with serious mental illness who attained initial abstinence with standard treatment, maintenance pharmacotherapy with varenicline and cognitive behavioral therapy improved prolonged tobacco abstinence rates compared with cognitive behavioral therapy alone after 1 year of treatment and at 6 months after treatment discontinuation.
Trial registration: clinicaltrials.gov Identifier: NCT00621777.
JAMA · randomised controlled trial · 157 citationsread the source →
Health risk behaviors and mental health problems as mediators of the relationship between childhood abuse and adult health.
Objectives: We examined the relationship between childhood abuse and adult health risk behaviors, and we explored whether adult health risk behaviors or mental health problems mediated the relationship between childhood abuse and adult health problems and health care utilization.
Methods: We used logistic regression to analyze data from the Mental Health Supplement of the Ontario Health Survey, a representative population sample (N = 8116) of respondents aged 15 to 64 years.
Results: We found relationships between childhood sexual abuse and smoking (odds ratio [OR] = 1.52; 95% confidence interval [CI] = 1.16, 1.99), alcohol problems (OR = 2.44; 95% CI = 1.74, 3.44), obesity (OR = 1.61; 95% CI = 1.14, 2.27), having more than 1 sexual partner in the previous year (OR = 2.34; 95% CI = 1.44, 3.80), and mental health problems (OR = 2.26; 95% CI = 1.78. 2.87). We also found relationships between these factors (with the exception of obesity) and childhood physical abuse. Mediation analysis suggested that health risk behaviors and particularly mental health problems are partial mediators of the relationship between childhood abuse and adult health.
Conclusions: Public health approaches that aim to decrease child abuse by supporting positive parent-child relationships, reducing the development of health risk behaviors, and addressing children's mental health are likely to improve long-term population health.
American journal of public health · 107 citationsread the source →
Attitudes, barriers and enablers to physical activity in pregnant women: a systematic review.
Question: What are the attitudes, barriers and enablers to physical activity perceived by pregnant women?
Design: In a systematic literature review, eight electronic databases were searched: AMED, CINAHL, Embase, Joanna Briggs Institute, Medline, PsycInfo, SPORTDiscus (from database inception until June 2016) and PubMed (from 2011 until June 2016). Quantitative data expressed as proportions were meta-analysed. Data collected using Likert scales were synthesised descriptively. Qualitative data were analysed thematically using an inductive approach and content analysis. Findings were categorised as intrapersonal, interpersonal or environmental, based on a social-ecological framework.
Participants: Pregnant women.
Intervention: Not applicable.
Outcome measures: Attitudes and perceived barriers and enablers to physical activity during pregnancy.
Results: Forty-nine articles reporting data from 47 studies (7655 participants) were included. Data were collected using questionnaires, interviews and focus groups. Meta-analyses of proportions showed that pregnant women had positive attitudes towards physical activity, identifying it as important (0.80, 95% CI 0.52 to 0.98), beneficial (0.71, 95% CI 0.58 to 0.83) and safe (0.86, 95% CI 0.79 to 0.92). This was supported by themes emerging in 15 qualitative studies that reported on attitudes (important, 12 studies; beneficial, 10 studies). Barriers to physical activity were predominantly intrapersonal such as fatigue, lack of time and pregnancy discomforts. Frequent enablers included maternal and foetal health benefits (intrapersonal), social support (interpersonal) and pregnancy-specific programs. Few environmental factors were identified. Little information was available about attitudes, barriers and enablers of physical activity for pregnant women with gestational diabetes mellitus who are at risk from inactivity.
Conclusion: Intrapersonal themes were the most frequently reported barriers and enablers to physical activity during pregnancy. Social support also played an enabling role. Person-centred strategies using behaviour change techniques should be used to address intrapersonal and social factors to translate pregnant women's positive attitudes into increased physical activity participation.
Registration: PROSPERO CRD42016037643. [Harrison AL, Taylor NF, Shields N, Frawley HC (2018) Attitudes, barriers and enablers to physical activity in pregnant women: a systematic review. Journal of Physiotherapy 64: 24-32].
Journal of physiotherapy · systematic review · 155 citationsread the source →
Singer AE, Goebel JR, Kim YS, Dy SM, Ahluwalia SC, Clifford M, Dzeng E, O'Hanlon CE, Motala A, Walling AM, Goldberg J, Meeker D, Ochotorena C, Shanman R, Cui M, Lorenz KA. (2016)MEDLINE-indexed journal, not yet read by usJournal of palliative medicine · systematic review 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 →
Pentecost C, Farrand P, Greaves CJ, Taylor RS, Warren FC, Hillsdon M, Green C, Welsman JR, Rayson K, Evans PH, Taylor AH. (2015)MEDLINE-indexed journal, not yet read by usTrials · randomised controlled trial Combining behavioural activation with physical activity promotion for adults with depression: findings of a parallel-group pilot randomised controlled trial (BAcPAc).
Background: Depression is associated with physical inactivity, which may mediate the relationship between depression and a range of chronic physical health conditions. However, few interventions have combined a psychological intervention for depression with behaviour change techniques, such as behavioural activation (BA), to promote increased physical activity.
Methods: To determine procedural and clinical uncertainties to inform a definitive randomised controlled trial (RCT), a pilot parallel-group RCT was undertaken within two Improving Access to Psychological Therapies (IAPT) services in South West England. We aimed to recruit 80 adults with depression and randomise them to a supported, written self-help programme based on either BA or BA plus physical activity promotion (BAcPAc). Data were collected at baseline and 4 months post-randomisation to evaluate trial retention, intervention uptake and variance in outcomes to inform a sample size calculation. Qualitative data were collected from participants and psychological wellbeing practitioners (PWPs) to assess the acceptability and feasibility of the trial methods and the intervention. Routine data were collected to evaluate resource use and cost.
Results: Sixty people with depression were recruited, and a 73 % follow-up rate was achieved. Accelerometer physical activity data were collected for 64 % of those followed. Twenty participants (33 %) attended at least one treatment appointment. Interview data were analysed for 15 participants and 9 study PWPs. The study highlighted the challenges of conducting an RCT within existing IAPT services with high staff turnover and absences, participant scheduling issues, PWP and participant preferences for cognitive focussed treatment, and deviations from BA delivery protocols. The BAcPAc intervention was generally acceptable to patients and PWPs.
Conclusions: Although recruitment procedures and data collection were challenging, participants generally engaged with the BAcPAc self-help booklets and reported willingness to increase their physical activity. A number of feasibility issues were identified, in particular the under-use of BA as a treatment for depression, the difficulty that PWPs had in adapting their existing procedures for study purposes and the instability of the IAPT PWP workforce. These problems would need to be better understood and resolved before proceeding to a full-scale RCT.
Trial registration: ISRCTN74390532 . Registered on 26 March 2013.
Trials · randomised controlled trial · 27 citationsread the source →
Mension E, Alonso I, Anglès-Acedo S, Ros C, Otero J, Villarino Á, Farré R, Saco A, Vega N, Castrejón N, Ordi J, Rakislova N, Tortajada M, Matas I, Gómez S, Ribera L, Castelo-Branco C. (2023)MEDLINE-indexed journal, not yet read by usJAMA network open · randomised controlled trial Effect of Fractional Carbon Dioxide vs Sham Laser on Sexual Function in Survivors of Breast Cancer Receiving Aromatase Inhibitors for Genitourinary Syndrome of Menopause: The LIGHT Randomized Clinical Trial.
Importance: Survivors of breast cancer present more severe symptoms of genitourinary syndrome of menopause (GSM) than patients without history of breast cancer. Recently, new treatments, such as vaginal laser therapy, have appeared, but evidence of their efficacy remains scarce.
Objective: To assess the safety and efficacy of carbon dioxide (CO2) vs sham vaginal laser therapy after 6 months of follow-up in survivors of breast cancer with GSM receiving aromatase inhibitors.
Design, setting, and participants: This prospective double-blind sham-controlled randomized clinical trial with two parallel study groups was performed during October 2020 to March 2022 in a tertiary referral hospital. Survivors of breast cancer using aromatase inhibitors were assessed for eligibility, and eligible patients were randomized into the 2 treatment groups. Follow-up was conducted at 6 months. Data were analyzed in July 2022.
Interventions: All patients from both groups were instructed to use the first-line treatment (FLT) based on nonhormonal moisturizers and vaginal vibrator stimulation. Patients for each group were allocated to 5 monthly sessions of fractional CO2 laser therapy (CLT) or sham laser therapy (SLT).
Main outcomes and measures: The primary outcome was sexual function, evaluated through Female Sexual Function Index (FSFI) score. Other subjective measures of efficacy included a visual analog scale of dyspareunia, vaginal pH, a Vaginal Health Index, quality of life (assessed via Short-Form 12), and body image (assessed with the Spanish Body Image Scale). Objective measures of efficacy included vaginal maturation index, vaginal epithelial elasticity (measured in Pascals) and vaginal epithelial thickness (measured in millimeters). Measures were assessed before and after the intervention. Tolerance (measured on a Likert scale), adverse effects, and estradiol levels were recorded.
Results: Among 211 survivors of breast cancer assessed, 84 women were deemed eligible and 72 women (mean [SD] age, 52.6 [8.3] years) were randomized to CLT (35 participants) or SLT (37 participants) and analyzed. There were no statistically significant differences between groups at baseline. At 6 months, both groups showed improvement in FSFI (mean [SD] score at baseline vs 6 months: CLT, 14.8 [8.8] points vs 20.0 [9.5] points; SLT, 15.6 [7.0] points vs 23.5 [6.5] points), but there was no significant difference between CLT and SLT groups in the improvement of sexual function evaluated through the FSFI test overall (mean [SD] difference, 5.2 [1.5] points vs 7.9 [1.2] points; P = .15) or after excluding women who were not sexually active (mean [SD] difference, 2.9 [1.4] points vs 5.5 [1.1] points; P = .15). There were also no differences between improvement of the 2 groups at 6 months of follow-up in the other assessed subjective outcomes, including dyspareunia (mean [SD] difference, -4.3 [3.4] vs -4.5 [2.3]; P = .73), Vaginal Health Index (mean [SD] difference, 3.3 [4.1] vs 5.0 [4.5]; P = .17), body image (mean [SD] difference, -3.7 [4.5] vs -2.7 [4.8]; P = .35), and quality of life (mean [SD] difference, -0.3 [3.6] vs -0.7 [3.2]; P = .39). Similarly, there were no differences in improvements in objective outcomes, including vaginal pH (mean [SD] difference, -0.6 [0.9] vs -0.8 [1.2]; P = .29), vaginal maturation index (mean [SD] difference, 10.2 [17.4] vs 14.4 [17.1]; P = .15), vaginal epithelial thickness (mean [SD] difference, 0.021 [0.014] mm vs 0.013 [0.012] mm; P = .30), vaginal epithelial elasticity (mean [SD] difference, -1373 [3197] Pascals vs -2103 [3771] Pascals; P = .64). There were significant improvements in the overall analysis regardless of group in many outcomes. The 2 interventions were well tolerated, but tolerance was significantly lower in the CLT group than the SLT group (mean [SD] Likert scale score, 3.3 [1.3] vs 4.1 [1.0]; P = .007). No differences were observed in complications or serum estradiol levels.
Conclusions and relevance: In this randomized clinical trial, vaginal laser treatment was found to be safe after 6 months of follow-up, but no statistically significant differences in efficacy were observed between CLT and SLT.
Trial registration: ClinicalTrials.gov identifier: NCT04619485.
JAMA network open · randomised controlled trial · 62 citationsread the source →
Patel V, Weobong B, Weiss HA, Anand A, Bhat B, Katti B, Dimidjian S, Araya R, Hollon SD, King M, Vijayakumar L, Park AL, McDaid D, Wilson T, Velleman R, Kirkwood BR, Fairburn CG. (2017)MEDLINE-indexed journal, not yet read by usLancet (London, England) · randomised controlled trial The Healthy Activity Program (HAP), a lay counsellor-delivered brief psychological treatment for severe depression, in primary care in India: a randomised controlled trial.
Background: Although structured psychological treatments are recommended as first-line interventions for depression, only a small fraction of people globally receive these treatments because of poor access in routine primary care. We assessed the effectiveness and cost-effectiveness of a brief psychological treatment (Healthy Activity Program [HAP]) for delivery by lay counsellors to patients with moderately severe to severe depression in primary health-care settings.
Methods: In this randomised controlled trial, we recruited participants aged 18-65 years scoring more than 14 on the Patient Health Questionnaire 9 (PHQ-9) indicating moderately severe to severe depression from ten primary health centres in Goa, India. Pregnant women or patients who needed urgent medical attention or were unable to communicate clearly were not eligible. Participants were randomly allocated (1:1) to enhanced usual care (EUC) alone or EUC combined with HAP in randomly sized blocks (block size four to six [two to four for men]), stratified by primary health centre and sex, and allocation was concealed with use of sequential numbered opaque envelopes. Physicians providing EUC were masked. Primary outcomes were depression symptom severity on the Beck Depression Inventory version II and remission from depression (PHQ-9 score of <10) at 3 months in the intention-to-treat population, assessed by masked field researchers. Secondary outcomes were disability, days unable to work, behavioural activation, suicidal thoughts or attempts, intimate partner violence, and resource use and costs of illness. We assessed serious adverse events in the per-protocol population. This trial is registered with the ISRCTN registry, number ISRCTN95149997.
Findings: Between Oct 28, 2013, and July 29, 2015, we enrolled and randomly allocated 495 participants (247 [50%] to the EUC plus HAP group [two of whom were subsequently excluded because of protocol violations] and 248 [50%] to the EUC alone group), of whom 466 (95%) completed the 3 month primary outcome assessment (230 [49%] in the EUC plus HAP group and 236 [51%] in the EUC alone group). Participants in the EUC plus HAP group had significantly lower symptom severity (Beck Depression Inventory version II in EUC plus HAP group 19·99 [SD 15·70] vs 27·52 [13·26] in EUC alone group; adjusted mean difference -7·57 [95% CI -10·27 to -4·86]; p<0·0001) and higher remission (147 [64%] of 230 had a PHQ-9 score of <10 in the HAP plus EUC group vs 91 [39%] of 236 in the EUC alone group; adjusted prevalence ratio 1·61 [1·34-1·93]) than did those in the EUC alone group. EUC plus HAP showed better results than did EUC alone for the secondary outcomes of disability (adjusted mean difference -2·73 [-4·39 to -1·06]; p=0·001), days out of work (-2·29 [-3·84 to -0·73]; p=0·004), intimate partner physical violence in women (0·53 [0·29-0·96]; p=0·04), behavioural activation (2·17 [1·34-3·00]; p<0·0001), and suicidal thoughts or attempts (0·61 [0·45-0·83]; p=0·001). The incremental cost per quality-adjusted life-year gained was $9333 (95% CI 3862-28 169; 2015 international dollars), with an 87% chance of being cost-effective in the study setting. Serious adverse events were infrequent and similar between groups (nine [4%] in the EUC plus HAP group vs ten [4%] in the EUC alone group; p=1·00).
Interpretation: HAP delivered by lay counsellors plus EUC was better than EUC alone was for patients with moderately severe to severe depression in routine primary care in Goa, India. HAP was readily accepted by this previously untreated population and was cost-effective in this setting. HAP could be a key strategy to reduce the treatment gap for depressive disorders, the leading mental health disorder worldwide.
Funding: Wellcome Trust.
Lancet (London, England) · randomised controlled trial · 295 citationsread the source →
Gilbody S, Peckham E, Bailey D, Arundel C, Heron P, Crosland S, Fairhurst C, Hewitt C, Li J, Parrott S, Bradshaw T, Horspool M, Hughes E, Hughes T, Ker S, Leahy M, McCloud T, Osborn D, Reilly J, Steare T, Ballantyne E, Bidwell P, Bonner S, Brennan D, Callen T, Carey A, Colbeck C, Coton D, Donaldson E, Evans K, Herlihy H, Khan W, Nyathi L, Nyamadzawo E, Oldknow H, Phiri P, Rathod S, Rea J, Romain-Hooper CB, Smith K, Stribling A, Vickers C. (2019)MEDLINE-indexed journal, not yet read by usThe lancet. Psychiatry · randomised controlled trial 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 →
O'Malley SS, Zweben A, Fucito LM, Wu R, Piepmeier ME, Ockert DM, Bold KW, Petrakis I, Muvvala S, Jatlow P, Gueorguieva R. (2018)MEDLINE-indexed journal, not yet read by usJAMA psychiatry · randomised controlled trial Effect of Varenicline Combined With Medical Management on Alcohol Use Disorder With Comorbid Cigarette Smoking: A Randomized Clinical Trial.
Importance: Individuals with alcohol use disorder have high rates of cigarette smoking. Varenicline tartrate, an approved treatment for smoking cessation, may reduce both drinking and smoking.
Objectives: To test the efficacy of varenicline with medical management for patients with alcohol use disorder and comorbid smoking seeking alcohol treatment, and to evaluate the secondary effects on smoking abstinence.
Design, setting, and participants: This phase 2, randomized, double-blind, parallel group, placebo-controlled trial was conducted at 2 outpatient clinics from September 19, 2012, to August 31, 2015. Eligible participants met alcohol-dependence criteria and reported heavy drinking (≥5 drinks for men and ≥4 drinks for women) 2 or more times per week and smoking 2 or more times per week; 131 participants were randomized to either varenicline or placebo stratified by sex and site. All analyses were of the intention-to-treat type. Data analysis was conducted from February 5, 2016, to September 29, 2017.
Interventions: Varenicline tartrate, 1 mg twice daily, and matching placebo pills for 16 weeks. Medical management emphasized medication adherence for 4 weeks followed by support for changing drinking.
Main outcomes and measures: Percentage of heavy drinking days (PHDD) weeks 9 to 16, no heavy drinking days (NHDD) weeks 9 to 16, and prolonged smoking abstinence weeks 13 to 16.
Results: Of 131 participants, 39 (29.8%) were women and 92 (70.2%) were men, the mean (SD) age was 42.7 (11.7) years, and the race/ethnicity self-identified by most respondents was black (69 [52.7%]). Sixty-four participants were randomized to receive varenicline, and 67 to receive placebo. Mean change in PHDD between varenicline and placebo across sex and site was not significantly different. However, a significant treatment by sex by time interaction for PHDD (F1,106 = 4.66; P = .03) revealed that varenicline compared with placebo resulted in a larger decrease in log-transformed PHDD in men (least square [LS] mean difference in change from baseline, 0.54; 95% CI, -0.09 to 1.18; P = .09; Cohen d = 0.45) but a smaller decrease in women (LS mean difference, -0.69; 95% CI, -1.63 to 0.25; P = .15; Cohen d = -0.53). Thirteen of 45 men (29%) had NHDD taking varenicline compared with 3 of 47 men (6%) taking placebo (Cohen h = 0.64; 95% CI, 0.22-1.03), whereas 1 of 19 women (5%) had NHDD compared with 5 of 20 women (25%) taking placebo (Cohen h = -0.60; 95% CI, -1.21 to 0.04). Taking varenicline, 8 of 64 participants (13%) achieved prolonged smoking abstinence; no one (0 of 67) quit smoking taking placebo (P = .003; Cohen h = 0.72; 95% CI, 0.38-1.07).
Conclusions and relevance: Varenicline with medical management resulted in decreased heavy drinking among men and increased smoking abstinence in the overall sample. Varenicline could be considered to promote improvements in men with these dual behavioral health risks.
Trial registration: clinicaltrials.gov Identifier: NCT01553136.
JAMA psychiatry · randomised controlled trial · 77 citationsread the source →
Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP, RAPIDO collaborative investigators. (2021)MEDLINE-indexed journal, not yet read by usThe Lancet. Oncology · randomised controlled trial Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial.
Background: Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control.
Methods: In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocarcinoma, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for chemotherapy, and could be assessed for staging within 5 weeks before randomisation. Eligible participants were randomly assigned (1:1), using a management system with a randomly varying block design (each block size randomly chosen to contain two to four allocations), stratified by centre, ECOG performance status, cT stage, and cN stage, to either the experimental or standard of care group. All investigators remained masked for the primary endpoint until a prespecified number of events was reached. Patients allocated to the experimental treatment group received short-course radiotherapy (5 × 5 Gy over a maximum of 8 days) followed by six cycles of CAPOX chemotherapy (capecitabine 1000 mg/m2 orally twice daily on days 1-14, oxaliplatin 130 mg/m2 intravenously on day 1, and a chemotherapy-free interval between days 15-21) or nine cycles of FOLFOX4 (oxaliplatin 85 mg/m2 intravenously on day 1, leucovorin [folinic acid] 200 mg/m2 intravenously on days 1 and 2, followed by bolus fluorouracil 400 mg/m2 intravenously and fluorouracil 600 mg/m2 intravenously for 22 h on days 1 and 2, and a chemotherapy-free interval between days 3-14) followed by total mesorectal excision. Choice of CAPOX or FOLFOX4 was per physician discretion or hospital policy. Patients allocated to the standard of care group received 28 daily fractions of 1·8 Gy up to 50·4 Gy or 25 fractions of 2·0 Gy up to 50·0 Gy (per physician discretion or hospital policy), with concomitant twice-daily oral capecitabine 825 mg/m2 followed by total mesorectal excision and, if stipulated by hospital policy, adjuvant chemotherapy with eight cycles of CAPOX or 12 cycles of FOLFOX4. The primary endpoint was 3-year disease-related treatment failure, defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour, or treatment-related death, assessed in the intention-to-treat population. Safety was assessed by intention to treat. This study is registered with the EudraCT, 2010-023957-12, and ClinicalTrials.gov, NCT01558921, and is now complete.
Findings: Between June 21, 2011, and June 2, 2016, 920 patients were enrolled and randomly assigned to a treatment, of whom 912 were eligible (462 in the experimental group; 450 in the standard of care group). Median follow-up was 4·6 years (IQR 3·5-5·5). At 3 years after randomisation, the cumulative probability of disease-related treatment failure was 23·7% (95% CI 19·8-27·6) in the experimental group versus 30·4% (26·1-34·6) in the standard of care group (hazard ratio 0·75, 95% CI 0·60-0·95; p=0·019). The most common grade 3 or higher adverse event during preoperative therapy in both groups was diarrhoea (81 [18%] of 460 patients in the experimental group and 41 [9%] of 441 in the standard of care group) and neurological toxicity during adjuvant chemotherapy in the standard of care group (16 [9%] of 187 patients). Serious adverse events occurred in 177 (38%) of 460 participants in the experimental group and, in the standard of care group, in 87 (34%) of 254 patients without adjuvant chemotherapy and in 64 (34%) of 187 with adjuvant chemotherapy. Treatment-related deaths occurred in four participants in the experimental group (one cardiac arrest, one pulmonary embolism, two infectious complications) and in four participants in the standard of care group (one pulmonary embolism, one neutropenic sepsis, one aspiration, one suicide due to severe depression).
Interpretation: The observed decreased probability of disease-related treatment failure in the experimental group is probably indicative of the increased efficacy of preoperative chemotherapy as opposed to adjuvant chemotherapy in this setting. Therefore, the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer.
Funding: Dutch Cancer Foundation, Swedish Cancer Society, Spanish Ministry of Economy and Competitiveness, and Spanish Clinical Research Network.
The Lancet. Oncology · randomised controlled trial · 1212 citationsread the source →
Both positive mental health and psychopathology should be monitored in psychotherapy: Confirmation for the dual-factor model in acceptance and commitment therapy.
The dual-factor model of mental health suggests that enhancing positive mental health and alleviating psychopathology do not automatically go hand-in-hand. This study investigates the relationship between the effectiveness on depression/anxiety symptoms and positive mental health of Acceptance and Commitment Therapy (ACT). It draws on RCT data (n = 250) of a self-help ACT. Patients' depression/anxiety symptoms and positive mental health were completed at baseline, at post-intervention after nine weeks, and at follow-up after five months. Percentage of unique variance of depression/anxiety symptoms explained by positive mental health (and vice versa), and the degree of classificatory agreement between improvements in positive mental health and depression/anxiety, were examined using regression analysis and Reliable Change Index (RCI). Positive mental health, i.e. baseline and change, explained 15% and 12% of the variance in follow-up depression and anxiety symptoms, beyond the 7% and 9% that was explained by baseline levels of depression and anxiety. Depression and anxiety symptoms, i.e., baseline and change, explained 10% and 9% of the variance in follow-up positive mental health, on top of the 35% that was explained by baseline levels of positive mental health. Cross-classification of the Reliable Changes showed that 64% of the participants that improved during the ACT-intervention, improved on either depression symptoms or positive mental health, and 72% of the participants improved on either anxiety symptoms or positive mental health. The findings support the dual-factor model and suggest that it is important to systematically implement measures of both psychopathology and positive mental health in mental health care and therapy evaluations.
Behaviour research and therapy · randomised controlled trial · 55 citationsread the source →
Freeman D, Loe BS, Yu LM, Freeman J, Chadwick A, Vaccari C, Shanyinde M, Harris V, Waite F, Rosebrock L, Petit A, Vanderslott S, Lewandowsky S, Larkin M, Innocenti S, Pollard AJ, McShane H, Lambe S. (2021)MEDLINE-indexed journal, not yet read by usThe Lancet. Public health · randomised controlled trial Effects of different types of written vaccination information on COVID-19 vaccine hesitancy in the UK (OCEANS-III): a single-blind, parallel-group, randomised controlled trial.
Background: The effectiveness of the COVID-19 vaccination programme depends on mass participation: the greater the number of people vaccinated, the less risk to the population. Concise, persuasive messaging is crucial, particularly given substantial levels of vaccine hesitancy in the UK. Our aim was to test which types of written information about COVID-19 vaccination, in addition to a statement of efficacy and safety, might increase vaccine acceptance.
Methods: For this single-blind, parallel-group, randomised controlled trial, we aimed to recruit 15 000 adults in the UK, who were quota sampled to be representative. Participants were randomly assigned equally across ten information conditions stratified by level of vaccine acceptance (willing, doubtful, or strongly hesitant). The control information condition comprised the safety and effectiveness statement taken from the UK National Health Service website; the remaining conditions addressed collective benefit, personal benefit, seriousness of the pandemic, and safety concerns. After online provision of vaccination information, participants completed the Oxford COVID-19 Vaccine Hesitancy Scale (outcome measure; score range 7-35) and the Oxford Vaccine Confidence and Complacency Scale (mediation measure). The primary outcome was willingness to be vaccinated. Participants were analysed in the groups they were allocated. p values were adjusted for multiple comparisons. The study was registered with ISRCTN, ISRCTN37254291.
Findings: From Jan 19 to Feb 5, 2021, 15 014 adults were recruited. Vaccine hesitancy had reduced from 26·9% the previous year to 16·9%, so recruitment was extended to Feb 18 to recruit 3841 additional vaccine-hesitant adults. 12 463 (66·1%) participants were classified as willing, 2932 (15·6%) as doubtful, and 3460 (18·4%) as strongly hesitant (ie, report that they will avoid being vaccinated for as long as possible or will never get vaccinated). Information conditions did not alter COVID-19 vaccine hesitancy in those willing or doubtful (adjusted p values >0·70). In those strongly hesitant, COVID-19 vaccine hesitancy was reduced, in comparison to the control condition, by personal benefit information (mean difference -1·49, 95% CI -2·16 to -0·82; adjusted p=0·0015), directly addressing safety concerns about speed of development (-0·91, -1·58 to -0·23; adjusted p=0·0261), and a combination of all information (-0·86, -1·53 to -0·18; adjusted p=0·0313). In those strongly hesitant, provision of personal benefit information reduced hesitancy to a greater extent than provision of information on the collective benefit of not personally getting ill (-0·97, 95% CI -1·64 to -0·30; adjusted p=0·0165) or the collective benefit of not transmitting the virus (-1·01, -1·68 to -0·35; adjusted p=0·0150). Ethnicity and gender were found to moderate information condition outcomes.
Interpretation: In the approximately 10% of the population who are strongly hesitant about COVID-19 vaccines, provision of information on personal benefit reduces hesitancy to a greater extent than information on collective benefits. Where perception of risk from vaccines is most salient, decision making becomes centred on the personal. As such, messaging that stresses the counterbalancing personal benefits is likely to prove most effective. The messaging from this study could be used in public health communications. Going forwards, the study highlights the need for future health campaigns to engage with the public on the terrain that is most salient to them.
Funding: National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and NIHR Oxford Health Biomedical Research Centre.
The Lancet. Public health · randomised controlled trial · 196 citationsread the source →
El-Jawahri A, LeBlanc TW, Kavanaugh A, Webb JA, Jackson VA, Campbell TC, O'Connor N, Luger SM, Gafford E, Gustin J, Bhatnagar B, Walker AR, Fathi AT, Brunner AM, Hobbs GS, Nicholson S, Davis D, Addis H, Vaughn D, Horick N, Greer JA, Temel JS. (2021)MEDLINE-indexed journal, not yet read by usJAMA oncology · randomised controlled trial Effectiveness of Integrated Palliative and Oncology Care for Patients With Acute Myeloid Leukemia: A Randomized Clinical Trial.
Importance: Patients with acute myeloid leukemia (AML) receiving intensive chemotherapy experience substantial decline in their quality of life (QOL) and mood during their hospitalization for induction chemotherapy and often receive aggressive care at the end of life (EOL). However, the role of specialty palliative care for improving the QOL and care for this population is currently unknown.
Objective: To assess the effect of integrated palliative and oncology care (IPC) on patient-reported and EOL outcomes in patients with AML.
Design, setting, and participants: We conducted a multisite randomized clinical trial of IPC (n = 86) vs usual care (UC) (n = 74) for patients with AML undergoing intensive chemotherapy. Data were collected from January 2017 through July 2019 at 4 tertiary care academic hospitals in the United States.
Interventions: Patients assigned to IPC were seen by palliative care clinicians at least twice per week during their initial and subsequent hospitalizations.
Main outcomes and measures: Patients completed the 44-item Functional Assessment of Cancer Therapy-Leukemia scale (score range, 0-176) to assess QOL; the 14-item Hospital Anxiety and Depression Scale (HADS), with subscales assessing symptoms of anxiety and depression (score range, 0-21); and the PTSD Checklist-Civilian version to assess posttraumatic stress disorder (PTSD) symptoms (score range, 17-85) at baseline and weeks 2, 4, 12, and 24. The primary end point was QOL at week 2. We used analysis of covariance adjusting and mixed linear effect models to evaluate patient-reported outcomes. We used Fisher exact test to compare patient-reported discussion of EOL care preferences and receipt of chemotherapy in the last 30 days of life.
Results: Of 235 eligible patients, 160 (68.1%) were enrolled; of the 160 participants, the median (range) age was 64.4 (19.7-80.1) years, and 64 (40.0%) were women. Compared with those receiving UC, IPC participants reported better QOL (adjusted mean score, 107.59 vs 116.45; P = .04), and lower depression (adjusted mean score, 7.20 vs 5.68; P = .02), anxiety (adjusted mean score, 5.94 vs 4.53; P = .02), and PTSD symptoms (adjusted mean score, 31.69 vs 27.79; P = .01) at week 2. Intervention effects were sustained to week 24 for QOL (β, 2.35; 95% CI, 0.02-4.68; P = .048), depression (β, -0.42; 95% CI, -0.82 to -0.02; P = .04), anxiety (β, -0.38; 95% CI, -0.75 to -0.01; P = .04), and PTSD symptoms (β, -1.43; 95% CI, -2.34 to -0.54; P = .002). Among patients who died, those receiving IPC were more likely than those receiving UC to report discussing EOL care preferences (21 of 28 [75.0%] vs 12 of 30 [40.0%]; P = .01) and less likely to receive chemotherapy near EOL (15 of 43 [34.9%] vs 27 of 41 [65.9%]; P = .01).
Conclusions and relevance: In this randomized clinical trial of patients with AML, IPC led to substantial improvements in QOL, psychological distress, and EOL care. Palliative care should be considered a new standard of care for patients with AML.
Trial registration: ClinicalTrials.gov Identifier: NCT02975869.
JAMA oncology · randomised controlled trial · 151 citationsread the source →
Ni Mhurchu C, Te Morenga L, Tupai-Firestone R, Grey J, Jiang Y, Jull A, Whittaker R, Dobson R, Dalhousie S, Funaki T, Hughes E, Henry A, Lyndon-Tonga L, Pekepo C, Penetito-Hemara D, Tunks M, Verbiest M, Humphrey G, Schumacher J, Goodwin D. (2019)MEDLINE-indexed journal, not yet read by usThe Lancet. Digital health · randomised controlled trial A co-designed mHealth programme to support healthy lifestyles in Māori and Pasifika peoples in New Zealand (OL@-OR@): a cluster-randomised controlled trial.
Background: The OL@-OR@ mobile health programme was co-designed with Māori and Pasifika communities in New Zealand, to support healthy lifestyle behaviours. We aimed to determine whether use of the programme improved adherence to health-related guidelines among Māori and Pasifika communities in New Zealand compared with a control group on a waiting list for the programme.
Methods: The OL@-OR@ trial was a 12-week, two-arm, cluster-randomised controlled trial. A cluster was defined as any distinct location or setting in New Zealand where people with shared interests or contexts congregated, such as churches, sports clubs, and community groups. Members of a cluster were eligible to participate if they were aged 18 years or older, had regular access to a mobile device or computer, and had regular internet access. Clusters of Māori and of Pasifika (separately) were randomly assigned (1:1) to either the intervention or control condition. The intervention group received the OL@-OR@ mHealth programme (smartphone app and website). The control group received a control version of the app that only collected baseline and outcome data. The primary outcome was self-reported adherence to health-related guidelines, which were measured with a composite health behaviour score (of physical activity, smoking, alcohol intake, and fruit and vegetable intake) at 12 weeks. The secondary outcomes were self-reported adherence to health-related behaviour guidelines at 4 weeks; self-reported bodyweight at 12 weeks; and holistic health and wellbeing status at 12 weeks, in all enrolled individuals in eligible clusters; and user engagement with the app, in individuals allocated to the intervention. Adverse events were not collected. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12617001484336.
Findings: Between Jan 24 and Aug 14, 2018, we enrolled 337 Māori participants from 19 clusters and 389 Pasifika participants from 18 clusters (n=726 participants) in the intervention group and 320 Māori participants from 15 clusters and 405 Pasifika participants from 17 clusters (n=725 participants) in the control group. Of these participants, 227 (67%) Māori participants and 347 (89%) Pasifika participants (n=574 participants) in the intervention group and 281 (88%) Māori participants and 369 (91%) Pasifika participants (n=650 participants) in the control group completed the 12-week follow-up and were included in the final analysis. Relative to baseline, adherence to health-related behaviour guidelines increased at 12 weeks in both groups (315 [43%] of 726 participants at baseline to 329 [57%] of 574 participants in the intervention group; 331 [46%] of 725 participants to 369 [57%] of 650 participants in the control group); however, there was no significant difference between intervention and control groups in adherence at 12 weeks (odds ratio [OR] 1·13; 95% CI 0·84-1·52; p=0·42). Furthermore, the proportion of participants adhering to guidelines on physical activity (351 [61%] of 574 intervention group participants vs 407 [63%] of 650 control group participants; OR 1·03, 95% CI 0·73-1·45; p=0·88), smoking (434 [76%] participants vs 501 [77%] participants; 1·12, 0·67-1·87; p=0·66), alcohol consumption (518 [90%] participants vs 596 [92%] participants; 0·73, 0·37-1·44; p=0·36), and fruit and vegetable intake (194 [34%] participants vs 196 [30%] participants; 1·08, 0·79-1·49; p=0·64) did not differ between groups. We found no significant differences between the intervention and control groups in any secondary outcome. 147 (26%) intervention group participants engaged with the OL@-OR@ programme (ie, set at least one behaviour change goal online).
Interpretation: The OL@-OR@ mobile health programme did not improve adherence to health-related behaviour guidelines amongst Māori and Pasifika individuals.
Funding: Healthier Lives He Oranga Hauora National Science Challenge.
The Lancet. Digital health · randomised controlled trial · 45 citationsread the source →
Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial.
Background: Patients with space-occupying hemispheric infarctions have a poor prognosis, with case fatality rates of up to 80%. In a pooled analysis of randomised trials, surgical decompression within 48 h of stroke onset reduced case fatality and improved functional outcome; however, the effect of surgery after longer intervals is unknown. The aim of HAMLET was to assess the effect of decompressive surgery within 4 days of the onset of symptoms in patients with space-occupying hemispheric infarction.
Methods: Patients with space-occupying hemispheric infarction were randomly assigned within 4 days of stroke onset to surgical decompression or best medical treatment. The primary outcome measure was the modified Rankin scale (mRS) score at 1 year, which was dichotomised between good (0-3) and poor (4-6) outcome. Other outcome measures were the dichotomy of mRS score between 4 and 5, case fatality, quality of life, and symptoms of depression. Analysis was by intention to treat. This trial is registered, ISRCTN94237756.
Findings: Between November, 2002, and October, 2007, 64 patients were included; 32 were randomly assigned to surgical decompression and 32 to best medical treatment. Surgical decompression had no effect on the primary outcome measure (absolute risk reduction [ARR] 0%, 95% CI -21 to 21) but did reduce case fatality (ARR 38%, 15 to 60). In a meta-analysis of patients in DECIMAL (DEcompressive Craniectomy In MALignant middle cerebral artery infarction), DESTINY (DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY), and HAMLET who were randomised within 48 h of stroke onset, surgical decompression reduced poor outcome (ARR 16%, -0.1 to 33) and case fatality (ARR 50%, 34 to 66).
Interpretation: Surgical decompression reduces case fatality and poor outcome in patients with space-occupying infarctions who are treated within 48 h of stroke onset. There is no evidence that this operation improves functional outcome when it is delayed for up to 96 h after stroke onset. The decision to perform the operation should depend on the emphasis patients and relatives attribute to survival and dependency.
The Lancet. Neurology · meta-analysis · 608 citationsread the source →
The Social Epidemiology of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome
Social epidemiology is defined as the study of the distribution of health outcomes and their social determinants (1). It builds on the classic epidemiologic triangle of host, agent, and environment to focus explicitly on the role of social determinants in infectious disease transmission and progression. These determinants are the “features of and pathways by which societal conditions affect health” (2, p. 697). Early studies of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) focused on individual characteristics and behaviors in determining HIV risk, an approach that Fee and Krieger (3) refer to as “biomedical individualism.” Biomedical individualism is the basis of risk factor epidemiology; by contrast, the social epidemiology perspective emphasizes social conditions as fundamental causes of disease (4) (table 1). Social epidemiologists examine how persons become exposed to risk or protective factors and under what social conditions individual risk factors are related to disease. Social factors are thus the focus of analysis and are not simply adjusted for as potentially confounding factors or used as proxies for unavailable individual-level data. Social factors are indeed critical to understanding nonuniform infectious disease patterns that emerge as a result of the dependent nature of disease transmission or the idea that an outcome in one person is dependent upon outcomes and exposures in others (5, 6). Contact patterns that enhance HIV/AIDS vulnerability may be conceptualized at multiple levels. Figure 1 distinguishes determinants of HIV/AIDS at three levels: individual, social, and structural. Individual factors include biologic, demographic, and behavioral risk factors that may influence the risk of HIV acquisition and disease progression. Social-level factors include critical pathways by which community and network structures link persons to society. These structures are central to understanding the diffusion and differential distribution of HIV/AIDS in population subgroups. Structural-level factors include social and economic factors, as well as laws and policies. These factors, in turn, affect HIV transmission dynamics and the differential distribution of HIV/AIDS. Infectious disease epidemiology provides models of the mechanisms through which social determinants affect HIV transmission (7). For example, the basic reproductive number of an infectious disease, R0 (8), describes secondary infections that arise from a primary infection. In the equation R0 = βCD, β is the probability of infection per contact, C is the number of contacts, and D is the duration of infectivity. The goal of intervention efforts is to reduce the empirical value of these terms by modifying the social conditions under which individual risk factors lead to disease. Examples of factors that affect the component terms of R0 in HIV epidemiology are presented in table 2. In this review, we present existing evidence linking social and structural determinants to HIV/AIDS. In addition, we discuss the implications of these findings for future social epidemiology research on HIV/AIDS as well as the design of more effective HIV/AIDS interventions. We searched the published literature to identify conceptual and empirical research reports on the social epidemiology of HIV/AIDS. Five databases were searched: PsycINFO (American Psychological Association, Washington, DC), PubMed (MEDLINE; National Institutes of Health, Bethesda, Maryland), Social Science Citation Index (Web of Science; Thomson ISI, Stamford, Connecticut), Sociological Abstracts (CSA, Bethesda, Maryland), and Digital Dissertations (ProQuest; UMI, Ann Arbor, Michigan). Searches were designed to include the factors we specified in our framework as social or structural factors (figure 1). Searches were limited to published articles in the English language for the period 1981–2003. The following keywords were included in each search: AIDS/acquired immunodeficiency syndrome, HIV, and epidemiol*. Additional searches were conducted by using combinations of keywords listed in Appendix table 1 corresponding with our framework. We identified four categories of social-level factors of importance to HIV/AIDS epidemiology: cultural context, social networks, neighborhood effects, and social capital. Each uses different conceptual and methodological approaches to examine the effects of social forces on population HIV/AIDS vulnerability. Anthropologist Edward Tylor defined culture as “that complex whole which includes knowledge, belief, art, law, morals, custom, and any other capabilities and habits acquired by man as a member of society” (9, p. 1). Anthropologic and epidemiologic approaches may be integrated in a variety of ways to identify features of the social environment that affect HIV/AIDS risk. One way to explore how the social environment affects HIV/AIDS epidemiology is through the use of mixed research methods. Mixed-methods study designs integrate qualitative and quantitative research methods either sequentially or concurrently (10). In sequential study designs, qualitative methods may be used to explore a topic under study or to explain quantitative epidemiologic findings. Concurrent study designs are meant to confirm, cross-validate, or corroborate findings within a single study. A common type of concurrent mixed methods study is “triangulation,” and this approach has been used extensively in rapid assessments of illicit drug use and HIV/AIDS (11–13). Mixed methods approaches are particularly well suited to the investigation of the often hidden and stigmatizing behavioral and social factors underlying HIV epidemics. One exemplary study combining qualitative methods with quantitative methods was conducted by Beyrer et al. (14) to examine the role of overland heroin trafficking routes in shaping explosive HIV/AIDS epidemics among injection drug users in Southeast Asia. Piecing together data from a variety of sources, including existing epidemiologic data, key informant interviews, and laboratory data, this study revealed that distinct HIV subtypes emerged and recombined along drug trafficking routes originating in Myanmar, one of the world’s largest heroin producers. Along these trafficking routes, communities of injection drug users formed, facilitating the spread of HIV into local communities in Laos, Thailand, Vietnam, India, and China (refer, for example, to Panda et al. (15)). This illustration highlights the broader understanding of HIV/AIDS epidemiology that can be achieved by examining the interplay between contextual factors and social and behavioral factors. Investigation of social networks in HIV/AIDS began with the mapping of relationships between one of the first identified AIDS cases, an airline steward, and a large number of his male sex partners in the early 1980s (16). Social network analysis generates measures of the quality, density, position, and structure of relationships between persons, including dyads (partnerships), personal networks (“egocentric” networks), and larger communities (“sociometric” networks) (17, 18). Social networks can influence health outcomes in direct and indirect ways, including 1) social influence, 2) social engagement and participation, 3) prevalence of infectious disease and network member mixing, 4) access to material goods and informational resources, and 5) social support (19). Researchers have demonstrated that patterns in the structure of relationships—rather than differences in individual risk behaviors alone—explain observed HIV patterns (20, 21). The theoretical foundation for examining social networks in HIV research is closely tied to advances in sexually transmitted disease (STD) epidemiology. A key concept from STD epidemiology is the notion of the “core group,” a small group of disease transmitters responsible for a large proportion of cases (22). Friedman et al. (23) found that individuals’ locations within sociometric risk networks were associated with HIV risk among a group of injection drug users in New York City. Other concepts from STD epidemiology, such as partner concurrency, bridging, and mixing patterns, are also important in understanding HIV risk (24–29). Specific network characteristics that have been associated with HIV/AIDS include the size of subgroups and their distribution in a network (23), the centrality of HIV-positive persons within networks (30), partner selection patterns (24, 31–33), and concurrent sexual partnerships (28). Inclusion of these variables has been shown to improve transmission estimates in mathematical modeling (34, 35). Social and normative influences have also been associated with individual HIV risks (36, 37). Network-related social and normative influences are predictive of illicit drug use (38) and condom use behavior (37, 39), highlighting the importance of network-based interventions for HIV prevention (18). Kelly et al. (40, 41) developed a popular opinion leader model that has been effective in reducing HIV risk in several populations, including men who have sex with men and women in low-income housing (42). The success of this model has led to its adaption for international use by the National Institute of Mental Health Collaborative HIV/STD Prevention Trial in China, India, Peru, Russia, and Zimbabwe. Neighborhoods represent the intersection of social networks and physical spatial locations, a confluence Wallace (43) has called the “sociogeographic networks” through which infectious diseases spread. Early interest in the role of neighborhood social environment in disease transmission was sparked by a study in Colorado Springs, Colorado, in which researchers found that gonorrhea was highly focused geographically in core residential neighborhoods (44). Both direct and indirect mechanisms may determine how neighborhood-level factors shape population HIV/AIDS patterns. Direct mechanisms are those that increase the likelihood of a person coming into contact with someone who is HIV positive, for example, through residential segregation and the social isolation of marginalized populations. Indirect mechanisms include those that increase population vulnerability to HIV/AIDS, such as exposure to poor socioeconomic conditions, high unemployment, or the proliferation of illicit drug markets. A range of neighborhood-level factors have been examined in relation to infectious disease, including poverty and income (45, 46), residential segregation (47), and neighborhood physical environment (48, 49). Current research in neighborhood and area effects on health emphasizes the importance of moving beyond documentation of associations to analyze the social and epidemiologic mechanisms through which neighborhood effects might operate (50–54). Increasing concentrations of affluence and poverty are contributing to what demographer Douglas Massey has called “a radical change in the geographic basis of human society” (55, p. 395). Powerful social and economic forces in US cities are increasing neighborhood segregation by class and race/ethnicity (56, 57). Resulting social disorganization and loss of resources and services in poor neighborhoods are in turn shaping HIV/AIDS patterns at the neighborhood level. In a number of studies in New York City, for example, Wallace (58–63) has examined the complex interplay of public policies such as “planned shrinkage” with HIV epidemic dynamics in the Bronx, documenting the “synergy of plagues” that has accompanied rapid social change and the destruction of essential protective networks in poor communities. Using AIDS surveillance data, ecologic studies conducted in various US cities have also consistently found significant associations between income and poverty measures and neighborhood-level AIDS incidence and prevalence rates, and these findings have been consistent across census block groups (46), census tracts (64), and zip codes (65, 66). Length of survival an AIDS has also been with neighborhood measures of income and the of highly a of health at the population may also a role in shaping HIV/AIDS patterns, associations between HIV/AIDS and income at the neighborhood have not been well segregation by race/ethnicity is neighborhood-level that may an important role in HIV/AIDS may affect infectious disease patterns through the and isolation of persons in one increasing the probability of transmission within that For example, found that measures of residential isolation were protective for at risk of disease. Indirect effects of segregation are associated with of neighborhood and with for those in poor neighborhoods segregation may to understanding disease we of studies examining neighborhood segregation in relation to HIV/AIDS that have been The physical environment of neighborhoods has also been examined in relation to infectious disease. et al. examined gonorrhea and neighborhood physical environment in New by using an of physical to explore and to this the of physical such as and a in social in a of community this concept to public et al. found a significant between neighborhood physical and gonorrhea rates, a by a ecologic study of US physical environment may HIV risk by illicit drug use such as injection behaviors and of the mechanisms through which the observed associations may be and associations between the physical environment and HIV/AIDS is research is to support the design of neighborhood-level HIV/AIDS interventions. has differences are not result from social and economic by policies. are and to p. The of evidence ecologic associations between neighborhood-level factors and infectious disease that to be to identify of and defined social as of social structures that that is the of that in its not be p. Social may affect health through 1) the of 2) access to services and 3) of in a and 4) participation, to policies that are more to published studies have explicitly examined social in the of HIV/AIDS. 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Epidemiologic Reviews · meta-analysis · 394 citationsread the source →
Moyo K, Igaba N, Wose Kinge C, Chasela C, Phohole M, Grove S, Makura C, Mudau L, Taljaard D, Rech D, Ramkissoon A, Searle C, Majuba P, Sanne I. (2022)MEDLINE-indexed journal, not yet read by usPloS one Voluntary medical male circumcision in selected provinces in South Africa: Outcomes from a programmatic setting.
Introduction: Voluntary medical male circumcision (VMMC) remains an effective biomedical intervention for HIV prevention in high HIV prevalence countries. In South Africa, United States Agency for International Development VMMC partners provide technical assistance to the Department of Health, at national and provincial levels in support of the establishment of VMMC sites as well as in providing direct VMMC services at site level since April 2012. We describe the outcomes of the Right to Care (RTC) VMMC program implemented in South Africa from 2012 to 2017.
Methods: This retrospective study was undertaken at RTC supported facilities across six provinces. Young males aged ≥10 years who presented at these facilities from 1 July 2012 to 31 September 2017 were included. Outcomes were VMMC uptake, HIV testing uptake and rate of adverse events (AEs). Using a de-identified observational database of these clients, summary statistics of the demographic characteristics and outcomes were calculated.
Results: There were a total 1,001,226 attendees of which 998,213 (99.7%) were offered VMMC and had a median age of 15 years (IQR = 12-23 years). Of those offered VMMC, 99.6% (994,293) consented, 96.7% (965,370) were circumcised and the majority (46.3%) were from Gauteng province. HIV testing uptake was 71% with a refusal rate of 15%. Of the newly diagnosed HIV positives, 64% (6,371 / 9,972) referrals were made. The rate of AEs, defined as bleeding, infection, and insufficient skin removal) declined from 3.26% in 2012 to 1.17% in 2017. There was a reduction in infection-related AEs from 2,448 of the 2,602 adverse events (94.08%) in 2012 to 129 of the 2,069 adverse events (6.23%) in 2017.
Conclusion: There was a high VMMC uptake with a decline in AEs over time. Adolescent men contributed the most to the circumcised population, an indication that the young population accesses medical circumcision more. VMMC programs need to implement innovative demand creation strategies to encourage older males (20-34 years) at higher risk of HIV acquisition to get circumcised for immediate impact in reduction of HIV incidence. HIV prevalence in the total population increased with increasing age, notably in clients above 25 years.
PloS one · 11 citationsread the source →
van der Steen JT, van Soest-Poortvliet MC, Hallie-Heierman M, Onwuteaka-Philipsen BD, Deliens L, de Boer ME, Van den Block L, van Uden N, Hertogh CM, de Vet HC. (2014)MEDLINE-indexed journal, not yet read by usJournal of Alzheimer's disease : JAD · systematic review Factors associated with initiation of advance care planning in dementia: a systematic review.
Background: Planning ahead may be particularly relevant in dementia considering patients' cognitive decline and difficulty to predict the course of the dementia.
Objective: To identify factors associated with initiation of advance care planning (ACP) regarding end-of-life issues in dementia.
Methods: Systematic review of the PubMed, Embase, Cinahl, Psychinfo, and Cochrane databases until January 2013. We included articles reporting on empirical research, identifying factors related to initiation of ACP defined as starting a discussion, starting the decision making, or having a documented patient-written advance directive.
Results: Of 4,647 unique articles, we assessed 178 as full-texts, and included 33. Most designs (64%) were qualitative; 42% limited to moderate to severe, and 6% to mild to moderate stages. Perspectives varied: family (33%), professional caregivers (24%), patient (15%), or multiple (27%). A variety of factors with complex interplay was involved in initiating ACP. Family factors dominated, with family's initiative or lack of it, and willingness or reluctance to engage in initiating ACP identified in a series of studies. Further, professional caregivers' initiative or lack of it and patient's health status were important factors that facilitated or hindered initiating ACP. Ethnic minority status of those involved and family distance may be barriers. Continuity of care and health care system factors also affected initiating of ACP.
Conclusion: Professional caregivers may initiate ACP early if strategies carefully consider timing and family and patient receptiveness or reluctance, and are family and patient-centered. Interventions should address the complexity of interrelated system and personal factors affecting initiation of ACP.
Journal of Alzheimer's disease : JAD · systematic review · 126 citationsread the source →
Hasin DS, Wall M, Witkiewitz K, Kranzler HR, Falk D, Litten R, Mann K, O'Malley SS, Scodes J, Robinson RL, Anton R, Alcohol Clinical Trials Initiative (ACTIVE) Workgroup. (2017)MEDLINE-indexed journal, not yet read by usThe lancet. Psychiatry · cohort or longitudinal Change in non-abstinent WHO drinking risk levels and alcohol dependence: a 3 year follow-up study in the US general population.
Background: Alcohol dependence is often untreated. Although abstinence is often the aim of treatment, many drinkers prefer drinking reduction goals. Therefore, if supported by evidence of benefit, drinking reduction goals could broaden the appeal of treatment. Regulatory agencies are considering non-abstinent outcomes as efficacy indicators in clinical trials, including reduction in WHO drinking risk levels-very high, high, moderate, and low-defined in terms of mean ethanol consumption (in grams) per day. We aimed to study the relationship between reductions in WHO drinking risk levels and subsequent reduction in the risk of alcohol dependence.
Methods: In this population-based cohort study, we included data from 22 005 drinkers who were interviewed in 2001-02 (Wave 1) and re-interviewed 3 years later (2004-05; Wave 2) in the US National Epidemiologic Survey on Alcohol and Related Conditions. Alcohol consumption (WHO drinking risk levels) and alcohol dependence (at least three of seven DSM-IV criteria in the previous 12 months) were assessed at both waves. We used logistic regression to test the relationship between change in WHO drinking risk levels between Waves 1 and 2, and alcohol dependence at Wave 2.
Findings: At Wave 1, 2·5% (weighted proportion) of the respondents were very-high-risk drinkers, 2·5% were high-risk drinkers, 4·8% were moderate-risk drinkers, and most (90·2%) were low-risk drinkers. Reduction in WHO drinking risk level predicted significantly lower odds of alcohol dependence at Wave 2, particularly among very-high-risk drinkers (adjusted odds ratios 0·27 [95% CI 0·18-0·41] for reduction by one level, 0·17 [0·10-0·27] for two levels, and 0·07 [0·05-0·10] for three levels) and high-risk drinkers (0·64 [0·54-0·75] for one level and 0·12 [0·09-0·15] for two levels), and among those with alcohol dependence at Wave 1 (0·29 [0·15-0·57] for one level, 0·06 [0·04-0·10] for two levels, and 0·04 [0·03-0·06] for three levels in very-high-risk drinkers).
Interpretation: Our results support the use of reductions in WHO drinking risk levels as an efficacy outcome in clinical trials. Because these risk levels can be readily translated into standard drink equivalents per day of different countries, the WHO risk levels could also be used internationally to guide treatment goals and clinical recommendations on drinking reduction.
Funding: US National Institute on Alcohol Abuse and Alcoholism, New York State Psychiatric Institute, the Alcohol Clinical Trials Initiative.
The lancet. Psychiatry · cohort or longitudinal · 117 citationsread the source →
Internet-based cognitive behavior therapy vs. cognitive behavioral group therapy for social anxiety disorder: a randomized controlled non-inferiority trial.
Background and aims: Cognitive behavioral group therapy (CBGT) is an effective, well-established, but not widely available treatment for social anxiety disorder (SAD). Internet-based cognitive behavior therapy (ICBT) has the potential to increase availability and facilitate dissemination of therapeutic services for SAD. However, ICBT for SAD has not been directly compared with in-person treatments such as CBGT and few studies investigating ICBT have been conducted in clinical settings. Our aim was to investigate if ICBT is at least as effective as CBGT for SAD when treatments are delivered in a psychiatric setting.
Methods: We conducted a randomized controlled non-inferiority trial with allocation to ICBT (n=64) or CBGT (n=62) with blinded assessment immediately following treatment and six months post-treatment. Participants were 126 individuals with SAD who received CBGT or ICBT for a duration of 15 weeks. The Liebowitz Social Anxiety Scale (LSAS) was the main outcome measure. The following non-inferiority margin was set: following treatment, the lower bound of the 95 % confidence interval (CI) of the mean difference between groups should be less than 10 LSAS-points.
Results: Both groups made large improvements. At follow-up, 41 (64%) participants in the ICBT group were classified as responders (95% CI, 52%-76%). In the CBGT group, 28 participants (45%) responded to the treatment (95% CI, 33%-58%). At post-treatment and follow-up respectively, the 95 % CI of the LSAS mean difference was 0.68-17.66 (Cohen's d between group=0.41) and -2.51-15.69 (Cohen's d between group=0.36) favoring ICBT, which was well within the non-inferiority margin. Mixed effects models analyses showed no significant interaction effect for LSAS, indicating similar improvement across treatments (F=1.58; df=2, 219; p=.21).
Conclusions: ICBT delivered in a psychiatric setting can be as effective as CBGT in the treatment of SAD and could be used to increase availability to CBT.
Trial registration: ClinicalTrials.gov NCT00564967.
PloS one · randomised controlled trial · 155 citationsread the source →
Zipfel S, Wild B, Groß G, Friederich HC, Teufel M, Schellberg D, Giel KE, de Zwaan M, Dinkel A, Herpertz S, Burgmer M, Löwe B, Tagay S, von Wietersheim J, Zeeck A, Schade-Brittinger C, Schauenburg H, Herzog W, ANTOP study group. (2014)MEDLINE-indexed journal, not yet read by usLancet (London, England) · randomised controlled trial Focal psychodynamic therapy, cognitive behaviour therapy, and optimised treatment as usual in outpatients with anorexia nervosa (ANTOP study): randomised controlled trial.
Background: Psychotherapy is the treatment of choice for patients with anorexia nervosa, although evidence of efficacy is weak. The Anorexia Nervosa Treatment of OutPatients (ANTOP) study aimed to assess the efficacy and safety of two manual-based outpatient treatments for anorexia nervosa--focal psychodynamic therapy and enhanced cognitive behaviour therapy--versus optimised treatment as usual.
Methods: The ANTOP study is a multicentre, randomised controlled efficacy trial in adults with anorexia nervosa. We recruited patients from ten university hospitals in Germany. Participants were randomly allocated to 10 months of treatment with either focal psychodynamic therapy, enhanced cognitive behaviour therapy, or optimised treatment as usual (including outpatient psychotherapy and structured care from a family doctor). The primary outcome was weight gain, measured as increased body-mass index (BMI) at the end of treatment. A key secondary outcome was rate of recovery (based on a combination of weight gain and eating disorder-specific psychopathology). Analysis was by intention to treat. This trial is registered at http://isrctn.org, number ISRCTN72809357.
Findings: Of 727 adults screened for inclusion, 242 underwent randomisation: 80 to focal psychodynamic therapy, 80 to enhanced cognitive behaviour therapy, and 82 to optimised treatment as usual. At the end of treatment, 54 patients (22%) were lost to follow-up, and at 12-month follow-up a total of 73 (30%) had dropped out. At the end of treatment, BMI had increased in all study groups (focal psychodynamic therapy 0·73 kg/m(2), enhanced cognitive behaviour therapy 0·93 kg/m(2), optimised treatment as usual 0·69 kg/m(2)); no differences were noted between groups (mean difference between focal psychodynamic therapy and enhanced cognitive behaviour therapy -0·45, 95% CI -0·96 to 0·07; focal psychodynamic therapy vs optimised treatment as usual -0·14, -0·68 to 0·39; enhanced cognitive behaviour therapy vs optimised treatment as usual -0·30, -0·22 to 0·83). At 12-month follow-up, the mean gain in BMI had risen further (1·64 kg/m(2), 1·30 kg/m(2), and 1·22 kg/m(2), respectively), but no differences between groups were recorded (0·10, -0·56 to 0·76; 0·25, -0·45 to 0·95; 0·15, -0·54 to 0·83, respectively). No serious adverse events attributable to weight loss or trial participation were recorded.
Interpretation: Optimised treatment as usual, combining psychotherapy and structured care from a family doctor, should be regarded as solid baseline treatment for adult outpatients with anorexia nervosa. Focal psychodynamic therapy proved advantageous in terms of recovery at 12-month follow-up, and enhanced cognitive behaviour therapy was more effective with respect to speed of weight gain and improvements in eating disorder psychopathology. Long-term outcome data will be helpful to further adapt and improve these novel manual-based treatment approaches.
Funding: German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF), German Eating Disorders Diagnostic and Treatment Network (EDNET).
Lancet (London, England) · randomised controlled trial · 230 citationsread the source →
Tyrer P, Cooper S, Salkovskis P, Tyrer H, Crawford M, Byford S, Dupont S, Finnis S, Green J, McLaren E, Murphy D, Reid S, Smith G, Wang D, Warwick H, Petkova H, Barrett B. (2014)MEDLINE-indexed journal, not yet read by usLancet (London, England) · randomised controlled trial Clinical and cost-effectiveness of cognitive behaviour therapy for health anxiety in medical patients: a multicentre randomised controlled trial.
Background: Health anxiety has been treated by therapists expert in cognitive behaviour therapy with some specific benefit in some patients referred to psychological services. Those in hospital care have been less often investigated. Following a pilot trial suggesting efficacy we carried out a randomised study in hospital medical clinics.
Methods: We undertook a multicentre, randomised trial on health anxious patients attending cardiac, endocrine, gastroenterological, neurological, and respiratory medicine clinics in secondary care. We included those aged 16-75 years, who satisfied the criteria for excessive health anxiety, and were resident in the area covered by the hospital, were not under investigation for new pathology or too medically unwell to take part. We used a computer-generated random scheme to allocate eligible medical patients to an active treatment group of five-to-ten sessions of adapted cognitive behaviour therapy (CBT-HA group) delivered by hospital-based therapists or to standard care in the clinics. The primary outcome was change in health anxiety symptoms measured by the Health Anxiety Inventory at 1 year and the main secondary hypothesis was equivalence of total health and social care costs over 2 years, with an equivalence margin of £150. Analysis was by intention to treat. The study is registered with controlled-trials.com, ISRCTN14565822.
Findings: Of 28,991 patients screened, 444 were randomly assigned to receive either adapted cognitive behaviour therapy (CBT-HA group, 219 participants) or standard care (standard care group, 225), with 205 participants in the CBT-HA group and 212 in the standard care group included in the analyses of the primary endpoints. At 1 year, improvement in health anxiety in the patients in the CBT-HA group was 2·98 points greater than in those in the standard care group (95% CI 1·64-4·33, p<0·0001), and twice as many patients receiving cognitive behaviour therapy achieved normal levels of health anxiety compared with those in the control group (13·9% vs 7·3%; odds ratio 2·15, 95% CI 1·09-4·23, p=0·0273). Similar differences were observed at 6 months and 2 years, and there were concomitant reductions in generalised anxiety and, to a lesser extent, depression. Of nine deaths, six were in the control group; all were due to pre-existing illness. Social functioning or health-related quality of life did not differ significantly between groups. Equivalence in total 2-year costs was not achieved, but the difference was not significant (adjusted mean difference £156, 95% CI -1446 to 1758, p=0·848).
Interpretation: This form of adapted cognitive behaviour therapy for health anxiety led to sustained symptomatic benefit over 2 years, with no significant effect on total costs. It deserves wider application in medical care.
Funding: National Institute for Health Research Health Technology Assessment Programme.
Lancet (London, England) · randomised controlled trial · 96 citationsread the source →
Cognitive Behavior Therapy for Generalized Anxiety Disorder Among Older Adults in Primary Care
CONTEXT: Cognitive behavior therapy (CBT) can be effective for late-life generalized anxiety disorder (GAD), but only pilot studies have been conducted in primary care, where older adults most often seek treatment. OBJECTIVE: To examine effects of CBT relative to enhanced usual care (EUC) in older adults with GAD in primary care. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial recruiting 134 older adults (mean age, 66.9 years) from March 2004 to August 2006 in 2 primary care settings. Treatment was provided for 3 months; assessments were conducted at baseline, posttreatment (3 months), and over 12 months of follow-up, with assessments at 6, 9, 12, and 15 months. INTERVENTION: Cognitive behavior therapy (n = 70) conducted in the primary care clinics. Treatment included education and awareness, motivational interviewing, relaxation training, cognitive therapy, exposure, problem-solving skills training, and behavioral sleep management. Patients assigned to receive EUC (n = 64) received biweekly telephone calls to ensure patient safety and provide minimal support. MAIN OUTCOME MEASURES: Primary outcomes included worry severity (Penn State Worry Questionnaire) and GAD severity (GAD Severity Scale). Secondary outcomes included anxiety ratings (Hamilton Anxiety Rating Scale, Beck Anxiety Inventory), coexistent depressive symptoms (Beck Depression Inventory II), and physical/mental health quality of life (12-Item Short Form Health Survey). RESULTS: Cognitive behavior therapy compared with EUC significantly improved worry severity (45.6 [95% confidence interval {CI}, 43.4-47.8] vs 54.4 [95% CI, 51.4-57.3], respectively; P < .001), depressive symptoms (10.2 [95% CI, 8.5-11.9] vs 12.8 [95% CI, 10.5-15.1], P = .02), and general mental health (49.6 [95% CI, 47.4-51.8] vs 45.3 [95% CI, 42.6-47.9], P = .008). There was no difference in GAD severity in patients receiving CBT vs those receiving EUC (8.6 [95% CI, 7.7-9.5] vs 9.9 [95% CI, 8.7-11.1], P = .19). In intention-to-treat analyses, response rates defined according to worry severity were higher following CBT compared with EUC at 3 months (40.0% [28/70] vs 21.9% [14/64], P = .02). CONCLUSIONS: Compared with EUC, CBT resulted in greater improvement in worry severity, depressive symptoms, and general mental health for older patients with GAD in primary care. However, a measure of GAD severity did not indicate greater improvement with CBT. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00308724.
JAMA · randomised controlled trial · 250 citationsread the source →
Ballard C, Lana MM, Theodoulou M, Douglas S, McShane R, Jacoby R, Kossakowski K, Yu LM, Juszczak E, Investigators DART AD. (2008)MEDLINE-indexed journal, not yet read by usPLoS medicine · randomised controlled trial A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial).
Background: There have been increasing concerns regarding the safety and efficacy of neuroleptics in people with dementia, but there are very few long-term trials to inform clinical practice. The aim of this study was to determine the impact of long-term treatment with neuroleptic agents upon global cognitive decline and neuropsychiatric symptoms in patients with Alzheimer disease.
Methods and findings:
Design: Randomised, blinded, placebo-controlled parallel two-group treatment discontinuation trial.
Setting: Oxfordshire, Newcastle and Gateshead, London and Edinburgh, United Kingdom.
Participants: Patients currently prescribed the neuroleptics thioridazine, chlorpromazine, haloperidol trifluoperazine or risperidone for behavioural or psychiatric disturbance in dementia for at least 3 mo.
Interventions: Continue neuroleptic treatment for 12 mo or switch to an identical placebo.
Outcome measures: Primary outcome was total Severe Impairment Battery (SIB) score. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory (NPI).
Results: 165 patients were randomised (83 to continue treatment and 82 to placebo, i.e., discontinue treatment), of whom 128 (78%) commenced treatment (64 continue/64 placebo). Of those, 26 were lost to follow-up (13 per arm), resulting in 51 patients per arm analysed for the primary outcome. There was no significant difference between the continue treatment and placebo groups in the estimated mean change in SIB scores between baseline and 6 mo; estimated mean difference in deterioration (favouring placebo) -0.4 (95% confidence interval [CI] -6.4 to 5.5), adjusted for baseline value (p = 0.9). For neuropsychiatric symptoms, there was no significant difference between the continue treatment and placebo groups (n = 56 and 53, respectively) in the estimated mean change in NPI scores between baseline and 6 mo; estimated mean difference in deterioration (favouring continue treatment) -2.4 (95% CI -8.2 to 3.5), adjusted for baseline value (p = 0.4). Both results became more pronounced at 12 mo. There was some evidence to suggest that those patients with initial NPI >/= 15 benefited on neuropsychiatric symptoms from continuing treatment.
Conclusions: For most patients with AD, withdrawal of neuroleptics had no overall detrimental effect on functional and cognitive status. Neuroleptics may have some value in the maintenance treatment of more severe neuropsychiatric symptoms, but this benefit must be weighed against the side effects of therapy.
Trial registration: Cochrane Central Registry of Controlled Trials/National Research Register (#ISRCTN33368770).
PLoS medicine · randomised controlled trial · 138 citationsread the source →
Efficacy of buspirone, a fundus-relaxing drug, in patients with functional dyspepsia.
Background & aims: Impaired accommodation and hypersensitivity to gastric distention are believed to be involved in the development of functional dyspepsia (FD). Buspirone, a 5-hydroxytryptamine 1A receptor agonist, relaxes the proximal stomach in healthy individuals. We studied the effects of buspirone on symptoms and mechanisms of FD.
Methods: We performed a randomized, double-blind, placebo-controlled, crossover study of 17 patients (13 women; mean age, 38.5 ± 2.4 years). The study included 2 treatment periods of 4 weeks each, separated by a 2-week washout period. In the first period, 7 participants were given buspirone (10 mg, 3 times daily for 4 weeks) and 10 were given placebo 15 minutes before meals; patients switched groups for the second period. We assessed meal-related symptoms and severity, along with gastric sensitivity, accommodation, and emptying (by using barostat and breath tests) before and after 4 weeks of treatment.
Results: Buspirone significantly reduced the overall severity of symptoms of dyspepsia (7.5 ± 1.3 vs 11.5 ± 1.2 for placebo; P < .005) and individual symptoms of postprandial fullness, early satiation, and upper abdominal bloating, whereas placebo had no significant effect (all P < .05). Buspirone did not alter the rate of gastric emptying of solids or sensitivity to gastric distention, but it significantly increased gastric accommodation, compared with placebo (229 ± 28 vs 141 ± 32 mL, respectively; P < .05), and delayed gastric emptying of liquids (half-life = 64 ± 5 vs 119 ± 24 minutes, respectively). Adverse events were similar when patients were given buspirone or placebo.
Conclusions: In patients with FD, 4 weeks of administration of buspirone significantly improved symptoms and gastric accommodation, compared with placebo, whereas gastric emptying of liquids was delayed.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · randomised controlled trial · 188 citationsread the source →
Zarate CA, Brutsche NE, Ibrahim L, Franco-Chaves J, Diazgranados N, Cravchik A, Selter J, Marquardt CA, Liberty V, Luckenbaugh DA. (2012)MEDLINE-indexed journal, not yet read by usBiological psychiatry · randomised controlled trial Replication of ketamine's antidepressant efficacy in bipolar depression: a randomized controlled add-on trial.
Background: Currently, no pharmacological treatments for bipolar depression exist that exert rapid (within hours) antidepressant or antisuicidal effects. We previously reported that intravenous administration of the N-methyl-D-aspartate antagonist ketamine produced rapid antidepressant effects in patients with treatment-resistant bipolar depression. The present study sought to replicate this finding in an independent sample.
Methods: In this double-blind, randomized, crossover, placebo-controlled study, 15 subjects with DSM-IV bipolar I or II depression maintained on therapeutic levels of lithium or valproate received a single intravenous infusion of either ketamine hydrochloride (.5 mg/kg) or placebo on 2 test days 2 weeks apart. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale, which was used to rate overall depressive symptoms at baseline; at 40, 80, 110, and 230 minutes postinfusion; and on days 1, 2, 3, 7, 10, and 14 postinfusion.
Results: Within 40 minutes, depressive symptoms, as well as suicidal ideation, significantly improved in subjects receiving ketamine compared with placebo (d = .89, 95% confidence interval = .61-1.16, and .98, 95% confidence interval = .64-1.33, respectively); this improvement remained significant through day 3. Seventy-nine percent of subjects responded to ketamine and 0% responded to placebo at some point during the trial. The most common side effect was dissociative symptoms, which occurred only at the 40-minute time point.
Conclusions: This study replicated our previous finding that patients with bipolar depression who received a single ketamine infusion experienced a rapid and robust antidepressant response. In addition, we found that ketamine rapidly improved suicidal ideation in these patients.
Biological psychiatry · randomised controlled trial · 586 citationsread the source →
A biobehavioral home-based intervention and the well-being of patients with dementia and their caregivers: the COPE randomized trial.
Context: Optimal treatment to postpone functional decline in patients with dementia is not established.
Objective: To test a nonpharmacologic intervention realigning environmental demands with patient capabilities.
Design, setting, and participants: Prospective 2-group randomized trial (Care of Persons with Dementia in their Environments [COPE]) involving patients with dementia and family caregivers (community-living dyads) recruited from March 2006 through June 2008 in Pennsylvania.
Interventions: Up to 12 home or telephone contacts over 4 months by health professionals who assessed patient capabilities and deficits; obtained blood and urine samples; and trained families in home safety, simplifying tasks, and stress reduction. Control group caregivers received 3 telephone calls and educational materials.
Main outcome measures: Functional dependence, quality of life, frequency of agitated behaviors, and engagement for patients and well-being, confidence using activities, and perceived benefits for caregivers at 4 months.
Results: Of 284 dyads screened, 270 (95%) were eligible and 237 (88%) randomized. Data were collected from 209 dyads (88%) at 4 months and 173 (73%) at 9 months. At 4 months, compared with controls, COPE patients had less functional dependence (adjusted mean difference, 0.24; 95% CI, 0.03-0.44; P = .02; Cohen d = 0.21) and less dependence in instrumental activities of daily living (adjusted mean difference, 0.32; 95% CI, 0.09-0.55; P = .007; Cohen d = 0.43), measured by a 15-item scale modeled after the Functional Independence Measure; COPE patients also had improved engagement (adjusted mean difference, 0.12; 95% CI, 0.07-0.22; P = .03; Cohen d = 0.26), measured by a 5-item scale. COPE caregivers improved in their well-being (adjusted mean difference in Perceived Change Index, 0.22; 95% CI, 0.08-0.36; P = .002; Cohen d = 0.30) and confidence using activities (adjusted mean difference, 0.81; 95% CI, 0.30-1.32; P = .002; Cohen d = 0.54), measured by a 5-item scale. By 4 months, 64 COPE dyads (62.7%) vs 48 control group dyads (44.9%) eliminated 1 or more caregiver-identified problems (chi(2/1) = 6.72, P = . 01).
Conclusion: Among community-living dyads, a nonpharmacologic biobehavioral environmental intervention compared with control resulted in better outcomes for COPE dyads at 4 months. Although no group differences were observed at 9 months for patients, COPE caregivers perceived greater benefits.
Trial registration: clinicaltrials.gov Identifier: NCT00259454.
JAMA · randomised controlled trial · 235 citationsread the source →
A randomized trial to improve the quality of treatment for panic and generalized anxiety disorders in primary care.
Context: Panic disorder and generalized anxiety disorder are prevalent in primary care, associated with poor functional outcomes, and are often unrecognized and ineffectively treated by primary care physicians.
Objective: To examine whether telephone-based collaborative care for panic and generalized anxiety disorders improves clinical and functional outcomes more than the usual care provided by primary care physicians.
Design: Randomized controlled trial.
Setting: Four Pittsburgh area primary care practices linked by a common electronic medical record system. Patients A total of 191 adults aged 18 to 64 years with panic and/or generalized anxiety disorder who were recruited from July 2000 to April 2002. Intervention Patients were randomly assigned to a telephone-based care management intervention (n = 116) or to notification alone of the anxiety disorder to patients and their physicians (usual care, n = 75). The intervention involved non-mental health professionals who provided patients with psychoeducation, assessed preferences for guideline-based care, monitored treatment responses, and informed physicians of their patients' care preferences and progress via an electronic medical record system under the direction of study investigators.
Main outcome measures: Independent blinded assessments of anxiety and depressive symptoms, mental health-related quality of life, and employment status at baseline, 2-, 4-, 8-, and 12-month follow-up.
Results: At 12-month follow-up, intervention patients reported reduced anxiety (effect size [ES], 0.33-0.38; 95% confidence interval [CI], 0.04 to 0.67; P</=.02) and depressive symptoms (ES, 0.35; 95% CI, 0.25-0.46; P = .03); improved mental health-related quality of life (ES, 0.39; 95% CI, 0.10 to 0.68; P = .01); and larger improvements relative to baseline in hours worked per week (5.7; 95% CI, 0.1 to 11.3; P = .05) and fewer work days absent in the past month (-2.6; 95% CI, - 4.8 to -0.3; P = .03) than usual care patients. If working at baseline, more intervention patients than usual care patients remained working at 12-month follow-up (94% vs 79% [15% absolute difference, 0.7%-28.6%]; P = .04).
Conclusions: Telephone-based collaborative care for panic disorder and generalized anxiety disorder is more effective than usual care at improving anxiety symptoms, health-related quality of life, and work-related outcomes.
Archives of general psychiatry · randomised controlled trial · 105 citationsread the source →
Internet-based intervention for smoking cessation (StopAdvisor) in people with low and high socioeconomic status: a randomised controlled trial.
Background: Internet-based interventions for smoking cessation could help millions of people stop smoking at very low unit costs; however, long-term biochemically verified evidence is scarce and such interventions might be less effective for smokers with low socioeconomic status than for those with high status because of lower online literacy to engage with websites. We aimed to assess a new interactive internet-based intervention (StopAdvisor) for smoking cessation that was designed with particular attention directed to people with low socioeconomic status.
Methods: We did this online randomised controlled trial between Dec 6, 2011, and Oct 11, 2013, in the UK. Participants aged 18 years and older who smoked every day were randomly assigned (1:1) to receive treatment with StopAdvisor or an information-only website. Randomisation was automated with an unseen random number function embedded in the website to establish which treatment was revealed after the online baseline assessment. Recruitment continued until the required sample size had been achieved from both high and low socioeconomic status subpopulations. Participants, and researchers who obtained data and did laboratory analyses, were masked to treatment allocation. The primary outcome was 6 month sustained, biochemically verified abstinence. The main secondary outcome was 6 month, 7 day biochemically verified point prevalence. Analysis was by intention to treat. Homogeneity of intervention effect across the socioeconomic subsamples was first assessed to establish whether overall or separate subsample analyses were appropriate. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN99820519.
Findings: We randomly assigned 4613 participants to the StopAdvisor group (n=2321) or the control group (n=2292); 2142 participants were of low socioeconomic status and 2471 participants were of high status. The overall rate of smoking cessation was similar between participants in the StopAdvisor and control groups for the primary (237 [10%] vs 220 [10%] participants; relative risk [RR] 1·06, 95% CI 0·89-1·27; p=0·49) and the secondary (358 [15%] vs 332 [15%] participants; 1·06, 0·93-1·22; p=0·37) outcomes; however, the intervention effect differed across socioeconomic status subsamples (1·44, 0·99-2·09; p=0·0562 and 1·37, 1·02-1·84; p=0·0360, respectively). StopAdvisor helped participants with low socioeconomic status stop smoking compared with the information-only website (primary outcome: 90 [8%] of 1088 vs 64 [6%] of 1054 participants; RR 1·36, 95% CI 1·00-1·86; p=0·0499; secondary outcome: 136 [13%] vs 100 [10%] participants; 1·32, 1·03-1·68, p=0·0267), but did not improve cessation rates in those with high socioeconomic status (147 [12%] of 1233 vs 156 [13%] of 1238 participants; 0·95, 0·77-1·17; p=0·61 and 222 [18%] vs 232 [19%] participants; 0·96, 0·81-1·13, p=0·64, respectively).
Interpretation: StopAdvisor was more effective than an information-only website in smokers of low, but not high, socioeconomic status. StopAdvisor could be implemented easily and made freely available, which would probably improve the success rates of smokers with low socioeconomic status who are seeking online support.
Funding: National Prevention Research Initiative.
The Lancet. Respiratory medicine · randomised controlled trial · 99 citationsread the source →
Patients' and Parents' Needs, Attitudes, and Perceptions About Early Palliative Care Integration in Pediatric Oncology.
Importance: Early palliative care integration for cancer patients is now touted as the optimal care model, yet significant barriers often prevent its implementation. A perceived barrier, especially for pediatric oncology patients, is the notion that patients and their families may not need or want palliative care involvement early in the disease trajectory.
Objective: To determine the perception of symptom burden early in treatment and assess attitudes toward early integration of palliative care in pediatric oncology patient-parent pairs.
Design, setting, and participants: Novel but pretested survey tools were administered to 129 patient-parent dyads of hospital-based pediatric oncology ambulatory clinics and inpatient units between September 2011 and January 2015. All patient participants were aged between 10 and 17 years and were diagnosed as having an oncologic condition 1 month to 1 year before enrollment. Both the patient and the parent in the dyad spoke English, and all participating parents provided written informed consent. A convenience sample was used for selection, with participants screened when otherwise presenting at a participating site. A total of 280 eligible participants were approached for study inclusion, 258 of whom were enrolled in the study (92.1% positive response-rate).
Main outcomes and measures: Degree of perceived suffering from early symptom-related causes, attitudes toward early palliative care integration, and patient-parent concordance. Statistical analysis included descriptive statistics, calculation of concordance, McNemar test results, and Cochran-Armitage trend test results.
Results: Of the 129 patients in the dyads, 68 were boys, and 61 girls; of the 129 parents, 15 were men, and 114 women. Patients reported the following symptoms in the first month of cancer therapy: nausea (n = 109; 84.5%), loss of appetite (n = 97; 75.2%), pain (n = 96; 74.4%), anxiety (n = 77; 59.7%), constipation (n = 69; 53.5%), depression (n = 64; 49.6%), and diarrhea (n = 52; 40.3%). A large proportion of those reporting suffering indicated substantial suffering severity from specific symptoms (ie, a great deal or a lot) including nausea, 52.3% (57 of 109), loss of appetite, 50.5% (49 of 97), constipation 30.4% (21 of 69), pain 30.2% (29 of 96), anxiety 28.6% (22 of 77), depression 28.1% (18 of 64), and diarrhea 23.1% (12 of 52). Few children and parents expressed opposition to early palliative care involvement (2 [1.6%] and 8 [6.2%]) or perceived any detrimental effects on their relationship with their oncologist (6 [4.7%] and 5 [3.9%]), loss of hope (3 [2.3%] and 10 [7.8%]), or therapy interference (3 [2.3%] and 2 [1.6%], respectively). Intradyad concordance was low overall: 26% to 29% for exact concordance and 40% to 69% for agreement within 1 response category. Significant differences in patient-parent attitudes toward aspects of early palliative care included child participants being more likely than their parents (40.3% [n = 52] vs 17.8% [n = 23]) to indicate that palliative care would have been helpful for treating their symptoms (P < .001).
Conclusions and relevance: Pediatric oncology patients experience a high degree of symptom-related suffering early in cancer therapy, and very few patients or parents in this study expressed negative attitudes toward early palliative care. Our findings suggest that pediatric oncology patients and families might benefit from, and are not a barrier to, early palliative care integration in oncology.
JAMA oncology · cohort or longitudinal · 148 citationsread the source →
Sun Q, Yu D, Fan J, Yu C, Guo Y, Pei P, Yang L, Chen Y, Du H, Yang X, Sansome S, Wang Y, Zhao W, Chen J, Chen Z, Zhao L, Lv J, Li L, China Kadoorie Biobank Collaborative Group. (2022)MEDLINE-indexed journal, not yet read by usThe Lancet. Public health · cohort or longitudinal Healthy lifestyle and life expectancy at age 30 years in the Chinese population: an observational study.
Background: The improvement of life expectancy is one of the aims of the Healthy China 2030 blueprint. We aimed to investigate the extent to which healthy lifestyles are associated with life expectancy in Chinese adults.
Methods: We used the prospective China Kadoorie Biobank (CKB) study to examine the relative risk of mortality associated with individual and combined lifestyle factors (never smoking or quitting not for illness, no excessive alcohol use, being physically active, healthy eating habits, and healthy body shape). Participants with coronary heart disease, stroke, cancer, or missing values for body-mass index were excluded. For analysis of chronic respiratory diseases, participants with chronic obstructive pulmonary disease or asthma were excluded. We estimated the national prevalence of lifestyle factors using data from the China Nutrition and Health Surveillance (CNHS; 2015) and derived mortality rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (2015). All three data sources were combined to estimate the life expectancy of individuals at age 30 years following different levels of lifestyle factors by using the life table method. The cause-specific decomposition of the life expectancy differences was analysed using Arriaga's method.
Findings: After the exclusion of CKB participants with coronary heart disease, stroke, cancer, or missing BMI data at baseline, 487 209 were included in the primary analysis. Participants with COPD or asthma at baseline were additionally excluded for chronic respiratory disease-related analysis, leaving 451 233 participants with data available for analysis. Data from 171 127 adults aged 30-84 years from the CNHS 2015 were used to estimate the sex-specific and age-specific prevalence of lifestyle-related factors. There were 42 496 deaths documented over a median follow-up of 11·1 years (IQR 10·2-12·1) in CKB. The adjusted hazard ratios (aHRs) of participants adopting five versus 0-1 low-risk factors was 0·38 (95% CI 0·34-0·43) for all-cause mortality, aHR 0·37 (0·30-0·46) for cardiovascular disease mortality, aHR 0·47 (0·39-0·56) for cancer mortality, and aHR 0·30 (0·14-0·64) for chronic respiratory disease mortality. The life expectancy at age 30 years for individuals with 0-1 low-risk factors was on average 41·7 years (95% CI 41·5-42·0) for men and 47·3 years (46·6-48·0) for women. For individuals with all five low-risk factors, the life expectancy at age 30 was 50·5 years (95% CI 48·5-52·4) for men and 55·4 years (53·5-57·4) for women; meaning a difference of 8·8 years (95% CI 6·8-10·7) for men and 8·1 years (6·5-9·9) for women. The estimated extended life expectancy for men and women was mainly attributable to reduced death from cardiovascular disease (2·4 years [27% of the total extended life expectancy] for men and 3·7 years [46%] for women), cancer (2·6 years [30%] for men and 0·9 years [11%] for women), and chronic respiratory disease (0·6 years [7%] for men and 1·2 years [15%] for women).
Interpretation: Our findings suggest that increasing the adoption of these five healthy lifestyle factors through public health interventions could be associated with substantial gains in life expectancy in the Chinese population.
Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Kadoorie Charitable Foundation, UK Wellcome Trust.
The Lancet. Public health · cohort or longitudinal · 129 citationsread the source →
Dose-dependent and joint associations between screen time, physical activity, and mental wellbeing in adolescents: an international observational study.
Background: Mental wellbeing in adolescents has declined considerably during past decades, making the identification of modifiable risk factors important. Prolonged screen time and insufficient physical activity appear to operate independently and synergistically to increase the risk of poor mental wellbeing in school-aged children. We aimed to examine the gender-stratified dose-dependent and joint associations of screen time and physical activity with mental wellbeing in adolescents.
Methods: We used data from three rounds of Health Behaviour in School-aged Children cross-sectional surveys (2006, 2010, and 2014) from 42 European and North American countries. Survey participants, aged 11 years, 13 years, and 15 years, provided self-reported information by completing an anonymous questionnaire that included items on health indicators and related behaviours. We used the self-reported variables of life satisfaction and psychosomatic complaints as indicators of adolescents' mental wellbeing, combining these with the self-reported discretionary use of screens and engagement in physical activity. We used generalised additive models and multilevel regression modelling to examine the gender-stratified relationships between mental wellbeing and screen time and physical activity.
Findings: Our sample included 577 475 adolescents (mean age 13·60 years, SD 1·64), with 296 542 (51·35%) girls and 280 933 (48·64%) boys. The mean reported life satisfaction score (on a scale of 0-10) was 7·70 (95% CI 7·69-7·71) in boys and 7·48 (7·46-7·50) in girls. Psychosomatic complaints were more common among girls (mean 9·26, 95% CI 9·23-9·28) than boys (6·89, 6·87-6·91). Generalised additive model analyses showed slightly non-linear associations of screen time and physical activity with life satisfaction and psychosomatic complaints for girls and boys. Detrimental associations between screen time and mental wellbeing started when screen time exceeded 1 h per day, whereas increases in physical activity levels were beneficially and monotonically associated with wellbeing. Multilevel modelling showed that screen time levels were negatively associated with life satisfaction and positively associated with psychosomatic complaints in a dose-dependent manner. Physical activity levels were positively associated with life satisfaction and negatively associated with psychosomatic complaints in a dose-dependent manner. Joint associations of screen time-physical activity with mental wellbeing showed that, compared with the least active participants with more than 8 h per day of screen time and no physical activity, most of the other screen time-physical activity groups had considerably higher life satisfaction and lower psychosomatic complaints.
Interpretation: Higher levels of screen time and lower levels of physical activity were associated with lower life satisfaction and higher psychosomatic complaints among adolescents from high-income countries. Public health strategies to promote adolescents' mental wellbeing should aim to decrease screen time and increase physical activity simultaneously.
Funding: None.
The Lancet. Child & adolescent health · cohort or longitudinal · 63 citationsread the source →
Seedat S, Scott KM, Angermeyer MC, Berglund P, Bromet EJ, Brugha TS, Demyttenaere K, de Girolamo G, Haro JM, Jin R, Karam EG, Kovess-Masfety V, Levinson D, Medina Mora ME, Ono Y, Ormel J, Pennell BE, Posada-Villa J, Sampson NA, Williams D, Kessler RC. (2009)MEDLINE-indexed journal, not yet read by usArchives of general psychiatry · cohort or longitudinal Cross-national associations between gender and mental disorders in the World Health Organization World Mental Health Surveys.
Context: Gender differences in mental disorders, including more anxiety and mood disorders among women and more externalizing disorders among men, are found consistently in epidemiological surveys. The gender roles hypothesis suggests that these differences narrow as the roles of women and men become more equal.
Objectives: To study time-space (cohort-country) variation in gender differences in lifetime DSM-IV mental disorders across cohorts in 15 countries in the World Health Organization World Mental Health Survey Initiative and to determine if this variation is significantly related to time-space variation in female gender role traditionality as measured by aggregate patterns of female education, employment, marital timing, and use of birth control.
Design: Face-to-face household surveys.
Setting: Africa, the Americas, Asia, Europe, the Middle East, and the Pacific.
Participants: Community-dwelling adults (N = 72,933).
Main outcome measures: The World Health Organization Composite International Diagnostic Interview assessed lifetime prevalence and age at onset of 18 DSM-IV anxiety, mood, externalizing, and substance disorders. Survival analyses estimated time-space variation in female to male odds ratios of these disorders across cohorts defined by the following age ranges: 18 to 34, 35 to 49, 50 to 64, and 65 years and older. Structural equation analysis examined predictive effects of variation in gender role traditionality on these odds ratios.
Results: In all cohorts and countries, women had more anxiety and mood disorders than men, and men had more externalizing and substance disorders than women. Although gender differences were generally consistent across cohorts, significant narrowing was found in recent cohorts for major depressive disorder and substance disorders. This narrowing was significantly related to temporal (major depressive disorder) and spatial (substance disorders) variation in gender role traditionality.
Conclusions: While gender differences in most lifetime mental disorders were fairly stable over the time-space units studied, substantial intercohort narrowing of differences in major depression was found to be related to changes in the traditionality of female gender roles. Additional research is needed to understand why this temporal narrowing was confined to major depression.
Archives of general psychiatry · cohort or longitudinal · 935 citationsread the source →
Technology-based and digital interventions for intimate partner violence: A systematic review and meta-analysis.
Background: A growing body of research shows the promise and efficacy of technology-based or digital interventions in improving the health and well-being of survivors of intimate partner violence (IPV). In addition, mental health comorbidities such as anxiety, post-traumatic stress disorder (PTSD), and depression occur three to five times more frequently in survivors of IPV than non-survivors, making these comorbidities prominent targets of technology-based interventions. Still, research on the long-term effectiveness of these interventions in reducing IPV victimization and adverse mental health effects is emergent. The significant increase in the number of trials studying technology-based therapies on IPV-related outcomes has allowed us to quantify the effectiveness of such interventions for mental health and victimization outcomes in survivors. This meta-analysis and systematic review provide critical insight from several randomized controlled trials (RCTs) on the overall short and long-term impact of technology-based interventions on the health and well-being of female IPV survivors.
Objectives: To synthesize current evidence on the effects of technology-based or digital interventions on mental health outcomes (depression, anxiety, and PTSD) and victimization outcomes (physical, psychological, and sexual abuse) among IPV survivors.
Search methods: We examined multiple traditional and grey databases for studies published from 2007 to 2021. Traditional databases (such as PubMed Central, Web of Science, CINAHL Plus, and PsychINFO) and grey databases were searched between April 2019 and February 2021. In addition, we searched clinical trial registries, government repositories, and reference lists. Authors were contacted where additional data was needed. We identified 3210 studies in traditional databases and 1257 from grey literature. Over 2198 studies were determined to be duplicates and eliminated, leaving 64 studies after screening titles and abstracts. Finally, 17 RCTs were retained for meta-analysis. A pre-registered protocol was developed and published before conducting this meta-analysis.
Selection criteria: We included RCTs targeting depression, anxiety, PTSD outcomes, and victimization outcomes (physical, sexual, and psychological violence) among IPV survivors using a technology-based intervention. Eligible RCTs featured a well-defined control group. There were no study restrictions based on participant gender, study setting, or follow-up duration. Included studies additionally supplied outcome data for calculating effect sizes for our desired outcome. Studies were available in full text and published between 2007 and 2021 in English.
Data collection and analysis: We extracted relevant data and coded eligible studies. Using Cochrane's RevMan software, summary effect sizes (Outcome by Time) were assessed using an independent fixed-effects model. Standardized mean difference (SMD) effect sizes (or Cohen's d) were evaluated using a Type I error rate and an alpha of 0.05. The overall intervention effects were analyzed using the Z-statistic with a p-value of 0.05. Cochran's Q test and Higgins' I 2 statistics were utilized to evaluate and confirm the heterogeneity of each cumulative effect size. The Cochrane risk of bias assessment for randomized trials (RoB 2) was used to assess the quality of the studies. Campbell Systematic Reviews registered and published this study's protocol in January 2021. No exploratory moderator analysis was conducted; however, we report our findings with and without outlier studies in each meta-analysis.
Main results: Pooled results from 17 RCTs yielded 18 individual effect size comparisons among 4590 survivors (all females). Survivors included college students, married couples, substance-using women in community prisons, pregnant women, and non-English speakers, and sample sizes ranged from 15 to 672. Survivors' ages ranged from 19 to 41.5 years. Twelve RCTs were conducted in the United States and one in Canada, New Zealand, China (People's Republic of), Kenya, and Australia. The results of this meta-analysis found that technology-based interventions significantly reduced depression among female IPV survivors at 0-3 months only (SMD = -0.08, 95% confidence interval [CI] = -0.17 to -0.00), anxiety among IPV survivors at 0-3 months (SMD = -0.27, 95% CI = -0.42 to -0.13, p = 0.00, I 2 = 25%), and physical violence victimization among IPV survivors at 0-6 months (SMD = -0.22, 95% CI = -0.38 to -0.05). We found significant reductions in psychological violence victimization at 0-6 months (SMD = -0.34, 95% CI = -0.47 to -0.20) and at >6 months (SMD = -0.29, 95% CI = -0.39 to -0.18); however, at both time points, there were outlier studies. At no time point did digital interventions significantly reduce PTSD (SMD = -0.04, 95% CI = -0.14 to 0.06, p = .46, I 2 = 0%), or sexual violence victimization (SMD = -0.02, 95% CI = -0.14 to 0.11, I 2 = 21%) among female IPV survivors for all. With outlier studies removed from our analysis, all summary effect sizes were small, and this small number of comparisons prevented moderator analyses.
Authors' conclusions: The results of this meta-analysis are promising. Our findings highlight the effectiveness of IPV-mitigating digital intervention as an add-on (not a replacement) to traditional modalities using a coordinated response strategy. Our findings contribute to the current understanding of "what works" to promote survivors' mental health, safety, and well-being. Future research could advance the science by identifying active intervention ingredients, mapping out intervention principles/mechanisms of action, best modes of delivery, adequate dosage levels using the treatment intensity matching process, and guidelines to increase feasibility and acceptability.
Campbell systematic reviews · review · 25 citationsread the source →
Lewis N, McCaffrey K, Sage K, Cheng CJ, Green J, Goldstein L, Campbell H, Ferrell D, Malan N, LaCross N, Maldonado A, Board A, Hanchey A, Harris D, Callahan S, Aberegg S, Risk I, Willardson S, Carter A, Nakashima A, Duncan J, Burnett C, Atkinson-Dunn R, Dunn A. (2019)MEDLINE-indexed journal, not yet read by usMMWR. Morbidity and mortality weekly report E-cigarette Use, or Vaping, Practices and Characteristics Among Persons with Associated Lung Injury - Utah, April-October 2019.
In August 2019, the Utah Department of Health (UDOH) received reports from health care providers of several cases of lung injury in persons who reported use of electronic cigarette (e-cigarette), or vaping, products (1,2). To describe the characteristics of medical care, potentially related conditions, and exposures among 83 patients in Utah, detailed medical abstractions were completed for 79 (95%) patients. Among patients receiving chart abstractions, 70 (89%) were hospitalized, 39 (49%) required breathing assistance, and many reported preexisting respiratory and mental health conditions. Interviews were conducted by telephone or in person with 53 (64%) patients or their proxies, and product samples from eight (15%) of the interviewed patients or proxies were tested. Among 53 interviewed patients, all of whom reported using e-cigarette, or vaping, products within 3 months of acute lung injury, 49 (92%) reported using any products containing tetrohydrocannabinol (THC), the principal psychoactive component of cannabis; 35 (66%) reported using any nicotine-containing products, and 32 (60%) reported using both. As reported in Wisconsin and Illinois (1), most THC-containing products were acquired from informal sources such as friends or illicit in-person and online dealers. THC-containing products were most commonly used one to five times per day, whereas nicotine-containing products were most commonly used >25 times per day. Product sample testing at the Utah Public Health Laboratory (UPHL) showed evidence of vitamin E acetate in 17 of 20 (89%) THC-containing cartridges, which were provided by six of 53 interviewed patients. The cause or causes of this outbreak is currently unknown (2); however, the predominant use among patients of e-cigarette, or vaping, products with prefilled THC-containing cartridges suggests that the substances in these products or the way in which they are heated and aerosolized play an important role in the outbreak. At present, persons should not use e-cigarette, or vaping, products that contain THC. In addition, because the specific cause or causes of lung injury are not yet known and while the investigation continues, persons should consider refraining from use of all e-cigarette, or vaping, products.
MMWR. Morbidity and mortality weekly report · 54 citationsread the source →
Effects of the menstrual cycle on bipolar disorder.
Objectives: Several lines of research suggest that reproductive events may affect the course of bipolar disorder (BD) in some women. With respect to the menstrual cycle, the focus has been on dysphoric symptoms [e.g., premenstrual dysphoric disorder (PMDD)], and the exacerbation of depression, in the premenstrual phase. This article reviews the literature on the potential effects of the menstrual cycle on BD.
Methods: A systematic search for published case reports and research studies available through March, 2013 was conducted. Several combinations of search terms were entered into PubMed and PsycInfo.
Results: Overall, 25 case reports, ten retrospective studies, and 11 prospective studies were identified. The majority (64%) of case reports involved hypomanic or manic episodes in the premenstrual phase. Retrospective results suggest that 25-77% and 15-27% of women with BD meet the criteria for premenstrual syndrome (PMS) and PMDD, respectively. Menstrual cycle-related mood changes were reported by 64-68% of women with BD in retrospective studies, and were displayed by 44-65% of women in prospective studies.
Conclusions: Although research has focused on the premenstrual phase to the neglect of the periovulatory phase, it appears that a subgroup of women with BD, possibly those with hormonal sensitivity, experience menstrual cycle effects on depressive, hypomanic, and manic episodes. These phase-episode effects appear to be heterogeneous and may have implications for treatment. Whether they might best be described using course specifiers, similar to postpartum onset and rapid cycling, or as diagnostic entities, like PMDD, requires further study.
Bipolar disorders · review · 57 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 →
Self-compassion in recovery following potentially traumatic stress: longitudinal study of at-risk youth.
Despite promising theory, empirical study of the putative protective properties of self-compassion (SC) with respect to resilience to and recovery from traumatic stress is limited. The present study tested the theorized protective role(s) of SC with respect to trauma-related psychopathology over time among an at-risk sample of adolescents (N = 64, 26 % females, M(SD) age = 17.5(1.07) years-old, range age = 15-19; grades 9-12) directly exposed to a potentially traumatic stressful event - the Mount Carmel Forest Fire Disaster. The longitudinal design involved three assessment time-points - within 30-days of the potentially traumatic event (T1) and then at 3- (T2) and 6-months (T3) follow-up intervals. Consistent with prediction, multi-level modeling of mediation documented the prospective protective function(s) of SC, above and beyond dispositional mindfulness, with respect to posttraumatic stress and panic symptoms, depressive symptoms, and suicidality symptoms, but not well-being. The findings are discussed, theoretically, with respect to SC as a malleable protective factor for trauma-related psychopathology outcomes; and, clinically, with respect to SC as a target for future trauma-related selective-prevention and -early intervention research.
Journal of abnormal child psychology · 64 citationsread the source →
Fatigue after traumatic brain injury: Association with neuroendocrine, sleep, depression and other factors.
Objective: Define associations between post-traumatic brain injury (TBI) fatigue and abnormalities in neuroendocrine axes, sleep, mood, cognition and physical functioning.
Design: Survey.
Setting: Large community hospital-based rehabilitation centre.
Participants: Convenience sample of 119 individuals at least 1 year post-TBI.
Outcome measures: Multidimensional Assessment of Fatigue (MAF); Fatigue Severity Scale (FSS); neuroendocrine assessments-growth hormone (GH) reserve, thyroid, cortisol and testosterone levels; visual analogue pain rating; Pittsburgh Sleep Quality Index; Beck Depression Inventory-II; Disability Rating Scale; Craig Handicap Assessment and Reporting Technique; Neurobehavioural Functioning Inventory.
Results: Fifty-three per cent reported fatigue on the MAF and one-third on the FSS; 65% were found to have moderate/severe GH deficiency; 64% had adrenal insufficiency (low fasting cortisol); 12% had central hypothyroidism; and 15% of men had testosterone deficiency. Pituitary dysfunction did not correlate with fatigue or other symptoms. Predictors of MAF total scores were female gender, depression, pain and self-assessed memory deficits. Predictors of FSS scores were depression, self-assessed motor deficits and anti-depressant usage.
Conclusions: Robust correlates of fatigue were gender, depression, pain and memory and motor dysfunction. Investigation of post-TBI fatigue should include screening for depression, pain and sleep disturbance. There was no correlation between pituitary dysfunction and fatigue; however, the relatively high prevalence of hypothyroidism and adrenal dysfunction suggests screening for these hormone deficiencies.
Brain injury · 83 citationsread the source →
Influence of a 30-Day Slow-Paced Breathing Intervention Compared to Social Media Use on Subjective Sleep Quality and Cardiac Vagal Activity.
Breathing techniques are part of traditional relaxation methods; however, their influence on psychophysiological variables related to sleep is still unclear. Consequently, the aim of this paper was to investigate the influence of a 30-day slow-paced breathing intervention compared to social media use on subjective sleep quality and cardiac vagal activity (CVA, operationalized via high-frequency heart rate variability). Healthy participants (n = 64, 33 male, 31 female, M = 22.11, SD = 3.12) were randomly allocated to an experimental or control group. In the experimental group, they had to perform slow-paced breathing for 15 min each evening across a 30-day period. This was administered through a smartphone application. The control group used social media (e.g., Facebook, Instagram, Whatsapp) for the same duration. The night before and after the intervention, their CVA was assessed via a light portable Electrocardiogram (ECG) device, and they had to fill out the Pittsburgh Sleep Quality Index questionnaire. Results showed that in comparison to the use of social media, the slow-paced breathing technique improved subjective sleep quality and increased overnight CVA, while a tendency was observed for morning awakening CVA. Slow-paced breathing appears a promising cost-effective technique to improve subjective sleep quality and cardiovascular function during sleep in young healthy individuals.
Journal of clinical medicine · 46 citationsread the source →
Cognitive ability at kindergarten entry and socioeconomic status.
Objective: To examine how gradients in socioeconomic status (SES) impact US children's reading and math ability at kindergarten entry and determine the contributions of family background, health, home learning, parenting, and early education factors to those gradients.
Methods: Analysis of 6600 children with cognitive assessments at kindergarten entry from the US Early Childhood Longitudinal Birth Cohort Study. A composite SES measure based on parent's occupation, education, and income was divided into quintiles. Wald F tests assessed bivariate associations between SES and child's cognitive ability and candidate explanatory variables. A decomposition methodology examined mediators of early cognitive gradients.
Results: Average reading percentile rankings increased from 34 to 67 across SES quintiles and math from 33 to 70. Children in lower SES quintiles had younger mothers, less frequent parent reading, less home computer use (27%-84%), and fewer books at home (26-114). Parent's supportive interactions, expectations for their child to earn a college degree (57%-96%), and child's preschool attendance (64%-89%) increased across quintiles. Candidate explanatory factors explained just over half the gradients, with family background factors explaining 8% to 13%, health factors 4% to 6%, home learning environment 18%, parenting style/beliefs 14% to 15%, and early education 6% to 7% of the gaps between the lowest versus highest quintiles in reading and math.
Conclusions: Steep social gradients in cognitive outcomes at kindergarten are due to many factors. Findings suggest policies targeting levels of socioeconomic inequality and a range of early childhood interventions are needed to address these disparities.
Pediatrics · 65 citationsread the source →
Palliative care experience and perceived gaps in training among transplant hepatology fellows: A national survey.
Despite the likely benefits of palliative care (PC) for patients with cirrhosis, physician experiences and perspectives about best practices are variable. We aimed to assess PC experience and gaps in training among transplant hepatology fellows. We conducted a national survey of all transplant hepatology fellows enrolled in accredited fellowship programs during the 2020-2021 academic year. We assessed the frequency of PC provision and comfort with physical and psychological symptom management, psychosocial care, communication skills, advance care planning, and end-of-life care. A total of 45 of 56 (79%) of transplant hepatology fellows responded to the survey; 50% (n = 22) were female. Most trained at centers performing over 100 transplants per year (67%, n = 29) distributed evenly across geographic regions. Most fellows (69%, n = 31) had a PC or hospice care rotation during residency, and 42% (n = 19) of fellows received education in PC during transplant hepatology fellowship. Fellows reported feeling moderately to very comfortable with communication skills such as breaking bad news (93%, n = 41) and leading family meetings (75%, n = 33), but nearly one-third (30%, n = 13) reported feeling not very or not at all comfortable assessing and managing anxiety and depression (30%, n = 13) and spiritual distress (34%, n = 15). Nearly one-quarter (22%, n = 10) had never discussed or documented advance care plans during fellowship. Fellows wished to receive future instruction on the assessment and management of physical symptoms (68%, n = 30) and anxiety and depression (64%, n = 28). Conclusion: Our survey highlights gaps in PC experience and education during transplant hepatology fellowship, lack of comfort in managing psychological distress and advance care planning, and desire to improve skills, particularly in symptom management. Future studies should investigate how to enhance transplant hepatology competencies in these PC domains and whether this impacts clinical care, advance care planning, or patient experience.
Hepatology communications · 13 citationsread the source →
Outcomes of community-based suicide prevention program in primary health care of Iran.
Background: Suicidal management and prevention in communities, especially in its first stages, is an effective intervention for the health systems. However, in numerous societies most cases go undetected. Primary Health Care (PHC) is an effective place for the management of Suicide Prevention Programs (SPP). In Malekan County, a health community assessment found suicide as the most important health problem. A regional SPP was performed for suicide prevention during 2014-2017.
Methods: This study was carried out in six steps: (1) Establishing a research team, (2) Improving a registry for suicidal behaviors (SBs), (3) Identifying local determinants of SBs, (4) Training healthcare providers, (5) Follow-up and monitoring of SBs, and (6) Public awareness campaigns. Our ultimate goal was to lower the rates of suicide, and suicide attempt (SA) by 15 and 20 %, respectively. Multiple logistic regression was used to estimate the adjusted odds ratios and the 95% confidence intervals.
Results: A total of 821 SAs and 32 suicides were identified. The gender distribution for suicides was 70% males whereas SAs were 64% among females. The majority of suicides occurred in spring 18 (56.25%) while summer was the most common season among SAs 288 (35.8%). Almost 62 and 75% of suicides and SAs have used hanging and poisoning methods, respectively. Hanging increased suicide risk significantly (OR: 8.5, 95% CI 2.9-76.99). During the study, 93 life-skill and parenting education sessions were held. The incidence rates of suicide and SA decreased from 11.22, and 203 per 100,000 in 2013 to 2.63, and 157 in 2017, respectively. Similarly, the re-attempt to SAs ratio decreased from 12% to 2013 to 6.7% in 2017. Moreover, more than 8% of SBs were collected from adjacent Counties.
Conclusions: At the study end, suicide, SA, and re-attempt were lowered by 75%, 22%, and 42%, respectively. The practical framework that achieved in this study could be used as a basis for developing future SPPs and suicide researches in the Iranian context. Furthermore, the various socio-economic and socio-cultural challenges highlight the need to consider a wide range of contextual factors when developing an SPP.
International journal of mental health systems · 22 citationsread the source →
Peer racial representation at school, social experiences, and inflammation among Black adolescents.
Objective: In the United States, Black adults experience higher rates of chronic diseases compared with White adults. Low-grade inflammation is considered a key biological pathway underlying these disparities, and Black-White differences in inflammation have been observed as early as adolescence. However, the psychosocial predictors of low-grade inflammation for Black adolescents remain incompletely understood, with few studies examining how broader school-level factors shape psychosocial experiences that may contribute to low-grade inflammation. This longitudinal study examined (a) whether Black adolescents attending schools with a lower (vs. higher) proportion of Black students would experience greater discrimination and loneliness and (b) whether discrimination and loneliness, in turn, predicted low-grade inflammation 1 year later.
Method: A sample of 306 Black adolescents (64% female, Mage = 17.6, range = 14-19) completed measures of discrimination and loneliness and provided blood samples to assess low-grade inflammation markers at baseline and 1 year later. School racial composition was obtained from the Department of Education databases.
Results: Results showed that attending schools with a lower proportion of Black students was associated with more discrimination (ß = -.15) but not loneliness (ß = -.01). In turn, discrimination and, less robustly, loneliness independently predicted prospective increases in low-grade inflammation over 1 year (ßs = .14).
Conclusion: These findings suggest that, for Black adolescents, the racial composition of school environments may indirectly contribute to early disease risk by shaping their psychosocial experiences. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Health psychology : official journal of the Division of Health Psychology, American Psychological Associationread the source →
Monson CM, Wagner AC, Mithoefer AT, Liebman RE, Feduccia AA, Jerome L, Yazar-Klosinski B, Emerson A, Doblin R, Mithoefer MC. (2020)MEDLINE-indexed journal, not yet read by usEuropean journal of psychotraumatology MDMA-facilitated cognitive-behavioural conjoint therapy for posttraumatic stress disorder: an uncontrolled trial.
Cognitive-behavioural conjoint therapy (CBCT) for PTSD has been shown to improve PTSD, relationship adjustment, and the health and well-being of partners. MDMA (3,4-methylenedioxymethamphetamine) has been used to facilitate an individual therapy for PTSD. This study was an initial test of the safety, tolerability, and efficacy of MDMA-facilitated CBCT. Six couples with varying levels of baseline relationship satisfaction in which one partner was diagnosed with PTSD participated in a condensed version of the 15-session CBCT protocol delivered over 7 weeks. There were two sessions in which both members of the couple were administered MDMA. All couples completed the treatment protocol, and there were no serious adverse events in either partner. There were significant improvements in clinician-assessed, patient-rated, and partner-rated PTSD symptoms (pre- to post-treatment/follow-up effect sizes ranged from d = 1.85-3.59), as well as patient depression, sleep, emotion regulation, and trauma-related beliefs. In addition, there were significant improvements in patient and partner-rated relationship adjustment and happiness (d =.64-2.79). These results are contextualized in relation to prior results from individual MDMA-facilitated psychotherapy and CBCT for PTSD alone. MDMA holds promise as a facilitator of CBCT to achieve more robust and broad effects on individual and relational functioning in those with PTSD and their partners.
European journal of psychotraumatology · 48 citationsread the source →
Mattila E, Lappalainen R, Välkkynen P, Sairanen E, Lappalainen P, Karhunen L, Peuhkuri K, Korpela R, Kolehmainen M, Ermes M. (2016)MEDLINE-indexed journal, not yet read by usJMIR mHealth and uHealth Usage and Dose Response of a Mobile Acceptance and Commitment Therapy App: Secondary Analysis of the Intervention Arm of a Randomized Controlled Trial.
Background: Mobile phone apps offer a promising medium to deliver psychological interventions. A mobile app based on Acceptance and Commitment Therapy (ACT) was developed and studied in a randomized controlled trial (RCT).
Objective: To study usage metrics of a mobile ACT intervention and dose-response relationship between usage and improvement in psychological flexibility.
Methods: An RCT was conducted to investigate the effectiveness of different lifestyle interventions for overweight people with psychological stress. This paper presents a secondary analysis of the group that received an 8-week mobile ACT intervention. Most of the analyzed 74 participants were female (n=64, 86%). Their median age was 49.6 (interquartile range, IQR 45.4-55.3) years and their mean level of psychological flexibility, measured with the Acceptance and Action Questionnaire II, was 20.4 (95% confidence interval 18.3-22.5). Several usage metrics describing the intensity of use, usage of content, and ways of use were calculated. Linear regression analyses were performed to study the dose-response relationship between usage and the change in psychological flexibility and to identify the usage metrics with strongest association with improvement. Binary logistic regression analyses were further used to assess the role of usage metrics between those who showed improvement in psychological flexibility and those who did not. In addition, associations between usage and baseline participant characteristics were studied.
Results: The median number of usage sessions was 21 (IQR 11.8-35), the number of usage days was 15 (IQR 9.0-24), and the number of usage weeks was 7.0 (IQR 4.0-8.0). The participants used the mobile app for a median duration of 4.7 (IQR 3.2-7.2) hours and performed a median of 63 (IQR 46-98) exercises. There was a dose-response relationship between usage and the change in psychological flexibility. The strongest associations with psychological flexibility (results adjusted with gender, age, and baseline psychological variables) were found for lower usage of Self as context related exercises (B=0.22, P=.001) and higher intensity of use, described by the number of usage sessions (B=-0.10, P=.01), usage days (B=-0.17, P=.008), and usage weeks (B=-0.73, P=.02), the number of exercises performed (B=-0.02, P=.03), and the total duration of use (B=-0.30, P=.04). Also, higher usage of Acceptance related exercises (B=-0.18, P=.04) was associated with improvement. Active usage was associated with female gender, older age, and not owning a smart mobile phone before the study.
Conclusions: The results indicated that active usage of a mobile ACT intervention was associated with improved psychological flexibility. Usage metrics describing intensity of use as well as two metrics related to the usage of content were found to be most strongly associated with improvement.
Trial registration: ClinicalTrials.gov NCT01738256; https://clinicaltrials.gov/ct2/show/NCT01738256 (Archived by WebCite at http://www.webcitation.org/6iTePjPLL).
JMIR mHealth and uHealth · 46 citationsread the source →
Modifiable early-life risk factors for childhood adiposity and overweight: an analysis of their combined impact and potential for prevention.
Background: Early life may be a "critical period" when appetite and regulation of energy balance are programmed, with lifelong consequences for obesity risk. Insight into the potential impact of modifying early-life risk factors on later obesity can be gained by evaluating their combined effects.
Objective: The objective was to examine the relation between the number of early-life risk factors and obesity outcomes among children in a prospective birth cohort (Southampton Women's Survey).
Design: Five risk factors were defined: maternal obesity [prepregnant body mass index (BMI; in kg/m(2)) >30], excess gestational weight gain (Institute of Medicine, 2009), smoking during pregnancy, low maternal vitamin D status (<64 nmol/L), and short duration of breastfeeding (none or <1 mo). Obesity outcomes examined when the children were aged 4 and 6 y were BMI, dual-energy X-ray absorptiometry-assessed fat mass, overweight, or obesity (International Obesity Task Force). Data were available for 991 mother-child pairs, with children born between 1998 and 2003.
Results: Of the children, 148 (15%) had no early-life risk factors, 330 (33%) had 1, 296 (30%) had 2, 160 (16%) had 3, and 57 (6%) had 4 or 5. At both 4 and 6 y, there were positive graded associations between number of early-life risk factors and each obesity outcome (all P < 0.001). After taking account of confounders, the relative risk of being overweight or obese for children who had 4 or 5 risk factors was 3.99 (95% CI: 1.83, 8.67) at 4 y and 4.65 (95% CI: 2.29, 9.43) at 6 y compared with children who had none (both P < 0.001).
Conclusions: Having a greater number of early-life risk factors was associated with large differences in adiposity and risk of overweight and obesity in later childhood. These findings suggest that early intervention to change these modifiable risk factors could make a significant contribution to the prevention of childhood obesity.
The American journal of clinical nutrition · 85 citationsread the source →
Burden of 375 diseases and injuries, risk-attributable burden of 88 risk factors, and healthy life expectancy in 204 countries and territories, including 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.
Background: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions.
Methods: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution.
Findings: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant).
Interpretation: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity.
Funding: Gates Foundation and Bloomberg Philanthropies.
Lancet (London, England) · 257 citationsread the source →
Conrad N, Judge A, Tran J, Mohseni H, Hedgecott D, Crespillo AP, Allison M, Hemingway H, Cleland JG, McMurray JJV, Rahimi K. (2018)MEDLINE-indexed journal, not yet read by usLancet (London, England) Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals.
Background: Large-scale and contemporary population-based studies of heart failure incidence are needed to inform resource planning and research prioritisation but current evidence is scarce. We aimed to assess temporal trends in incidence and prevalence of heart failure in a large general population cohort from the UK, between 2002 and 2014.
Methods: For this population-based study, we used linked primary and secondary electronic health records of 4 million individuals from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex. Eligible patients were aged 16 years and older, had contributed data between Jan 1, 2002, and Dec 31, 2014, had an acceptable record according to CPRD quality control, were approved for CPRD and Hospital Episodes Statistics linkage, and were registered with their general practice for at least 12 months. For patients with incident heart failure, we extracted the most recent measurement of baseline characteristics (within 2 years of diagnosis) from electronic health records, as well as information about comorbidities, socioeconomic status, ethnicity, and region. We calculated standardised rates by applying direct age and sex standardisation to the 2013 European Standard Population, and we inferred crude rates by applying year-specific, age-specific, and sex-specific incidence to UK census mid-year population estimates. We assumed no heart failure for patients aged 15 years or younger and report total incidence and prevalence for all ages (>0 years).
Findings: From 2002 to 2014, heart failure incidence (standardised by age and sex) decreased, similarly for men and women, by 7% (from 358 to 332 per 100 000 person-years; adjusted incidence ratio 0·93, 95% CI 0·91-0·94). However, the estimated absolute number of individuals with newly diagnosed heart failure in the UK increased by 12% (from 170 727 in 2002 to 190 798 in 2014), largely due to an increase in population size and age. The estimated absolute number of prevalent heart failure cases in the UK increased even more, by 23% (from 750 127 to 920 616). Over the study period, patient age and multi-morbidity at first presentation of heart failure increased (mean age 76·5 years [SD 12·0] to 77·0 years [12·9], adjusted difference 0·79 years, 95% CI 0·37-1·20; mean number of comorbidities 3·4 [SD 1·9] vs 5·4 [2·5]; adjusted difference 2·0, 95% CI 1·9-2·1). Socioeconomically deprived individuals were more likely to develop heart failure than were affluent individuals (incidence rate ratio 1·61, 95% CI 1·58-1·64), and did so earlier in life than those from the most affluent group (adjusted difference -3·51 years, 95% CI -3·77 to -3·25). From 2002 to 2014, the socioeconomic gradient in age at first presentation with heart failure widened. Socioeconomically deprived individuals also had more comorbidities, despite their younger age.
Interpretation: Despite a moderate decline in standardised incidence of heart failure, the burden of heart failure in the UK is increasing, and is now similar to the four most common causes of cancer combined. The observed socioeconomic disparities in disease incidence and age at onset within the same nation point to a potentially preventable nature of heart failure that still needs to be tackled.
Funding: British Heart Foundation and National Institute for Health Research.
Lancet (London, England) · 925 citationsread the source →
Gregor Hasler (2010)MEDLINE-indexed journal, not yet read by usWorld Psychiatry · editorial or comment PATHOPHYSIOLOGY OF DEPRESSION: DO WE HAVE ANY SOLID EVIDENCE OF INTEREST TO CLINICIANS?
Major depressive disorder (MDD) is a common and costly disorder which is usually associated with severe and persistent symptoms leading to important social role impairment and increased mortality 1,2. It is one of the most important causes of disability worldwide 3. The high rate of inadequate treatment of the disorder remains a serious concern 1. This review is aimed at summarizing the solid evidence on the etiology and pathophysiology of MDD that is likely relevant for clinical psychiatry. Neurobiological findings are regarded as solid when they are consistent and convergent, i.e., they have been confirmed by several studies using the same method and fit into results from studies using different methodological approaches. Family, twin, and adoption studies provide very solid and consistent evidence that MDD is a familial disorder and that this familiality is mostly or entirely due to genetic factors 4. This important finding suggests that parental social behavior and other familial environmental risk factors are not as important in the pathogenesis of MDD as previously assumed and should not be the major focus of the treatment of the disorder. The above-mentioned studies consistently show that the influence of genetic factors is around 30–40% 4. Non-genetic factors, explaining the remaining 60–70% of the variance in susceptibility to MDD, are individual-specific environmental effects (including measurement error effects and gene-environment interactions). These effects are mostly adverse events in childhood and ongoing or recent stress due to interpersonal adversities, including childhood sexual abuse, other lifetime trauma, low social support, marital problems, and divorce 5,6. These results suggest that there is a huge potential in the prevention of MDD by means of psychosocial interventions (e.g., in schools, at workplace). In addition, these results mirror the clinical practice of empirically validated psychotherapies to treat depression 7,8,9, including interpersonal, psychodynamic and cognitive behavioral psychotherapies and cognitive behavioural analysis system of psychotherapy, which all focus directly or indirectly on interpersonal difficulties and skills. This does not exclude the fact that unidentified non-genetic, non-psychosocial risk factors may also play important roles in some patients (e.g., climatic change, medical conditions). Stress sensitivity in depression is partly gender-specific. While men and women are, in general, equally sensitive to the depressogenic effects of stressful life events, their responses vary depending upon the type of stressor. Specifically, men are more likely to have depressive episodes following divorce, separation, and work difficulties, whereas women are more sensitive to events in their proximal social network, such as difficulty getting along with an individual, serious illness, or death 10. These findings point to the importance of gender-sensitive psychosocial approaches in the prevention and treatment of MDD. In contrast to the very solid evidence from epidemiological studies on broad risk factor domains, there is no solid evidence for specific genes and specific gene-by-environment interactions in the pathogenesis of MDD. Genome-wide association studies have indicated that many genes with small effects are involved in complex diseases, increasing the difficulty in identifying such genes 11. While there has been progress in the search for risk genes for several complex diseases despite this methodological problem 12, psychiatric conditions have turned out to be very resistant to robust gene identification. For example, based on a community-based prospective study, it has been proposed that a specific genetic variation in the promoter region of the serotonin transporter (a target of antidepressant drugs) interacts with stressful life events in the pathogenesis of depression 13. Although there is high clinical and neurobiological plausibility of this interaction, a recent meta-analysis yielded no evidence that the serotonin transporter gene alone or in interaction with psychological stress was associated with the risk of depression 14. The limited success of genetic studies of depression has been related to use of current classification schemas including ICD-10 and DSM-IV. These diagnostic manuals are based on clusters of symptoms and characteristics of clinical course that do not necessarily describe homogenous disorders but instead reflect common final pathways of different pathophysiolgical processes 15,16. The clinician should be aware that family history will continue to be the most solid source of information to estimate the genetic risk of MDD. Corticotropin-releasing hormone (CRH) is released from the hypothalamus in response to the perception of psychological stress by cortical brain regions. This hormone induces the secretion of pituitary corticotropin, which stimulates the adrenal gland to release cortisol into the plasma. The physiologic response to stress is partly gender-specific: women show generally greater stress responsiveness than men, which is consistent with the greater incidence of major depression in women 17. Moreover, men show greater cortisol responses to achievement challenges, whereas women show greater cortisol responses to social rejection challenges 18. Although MDD is considered as a stress disorder, most subjects treated for MDD have no evidence of dysfunctions of the hypothalamic-pituitary-adrenal axis (HPA) 19. However, some subjects with MDD do show abnormalities of that axis and of the extrahypothalamic CRH system 20. Altered stress hormone secretion appeared to be most prominent in depressed subjects with a history of childhood trauma 21. Elevated cortisol may act as a mediator between major depression and its physical long-term consequences such as coronary heart disease, type II diabetes, and osteoporosis 22. The importance of HPA axis dysfunction for the efficacy of antidepressants is a matter of debate 23. This axis is regulated through a dual system of mineralocorticoid (MR) and glucocorticoid (GR) receptors. Decreased limbic GR receptor function 24,25 and increased functional activity of the MR system 26 suggest an imbalance in the MR/GR ratio in stress-related conditions such as MDD. Epigenetic regulation of the glucocorticoid receptors has been associated with childhood abuse 27. Such environmental programming of gene expression may represent one possible mechanism that links early life stress to abnormal HPA axis function and increased risk of MDD in adults. While the CRH stimulation test (dex/CRH test) 28 is a sensitive measure of the HPA axis dysfunction in depression, the specificity of this test for MDD is low. However, non-suppression in the dex/CRH test has consistently predicted increased risk for depressive relapse during clinical remission 23. Additionally, the measurement of waking salivary cortisol concentration has been shown to be a simple and sensitive test for HPA axis hyperactivity in depression 29. Hypercortisolemia is almost exclusively found in subjects with severe and psychotic depression, in whom glucocorticoid antagonists may have some therapeutic effect 30. There is convergent evidence for CRH to play a major role in the pathogenesis of certain types of depression. Levels of CRH in the cerebrospinal fluid are elevated in some depressed subjects 31. Post-mortem studies reported an increased number of CRH secreting neurons in limbic brain regions in depression 32, likely reflecting a compensatory response to increased CRH concentrations 33. In addition, CRH produces a number of physiological and behavioral alterations that resemble the symptoms of major depression, including decreased appetite, disrupted sleep, decreased libido, and psychomotor alterations 34. There is also preliminary evidence that CRH1 receptor antagonists reduce symptoms of depression and anxiety 35. “Sickness behavior” as a result of an activation of the inflammatory response system shares many symptoms with depression, including fatigue, anhedonia, psychomotor retardation, and cognitive impairment. Sickness is mediated by pro-inflammatory cytokines such as interleukin-1α, tumor necrosis factor-α, and interleukin-6, which activate the HPA axis and impair the central serotonin system 36. The prevalence of depression as an unwanted effect of recombinant interferons is around 30% 37. In animals, blocking pro-inflammatory cytokine-mediated signaling produces antidepressant-like effects 38. Clinical data suggest that cytokines may play a role in the pathophysiology of a subgroup of depressed subjects, particularly those with comorbid physical conditions 36. The antidepressant enhancing effect of acetylsalicylic acid 39 points to the possible clinical relevance of psychoneuroimmunology in clinical depression research. Taken together, the laboratory tests with the highest potential to be clinically useful in the care of depressed individuals are based on abnormalities of the neuroendocrine and neuroimmune systems. Despite the large amount of basic science data suggesting that the HPA axis is importantly involved in the pathophysiology of depression, the effect of pharmacological modulation of this neuroendocrine system as antidepressant therapy has been disappointing. The link between childhood trauma and a permanently altered physiologic stress system points to the use of specific psychotherapies in the treatment of depressed patients with a history of early life trauma 40. Most of the serotonergic, noradrenergic and dopaminergic neurons are located in midbrain and brainstem nuclei and project to large areas of the entire brain. This anatomy suggests that monoaminergic systems are involved in the regulation of a broad range of brain functions, including mood, attention, reward processing, sleep, appetite, and cognition. Almost every compound that inhibits monoamine reuptake, leading to an increased concentration of monoamines in the synaptic cleft, has been proven to be a clinically effective antidepressant 19. Inhibiting the enzyme monoamine oxidase, which induces an increased availability of monoamines in presynaptic neurons, also has antidepressant effects. These observations led to the pharmacologically most relevant theory of depression, referred to as the monoamine-deficiency hypothesis. The monoamine-deficiency theory posits that the underlying pathophysiological basis of depression is a depletion of the neurotransmitters serotonin, norepinephrine or dopamine in the central nervous system. Serotonin is the most extensively studied neurotransmitter in depression. The most direct evidence for an abnormally reduced function of central serotonergic system comes from studies using tryptophan depletion, which reduces central serotonin synthesis. Such a reduction leads to the development of depressive symptoms in subjects at increased risk of depression (subjects with MDD in full remission, healthy subjects with a family history of depression) 41,42, possibly mediated by increased brain metabolism in the ventromedial prefrontal cortex and subcortical brain regions 42. Experimentally reduced central serotonin has been associated with mood congruent memory bias, altered reward-related behaviors, and disruption of inhibitory affective processing 16, all of which add to the clinical plausibility of the serotonin deficiency hypothesis. There is also evidence for abnormalities of serotonin receptors in depression, with the most solid evidence pointing to the serotonin-1A receptor, which regulates serotonin function. Decreased availability of this receptor has been found in multiple brain areas of patients with MDD 43, although this abnormality is not highly specific for MDD and has been found in patients with panic disorder 44 and temporal lobe epilepsy 45, possibly contributing to the considerable comorbidity among these conditions. However, there is no explanation for the mechanism of serotonin loss in depressed patients, and studies of serotonin metabolites in plasma, urine and cerebrospinal fluid, as well as post-mortem research on the serotonergic system in depression, have yielded inconsistent results. There is preliminary evidence that an increased availability of the brain monoamine oxidase, which metabolizes serotonin, may cause serotonin deficiency 46. In addition, loss-of-function mutations in the gene coding for the brain-specific enzyme tryptophan hydroxylase-2 may explain the loss of serotonin production as a rare risk factor for depression 47. Dysfunction of the central noradrenergic system has been hypothesized to play a role in the pathophysiology of MDD, based upon evidence of decreased norepinephrine metabolism, increased activity of tyrosine hydroxylase, and decreased density of norepinephrine transporter in the locus coeruleus in depressed patients 48. In addition, decreased neuronal counts in the locus coeruleus, increased alpha-2 adrenergic receptor density, and decreased alpha-1 adrenergic receptor density have been found in the brains of depressed suicide victims post-mortem 49. Since there is no method to selectively deplete central norepinephrine and no imaging tool to study the central norepinephrine system, solid evidence for abnormalities of this system in depression is lacking. While the classical theories of the neurobiology of depression mainly focused on serotonin and norepinephrine, there is increasing interest in the role of dopamine 50. Dopamine reuptake inhibitors (e.g., nomifensine) and dopamine receptor agonists (e.g., pramipexole) had antidepressant effects in placebo-controlled studies of MDD 51. In the cerebrospinal fluid and jugular vein plasma, levels of dopamine metabolites were consistently reduced in depression, suggesting decreased dopamine turnover 52. Striatal dopamine transporter binding and dopamine uptake were reduced in MDD, consistent with a reduction in dopamine neurotransmission 53. Degeneration of dopamine projections to the striatum in Parkinson's disease was associated with a major depressive syndrome in about one half of cases, which usually preceded the appearance of motor signs 54. Experimentally reduced dopaminergic transmission into the accumbens has been associated with anhedonic symptoms and performance deficits on a reward processing task in subjects at increased risk of depression 55,56. These findings are consistent with the clinical observation that depressed patients have a blunted reaction to positive reinforcers and an abnormal response to negative feedback 57. Almost all established antidepressants target the monoamine systems 58. However, full and partial resistance to these drugs and their delayed onset of action suggest that dysfunctions of monoaminergic neurotransmitter systems found in MDD represent the downstream effects of other, more primary abnormalities. Despite this limitation, the monoamine-deficiency hypothesis has proved to be the most clinically relevant neurobiological theory of depression. New findings on the role of dopamine in depression emphasize the scientific potential of this theory, and promising reports of antidepressant effects of drugs that modulate the dopaminergic system (e.g., pramipexole, modafinil) in difficult-to-treat depression underline its clinical relevance 51,59. Although many historical attempts to localize mental functions have failed, they have considerably contributed to a modern neuroscientific understanding of mental disorders 60. The development of neuroimaging techniques has opened up the potential to investigate structural and functional abnormalities in living depressed patients. Unfortunately, the diversity of imaging techniques used, the relatively small and heterogeneous study samples studied, and the limited overlap of results across imaging paradigms 61 make it difficult to reliably identify neuronal regions or networks with consistently abnormal structure or function in MDD. Functional imaging studies have provided the most limited overlap of findings. This may be due to methodological limitations and/or the complexity of neurocircuitry involved in MDD. A recent meta-analytic study found the best evidence for abnormal brain activity in MDD in lateral frontal and temporal cortices, insula, and cerebellum. In these brain regions activity was decreased at rest, they showed a relative lack of activation during induction of negative emotions, and an increase in activity following treatment with serotonin reuptake inhibitors. Opposite changes may exist in ventromedial frontal areas, striatum and possibly other subcortical brain regions 61. More solid evidence has been provided by structural imaging and post-mortem studies. A recent meta-analytic study on brain volume abnormalities in MDD revealed relatively large volume reductions in the ventromedial prefrontal cortex, particularly in the left anterior cingulate and in the orbitofrontal cortex. Moderate volume reductions were found in the lateral prefrontal cortex, hippocampus and striatum 62. Post-mortem studies consistently identified a reduction in glia cell density in dorsal, orbital and subgenual prefrontal cortices, as well as in the amygdala 63,64. Overall, functional, structural and post-mortem studies suggest that structural and functional abnormalities in the left subgenual cingulate cortex are the most solid neuroanatomical finding in MDD. Volume reduction in this region was found early in illness and in young adults at high familial risk for MDD 65, suggesting a primary neurobiological abnormality associated with the etiology of the illness. Humans with lesions that include the subgenual prefrontal cortex showed abnormal autonomic responses to social stimuli 66, and rats with left-sided lesions in this region had increased sympathetic arousal and corticosterone responses to restraint stress 67. Most importantly, chronic deep brain stimulation to reduce the potentially elevated activity in the subgenual cingulated cortex produced clinical benefits in patients with treatment-resistant depression 68. In summary, despite the considerable heterogeneity of findings from neuroimaging studies, there is convergent evidence for the presence of abnormalities in the subgenual prefrontal cortex in some patients with MDD. Neuroanatomical research in depression is of great clinical interest, since novel antidepressant treatments such as deep brain stimulation can target specific brain regions. In addition, there are promising leads for neuroimaging findings to predict the likelihood of responses to specific treatments 69. Risk factors for depressive episodes change during the course of the illness. The first depressive episode is usually “reactive”, i.e., triggered by important psychosocial stressors, while subsequent episodes become increasingly “endogenous”, i.e., triggered by minor stressors or occurring spontaneously 70. There is consistent evidence that the volume loss of the hippocampus and other brain regions is related to the duration of depression 71, suggesting that untreated depression leads to hippocampal volume loss, possibly resulting in increased stress sensitivity 72 and increased risk of recurrence 73. Glucocorticoid neurotoxicity, glutamatergic toxicity, decreased neurotrophic factors, and decreased neurogenesis have been proposed as possible mechanisms explaining brain volume loss in depression. There is no solid evidence on of these since there are no imaging to directly and neurotrophic processes in neurotrophic factor has considerable Specifically, studies have shown between and in hippocampal as well as expression of following antidepressant treatment The clinician should be aware of the potentially effect of depression and treat depressed patients as early and as A of studies consistently showed reductions in acid concentrations in the prefrontal and cortex in depression This may reflect stress since psychological stress to presynaptic of prefrontal neurotransmission low concentration may reflect reduction in the density and of In addition, chronic stress may reduce receptor possibly through changes in evidence of the hypothesis of depression the lack of effects of drugs on depressive symptoms and prefrontal concentration in subjects with MDD of evidence suggest a dysfunction of the neurotransmitter system in a of the receptor produced and large antidepressant effects in patients with treatment-resistant MDD inhibitors of release (e.g., antidepressant abnormal levels were found in depressed subjects as by and there is evidence for abnormal signaling in post-mortem Since is the major neurotransmitter involved in almost every brain the of the specific role of in depression (e.g., there are promising leads that the receptor is involved in MDD and are diagnostic for MDD, suggesting regulation in depressed patients. In addition, some depressive symptoms may show psychomotor of of positive and negative and a subgroup of patients with MDD may have a disorder In healthy young subjects, changes in the of the had specific effects on subsequent mood In depressed patients, of can have antidepressant on these abnormalities have been hypothesized to be associated with MDD The association between of the and in cortisol in some subjects with and the effect of antidepressants on of and to the of this hypothesis Despite of the many promising the and genetic of this hypothesis are It remains to be antidepressant effects of such as directly to of on these abnormalities have been hypothesized to be associated with MDD The association between of the and in cortisol in some subjects with and the effect of antidepressants on of and to the of this hypothesis Despite of the many promising the and genetic of this hypothesis are It remains to be antidepressant effects of such as directly to of The and of the neurobiological of depression are in 1. The many theories of depression and the relatively low response rate of all antidepressant treatments a hypothesis of and suggest that depression is a clinically and heterogeneous disorder. This research on of the response to therapeutic interventions using such as neuroimaging and neuroendocrine tests in with for with to stress sensitivity and antidepressant The of of therapeutic will for the development of that has the potential to interventions and to up pathways in the of novel therapeutic approaches.
World Psychiatry · editorial or comment · 607 citationsread the source →
A cost-utility analysis of lung cancer screening and the additional benefits of incorporating smoking cessation interventions.
Background: A 2011 report from the National Lung Screening Trial indicates that three annual low-dose computed tomography (LDCT) screenings for lung cancer reduced lung cancer mortality by 20% compared to chest X-ray among older individuals at high risk for lung cancer. Discussion has shifted from clinical proof to financial feasibility. The goal of this study was to determine whether LDCT screening for lung cancer in a commercially-insured population (aged 50-64) at high risk for lung cancer is cost-effective and to quantify the additional benefits of incorporating smoking cessation interventions in a lung cancer screening program.
Methods and findings: The current study builds upon a previous simulation model to estimate the cost-utility of annual, repeated LDCT screenings over 15 years in a high risk hypothetical cohort of 18 million adults between age 50 and 64 with 30+ pack-years of smoking history. In the base case, the lung cancer screening intervention cost $27.8 billion over 15 years and yielded 985,284 quality-adjusted life years (QALYs) gained for a cost-utility ratio of $28,240 per QALY gained. Adding smoking cessation to these annual screenings resulted in increases in both the costs and QALYs saved, reflected in cost-utility ratios ranging from $16,198 per QALY gained to $23,185 per QALY gained. Annual LDCT lung cancer screening in this high risk population remained cost-effective across all sensitivity analyses.
Conclusions: The findings of this study indicate that repeat annual lung cancer screening in a high risk cohort of adults aged 50-64 is highly cost-effective. Offering smoking cessation interventions with the annual screening program improved the cost-effectiveness of lung cancer screening between 20% and 45%. The cost-utility ratios estimated in this study were in line with other accepted cancer screening interventions and support inclusion of annual LDCT screening for lung cancer in a high risk population in clinical recommendations.
PloS one · 177 citationsread the source →
Caregiver characteristics are associated with neuropsychiatric symptoms of dementia.
Objectives: To determine whether caregiver characteristics are independently associated with neuropsychiatric symptoms of dementia (NPS) after accounting for patient characteristics.
Design: Cross-sectional analysis of data from the Medicare Alzheimer's Disease Demonstration and Evaluation study.
Setting: Community-dwelling residents in eight U.S. cities.
Participants: Five thousand seven hundred eighty-eight patients with dementia and their caregivers.
Measurements: Caregivers were asked about the presence of 12 NPS in patients with dementia. Caregiver predictors included age, sex, education, income, marital status, relationship to the patient, whether they lived with patient, number of hours per week spent caregiving, self-reported health, dependency in activities of daily living (ADLs) and instrumental activities of daily living (IADLs), depression, and burden. Multivariate linear regression was used to determine which caregiver characteristics were independently associated with reports of more NPS in patients after controlling for the patient's age, sex, dementia severity, level of ADL dependency, and dementia type.
Results: Caregivers were on average 64 years old, 72% female, and 49% were the spouse of the patient (32% wives, 17% husbands). The mean burden score of caregivers was 15 (range 0-32, with higher scores indicating more burden), and 32% had significant depressive symptoms. Patients were on average 79 years old, 60% were female, and most had moderate to severe dementia. The mean number of NPS+/-standard deviation was 4.8+/-2.8. After adjusting for patient characteristics, caregivers who were younger, less educated, more depressed, more burdened, or spent more hours per week giving care reported more NPS in care recipients (all P< or =.005).
Conclusion: Certain caregiver characteristics are associated with NPS, independent of patient characteristics, including dementia severity. Clinicians should consider the dynamics between patients and caregivers when managing NPS. Understanding how different caregiver characteristics influence NPS may help tailor caregiver education and interventions.
Journal of the American Geriatrics Society · 116 citationsread the source →
Parents' perspective on symptoms, quality of life, characteristics of death and end-of-life decisions for children dying from cancer.
Background: In the present study, we investigated the situation of children who had succumbed to their malignancy in Germany as perceived by their parents. Specifically, we were interested in bereaved parents' perspective on five essential areas: 1) symptoms and quality of life, 2) characteristics of the child's death, 3) anticipation of their child's death and care delivery, 4) end-of-life decisions and 5) impact of the child's death on the parents and perceived social support by the health care team.
Materials and methods: We contacted all existing departments for paediatric oncology in the German federal state of Nordrhein Westfalen and asked them to contact all parents for participation in our study who had lost their child to cancer in 1999 and 2000. Upon agreement, we interviewed the parents utilising a validated semi-structured interview on distressing symptoms and quality of life of their children during the end-of-life care period.
Results: Six of the 19 departments agreed to participate. Parents of 48 children (31 boys, 17 girls) were interviewed. The main distressing symptoms were fatigue, pain, loss of appetite, and dyspnoea according to the parents. While parents perceived pain and constipation to have been treated successfully, loss of appetite and anxiety were not treated effectively. 75% of the children died due to a progression of their malignancy. Of these, 50% obtained cancer-directed therapy at the end of life, which was negatively rated by the parents in hindsight. 48% of the children died at home even though 88% of the parents chose 'at home' as the most appropriate locale of death in hindsight. Parents anticipated their child's death on average 9 weeks prior to the child's death. 41% of the parents provided palliative home care for their child and the majority (88%) rated the quality of care as good or very good. 64% discussed end-of-life decisions with the health care team, 36% did not have a discussion. Parents were clearly affected by their child's death. However, 15% of the parents were not contacted by the health care team following the child's death.
Conclusions: The present study demonstrated that psychological symptoms (e.g. anxiety) are frequent symptoms in the end-of-life care period and cause severe suffering in the children. Questions in terms of benefits and costs of cancer-directed therapy in the end-of-life care period need to be addressed in future prospective studies. Parents' perspective on their child's death and related end-of-life decisions highlighted the importance of communication between parents and the health care team. Future studies need to investigate potential barriers in the communication between parents and the team to optimise end-of-life decisions and hence, reduce parents' long-term distress. In line with the previous, the present data demonstrated that there is still a lack of routine contact from the health care team following the child's death despite existing guidelines. Research is therefore needed into the implementation of guidelines for routine contact into clinical practice following a child's death.
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