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

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

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

Efficacy of cognitive-behavioral therapy for insomnia associated with traumatic brain injury: a single-case experimental design.

Objective: To test the efficacy of a cognitive-behavioral therapy (CBT) for insomnia in persons having sustained traumatic brain injury (TBI). Design: Single-case design with multiple baselines across participants. Setting: Outpatient rehabilitation center. Participants: Eleven subjects having sustained mild to severe TBI who developed insomnia after the injury. Intervention: Eight-week CBT for insomnia including stimulus control, sleep restriction, cognitive restructuring, sleep hygiene education, and fatigue management. Main outcome measures: Total wake time, sleep efficiency, and diagnostic criteria. Results: Visual analyses, corroborated by intervention time series analyses and t tests, revealed clinically and statistically significant reductions in total wake time and sleep efficiency for 8 (73%) of 11 participants. An average reduction of 53.9% in total wake time was observed across participants from pre- to post-treatment. Progress was in general well maintained at the 1-month and 3-month follow-ups. The average sleep efficiency augmented significantly from pretreatment (77.2%) to post-treatment (87.9%), and also by the 3-month follow-up (90.9%). Improvements in sleep were accompanied by a reduction in symptoms of general and physical fatigue. Conclusions: The results of this study show that psychologic interventions for insomnia are a promising therapeutic avenue for TBI survivors.

Archives of physical medicine and rehabilitation · clinical trial · 105 citationsread the source →

Centralized, stepped, patient preference-based treatment for patients with post-acute coronary syndrome depression: CODIACS vanguard randomized controlled trial.

Importance: Controversy remains about whether depression can be successfully managed after acute coronary syndrome (ACS) and the costs and benefits of doing so. Objective: To determine the effects of providing post-ACS depression care on depressive symptoms and health care costs. Design: Multicenter randomized controlled trial. Setting: Patients were recruited from 2 private and 5 academic ambulatory centers across the United States. Participants: A total of 150 patients with elevated depressive symptoms (Beck Depression Inventory [BDI] score ≥10) 2 to 6 months after an ACS, recruited between March 18, 2010, and January 9, 2012. Interventions: Patients were randomized to 6 months of centralized depression care (patient preference for problem-solving treatment given via telephone or the Internet, pharmacotherapy, both, or neither), stepped every 6 to 8 weeks (active treatment group; n = 73), or to locally determined depression care after physician notification about the patient's depressive symptoms (usual care group; n = 77). Main outcome measures: Change in depressive symptoms during 6 months and total health care costs. Results: Depressive symptoms decreased significantly more in the active treatment group than in the usual care group (differential change between groups, -3.5 BDI points; 95% CI, -6.1 to -0.7; P = .01). Although mental health care estimated costs were higher for active treatment than for usual care, overall health care estimated costs were not significantly different (difference adjusting for confounding, -$325; 95% CI, -$2639 to $1989; P = .78). Conclusions: For patients with post-ACS depression, active treatment had a substantial beneficial effect on depressive symptoms. This kind of depression care is feasible, effective, and may be cost-neutral within 6 months; therefore, it should be tested in a large phase 3 pragmatic trial. Trial registration: clinicaltrials.gov Identifier: NCT01032018.

JAMA internal medicine · randomised controlled trial · 107 citationsread the source →

Trajectory of post-traumatic stress following traumatic injury: 6-year follow-up.

Background: Traumatic injuries affect millions of patients each year, and resulting post-traumatic stress disorder (PTSD) significantly contributes to subsequent impairment. Aims: To map the distinctive long-term trajectories of PTSD responses over 6 years by using latent growth mixture modelling. Method: Randomly selected injury patients (n = 1084) admitted to four hospitals around Australia were assessed in hospital, and at 3, 12, 24 and 72 months. Lifetime psychiatric history and current PTSD severity and funxctioning were assessed. Results: Five trajectories of PTSD response were noted across the 6 years: (a) chronic (4%), (b) recovery (6%), (c) worsening/recovery (8%), (d) worsening (10%) and (e) resilient (73%). A poorer trajectory was predicted by female gender, recent life stressors, presence of mild traumatic brain injury and admission to intensive care unit. Conclusions: These findings demonstrate the long-term PTSD effects that can occur following traumatic injury. The different trajectories highlight that monitoring a subset of patients over time is probably a more accurate means of identifying PTSD rather than relying on factors that can be assessed during hospital admission.

The British journal of psychiatry : the journal of mental science · cohort or longitudinal · 136 citationsread the source →

Effectiveness of Mindfulness Meditation vs Headache Education for Adults With Migraine: A Randomized Clinical Trial.

Importance: Migraine is the second leading cause of disability worldwide. Most patients with migraine discontinue medications due to inefficacy or adverse effects. Mindfulness-based stress reduction (MBSR) may provide benefit. Objective: To determine if MBSR improves migraine outcomes and affective/cognitive processes compared with headache education. Design, setting, and participants: This randomized clinical trial of MBSR vs headache education included 89 adults who experienced between 4 and 20 migraine days per month. There was blinding of participants (to active vs comparator group assignments) and principal investigators/data analysts (to group assignment). Interventions: Participants underwent MBSR (standardized training in mindfulness/yoga) or headache education (migraine information) delivered in groups that met for 2 hours each week for 8 weeks. Main outcomes and measures: The primary outcome was change in migraine day frequency (baseline to 12 weeks). Secondary outcomes were changes in disability, quality of life, self-efficacy, pain catastrophizing, depression scores, and experimentally induced pain intensity and unpleasantness (baseline to 12, 24, and 36 weeks). Results: Most participants were female (n = 82, 92%), with a mean (SD) age of 43.9 (13.0) years, and had a mean (SD) of 7.3 (2.7) migraine days per month and high disability (Headache Impact Test-6: 63.5 [5.7]), attended class (median attendance, 7 of 8 classes), and followed up through 36 weeks (33 of 45 [73%] of the MBSR group and 32 of 44 [73%] of the headache education group). Participants in both groups had fewer migraine days at 12 weeks (MBSR: -1.6 migraine days per month; 95% CI, -0.7 to -2.5; headache education: -2.0 migraine days per month; 95% CI, -1.1 to -2.9), without group differences (P = .50). Compared with those who participated in headache education, those who participated in MBSR had improvements from baseline at all follow-up time points (reported in terms of point estimates of effect differences between groups) on measures of disability (5.92; 95% CI, 2.8-9.0; P < .001), quality of life (5.1; 95% CI, 1.2-8.9; P = .01), self-efficacy (8.2; 95% CI, 0.3-16.1; P = .04), pain catastrophizing (5.8; 95% CI, 2.9-8.8; P < .001), depression scores (1.6; 95% CI, 0.4-2.7; P = .008), and decreased experimentally induced pain intensity and unpleasantness (MBSR group: 36.3% [95% CI, 12.3% to 60.3%] decrease in intensity and 30.4% [95% CI, 9.9% to 49.4%] decrease in unpleasantness; headache education group: 13.5% [95% CI, -9.9% to 36.8%] increase in intensity and an 11.2% [95% CI, -8.9% to 31.2%] increase in unpleasantness; P = .004 for intensity and .005 for unpleasantness, at 36 weeks). One reported adverse event was deemed unrelated to study protocol. Conclusions and relevance: Mindfulness-based stress reduction did not improve migraine frequency more than headache education, as both groups had similar decreases; however, MBSR improved disability, quality of life, self-efficacy, pain catastrophizing, and depression out to 36 weeks, with decreased experimentally induced pain suggesting a potential shift in pain appraisal. In conclusion, MBSR may help treat total migraine burden, but a larger, more definitive study is needed to further investigate these results. Trial registration: ClinicalTrials.gov Identifier: NCT02695498.

JAMA internal medicine · randomised controlled trial · 132 citationsread the source →

Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors.

Background: Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical precancer and cancer. HPV types 16 and 18 cause approximately 70% of cervical cancers worldwide. Objectives: To evaluate the harms and protection of prophylactic human papillomaviruses (HPV) vaccines against cervical precancer and HPV16/18 infection in adolescent girls and women. Search methods: We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase (June 2017) for reports on effects from trials. We searched trial registries and company results' registers to identify unpublished data for mortality and serious adverse events. Selection criteria: Randomised controlled trials comparing efficacy and safety in females offered HPV vaccines with placebo (vaccine adjuvants or another control vaccine). Data collection and analysis: We used Cochrane methodology and GRADE to rate the certainty of evidence for protection against cervical precancer (cervical intraepithelial neoplasia grade 2 and above [CIN2+], CIN grade 3 and above [CIN3+], and adenocarcinoma-in-situ [AIS]), and for harms. We distinguished between the effects of vaccines by participants' baseline HPV DNA status. The outcomes were precancer associated with vaccine HPV types and precancer irrespective of HPV type. Results are presented as risks in control and vaccination groups and risk ratios (RR) with 95% confidence intervals in brackets. Main results: We included 26 trials (73,428 participants). Ten trials, with follow-up of 1.3 to 8 years, addressed protection against CIN/AIS. Vaccine safety was evaluated over a period of 6 months to 7 years in 23 studies. Studies were not large enough or of sufficient duration to evaluate cervical cancer outcomes. All but one of the trials was funded by the vaccine manufacturers. We judged most included trials to be at low risk of bias. Studies involved monovalent (N = 1), bivalent (N = 18), and quadrivalent vaccines (N = 7). Most women were under 26 years of age. Three trials recruited women aged 25 and over. We summarize the effects of vaccines in participants who had at least one immunisation. Efficacy endpoints by initial HPV DNA statushrHPV negativeHPV vaccines reduce CIN2+, CIN3+, AIS associated with HPV16/18 compared with placebo in adolescent girls and women aged 15 to 26. There is high-certainty evidence that vaccines lower CIN2+ from 164 to 2/10,000 (RR 0.01 (0 to 0.05)) and CIN3+ from 70 to 0/10,000 (RR 0.01 (0.00 to 0.10). There is moderate-certainty evidence that vaccines reduce the risk of AIS from 9 to 0/10,000 (RR 0.10 (0.01 to 0.82).HPV vaccines reduce the risk of any CIN2+ from 287 to 106/10,000 (RR 0.37 (0.25 to 0.55), high certainty) and probably reduce any AIS lesions from 10 to 0/10,000 (RR 0.1 (0.01 to 0.76), moderate certainty). The size of reduction in CIN3+ with vaccines differed between bivalent and quadrivalent vaccines (bivalent: RR 0.08 (0.03 to 0.23), high certainty; quadrivalent: RR 0.54 (0.36 to 0.82), moderate certainty). Data in older women were not available for this comparison.HPV16/18 negativeIn those aged 15 to 26 years, vaccines reduce CIN2+ associated with HPV16/18 from 113 to 6 /10,000 (RR 0.05 (0.03 to 0.10). In women 24 years or older the absolute and relative reduction in the risk of these lesions is smaller (from 45 to 14/10,000, (RR 0.30 (0.11 to 0.81), moderate certainty). HPV vaccines reduce the risk of CIN3+ and AIS associated with HPV16/18 in younger women (RR 0.05 (0.02 to 0.14), high certainty and RR 0.09 (0.01 to 0.72), moderate certainty, respectively). No trials in older women have measured these outcomes. Vaccines reduce any CIN2+ from 231 to 95/10,000, (RR 0.41 (0.32 to 0.52)) in younger women. No data are reported for more severe lesions. Regardless of HPV DNA statusIn younger women HPV vaccines reduce the risk of CIN2+ associated with HPV16/18 from 341 to 157/10,000 (RR 0.46 (0.37 to 0.57), high certainty). Similar reductions in risk were observed for CIN3+ associated with HPV16/18 (high certainty). The number of women with AIS associated with HPV16/18 is reduced from 14 to 5/10,000 with HPV vaccines (high certainty).HPV vaccines reduce any CIN2+ from 559 to 391/10,000 (RR 0.70 (0.58 to 0.85, high certainty) and any AIS from 17 to 5/10,000 (RR 0.32 (0.15 to 0.67), high certainty). The reduction in any CIN3+ differed by vaccine type (bivalent vaccine: RR 0.55 (0.43 to 0.71) and quadrivalent vaccine: RR 0.81 (0.69 to 0.96)).In women vaccinated at 24 to 45 years of age, there is moderate-certainty evidence that the risks of CIN2+ associated with HPV16/18 and any CIN2+ are similar between vaccinated and unvaccinated women (RR 0.74 (0.52 to 1.05) and RR 1.04 (0.83 to 1.30) respectively). No data are reported in this age group for CIN3+ or AIS.Adverse effectsThe risk of serious adverse events is similar between control and HPV vaccines in women of all ages (669 versus 656/10,000, RR 0.98 (0.92 to 1.05), high certainty). Mortality was 11/10,000 in control groups compared with 14/10,000 (9 to 22) with HPV vaccine (RR 1.29 [0.85 to 1.98]; low certainty). The number of deaths was low overall but there is a higher number of deaths in older women. No pattern in the cause or timing of death has been established. Pregnancy outcomesAmong those who became pregnant during the studies, we did not find an increased risk of miscarriage (1618 versus 1424/10,000, RR 0.88 (0.68 to 1.14), high certainty) or termination (931 versus 838/10,000 RR 0.90 (0.80 to 1.02), high certainty). The effects on congenital abnormalities and stillbirths are uncertain (RR 1.22 (0.88 to 1.69), moderate certainty and (RR 1.12 (0.68 to 1.83), moderate certainty, respectively). Authors' conclusions: There is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26. The effect is higher for lesions associated with HPV16/18 than for lesions irrespective of HPV type. The effect is greater in those who are negative for hrHPV or HPV16/18 DNA at enrolment than those unselected for HPV DNA status. There is moderate-certainty evidence that HPV vaccines reduce CIN2+ in older women who are HPV16/18 negative, but not when they are unselected by HPV DNA status. We did not find an increased risk of serious adverse effects. Although the number of deaths is low overall, there were more deaths among women older than 25 years who received the vaccine. The deaths reported in the studies have been judged not to be related to the vaccine. Increased risk of adverse pregnancy outcomes after HPV vaccination cannot be excluded, although the risk of miscarriage and termination are similar between trial arms. Long-term of follow-up is needed to monitor the impact on cervical cancer, occurrence of rare harms and pregnancy outcomes.

The Cochrane database of systematic reviews · systematic review · 290 citationsread the source →

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

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

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

Ethnoracial and social trends in breast cancer staging at diagnosis in Brazil, 2001-14: a case only analysis.

Background: Policies for early detection of breast cancer, including clinical breast examinations and mammographic screening, were introduced in Brazil in 2004, but their effect on disease stage at diagnosis is unclear. We aimed to assess whether these policies have led to a decrease in the prevalence of late-stage breast cancer at diagnosis. Methods: In this case only analysis, using an anonymised nationwide hospital based-cancer registry network, we identified women aged 18-89 years who had been diagnosed with an invasive breast cancer in Brazil during 2001-14. We extracted individual patient-level data on patient demographics, tumour variables, and health-care provider variables for the centre where the patient was diagnosed. Our objectives were to estimate the prevalence of late-stage breast cancer (TNM stage III or IV) at diagnosis overall, across age groups, and by ethnoracial and social strata (ie, self-reported ethnoracial group, as white, black, brown, Asian, or Indigenous, and educational level, marital status, and region of residence) across the study period, and compare these estimates with international data from high-income countries (Norway and the USA). We used logistic regression to estimate odds ratios (ORs) for late-stage versus early-stage (TNM stage I or II) breast cancer at diagnosis in relation to relevant exposures, either minimally adjusted (for age, year of diagnosis, and region of residence) or fully adjusted (for all patient, tumour, and health-care provider variables). Findings: We identified 247 719 women who were diagnosed with invasive breast cancer between Jan 1, 2001, and Dec 31, 2014, with a mean age at diagnosis of 55·4 years (SD 13·3), of whom 36·2% (n=89 550) identified as white, 29·8% (n=73 826) as black or brown, and 0·7% (n=1639) as Asian or Indigenous. Prevalence of late-stage breast cancer at diagnosis remained high throughout 2001-14, at approximately 40%, was inversely associated with educational level (p value for linear trend <0·0001), and was higher for women who identified as black (minimally adjusted OR 1·61, 95% CI 1·53-1·70; fully adjusted OR 1·45, 95% CI 1·38-1·54) and brown (minimally adjusted OR 1·26, 95% CI 1·22-1·30; fully adjusted OR 1·18, 1·14-1·23) than those who identified as white. The predicted prevalence of late-stage cancer at diagnosis was highest for women who were black or brown with little or no formal education (48·8%, 95% CI 48·2-49·5) and lowest for women who were white with university education (29·4%, 28·2-30·6), but both these prevalences were higher than that of all women diagnosed with breast cancer in Norway before the introduction of mammography screening (ie, 16·3%, 95% CI 15·4%-17·2% in 1970-74). Similar ethnoracial and social patterns emerged in analyses restricted to the age group targeted by screening (50-69 years). Interpretation: The persistently high prevalence of late-stage breast cancer at diagnosis across all ethnoracial and social strata in Brazil, although more substantially among the most disadvantaged populations, implies that early detection policies might have had little effect on breast cancer mortality so far, and highlights the need to focus primarily on timely diagnosis of symptomatic breast cancer rather than on screening for asymptomatic disease. Funding: Newton Fund, Research Councils UK, and Conselho Nacional das Fundações Estaduais de Amparo à Pesquisa.

The Lancet. Global health · 56 citationsread the source →

Predictors of participation of adolescents with cerebral palsy: A European multi-centre longitudinal study.

We investigated whether childhood factors that are amenable to intervention (parenting stress, child psychological problems and pain) predicted participation in daily activities and social roles of adolescents with cerebral palsy (CP). We randomly selected 1174 children aged 8-12 years from eight population-based registers of children with CP in six European countries; 743 (63%) agreed to participate. One further region recruited 75 children from multiple sources. These 818 children were visited at home at age 8-12 years, 594 (73%) agreed to follow-up at age 13-17 years. We used the following measures: parent reported stress (Parenting Stress Index Short Form), their child's psychological difficulties (Strength and Difficulties Questionnaire) and frequency and severity of pain; either child or parent reported the child's participation (LIFE Habits questionnaire). We fitted a structural equation model to each of the participation domains, regressing participation in childhood and adolescence on parenting stress, child psychological problems and pain, and regressing adolescent factors on the corresponding childhood factors; models were adjusted for impairment, region, age and gender. Pain in childhood predicted restricted adolescent participation in all domains except Mealtimes and Communication (standardized total indirect effects β -0.05 to -0.18, 0.01<p<0.05 to p<0.001, depending on domain). Psychological problems in childhood predicted restricted adolescent participation in all domains of social roles, and in Personal Care and Communication (β -0.07 to -0.17, 0.001<p<0.01 to p<0.001). Parenting stress in childhood predicted restricted adolescent participation in Health Hygiene, Mobility and Relationships (β -0.07 to -0.18, 0.001<p<0.01 to p<0.001). These childhood factors predicted adolescent participation largely via their effects on childhood participation; though in some domains early psychological problems and parenting stress in childhood predicted adolescent participation largely through their persistence into adolescence. We conclude that participation of adolescents with CP was predicted by early modifiable factors related to the child and family. Interventions for reduction of pain, psychological difficulties and parenting stress in childhood are justified not only for their intrinsic value, but also for probable benefits to childhood and adolescent participation.

Research in developmental disabilities · 50 citationsread the source →

The impact of occupational shift work and working hours during pregnancy on health outcomes: a systematic review and meta-analysis.

Backgroud: An increasing number of original studies suggest that exposure to shift work and long working hours during pregnancy could be associated with the risk of adverse pregnancy outcomes, but the results remain conflicting and inconclusive. Objective: To examine the influences of shift work and longer working hours during pregnancy on maternal and fetal health outcomes. Data sources: Five electronic databases and 3 gray literature sources were searched up to March 15, 2019. Methods of study selection: Studies of all designs (except case studies and reviews) were included, which contained information on the relevant population (women who engaged in paid work during pregnancy); exposure (rotating shift work [shifts change according to a set schedule], fixed night shift [typical working period is between 11:00 pm and 11:00 am] or longer working hours [>40 hours per week]);comparator (fixed day shift [typical working period is between 8:00 am and 6:00 pm] or standard working hours [≤40 hours per week]); and outcomes (preterm delivery, low birthweight [birthweight <2500 g], small for gestational age, miscarriage, gestational hypertension, preeclampsia, intrauterine growth restriction, stillbirth, and gestational diabetes mellitus). Tabulation, integration, and results: From 3305 unique citations, 62 observational studies (196,989 women) were included. "Low" to "very low" certainty evidence from these studies revealed that working rotating shifts was associated with an increased odds of preterm delivery (odds ratio, 1.13; 95% confidence interval, 1.00-1.28, I2 = 31%), an infant small for gestational age (odds ratio, 1.18, 95% confidence interval, 1.01-1.38, I2 = 0%), preeclampsia (odds ratio, 1.75, 95% confidence interval, 1.01-3.01, I2 = 75%), and gestational hypertension (odds ratio, 1.19, 95% confidence interval, 1.10-1.29, I2 = 0%), compared to those who worked a fixed day shift. Working fixed night shifts was associated with an increased odds of preterm delivery (odds ratio, 1.21; 95% confidence interval, 1.03-1.42; I2 = 36%) and miscarriage (odds ratio, 1.23; 95% confidence interval, 1.03-1.47; I2 = 37%). Compared with standard hours, working longer hours was associated with an increased odds of miscarriage (odds ratio, 1.38; 95% confidence interval, 1.08-1.77; I2 = 73%), preterm delivery (odds ratio, 1.21; 95% confidence interval, 1.11-1.33; I2 = 30%), an infant of low birthweight (odds ratio, 1.43; 95% confidence interval, 1.11-1.84; I2 = 0%), or an infant small for gestational age (odds ratio, 1.16, 95% confidence interval, 1.00-1.36, I2 = 57%). Dose-response analysis showed that women working more than 55.5 hours (vs 40 hours) per week had a 10% increase in the odds of having a preterm delivery. Conclusion: Pregnant women who work rotating shifts, fixed night shifts, or longer hours have an increased risk of adverse pregnancy outcomes.

American journal of obstetrics and gynecology · meta-analysis · 219 citationsread the source →

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

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

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

Audiologist-Guided Internet-Based Cognitive Behavior Therapy for Adults With Tinnitus in the United Kingdom: A Randomized Controlled Trial.

Objectives: Specialist tinnitus services are in high demand as a result of the negative effect tinnitus may have on quality of life. Additional clinically and cost-effective tinnitus management routes are needed. One potential route is providing Cognitive Behavioural Therapy for tinnitus via the Internet (iCBT). This study aimed to determine the efficacy of guided iCBT, using audiological support, on tinnitus distress and tinnitus-related comorbidities, in the United Kingdom. A further aim was to establish the stability of intervention effects 2-months postintervention. The hypothesis was that iCBT for tinnitus would be more effective at reducing tinnitus distress than weekly monitoring. Design: A randomized, delayed intervention efficacy trial, with a 2-month follow-up was implemented to evaluate the efficacy of iCBT in the United Kingdom. Participants were randomly assigned to the experimental (n = 73) or weekly monitoring control group (n = 73) after being stratified for tinnitus severity and age. After the experimental group completed the 8-week long iCBT intervention, the control group undertook the same intervention. Intervention effects were, therefore, evaluated in two independent groups at two time points. The primary outcome was a change in tinnitus distress between the groups as assessed by the Tinnitus Functional Index. Secondary assessment measures were included for insomnia, anxiety, depression, hearing disability, hyperacusis, cognitive failures, and satisfaction with life. These were completed at baseline, postintervention, and at a 2-month postintervention follow-up. Results: After undertaking the iCBT intervention, the experimental group had a greater reduction in tinnitus distress when compared with the control group. This reduction was statistically significant (Cohen's d = 0.7) and was clinically significant for 51% of the experimental group and 5% of the control group. This reduction was evident 4 weeks after commencing the iCBT intervention. Furthermore, the experimental group had a greater reduction in insomnia, depression, hyperacusis, cognitive failures, and a greater improvement in quality of life, as evidenced by the significant differences in these assessment measures postintervention. Results were maintained 2 months postintervention. Conclusions: Guided (using audiological support) iCBT for tinnitus resulted in statistically significant reductions in tinnitus distress and comorbidities (insomnia, depression, hyperacusis, cognitive failures) and a significant increase in quality of life. These effects remained stable at 2-months postintervention. Further trials to determine the longer term efficacy of iCBT to investigate predictors of outcome and to compare iCBT with standard clinical care in the United Kingdom are required. Registered at clinicaltrials.gov: NCT02370810 on 5/03/2015.

Ear and hearing · randomised controlled trial · 74 citationsread the source →

Sympathetic activity in major depressive disorder: identifying those at increased cardiac risk?

Background: Evidence exists linking major depressive disorder (MDD) with clinical cardiovascular events. The importance of the sympathetic nervous system in the generation of cardiac risk in other contexts is established. Objective: To examine the importance of the sympathetic nervous system in the generation of cardiac risk in patients with major depressive disorder (MDD). Methods: Studies were performed in 39 patients meeting the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria for MDD and in 76 healthy subjects. Treatment for patients consisted of selective serotonin reuptake inhibition (SSRI) for 12 weeks. Whole body and cardiac sympathetic activity were examined using noradrenaline isotope dilution methodology and sympathetic nerve recording techniques. Measurement of the extraction of infused tritiated noradrenaline by the heart, and estimation of cardiac dihydroxyphenylglycol production provided direct quantification of neuronal noradrenaline reuptake. Results: Sympathetic activity, particularly in the heart and for the whole body, in patients with MDD followed a bimodal distribution. Elevated values were observed in patients with co-morbid panic disorder (P = 0.006). Consistent with a defect in noradrenaline reuptake, the cardiac extraction of tritiated noradrenaline (0.80 +/- 0.01 versus 0.56 +/- 0.04%, P < 0.001) and cardiac dihydroxyphenylglycol overflow (109 +/- 8 versus 73 +/- 11, P = 0.01) were reduced in patients with MDD. SSRI therapy abolished the excessive sympathetic activation, with whole body noradrenaline spillover falling from 518 +/- 83 to 290 +/- 41 ng/min (P = 0.008). Conclusions: We have identified a subset of patients with MDD in whom sympathetic nervous activity is extraordinarily high, including in the sympathetic outflow to the heart. Treatment with an SSRI may reduce sympathetic activity in a manner likely to reduce cardiac risk.

Journal of hypertension · 201 citationsread the source →

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

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

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

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 →

Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial.

Background: Treatment of patients with ileocaecal Crohn's disease who have not responded to conventional therapy is commonly scaled up to biological agents, but surgery can also offer excellent short-term and long-term results. We compared laparoscopic ileocaecal resection with infliximab to assess how they affect health-related quality of life. Methods: In this randomised controlled, open-label trial, in 29 teaching hospitals and tertiary care centres in the Netherlands and the UK, adults with non-stricturing, ileocaecal Crohn's disease, in whom conventional therapy has failed were randomly allocated (1:1) by an internet randomisation module with biased-coin minimisation for participating centres and perianal fistula to receive laparoscopic ileocaecal resection or infliximab. Eligible patients were aged 18-80 years, had active Crohn's disease of the terminal ileum, and had not responded to at least 3 months of conventional therapy with glucocorticosteroids, thiopurines, or methotrexate. Patients with diseased terminal ileum longer than 40 cm or abdominal abscesses were excluded. The primary outcome was quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ) at 12 months. Secondary outcomes were general quality of life, measured by the Short Form-36 (SF-36) health survey and its physical and mental component subscales, days unable to participate in social life, days on sick leave, morbidity (additional procedures and hospital admissions), and body image and cosmesis. Analyses of the primary outcome were done in the intention-to-treat population, and safety analyses were done in the per-protocol population. This trial is registered at the Dutch Trial Registry (NTR1150). Findings: Between May 2, 2008, and October 14, 2015, 73 patients were allocated to have resection and 70 to receive infliximab. Corrected for baseline differences, the mean IBDQ score at 12 months was 178·1 (95% CI 171·1-185·0) in the resection group versus 172·0 (164·3-179·6) in the infliximab group (mean difference 6·1 points, 95% CI -4·2 to 16·4; p=0·25). At 12 months, the mean SF-36 total score was 112·1 (95% CI 108·0-116·2) in the resection group versus 106·5 (102·1-110·9) in the infliximab group (mean difference 5·6, 95% CI -0·4 to 11·6), the mean physical component score was 47·7 (45·7-49·7) versus 44·6 (42·5-46·8; mean difference 3·1, 4·2 to 6·0), and the mean mental component score was 49·5 (47·0-52·1) versus 46·1 (43·3-48·9; mean difference 3·5, -0·3 to 7·3). Mean numbers of days of sick leave were 3·4 days (SD 7·1) in the resection group versus 1·4 days (4·7) in the infliximab group (p<0·0001), days not able to take part in social life were 1·8 days (6·3) versus 1·1 days (4·5; p=0·20), days of scheduled hospital admission were 6·5 days (3·8) versus 6·8 days (3·2; p=0·84), and the number of patients who had unscheduled hospital admissions were 13 (18%) of 73 versus 15 (21%) of 70 (p=0·68). Body-image scale mean scores in the patients who had resection were 16·0 (95% CI 15·2-16·8) at baseline versus 17·8 (17·1-18·4) at 12 months, and cosmetic scale mean scores were 17·6 (16·6-18·6) versus 18·6 (17·6-19·6). Surgical intervention-related complications classified as IIIa or worse on the Clavien-Dindo scale occurred in four patients in the resection group. Treatment-related serious adverse events occurred in two patients in the infliximab group. During a median follow-up of 4 years (IQR 2-6), 26 (37%) of 70 patients in the infliximab group had resection, and 19 (26%) of 73 patients in the resection group received anti-TNF. Interpretation: Laparoscopic resection in patients with limited (diseased terminal ileum <40 cm), non-stricturing, ileocaecal Crohn's disease in whom conventional therapy has failed could be considered a reasonable alternative to infliximab therapy. Funding: Netherlands Organisation for Health Research and Development.

The lancet. Gastroenterology & hepatology · randomised controlled trial · 228 citationsread the source →

Digital smartphone intervention to recognise and manage early warning signs in schizophrenia to prevent relapse: the EMPOWER feasibility cluster RCT.

Background: Relapse is a major determinant of outcome for people with a diagnosis of schizophrenia. Early warning signs frequently precede relapse. A recent Cochrane Review found low-quality evidence to suggest a positive effect of early warning signs interventions on hospitalisation and relapse. Objective: How feasible is a study to investigate the clinical effectiveness and cost-effectiveness of a digital intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse? Design: A multicentre, two-arm, parallel-group cluster randomised controlled trial involving eight community mental health services, with 12-month follow-up. Settings: Glasgow, UK, and Melbourne, Australia. Participants: Service users were aged > 16 years and had a schizophrenia spectrum disorder with evidence of a relapse within the previous 2 years. Carers were eligible for inclusion if they were nominated by an eligible service user. Interventions: The Early signs Monitoring to Prevent relapse in psychosis and prOmote Wellbeing, Engagement, and Recovery (EMPOWER) intervention was designed to enable participants to monitor changes in their well-being daily using a mobile phone, blended with peer support. Clinical triage of changes in well-being that were suggestive of early signs of relapse was enabled through an algorithm that triggered a check-in prompt that informed a relapse prevention pathway, if warranted. Main outcome measures: The main outcomes were feasibility of the trial and feasibility, acceptability and usability of the intervention, as well as safety and performance. Candidate co-primary outcomes were relapse and fear of relapse. Results: We recruited 86 service users, of whom 73 were randomised (42 to EMPOWER and 31 to treatment as usual). Primary outcome data were collected for 84% of participants at 12 months. Feasibility data for people using the smartphone application (app) suggested that the app was easy to use and had a positive impact on motivations and intentions in relation to mental health. Actual app usage was high, with 91% of users who completed the baseline period meeting our a priori criterion of acceptable engagement (> 33%). The median time to discontinuation of > 33% app usage was 32 weeks (95% confidence interval 14 weeks to ∞). There were 8 out of 33 (24%) relapses in the EMPOWER arm and 13 out of 28 (46%) in the treatment-as-usual arm. Fewer participants in the EMPOWER arm had a relapse (relative risk 0.50, 95% confidence interval 0.26 to 0.98), and time to first relapse (hazard ratio 0.32, 95% confidence interval 0.14 to 0.74) was longer in the EMPOWER arm than in the treatment-as-usual group. At 12 months, EMPOWER participants were less fearful of having a relapse than those in the treatment-as-usual arm (mean difference -4.29, 95% confidence interval -7.29 to -1.28). EMPOWER was more costly and more effective, resulting in an incremental cost-effectiveness ratio of £3041. This incremental cost-effectiveness ratio would be considered cost-effective when using the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year gained. Limitations: This was a feasibility study and the outcomes detected cannot be taken as evidence of efficacy or effectiveness. Conclusions: A trial of digital technology to monitor early warning signs that blended with peer support and clinical triage to detect and prevent relapse is feasible. Future work: A main trial with a sample size of 500 (assuming 90% power and 20% dropout) would detect a clinically meaningful reduction in relapse (relative risk 0.7) and improvement in other variables (effect sizes 0.3-0.4). Trial registration: This trial is registered as ISRCTN99559262. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 27. See the NIHR Journals Library website for further project information. Funding in Australia was provided by the National Health and Medical Research Council (APP1095879).

Health technology assessment (Winchester, England) · randomised controlled trial · 24 citationsread the source →

Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

Background: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. Methods: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. Findings: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. Interpretation: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. Funding: National Institute for Health Research, Health Technology Assessment programme.

The lancet. Psychiatry · randomised controlled trial · 192 citationsread the source →

Promoting resilience in adolescents and young adults with cancer: Results from the PRISM randomized controlled trial.

Background: Adolescents and young adults (AYAs) with cancer are at risk for poor psychosocial outcomes. This study aimed to determine whether a novel intervention targeting resilience resources would improve patient-reported resilience, quality of life, and psychological distress. Methods: In this parallel, phase 2 randomized controlled trial, English-speaking AYAs (12-25 years old) with cancer were randomized to the Promoting Resilience in Stress Management (PRISM) intervention or usual care (UC). PRISM is a brief, skills-based intervention targeting stress management, goal setting, cognitive reframing, and meaning making. Participants completed surveys at enrollment and 6 months. Mixed effects regression models evaluated associations between PRISM and the primary outcome (10-item Connor-Davidson Resilience Scale scores) and secondary outcomes (generic and cancer-related quality of life [Pediatric Quality of Life modules], psychological distress [Kessler-6], and anxiety/depression [Hospital Anxiety and Depression]) at 6 months. Results: Ninety-two AYAs were enrolled, were randomized, and completed baseline surveys (48 in the PRISM group and 44 in the UC group); 73% were 12 to 17 years old, and 62% had leukemia or lymphoma. Attrition was primarily due to medical complications and/or death; 36 PRISM participants and 38 UC participants completed 6-month surveys. PRISM was associated with improved resilience (+3.0 points; 95% confidence interval [CI], 0.5-5.4; P = .02) and cancer-specific quality of life (+9.6; 95% CI, 2.6-16.7; P = .01) and reduced psychological distress (-2.1; 95% CI, -4.1 to -0.2; P = .03) but not generic quality of life (+7.2; 95% CI, -0.8 to 15.2; P = .08). Although anxiety was similar between the groups, 2 PRISM participants (6%) and 8 UC participants (21%) met the criteria for depression at 6 months (odds ratio, 0.09; 95% CI, 0.01-1.09; P = .06). Conclusions: PRISM was associated with improved psychosocial outcomes in comparison with UC, suggesting that brief, skills-based interventions for AYAs may provide a benefit.

Cancer · randomised controlled trial · 143 citationsread the source →

The benefit of minocycline on negative symptoms of schizophrenia in patients with recent-onset psychosis (BeneMin): a randomised, double-blind, placebo-controlled trial.

Background: The antibiotic minocycline has neuroprotective and anti-inflammatory properties that could prevent or reverse progressive neuropathic changes implicated in recent-onset schizophrenia. In the BeneMin study, we aimed to replicate the benefit of minocycline on negative symptoms reported in previous pilot studies, and to understand the mechanisms involved. Methods: In this randomised, double-blind, placebo-controlled trial, we recruited people with a schizophrenia-spectrum disorder that had begun within the past 5 years with continuing positive symptoms from 12 National Health Service (NHS) trusts. Participants were randomly assigned according to an automated permuted blocks algorithm, stratified by pharmacy, to receive minocycline (200 mg per day for 2 weeks, then 300 mg per day for the remainder of the 12-month study period) or matching placebo, which were added to their continuing treatment. The primary clinical outcome was the negative symptom subscale score of the Positive and Negative Syndrome Scales (PANSS) across follow-ups at months 2, 6, 9, and 12. The primary biomarker outcomes were medial prefrontal grey-matter volume, dorsolateral prefrontal cortex activation during a working memory task, and plasma concentration of interleukin 6. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN49141214, and the EU Clinical Trials register (EudraCT) number is 2010-022463-35I. Findings: Between April 16, 2013, and April 30, 2015, we recruited 207 people and randomly assigned them to receive minocycline (n=104) or placebo (n=103). Compared with placebo, the addition of minocycline had no effect on ratings of negative symptoms (treatment effect difference -0·19, 95% CI -1·23 to 0·85; p=0·73). The primary biomarker outcomes did not change over time and were not affected by minocycline. The groups did not differ in the rate of serious adverse events (n=11 in placebo group and n=18 in the minocycline group), which were mostly due to admissions for worsening psychiatric state (n=10 in the placebo group and n=15 in the minocycline group). The most common adverse events were gastrointestinal (n=12 in the placebo group, n=19 in the minocycline group), psychiatric (n=16 in placebo group, n=8 in minocycline group), nervous system (n=8 in the placebo group, n=12 in the minocycline group), and dermatological (n=10 in the placebo group, n=8 in the minocycline group). Interpretation: Minocycline does not benefit negative or other symptoms of schizophrenia over and above adherence to routine clinical care in first-episode psychosis. There was no evidence of a persistent progressive neuropathic or inflammatory process underpinning negative symptoms. Further trials of minocycline in early psychosis are not warranted until there is clear evidence of an inflammatory process, such as microgliosis, against which minocycline has known efficacy. Funding: National Institute for Health Research Efficacy and Mechanism Evaluation (EME) programme, an MRC and NIHR partnership.

The lancet. Psychiatry · randomised controlled trial · 137 citationsread the source →

Promoting school climate and health outcomes with the SEHER multi-component secondary school intervention in Bihar, India: a cluster-randomised controlled trial.

Background: School environments affect health and academic outcomes. With increasing secondary school retention in low-income and middle-income countries, promoting quality school social environments could offer a scalable opportunity to improve adolescent health and wellbeing. Methods: We did a cluster-randomised trial to assess the effectiveness of a multi-component whole-school health promotion intervention (SEHER) with integrated economic and process evaluations in grade 9 students (aged 13-14 years) at government-run secondary schools in the Nalanda district of Bihar state, India. Schools were randomly assigned (1:1:1) to three groups: the SEHER intervention delivered by a lay counsellor (the SEHER Mitra [SM] group), the SEHER intervention delivered by a teacher (teacher as SEHER Mitra [TSM] group), and a control group in which only the standard government-run classroom-based life-skills Adolescence Education Program was implemented. The primary outcome was school climate measured with the Beyond Blue School Climate Questionnaire (BBSCQ). Students were assessed at the start of the academic year (June, 2015) and again 8 months later at the end of the academic year (March, 2016) via self-completed questionnaires. This study is registered with ClinicalTrials.gov, number NCT02484014. Findings: Of the 112 eligible schools in the Nalanda district, 75 were randomly selected to participate in the trial. We randomly assigned 25 schools to each of the three groups. One school subsequently dropped out of the TSM group, leaving 24 schools in this group. The baseline survey included a total of 13 035 participants, and the endpoint survey included 14 414 participants. Participants in the SM-delivered intervention schools had substantially higher school climate scores at endpoint survey than those in the control group (BBSCQ baseline-adjusted mean difference [aMD] 7·57 [95% CI 6·11-9·03]; effect size 1·88 [95% CI 1·44-2·32], p<0·0001) and the TSM-delivered intervention (aMD 7·57 [95% CI 6·06-9·08]; effect size 1·88 [95% CI 1·43-2·34], p<0·0001). There was no effect of the TSM-delivered intervention compared with control (aMD -0·009 [95% CI -1·53 to 1·51], effect size 0·00 [95% CI -0·45 to 0·44], p=0·99). Compared with the control group, participants in the SM-delivered intervention schools had moderate to large improvements in the secondary outcomes of depression (aMD -1·23 [95% CI -1·89 to -0·57]), bullying (aMD -0·91 [95% CI -1·15 to -0·66]), violence victimisation (odds ratio [OR] 0·62 [95% CI 0·46-0·84]), violence perpetration (OR 0·68 [95% CI 0·48-0·96]), attitude towards gender equity (aMD 0·41 [95% CI 0·21-0·61]), and knowledge of reproductive and sexual health (aMD 0·29 [95% CI 0·06-0·53]). Similar results for these secondary outcomes were noted for the comparison between SM-delivered intervention schools and TSM-delivered intervention schools (depression: aMD -1·23 [95% CI -1·91 to -0·55]; bullying: aMD -0·83 [95% CI -1·08 to -0·57]; violence victimisation: OR 0·49 [95% CI 0·35-0·67]; violence perpetration: OR 0·49 [95% CI 0·34-0·71]; attitude towards gender equity: aMD 0·23 [95% CI 0·02-0·44]; and knowledge of reproductive and sexual health: aMD 0·22 [95% CI -0·02 to 0·47]). However, no effects on these secondary outcomes were observed for the TSM-delivered intervention schools compared with the control group (depression: aMD -0·03 [95% CI -0·70 to 0·65]; bullying: aMD -0·08 [95% CI -0·34 to 0·18]; violence victimisation: OR 1·27 [95% CI 0·93-1·73]; violence perpetration: OR 1·37 [95% CI 0·95-1·95]; attitude towards gender equity: aMD 0·17 [95% CI -0·09 to 0·38]; and knowledge of reproductive and sexual health: aMD 0·06 [95% CI -0·18 to 0·32]). Interpretation: The multi-component whole-school SEHER health promotion intervention had substantial beneficial effects on school climate and health-related outcomes when delivered by lay counsellors, but no effects when delivered by teachers. Future research should focus on the evaluation of the scaling up of the SEHER intervention in diverse contexts and delivery agents. Funding: John D. and Catherine T. MacArthur Foundation, USA and the United Nations Population Fund India Office.

Lancet (London, England) · randomised controlled trial · 121 citationsread the source →

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 →

Towards universal voluntary HIV testing and counselling: a systematic review and meta-analysis of community-based approaches.

Background: Effective national and global HIV responses require a significant expansion of HIV testing and counselling (HTC) to expand access to prevention and care. Facility-based HTC, while essential, is unlikely to meet national and global targets on its own. This article systematically reviews the evidence for community-based HTC. Methods and findings: PubMed was searched on 4 March 2013, clinical trial registries were searched on 3 September 2012, and Embase and the World Health Organization Global Index Medicus were searched on 10 April 2012 for studies including community-based HTC (i.e., HTC outside of health facilities). Randomised controlled trials, and observational studies were eligible if they included a community-based testing approach and reported one or more of the following outcomes: uptake, proportion receiving their first HIV test, CD4 value at diagnosis, linkage to care, HIV positivity rate, HTC coverage, HIV incidence, or cost per person tested (outcomes are defined fully in the text). The following community-based HTC approaches were reviewed: (1) door-to-door testing (systematically offering HTC to homes in a catchment area), (2) mobile testing for the general population (offering HTC via a mobile HTC service), (3) index testing (offering HTC to household members of people with HIV and persons who may have been exposed to HIV), (4) mobile testing for men who have sex with men, (5) mobile testing for people who inject drugs, (6) mobile testing for female sex workers, (7) mobile testing for adolescents, (8) self-testing, (9) workplace HTC, (10) church-based HTC, and (11) school-based HTC. The Newcastle-Ottawa Quality Assessment Scale and the Cochrane Collaboration's "risk of bias" tool were used to assess the risk of bias in studies with a comparator arm included in pooled estimates. 117 studies, including 864,651 participants completing HTC, met the inclusion criteria. The percentage of people offered community-based HTC who accepted HTC was as follows: index testing, 88% of 12,052 participants; self-testing, 87% of 1,839 participants; mobile testing, 87% of 79,475 participants; door-to-door testing, 80% of 555,267 participants; workplace testing, 67% of 62,406 participants; and school-based testing, 62% of 2,593 participants. Mobile HTC uptake among key populations (men who have sex with men, people who inject drugs, female sex workers, and adolescents) ranged from 9% to 100% (among 41,110 participants across studies), with heterogeneity related to how testing was offered. Community-based approaches increased HTC uptake (relative risk [RR] 10.65, 95% confidence interval [CI] 6.27-18.08), the proportion of first-time testers (RR 1.23, 95% CI 1.06-1.42), and the proportion of participants with CD4 counts above 350 cells/µl (RR 1.42, 95% CI 1.16-1.74), and obtained a lower positivity rate (RR 0.59, 95% CI 0.37-0.96), relative to facility-based approaches. 80% (95% CI 75%-85%) of 5,832 community-based HTC participants obtained a CD4 measurement following HIV diagnosis, and 73% (95% CI 61%-85%) of 527 community-based HTC participants initiated antiretroviral therapy following a CD4 measurement indicating eligibility. The data on linking participants without HIV to prevention services were limited. In low- and middle-income countries, the cost per person tested ranged from US$2-US$126. At the population level, community-based HTC increased HTC coverage (RR 7.07, 95% CI 3.52-14.22) and reduced HIV incidence (RR 0.86, 95% CI 0.73-1.02), although the incidence reduction lacked statistical significance. No studies reported any harm arising as a result of having been tested. Conclusions: Community-based HTC achieved high rates of HTC uptake, reached people with high CD4 counts, and linked people to care. It also obtained a lower HIV positivity rate relative to facility-based approaches. Further research is needed to further improve acceptability of community-based HTC for key populations. HIV programmes should offer community-based HTC linked to prevention and care, in addition to facility-based HTC, to support increased access to HIV prevention, care, and treatment. Review registration: International Prospective Register of Systematic Reviews CRD42012002554 Please see later in the article for the Editors' Summary.

PLoS medicine · meta-analysis · 313 citationsread the source →

"There Was a Sense That Our Load Had Been Lightened": Evaluating Outcomes of Virtual Ethics Rounds for Veterinary Team Members.

Clinical ethics support services (CESS) are employed in healthcare to improve patient care and help team members develop skills to recognize and navigate ethically challenging situations (ECS). The objective of this study was to evaluate the impact of ethics rounds, one form of CESS, on veterinary team members. An anonymous, online mixed-methods survey incorporating a 15-item instrument designed to assess the outcomes of moral case deliberation originally developed for human healthcare workers (the Euro-MCD 2.0), was developed. The survey was administered to veterinary team members prior to and following participation in a 90-min virtual ethics rounds session. A total of 23 sessions of virtual ethics rounds were held. In total, 213 individuals participated, and 89 completed both surveys (response rate 41.8%). Most respondents were female (n = 70, 81%). Most were veterinarians (n = 51, 59%), followed by other veterinary team members (practice manager, animal attendant) (n = 18, 21%), veterinary nurses or animal health technicians (n = 10, 12%) and veterinary students (n = 8, 9%). Age ranged from 20 to 73 (median 41, IQR 32-52, n = 87). While there was no statistically significant difference between overall modified Euro-MCD 2.0 scores between T1 and T2, there were statistically significant changes in 7 out of 15 Euro-MCD 2.0 items in the domains of moral competence and moral teamwork. Reflexive thematic analysis of free-text responses identified themes including the types, impact and barriers to resolving ECS, the impacts of ethics rounds on veterinary team members and constraints preventing veterinary team members from speaking up in the face of ECS. While participants largely described the impact of ethics rounds as beneficial (for example, by facilitating clarification of thinking about ECS, allowing participants to see ECS from the perspective of others and providing a safe space for discussion), reflecting on ECS could be stressful for participants. Active participation in ethics rounds may be inhibited in the context of power imbalance, or in settings where bullying occurs. Overall, carefully facilitated ethics rounds has the potential to improve the ability of veterinary team members to identify and navigate ECS, and potentially mitigate moral distress.

Frontiers in veterinary science · 8 citationsread the source →

A systematic review of interventions in primary care to improve health literacy for chronic disease behavioral risk factors.

Background: To evaluate the effectiveness of interventions used in primary care to improve health literacy for change in smoking, nutrition, alcohol, physical activity and weight (SNAPW). Methods: A systematic review of intervention studies that included outcomes for health literacy and SNAPW behavioral risk behaviors implemented in primary care settings. We searched the Cochrane Library, Johanna Briggs Institute, Medline, Embase, CINAHL, Psychinfo, Web of Science, Scopus, APAIS, Australasian Medical Index, Google Scholar, Community of Science and four targeted journals (Patient Education and Counseling, Health Education and Behaviour, American Journal of Preventive Medicine and Preventive Medicine).Study inclusion criteria: Adults over 18 years; undertaken in a primary care setting within an Organisation for Economic Co-operation and Development (OECD) country; interventions with at least one measure of health literacy and promoting positive change in smoking, nutrition, alcohol, physical activity and/or weight; measure at least one outcome associated with health literacy and report a SNAPW outcome; and experimental and quasi-experimental studies, cohort, observational and controlled and non-controlled before and after studies. Papers were assessed and screened by two researchers (JT, AW) and uncertain or excluded studies were reviewed by a third researcher (MH). Data were extracted from the included studies by two researchers (JT, AW). Effectiveness studies were quality assessed. A typology of interventions was thematically derived from the studies by grouping the SNAPW interventions into six broad categories: individual motivational interviewing and counseling; group education; multiple interventions (combination of interventions); written materials; telephone coaching or counseling; and computer or web based interventions. Interventions were classified by intensity of contact with the subjects (High ≥ 8 points of contact/hours; Moderate >3 and <8; Low ≤ 3 points of contact hours) and setting (primary health, community or other).Studies were analyzed by intervention category and whether significant positive changes in SNAPW and health literacy outcomes were reported. Results: 52 studies were included. Many different intervention types and settings were associated with change in health literacy (73% of all studies) and change in SNAPW (75% of studies). More low intensity interventions reported significant positive outcomes for SNAPW (43% of studies) compared with high intensity interventions (33% of studies). More interventions in primary health care than the community were effective in supporting smoking cessation whereas the reverse was true for diet and physical activity interventions. Conclusion: Group and individual interventions of varying intensity in primary health care and community settings are useful in supporting sustained change in health literacy for change in behavioral risk factors. Certain aspects of risk behavior may be better handled in clinical settings while others more effectively in the community. Our findings have implications for the design of programs.

BMC family practice · systematic review · 158 citationsread the source →

Systematic review of the psychological consequences of false-positive screening mammograms.

Background: In the UK, women aged 50-73 years are invited for screening by mammography every 3 years. In 2009-10, more than 2.24 million women in this age group in England were invited to take part in the programme, of whom 73% attended a screening clinic. Of these, 64,104 women were recalled for assessment. Of those recalled, 81% did not have breast cancer; these women are described as having a false-positive mammogram. Objective: The aim of this systematic review was to identify the psychological impact on women of false-positive screening mammograms and any evidence for the effectiveness of interventions designed to reduce this impact. We were also looking for evidence of effects in subgroups of women. Data sources: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Health Management Information Consortium, Cochrane Central Register for Controlled Trials, Cochrane Database of Systematic Reviews, Centre for Reviews and Dissemination (CRD) Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment (HTA), Cochrane Methodology, Web of Science, Science Citation Index, Social Sciences Citation Index, Conference Proceedings Citation Index-Science, Conference Proceeding Citation Index-Social Science and Humanities, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Sociological Abstracts, the International Bibliography of the Social Sciences, the British Library's Electronic Table of Contents and others. Initial searches were carried out between 8 October 2010 and 25 January 2011. Update searches were carried out on 26 October 2011 and 23 March 2012. Review methods: Based on the inclusion criteria, titles and abstracts were screened independently by two reviewers. Retrieved papers were reviewed and selected using the same independent process. Data were extracted by one reviewer and checked by another. Each included study was assessed for risk of bias. Results: Eleven studies were found from 4423 titles and abstracts. Studies that used disease-specific measures found a negative psychological impact lasting up to 3 years. Distress increased with the level of invasiveness of the assessment procedure. Studies using instruments designed to detect clinical levels of morbidity did not find this effect. Women with false-positive mammograms were less likely to return for the next round of screening [relative risk (RR) 0.97; 95% confidence interval (CI) 0.96 to 0.98] than those with normal mammograms, were more likely to have interval cancer [odds ratio (OR) 3.19 (95% CI 2.34 to 4.35)] and were more likely to have cancer detected at the next screening round [OR 2.15 (95% CI 1.55 to 2.98)]. Limitations: This study was limited to UK research and by the robustness of the included studies, which frequently failed to report quality indicators, for example failure to consider the risk of bias or confounding, or failure to report participants' demographic characteristics. Conclusions: We conclude that the experience of having a false-positive screening mammogram can cause breast cancer-specific psychological distress that may endure for up to 3 years, and reduce the likelihood that women will return for their next round of mammography screening. These results should be treated cautiously owing to inherent weakness of observational designs and weaknesses in reporting. Future research should include a qualitative interview study and observational studies that compare generic and disease-specific measures, collect demographic data and include women from different social and ethnic groups.

Health technology assessment (Winchester, England) · systematic review · 117 citationsread the source →

Effect of immunotherapy time-of-day infusion on overall survival among patients with advanced melanoma in the USA (MEMOIR): a propensity score-matched analysis of a single-centre, longitudinal study.

Background: The dependence of the adaptive immune system on circadian rhythm is an emerging field of study with potential therapeutic implications. We aimed to determine whether specific time-of-day patterns of immune checkpoint inhibitor infusions might alter melanoma treatment efficacy. Methods: Melanoma Outcomes Following Immunotherapy (MEMOIR) is a longitudinal study of all patients with melanoma who received ipilimumab, nivolumab, or pembrolizumab, or a combination of these at a single tertiary cancer centre (Winship Cancer Institute of Emory University, Atlanta, GA, USA). For this analysis, we collected deidentified participant-level data from the MEMOIR database for adults (age ≥18 years) diagnosed with stage IV melanoma between 2012 and 2020. Those who received fewer than four infusions were excluded. Standard of care doses were used, with modifications at the treating physicians' discretion. The primary outcome was overall survival, defined as death from any cause and indexed from date of first infusion of immune checkpoint inhibitor. We calculated the association between overall survival and proportion of infusions of immune checkpoint inhibitors received after 1630 h (a composite time cutoff derived from seminal studies of the immune-circadian rhythm to represent onset of evening) using Cox regression and propensity score-matching on age, Eastern Cooperative Oncology Group performance status, serum lactate dehydrogenase concentration, and receipt of corticosteroids and radiotherapy. Treatment-related adverse events that led to change or discontinuation of immune checkpoint inhibitors were also assessed. Findings: Between Jan 1, 2012, and Dec 31, 2020, 481 patients with melanoma received treatment with immune checkpoint inhibitors at the study centre, of whom 299 had stage IV disease and were included in this study; median follow-up was 27 months (IQR 14 to 47). In the complete unmatched sample, 102 (34%) patients were female and 197 (66%) were male, with a median age of 61 years (IQR 51 to 72). Every additional 20% of infusions of immune checkpoint inhibitors received after 1630 h (among all infusions received by a patient) conferred an overall survival hazard ratio (HR) of 1·31 (95% CI 1·00 to 1·71; p=0·046). A propensity score-matched analysis of patients who did (n=73) and did not (n=73) receive at least 20% of their infusions of immune checkpoint inhibitors after 1630 h (54 [37%] of 146 patients were women and 92 [63%] were men, with a median age of 58 years [IQR 48 to 68]) showed that having at least 20% of infusions in the evening was associated with shorter overall survival (median 4·8 years [95% CI 3·9 to not estimable] vs not reached; HR 2·04 [1·04 to 4·00; p=0·038]). This result remained robust to multivariable proportional hazards adjustment with (HR 1·80 [1·08 to 2·98; p=0·023]) and without (2·16 [1·10 to 4·25; p=0·025]) inclusion of the complete unmatched study sample. The most common adverse events were colitis (54 [18%] of 299 patients), hepatitis (27 [9%]), and hypophysitis (15 [5%]), and there were no treatment-related deaths. Interpretation: Our findings are in line with an increasing body of evidence that adaptive immune responses are less robust when initially stimulated in the evening than if stimulated in the daytime. Although prospective studies of the timing of immune checkpoint inhibitor infusions are warranted, efforts towards scheduling infusions before mid-afternoon could be considered in the multidisciplinary management of advanced melanoma. Funding: National Institutes of Health, American Society for Radiation Oncology and Melanoma Research Alliance, and Winship Cancer Institute.

The Lancet. Oncology · clinical trial · 146 citationsread the source →

Predicting treatment response to cognitive behavioral therapy in panic disorder with agoraphobia by integrating local neural information.

Importance: Although neuroimaging research has made substantial progress in identifying the large-scale neural substrate of anxiety disorders, its value for clinical application lags behind expectations. Machine-learning approaches have predictive potential for individual-patient prognostic purposes and might thus aid translational efforts in psychiatric research. Objective: To predict treatment response to cognitive behavioral therapy (CBT) on an individual-patient level based on functional magnetic resonance imaging data in patients with panic disorder with agoraphobia (PD/AG). Design, setting, and participants: We included 49 patients free of medication for at least 4 weeks and with a primary diagnosis of PD/AG in a longitudinal study performed at 8 clinical research institutes and outpatient centers across Germany. The functional magnetic resonance imaging study was conducted between July 2007 and March 2010. Interventions: Twelve CBT sessions conducted 2 times a week focusing on behavioral exposure. Main outcomes and measures: Treatment response was defined as exceeding a 50% reduction in Hamilton Anxiety Rating Scale scores. Blood oxygenation level-dependent signal was measured during a differential fear-conditioning task. Regional and whole-brain gaussian process classifiers using a nested leave-one-out cross-validation were used to predict the treatment response from data acquired before CBT. Results: Although no single brain region was predictive of treatment response, integrating regional classifiers based on data from the acquisition and the extinction phases of the fear-conditioning task for the whole brain yielded good predictive performance (accuracy, 82%; sensitivity, 92%; specificity, 72%; P < .001). Data from the acquisition phase enabled 73% correct individual-patient classifications (sensitivity, 80%; specificity, 67%; P < .001), whereas data from the extinction phase led to an accuracy of 74% (sensitivity, 64%; specificity, 83%; P < .001). Conservative reanalyses under consideration of potential confounders yielded nominally lower but comparable accuracy rates (acquisition phase, 70%; extinction phase, 71%; combined, 79%). Conclusions and relevance: Predicting treatment response to CBT based on functional neuroimaging data in PD/AG is possible with high accuracy on an individual-patient level. This novel machine-learning approach brings personalized medicine within reach, directly supporting clinical decisions for the selection of treatment options, thus helping to improve response rates.

JAMA psychiatry · clinical trial · 92 citationsread the source →

An advance directive redesigned to meet the literacy level of most adults: a randomized trial.

Objective: To determine whether an advance directive redesigned to meet most adults' literacy needs (fifth grade reading level with graphics) was more useful for advance care planning than a standard form (>12th grade level). Methods: We enrolled 205 English and Spanish-speaking patients, aged >/=50 years from an urban, general medicine clinic. We randomized participants to review either form. Main outcomes included acceptability and usefulness in advance care planning. Participants then reviewed the alternate form; we assessed form preference and six-month completion rates. Results: Forty percent of enrolled participants had limited literacy. Compared to the standard form, the redesigned form was rated higher for acceptability and usefulness in care planning, P</=0.03, particularly for limited literacy participants (P for interaction </=0.07). The redesigned form was preferred by 73% of participants. More participants randomized to the redesigned form completed an advance directive at six months (19% vs. 8%, P=0.03); of these, 95% completed the redesigned form. Conclusions: The redesigned advance directive was rated more acceptable and useful for advance care planning and was preferred over a standard form. It also resulted in higher six-month completion rates. Practice implications: An advance directive redesigned to meet most adults' literacy needs may better enable patients to engage in advance care planning.

Patient education and counseling · randomised controlled trial · 118 citationsread the source →

Effect of essential amino acid supplementation on quality of life, amino acid profile and strength in institutionalized elderly patients.

Background & aims: This study assessed the efficacy of supplemented essential amino acids on depressive symptoms, nutrition, muscle function, daily physical activity, and health-related quality of life (HRQoL) of institutionalized elderly patients. Methods: Forty-one patients (58.5% women; mean age 79.8 yrs) with sequelae of coronary artery disease (73%), femoral fracture (34%), were randomly assigned to receive oral essential amino acids 4 gr 2 times a day for 8 weeks or isocaloric placebo. Before randomization and 8 weeks after the protocol started, the following variables were measured: depressive symptoms (Geriatric Depression Scale, GDS), nutritional panel (Mini Nutritional Assessment, MNA; serum albumin and prealbumin levels), muscle strength (Hand Grip, HG), Activity Daily Life (ADL), Quality of Life (SF-36, HRQoL) and amino acid profile. Results: Compared with the placebo group, EAA patients improved nutrition (MNA score 22.6 ± 1.5 post vs 21.8 ± 1.6 pre; p < 0. 04, albumin g/dl 4.04 ± 0.35 post vs 3.88 ± 0.3 pre; p < 0.01), GDS(score 10.3 ± 1.75 post vs 13.85 ± 3.37 pre; p < 0.001), HG (Kg 19.75 ± 1.7 post vs 18.68 ± 1.36 pre; p = 0.001), ADL (p < 0.04) and both physical and mental components of SF-36 (p < 0.002). Conclusions: Oral supplementation with essential amino acids improved several determinants of quality of life in institutionalized elderly patients, including depressive symptoms, nutrition, muscle function and daily life activity.

Clinical nutrition (Edinburgh, Scotland) · randomised controlled trial · 62 citationsread the source →

Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial.

Background: Obesity is associated with a reduction in life expectancy and an increase in mortality from cardiovascular diseases, cancer, and other causes. We therefore assessed the efficacy and safety of two doses of phentermine plus topiramate controlled-release combination as an adjunct to diet and lifestyle modification for weight loss and metabolic risk reduction in individuals who were overweight and obese, with two or more risk factors. Methods: In this 56-week phase 3 trial, we randomly assigned overweight or obese adults (aged 18-70 years), with a body-mass index of 27-45 kg/m(2) and two or more comorbidities (hypertension, dyslipidaemia, diabetes or prediabetes, or abdominal obesity) to placebo, once-daily phentermine 7·5 mg plus topiramate 46·0 mg, or once-daily phentermine 15·0 mg plus topiramate 92·0 mg in a 2:1:2 ratio in 93 centres in the USA. Drugs were administered orally. Patients were randomly assigned by use of a computer-generated algorithm that was implemented through an interactive voice response system, and were stratified by sex and diabetic status. Investigators, patients, and study sponsors were masked to treatment. Primary endpoints were the percentage change in bodyweight and the proportion of patients achieving at least 5% weight loss. Analysis was by intention to treat. This study is registered with Clinical Trials.gov, number NCT00553787. Findings: Of 2487 patients, 994 were assigned to placebo, 498 to phentermine 7·5 mg plus topiramate 46·0 mg, and 995 to phentermine 15·0 mg plus topiramate 92·0 mg; 979, 488, and 981 patients, respectively, were analysed. At 56 weeks, change in bodyweight was -1·4 kg (least-squares mean -1·2%, 95% CI -1·8 to -0·7), -8·1 kg (-7·8%, -8·5 to -7·1; p<0·0001), and -10·2 kg (-9·8%, -10·4 to -9·3; p<0·0001) in the patients assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively. 204 (21%) patients achieved at least 5% weight loss with placebo, 303 (62%; odds ratio 6·3, 95% CI 4·9 to 8·0; p<0·0001) with phentermine 7·5 mg plus topiramate 46·0 mg, and 687 (70%; 9·0, 7·3 to 11·1; p<0·0001) with phentermine 15·0 mg plus topiramate 92·0 mg; for ≥10% weight loss, the corresponding numbers were 72 (7%), 182 (37%; 7·6, 5·6 to 10·2; p<0·0001), and 467 (48%; 11·7, 8·9 to 15·4; p<0·0001). The most common adverse events were dry mouth (24 [2%], 67 [13%], and 207 [21%] in the groups assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively), paraesthesia (20 [2%], 68 [14%], and 204 [21%], respectively), constipation (59 [6%], 75 [15%], and 173 [17%], respectively), insomnia (47 [5%], 29 [6%], and 102 [10%], respectively), dizziness (31 [3%], 36 [7%], 99 [10%], respectively), and dysgeusia (11 [1%], 37 [7%], and 103 [10%], respectively). 38 (4%) patients assigned to placebo, 19 (4%) to phentermine 7·5 mg plus topiramate 46·0 mg, and 73 (7%) to phentermine 15·0 mg plus topiramate 92·0 mg had depression-related adverse events; and 28 (3%), 24 (5%), and 77 (8%), respectively, had anxiety-related adverse events. Interpretation: The combination of phentermine and topiramate, with office-based lifestyle interventions, might be a valuable treatment for obesity that can be provided by family doctors. Funding: Vivus.

Lancet (London, England) · randomised controlled trial · 667 citationsread the source →

An exercise and education program improves well-being of new mothers: a randomized controlled trial.

Objective: The purpose of this study was to evaluate the effect of a physical therapy exercise and health care education program on the psychological well-being of new mothers. Design: This was a randomized controlled trial. Participants: Primiparous and multiparous English-speaking women ready for discharge from The Angliss Hospital postnatal ward were eligible for this study. Women who were receiving psychiatric care were excluded. One hundred sixty-one women were randomized into the trial. Intervention: The experimental group (n=62) received an 8-week "Mother and Baby" (M&B) program, including specialized exercise provided by a women's health physical therapist combined with parenting education. The other group (education only [EO], n=73) received only the same educational material as the experimental group. Main outcome measures: Psychological well-being (Positive Affect Balance Scale), depressive symptoms (Edinburgh Postnatal Depression Scale), and physical activity levels were assessed at baseline, after 8 weeks (post-program), and then 4 weeks later. Results: There was significant improvement in well-being scores and depressive symptoms of the M&B group compared with the EO group over the study period. More specifically, there was a significant positive effect on well-being scores and depressive symptoms at 8 weeks, and this effect was maintained 4 weeks after completion of the program. The number of women identified as "at risk" for postnatal depression pre-intervention was reduced by 50% by the end of the intervention. Limitations: Although this study provides promising short-term (4-week) outcomes, further work is needed to explore whether the intervention effects are maintained as sustained psychological and behavioral benefits at 6 months. Conclusions: A physical therapy exercise and health education program is effective in improving postnatal well-being. Routine use of this program may reduce longer-term problems such as postnatal depression.

Physical therapy · randomised controlled trial · 80 citationsread the source →

Antidepressant Monotherapy vs Sequential Pharmacotherapy and Mindfulness-Based Cognitive Therapy, or Placebo, for Relapse Prophylaxis in Recurrent Depression

CONTEXT: Mindfulness-based cognitive therapy (MBCT) is a group-based psychosocial intervention designed to enhance self-management of prodromal symptoms associated with depressive relapse. OBJECTIVE: To compare rates of relapse in depressed patients in remission receiving MBCT against maintenance antidepressant pharmacotherapy, the current standard of care. DESIGN: Patients who met remission criteria after 8 months of algorithm-informed antidepressant treatment were randomized to receive maintenance antidepressant medication, MBCT, or placebo and were followed up for 18 months. SETTING: Outpatient clinics at the Centre for Addiction and Mental Health, Toronto, Ontario, Canada, and St Joseph's Healthcare, Hamilton, Ontario. PARTICIPANTS: One hundred sixty patients aged 18 to 65 years meeting DSM-IV criteria for major depressive disorder with a minimum of 2 past episodes. Of these, 84 achieved remission (52.5%) and were assigned to 1 of the 3 study conditions. INTERVENTIONS: Patients in remission discontinued their antidepressants and attended 8 weekly group sessions of MBCT, continued taking their therapeutic dose of antidepressant medication, or discontinued active medication and were switched to placebo. MAIN OUTCOME MEASURE: Relapse was defined as a return, for at least 2 weeks, of symptoms sufficient to meet the criteria for major depression on module A of the Structured Clinical Interview for DSM-IV. RESULTS: Intention-to-treat analyses showed a significant interaction between the quality of acute-phase remission and subsequent prevention of relapse in randomized patients (P = .03). Among unstable remitters (1 or more Hamilton Rating Scale for Depression score >7 during remission), patients in both MBCT and maintenance treatment showed a 73% decrease in hazard compared with placebo (P = .03), whereas for stable remitters (all Hamilton Rating Scale for Depression scores ≤7 during remission) there were no group differences in survival. CONCLUSIONS: For depressed patients achieving stable or unstable clinical remission, MBCT offers protection against relapse/recurrence on a par with that of maintenance antidepressant pharmacotherapy. Our data also highlight the importance of maintaining at least 1 long-term active treatment in unstable remitters.

Archives of General Psychiatry · randomised controlled trial · 435 citationsread the source →

Efficacy and safety of baclofen for alcohol dependence: a randomized, double-blind, placebo-controlled trial.

Background: Recent clinical trials and case-reports indicate that baclofen, a GABA(B) agonist, may have efficacy for alcohol dependence. Baclofen has been shown to enhance abstinence, to reduce drinking quantity, to reduce craving, and to reduce anxiety in alcohol-dependent individuals in 2 placebo-controlled trials in Italy. However, the clinical trial data with baclofen is limited. The purpose of the present study was to test the efficacy and tolerability of baclofen in alcohol dependence in the United States. Methods: The study was a double-blind, placebo-controlled, randomized study comparing 30 mg/d of baclofen to placebo over 12 weeks of treatment and utilizing 8 sessions of BRENDA, a low-intensity psychosocial intervention. One hundred and twenty-one subjects were screened to yield 80 randomized subjects (44 men) with randomization balanced for gender. Percent heavy drinking days was the primary outcome measure with other drinking outcomes, anxiety levels, and craving as secondary outcomes. Tolerability was examined. Results: Seventy-six percent of subjects completed the study. No difference by drug condition was seen in percentage of heavy drinking days where on-average rates were 25.5% (±23.6%) for placebo and 25.9% (±23.2%) for baclofen during treatment (t(73)=0.59, p=0.56). Similarly, no differences were seen by drug condition in percentage of days abstinent, time to first drink, or time to relapse to heavy drinking. Baclofen was associated with a significant reduction in state anxiety (F(1,73)= 5.39, p=0.02). Baclofen was well tolerated with only 2 individuals stopping baclofen because of adverse events. There were no serious adverse events. Conclusions: Baclofen, a GABA(B) agonist, represents a possible new pharmacotherapeutic approach to alcohol dependence. Despite encouraging preclinical data and prior positive clinical trials with baclofen in Italy, the current trial did not find evidence that baclofen is superior to placebo in the treatment of alcohol dependence. Additional clinical trial work is necessary to establish whether baclofen does or does not have therapeutic efficacy in alcohol dependence and, if it does, what factors are predictive of response.

Alcoholism, clinical and experimental research · randomised controlled trial · 202 citationsread the source →

Telemedicine-Based Collaborative Care for Posttraumatic Stress Disorder

IMPORTANCE: Posttraumatic stress disorder (PTSD) is prevalent, persistent, and disabling. Although psychotherapy and pharmacotherapy have proven efficacious in randomized clinical trials, geographic barriers impede rural veterans from engaging in these evidence-based treatments. OBJECTIVE: To test a telemedicine-based collaborative care model designed to improve engagement in evidence-based treatment of PTSD. DESIGN, SETTING, AND PARTICIPANTS: The Telemedicine Outreach for PTSD (TOP) study used a pragmatic randomized effectiveness trial design with intention-to-treat analyses. Outpatients were recruited from 11 Department of Veterans Affairs (VA) community-based outpatient clinics serving predominantly rural veterans. Inclusion required meeting diagnostic criteria for current PTSD according to the Clinician-Administered PTSD Scale. Exclusion criteria included receiving PTSD treatment at a VA medical center or a current diagnosis of schizophrenia, bipolar disorder, or substance dependence. Two hundred sixty-five veterans were enrolled from November 23, 2009, through September 28, 2011, randomized to usual care (UC) or the TOP intervention, and followed up for 12 months. INTERVENTIONS: Off-site PTSD care teams located at VA medical centers supported on-site community-based outpatient clinic providers. Off-site PTSD care teams included telephone nurse care managers, telephone pharmacists, telepsychologists, and telepsychiatrists. Nurses conducted care management activities. Pharmacists reviewed medication histories. Psychologists delivered cognitive processing therapy via interactive video. Psychiatrists supervised the team and conducted interactive video psychiatric consultations. MAIN OUTCOMES AND MEASURES: The primary outcome was PTSD severity as measured by the Posttraumatic Diagnostic Scale. Process-of-care outcomes included medication prescribing and regimen adherence and initiation of and adherence to cognitive processing therapy. RESULTS: During the 12-month follow-up period, 73 of the 133 patients randomized to TOP (54.9%) received cognitive processing therapy compared with 16 of 132 randomized to UC (12.1%) (odds ratio, 18.08 [95% CI, 7.96-41.06]; P < .001). Patients in the TOP arm had significantly larger decreases in Posttraumatic Diagnostic Scale scores (from 35.0 to 29.1) compared with those in the UC arm (from 33.5 to 32.1) at 6 months (β = -3.81; P = .002). Patients in the TOP arm also had significantly larger decreases in Posttraumatic Diagnostic Scale scores (from 35.0 to 30.1) compared with those in the UC arm (from 33.5 to 31.7) at 12 months (β = -2.49; P=.04). There were no significant group differences in the number of PTSD medications prescribed and adherence to medication regimens were not significant. Attendance at 8 or more sessions of cognitive processing therapy significantly predicted improvement in Posttraumatic Diagnostic Scale scores (β = -3.86 [95% CI, -7.19 to -0.54]; P = .02) and fully mediated the intervention effect at 12 months. CONCLUSIONS AND RELEVANCE: Telemedicine-based collaborative care can successfully engage rural veterans in evidence-based psychotherapy to improve PTSD outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00821678.

JAMA Psychiatry · randomised controlled trial · 277 citationsread the source →

Dementia and Alzheimer's disease in community-dwelling elders taking vitamin C and/or vitamin E.

Background: Since increased oxidative stress may impair cognition and be a risk factor for dementia, there has been interest in determining whether use of antioxidants could protect against such events. Objective: To determine whether supplement use of vitamins C and/or E in a community-based sample of older African American and white individuals delayed incident dementia or Alzheimer's disease (AD). Methods: We selected a subgroup from the Duke Established Populations for Epidemiologic Studies of the Elderly, a longitudinal study of community-representative persons aged 65-105 years living in 5 adjacent counties in North Carolina, and followed them for dementia (1986-1987 through June 2000). Information gathered during in-home interviews included sociodemographic characteristics, health status, health service use, and vitamin use. Diagnosis of dementia and AD was based on evaluations using the clinical and neuropsychological batteries of the Consortium to Establish a Registry for Alzheimer's Disease, with final determination by consensus agreement of specialists using Diagnostic and Statistical Manual of Mental Disorders, third revision, and National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders criteria. Results: Of 616 persons initially dementia-free (mean age 73 y; 62% female; 62% African American), 141 developed dementia, of whom 93 developed AD. Increased age and mobility problems were risk factors for dementia (only age for AD), while an increased number of outpatient visits reduced the likelihood of developing dementia. Neither use of any vitamins C and/or E (used by 8% of subjects at baseline) nor high-dose use reduced the time to dementia or AD. Conclusions: In this community in the southeastern US where vitamin supplement use is low, use of vitamins C and/or E did not delay the incidence of dementia or AD.

The Annals of pharmacotherapy · clinical trial · 70 citationsread the source →

An open trial of a brief transdiagnostic internet treatment for anxiety and depression.

The present study evaluated the efficacy of a brief version of an internet-administered transdiagnostic CBT protocol, the Wellbeing Program (Titov et al., 2011), designed to treat three anxiety disorders and major depression within the same program. This brief version included the same core CBT skills as the original, but condensed the materials from 8 to 5 online lessons, reduced the duration of treatment from 10 to 8 weeks and did not include an online forum. Thirty-two individuals with a principal diagnosis of major depression, generalised anxiety disorder, panic disorder or social phobia received CBT-based online educational lessons, homework assignments, weekly contact from a clinical psychologist and automated emails. Eighty-one percent of participants completed the lessons within the 8 week program. Post-treatment and 3-month follow-up data were collected from 28/32 and 31/32 participants respectively. Participants improved significantly on the Depression Anxiety and Stress Scales - 21 Item, Patient Health Questionnaire - 9 Item, and Generalised Anxiety Disorder - 7 Item scales, with corresponding within-group effect sizes (Cohen's d) at follow-up of 1.05, .73, and .95, respectively. Participants rated the procedure as highly acceptable with gains of a similar magnitude as those found for the original program, but less time was spent per participant by the clinician in the present trial (mean=44.61 min, SD=34.45) compared to the original program (mean=84.76 min, SD=50.37). These results provide additional support for the efficacy of transdiagnostic iCBT in the treatment of anxiety and depressive disorders and indicate that a brief version may be of benefit.

Behaviour research and therapy · clinical trial · 63 citationsread the source →

Norms of decision making in the ICU: a case study of two academic medical centers at the extremes of end-of-life treatment intensity.

Purpose: To explore norms of decision making regarding life-sustaining treatments (LSTs) at two academic medical centers (AMCs) that contribute to their opposite extremes of end-of-life ICU use. Methods: We conducted a 4-week mixed methods case study at each AMC in 2008-2009 involving direct observation of patient care during rounds in the main medical ICU, semi-structured interviews with staff, patients, and families, and collection of artifacts (e.g., patient lists, standardized forms). We compared patterns of decision making regarding initiation, continuation, and withdrawal of LST using tests of proportions and grounded theory analysis of field note and interview transcripts. Results: We observed 80 patients [26 (32.5 %) ≥65 years old] staffed by 4 attendings, and interviewed 23 staff and 3 patients/families at the low-intensity AMC (LI-AMC), and observed 73 patients [26 (35.6 %) ≥65 years old] staffed by 4 attending physicians and interviewed 26 staff and 4 patients/families at the high-intensity AMC (HI-AMC). LST initiation among patients over 65 was similar, except feeding tubes (0 % LI-AMC versus 31 % HI-AMC, p = 0.002). The LI-AMC was more likely to use a time-limited trial of LST, followed by withdrawal (27 vs. 8 %, p = 0.01) and to have a known outcome of death (31 vs. 4 %, p < 0.001). We identified qualitative differences in goals of LST, the determination of "dying," concern about harms of commission versus omission, and physician self-efficacy for LST decision making. Conclusions: Time-limited trials of LST at the LI-AMC and open-ended use of LST at the HI-AMC explain some of the AMCs' nationally profiled differences in end-of-life ICU use.

Intensive care medicine · cohort or longitudinal · 86 citationsread the source →

Spanish-Latin American multicenter study of attitudes toward organ donation among personnel from hospital healthcare centers.

Introduction: Hospital personnel are a group which has an influence on the opinion of the rest of the population about healthcare matters. Any unfavorable attitude of this group would be an obstacle to an increase in organ donation. Objective: To analyze the attitude of hospital workers toward the donation of one's own organs in Spanish and Latin American hospitals and to determine the factors affecting this attitude. Material and method: Eleven hospitals from the "International Collaborative Donor Project" were selected, 3 in Spain, 5 in Mexico, 2 in Cuba and one in Costa Rica. A random sample was stratified by the type of service and job category. Attitude toward donation and transplantation was assessed using a validated survey. The questionnaire was completed anonymously and was self-administered. Statistical analysis: Student's t-test, the χ2 test and logistic regression analysis. Results: Of the 2,785 workers surveyed, 822 were from Spain, 1,595 from Mexico, 202 from Cuba and 166 from Costa Rica and 79% (n=2,191) were in favor of deceased organ donation. According to country, 94% (n=189) of Cubans were in favor, compared to 82% (n=1,313) of the Mexicans, 73% (n=121) of the Costa Ricans and 69% (n=568) of the Spanish (P<.001). In the multivariate analysis, the following variables had the most specific weight: 1) originating from Cuba (odds ratio=8.196; P<.001); 2) being a physician (OR= 2.544; P<.001); 3) performing a job related to transplantation (OR = 1.610; P=.005); 4) having discussed the subject of donation and transplantation within the family (OR= 3.690; P<.001); 5) having a partner with a favorable attitude toward donation and transplantation (OR= 3.289; P<.001); 6) a respondent's belief that his or her religion is in favor of donation and transplantation (OR= 3.021; P=.001); 7) not being concerned about the possible mutilation of the body after donation (OR= 2.994; P<.001); 8) the preference for other options apart from burial for treating the body after death (OR= 2.770; P<.001); and 9) acceptance of carrying out an autopsy if one were needed (OR= 2.808; P<.001). Conclusions: Hospital personnel in Spanish and Latin American healthcare centers had a favorable attitude toward donation, although 21% of respondents were not in favor of donating. This attitude was more favorable among Latin American workers and was very much conditioned by job-related and psychosocial factors.

Cirugia espanola · cohort or longitudinal · 40 citationsread the source →

The neighborhood social environment and physical activity: a systematic scoping review.

Background: Investigating the association of the neighborhood social environment on physical activity is complex. A systematic scoping review was performed to (1) provide an inventory of studies assessing the influence of the neighborhood social environment on physical activity since 2006; (2) describe methodologies employed; and (3) formulate recommendations for the field. Methods: Two databases were searched using terms related to 'physical activity,' 'neighborhood,' and 'social environment' in January 2017. Eligibility criteria included: 1) physical activity as an outcome; 2) neighborhood social environment as a predictor; 3) healthy population (without diagnosed clinical condition or special population); 4) observational or experimental design. Of 1352 studies identified, 181 were included. Textual data relevant to the social environment measurement and analysis were extracted from each article into qualitative software (MAXQDA) and coded to identify social environmental constructs, measurement methods, level of measurement (individual vs. aggregated to neighborhood), and whether authors explicitly recognized the construct as the social environment. The following measures were generated for each construct: number of unique measurements; % of times measured at an aggregate level; % of times authors referred to the construct as the social environment. Social environmental constructs were then grouped into larger descriptive dimensions. Results/findings: Fifty-nine social environmental constructs were identified and grouped into 9 dimensions: Crime & Safety (n = 133 studies; included in 73% of studies); Economic & Social Disadvantage (n = 55, 33%); Social Cohesion & Capital (n = 47, 26%); Social Relationships (n = 22, 12%); Social Environment (n = 16, 9%); Disorder & Incivilities (n = 15, 8%); Sense of Place/Belonging (n = 8, 4%); Discrimination/Segregation (n = 3, 2%); Civic Participation & Engagement (n = 2, 1%). Across all articles, the social environment was measured using 176 different methods, was measured at an aggregate-level 38% of the time, and referred to as the social environment 23% of the time. Conclusions: Inconsistent terminology, definitions, and measurement of the social environment and the lack of explicit language identifying constructs as the social environment make it challenging to compare results across studies and draw conclusions. Improvements are needed to increase our understanding of social environmental correlates and/or determinants of physical activity and facilitate cross-disciplinary conversations necessary to effectively intervene to promote physical activity. Trial registration: PROSPERO CRD42017059580.

The international journal of behavioral nutrition and physical activity · review · 81 citationsread the source →

Carbamylated low-density lipoprotein induces oxidative stress and accelerated senescence in human endothelial progenitor cells.

Carbamylated low-density lipoprotein (cLDL) plays a role in atherosclerosis. In this study we evaluate the effect of uremia on LDL carbamylation and the effect of cLDL and oxidized LDL (oxLDL; 200 μg/ml) on number, function, and genomic stability of endothelial progenitor cells (EPCs) obtained from healthy volunteers. cLDL was generated after incubation of native LDL (nLDL) with uremic serum from patients with chronic kidney disease (CKD) stages 2-4. Oxidative stress was measured by flow cytometry and fluorescent microscopy, mitochondrial depolarization by flow cytometry, senescence by β-galactosidase activity and telomere length, and DNA damage by phosphorylated histone H2AX (γH2AX). The percentage of cLDL by uremic serum was related to the severity of CKD. Compared with nLDL, cLDL induced an increase in oxidative stress (62±5 vs. 8±3%, P<0.001) and cells with mitochondrial depolarization (73±7 vs. 9±5%, P<0.001), and a decrease in EPC proliferation and angiogenesis. cLDL also induced accelerated senescence (73±16 vs. 12±9%, P<0.001), which was associated with a decrease in the expression of γH2AX (62±9 vs. 5±3%, P<0.001). The degree of injury induced by cLDL was comparable to that observed with oxLDL. This study supports the hypothesis that cLDL triggers genomic damage in EPCs, resulting in premature senescence. We can, therefore, hypothesize that EPCs injury by cLDL contributes to an increase in atherosclerotic disease in CKD.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 71 citationsread the source →

Attitudes and beliefs about deceased organ donation in the Arabic-speaking community in Australia: a focus group study.

Objectives: To describe the beliefs and attitudes to organ donation in the Arabic-speaking community. Design: Arabic-speaking participants were purposively recruited to participate in 6 focus groups. Transcripts were analysed thematically. Participants: 53 participants, aged 19-77 years, and originating from 8 countries, participated in 1 of 6 focus groups. Participants identified as Christian (73%), Islam (26%), Buddhist (2%) or did not identify with any religion (2%). Results: 6 themes (with subthemes) were identified; religious conviction; invisibility of organ donation; medical suspicion; owning the decision; and reciprocal benefit. Conclusions: Although organ donation is considered a generous life-saving 'gift', representative members of the Arabic-speaking community in Australia were unfamiliar with, unnerved by and sceptical about the donation process. Making positive decisions about organ donation would likely require resolving tensions between respecting family, community and religious values versus their individual autonomy. Providing targeted education about the process and benefits of organ donation within the Arabic community may clarify ambiguities surrounding cultural and religious-based views on organ donation, reduce taboos and suspicion towards donation, and in turn, lead to increased organ donation rates.

BMJ open · 26 citationsread the source →

Contribution of risk factors to excess mortality in isolated and lonely individuals: an analysis of data from the UK Biobank cohort study.

Background: The associations of social isolation and loneliness with premature mortality are well known, but the risk factors linking them remain unclear. We sought to identify risk factors that might explain the increased mortality in socially isolated and lonely individuals. Methods: We used prospective follow-up data from the UK Biobank cohort study to assess self-reported isolation (a three-item scale) and loneliness (two questions). The main outcomes were all-cause and cause-specific mortality. We calculated the percentage of excess risk mediated by risk factors to assess the extent to which the associations of social isolation and loneliness with mortality were attributable to differences between isolated and lonely individuals and others in biological (body-mass index, systolic and diastolic blood pressure, and handgrip strength), behavioural (smoking, alcohol consumption, and physical activity), socioeconomic (education, neighbourhood deprivation, and household income), and psychological (depressive symptoms and cognitive capacity) risk factors. Findings: 466 901 men and women (mean age at baseline 56·5 years [SD 8·1]) were included in the analyses, with a mean follow-up of 6·5 years (SD 0·8). The hazard ratio for all-cause mortality for social isolation compared with no social isolation was 1·73 (95% CI 1·65-1·82) after adjustment for age, sex, ethnic origin, and chronic disease (ie, minimally adjusted), and was 1·26 (95% CI 1·20-1·33) after further adjustment for socioeconomic factors, health-related behaviours, depressive symptoms, biological factors, cognitive performance, and self-rated health (ie, fully adjusted). The minimally adjusted hazard ratio for mortality risk related to loneliness was 1·38 (95% CI 1·30-1·47), which reduced to 0·99 (95% CI 0·93-1·06) after full adjustment for baseline risks. Interpretation: Isolated and lonely people are at increased risk of death. Health policies addressing risk factors such as adverse socioeconomic conditions, unhealthy lifestyle, and lower mental wellbeing might reduce excess mortality among the isolated and the lonely. Funding: Academy of Finland, NordForsk, and the UK Medical Research Council.

The Lancet. Public health · 295 citationsread the source →

Social inequalities in multimorbidity, frailty, disability, and transitions to mortality: a 24-year follow-up of the Whitehall II cohort study.

Background: Social inequalities in mortality persist in high-income countries with universal health care, and the mechanisms by which these inequalities are generated remain unclear. We aimed to examine whether social inequalities were present before or after the onset of adverse health conditions (multimorbidity, frailty, and disability). Methods: Our analysis was based on data from the ongoing Whitehall II cohort study, which enrolled British civil servants aged 35-55 years in 1985-88. Participants were assessed for three indicators of socioeconomic status (education, occupational position, and literacy) at age 50 years. Participants underwent clinical examinations (in 2002-04, 2007-09, 2012-13, and 2015-16) for assessment of frailty (two or more of low physical activity, slow walking speed, poor grip strength, weight loss, and exhaustion) and disability (two or more difficulties in bathing, dressing, going to the toilet, transferring, feeding, and walking). In addition, electronic health records were used to assess the incidence of multimorbidity (two or more of diabetes, coronary heart disease, stroke, chronic obstructive pulmonary disease, depression, arthritis, cancer, dementia, and Parkinson's disease) and mortality. In analyses adjusted for sociodemographic factors, we used multistate models to examine social inequalities in transitions from healthy state to adverse health conditions and subsequently to mortality. Findings: Of 10 308 individuals in the Whitehall II study cohort, 6425 had relevant data available at 50 years and to the end of follow-up on Aug 31, 2017, and were included in our analysis. Participants were followed up for a median of 23·6 years (IQR 19·6-28·9). 1694 (26·4%) of 6425 participants developed multimorbidity, 1733 (27·0%) became frail, 692 (10·8%) had a disability, and 611 (9·5%) died. Multimorbidity (hazard ratio [HR] 4·12 [95% CI 3·41-4·98]), frailty (HR 2·38 [95% CI 1·93-2·93]), and disability (HR 1·73 [95% CI 1·34-2·22]) were associated with increased risk of mortality; these associations were not modified by socioeconomic status. In multistate models, occupation was the socioeconomic status indicator that was most strongly associated with inequalities in the transition from healthy state to multimorbidity (HR 1·54 [95% CI 1·37-1·73]), to frailty (HR 2·08 [95% CI 1·85-2·33]), and to disability (HR 1·44 [95% CI 1·18-1·74]). Socioeconomic status indicators did not affect transitions to mortality in those with multimorbidity, frailty, or disability. Interpretation: Socioeconomic status affects the risk of multimorbidity, frailty, and disability, but does not affect the risk of mortality after the onset of these adverse health conditions. Therefore, primary prevention is key to reducing social inequalities in mortality. Of the three adverse health conditions, multimorbidity had the strongest association with mortality, making it a central target for improving population health. Funding: UK Medical Research Council; National Institute on Aging, National Institutes of Health; British Heart Foundation.

The Lancet. Public health · 239 citationsread the source →

Reproductive agency and the acceptability of divorce, abortion, and homosexuality among migrants from the Middle East and Africa living in Sweden-a cross-sectional analysis.

Background: Sweden has a longstanding history of promoting sexual reproductive health and rights. Reproductive decision-making is a fundamental right, but an individual's decision-making power differs across contexts. We examined self-reported reproductive agency and the acceptability of divorce, abortion and homosexuality among migrants in Sweden originating from the Middle East or North Africa (MENA) and Sub-Saharan Africa (SSA). Methods: This cross-sectional study used face-to-face interview data from the 2018-2019 Migrant World Values Survey (MWVS) and included individuals 18-49 years old who migrated to Sweden from MENA or SSA. Partial proportional odds models were used to estimate adjusted odds ratios (aOR) and corresponding confidence intervals (CI) of associations between sociodemographic factors and two outcomes: 1) reproductive agency (decision-making power on when, with whom, and how many children to have), measured on a 10-point scale categorized as low (1-4), moderate (5-7), and high (8-10); and 2) the Choice Sub-Index (CSI), a composite index of the acceptability of divorce, abortion, and homosexuality, categorized as 0- < 0.4 (low), 0.4- < 0.7 (moderate), and 0.7-1.0 (high). Results: Between September 2018 and November 2019, 7991 participants responded to the MWVS, of whom 4669 met the inclusion criteria. Almost 3/4 (73%) of respondents expressed a high degree of reproductive agency, but less than five per cent of respondents had a high value on the CSI. Living in Sweden ≥ 4 years was associated with higher values on the CSI (aOR 1.76, 95% CI 1.15-2.67), while identifying as Muslim was associated with having a low value on the CSI (aOR 0.44, 95% CI 0.32-0.63). Neither duration of time in Sweden nor identifying as Muslim were associated with reproductive agency. Age and reason for migration (family reunification or as a refugee) were not associated with either outcome. Conclusion: Our study found that migrants from MENA and SSA expressed a high degree of reproductive agency. Migrants had low values of a combined measure of the acceptability of divorce, abortion and homosexuality; however, acceptance increased with time spent in Sweden. Understanding factors associated with migrants' sense of reproductive agency and their values and how these change over time in Sweden provides a foundation for working towards equitable sexual and reproductive health and rights.

International journal for equity in healthread the source →

Exploring Proof of Concept for a Novel Web-Based Self-Management Support Intervention for Polycystic Ovary Syndrome: Multimethod Study.

Background: Polycystic ovary syndrome (PCOS) is a common chronic hormonal condition affecting 8%-13% of women and individuals assigned female at birth. Symptoms may include subfertility, menstrual, skin, and metabolic problems, with long-term health risks including diabetes and cardiovascular disease. PCOS has a significant negative impact on mental health, quality of life, and well-being. We explored proof of concept for a web-based self-management support intervention, "Hope PCOS," designed to reduce anxiety and depression and increase positive well-being for women living with PCOS. Objective: We aim to pilot the intervention to test feasibility for web-based recruitment and delivery, acceptability, and potential to reduce anxiety and depression and increase positive well-being. Methods: Women with PCOS were recruited via social media with support from a patient advocacy charity and offered places on a 6-session cohort of the intervention. In a pre-post design, participants reported depression (Patient Health Questionnaire 9-Items), anxiety (Generalized Anxiety Disorder 7-Items), well-being (Warwick-Edinburgh Mental Wellbeing Scale), hope (SHS [State Hope Scale]), and gratitude (GQ-6 [Gratitude Questionnaire]) at baseline and 6 weeks. All participants who accessed 3 or more sessions were invited to a follow-up qualitative interview to explore user experience. Data from 8 interviews were thematically analyzed, and pre-post data were explored with descriptive statistics. Results: A total of 63 eligible women responded and were given access to the intervention. Three withdrew, leaving a baseline sample of 60, aged 20-58 (median 30, IQR 25-36) years. Further, 48 of the 60 started, of whom 46% (22/48) completed at least 3 sessions, and 29% (14/48) completed all 6. Additionally, 8 women (aged 25-38, median 29, IQR 26-35) years who completed between 3 and 6 sessions reported acceptability and experiences in exit interviews, including prioritizing self-care, developing a self-management mindset, setting motivating goals, improved mental health, self-compassion, reduced shame, openness about PCOS, preparedness for future health concerns, and continuing practice to consolidate behavior change. Furthermore, 11 women aged 25-43 (median 31, IQR 27-37) years, who completed 1-6 sessions (median 6, IQR 6-6), completed pre- and postintervention outcomes. Descriptive quantitative analysis indicated decreases in anxiety and depression and increases in hope agency, hope pathways, and gratitude. There was a meaningful (≥3 points) increase in well-being. Among patients with baseline and follow-up data, 73% (8/11) met clinical caseness for depression at baseline and 36% (4/11) post intervention. Conclusions: We explored proof of concept. Web-based recruitment and delivery online were feasible. We detected early signs of acceptability and potential benefits for anxiety, depression, and positive well-being that warrant testing in a controlled trial. Future research should assess the feasibility of a randomized controlled trial to evaluate effectiveness, acceptability, and cost-effectiveness.

JMIR formative researchread the source →

A Novel Multimodal Digital Service (Moderated Online Social Therapy+) for Help-Seeking Young People Experiencing Mental Ill-Health: Pilot Evaluation Within a National Youth E-Mental Health Service.

Background: Mental ill-health is the leading cause of disability worldwide. Moreover, 75% of mental health conditions emerge between the ages of 12 and 25 years. Unfortunately, due to lack of resources and limited engagement with services, a majority of young people affected by mental ill-health do not access evidence-based support. To address this gap, our team has developed a multimodal, scalable digital mental health service (Enhanced Moderated Online Social Therapy [MOST+]) merging real-time, clinician-delivered web chat counseling; interactive user-directed online therapy; expert and peer moderation; and peer-to-peer social networking. Objective: The primary aim of this study is to ascertain the feasibility, acceptability, and safety of MOST+. The secondary aims are to assess pre-post changes in clinical, psychosocial, and well-being outcomes and to explore the correlations between system use, perceived helpfulness, and secondary outcome variables. Methods: Overall, 157 young people seeking help from a national youth e-mental health service were recruited over 5 weeks. MOST+ was active for 9 weeks. All participants had access to interactive online therapy and integrated web chat counseling. Additional access to peer-to-peer social networking was granted to 73 participants (46.5%) for whom it was deemed safe. The intervention was evaluated via an uncontrolled single-group study. Results: Overall, 93 participants completed the follow-up assessment. Most participants had moderate (52/157, 33%) to severe (96/157, 61%) mental health conditions. All a priori feasibility, acceptability, and safety criteria were met. Participants provided mean scores of ≥3.5 (out of 5) on ease of use (mean 3.7, SD 1.1), relevancy (mean 3.9, SD 1.0), helpfulness (mean 3.5, SD 0.9), and overall experience (mean 3.9, SD 0.8). Moreover, 98% (91/93) of participants reported a positive experience using MOST+, 82% (70/93) reported that using MOST+ helped them feel better, 86% (76/93) felt more socially connected using it, and 92% (86/93) said they would recommend it to others. No serious adverse events or inappropriate use were detected, and 97% (90/93) of participants reported feeling safe. There were statistically significant improvements in 8 of the 11 secondary outcomes assessed: psychological distress (d=-0.39; P<.001), perceived stress (d=-0.44; P<.001), psychological well-being (d=0.51; P<.001), depression (d=-0.29; P<.001), loneliness (d=-0.23; P=.04), social support (d=0.30; P<.001), autonomy (d=0.36; P=.001), and self-competence (d=0.30; P<.001). There were significant correlations between system use, perceived helpfulness, and a number of secondary outcome variables. Conclusions: MOST+ is a feasible, acceptable, and safe online clinical service for young people with mental ill-health. The high level of perceived helpfulness, the significant improvements in secondary outcomes, and the correlations between indicators of system use and secondary outcome variables provide initial support for the therapeutic potential of MOST+. MOST+ is a promising and scalable platform to deliver standalone e-mental health services as well as enhance the growing international network of face-to-face youth mental health services.

Journal of medical Internet research · 74 citationsread the source →

Long-term developmental effect of withholding parenteral nutrition in paediatric intensive care units: a 4-year follow-up of the PEPaNIC randomised controlled trial.

Background: The PEPaNIC randomised controlled trial, which recruited 1440 critically ill infants and children in 2012-15, showed that withholding parenteral nutrition for 1 week (late-parenteral nutrition), compared with early supplementation within 24 h of admission to the paediatric intensive care unit (early-parenteral nutrition), prevented infections, accelerated recovery, and improved neurocognitive development assessed 2 years later. Because several neurocognitive domains can only be thoroughly assessed from age 4 years onwards, we aimed to determine the effect of late-parenteral nutrition versus early-parenteral nutrition on physical, neurocognitive, and emotional and behavioural development 4 years after randomisation. Methods: This is a preplanned, blinded, 4-year follow-up study of participants included in the PEPaNIC trial (done at University Hospitals Leuven, Belgium; Erasmus Medical Centre Sophia Children's Hospital, Rotterdam, Netherlands; and Stollery Children's Hospital, Edmonton, AB, Canada) and of matched healthy children. Studied outcomes were anthropometrics; health status; parent-reported or caregiver-reported executive functions, and emotional and behavioural problems; and clinical tests for intelligence, visual-motor integration, alertness, motor coordination, and memory. Through multivariable linear and logistic regression analyses, after imputation for missing values (≤30%) and adjustment for risk factors, we investigated the effect of early-parenteral nutrition versus late-parenteral nutrition. This trial is registered with ClinicalTrials.gov, NCT01536275. Findings: Between March 8, 2016, and Nov 8, 2019, 684 children from the original PEPaNIC trial (356 from the late-parenteral nutrition group and 328 from the early-parenteral nutrition group) were assessed for neurocognitive development at 4-years follow-up. Compared with the control group (369 healthy children), children who had critical illness had lower height (β-estimate -2·11 [95% CI -3·15 to -1·06]; p<0·0001) and head circumference (-0·42 [-0·67 to -0·18]; p=0.00077); and worse health status (eg, hospital admission odds ratio 4·27 [95% CI 3·12 to 5·84]; p<0·0001), neurocognitive (eg, parent-reported or caregiver-reported total executive functioning β-estimate 3·57 [95% CI 1·95 to 5·18], p<0·0001; total intelligence quotient -7·35 [-9·31 to -5·39], p<0·0001), and parent-reported or caregiver-reported emotional and behavioural developmental outcomes (internalising 2·73 [1·19 to 4·28], p=0·00055; externalising 1·63 [0·19 to 3·08], p=0·027; and total behavioural problems 2·95 [1·44 to 4·46], p=0·00013), adjusted for risk factors. Outcomes were never worse in the late-parenteral nutrition group compared with the early-parenteral nutrition group, but patients in the late-parenteral nutrition group had fewer parent-reported or caregiver-reported internalising (β-estimate -1·88 [95% CI -3·69 to -0·07]; p=0·042), externalising (-1·73 [-3·43 to -0·03]; p=0·046), and total emotional and behavioural problems (-2·44 [-4·22 to -0·67]; p=0·0070) than patients who had received early-parenteral nutrition, after adjusting for risk factors, and were no longer different from healthy controls for these outcomes. Interpretation: Omitting early parenteral nutrition use for critically ill children did not adversely affect long-term outcomes 4 years after randomisation and protected against emotional and behavioural problems, further supporting the deimplementation of early parenteral nutrition. Funding: European Research Council, Methusalem, Flanders Institute for Science and Technology, Research Foundation Flanders, Sophia Foundation, Stichting Agis Zorginnovatie, Erasmus Trustfonds, and the European Society for Clinical Nutrition and Metabolism.

The Lancet. Child & adolescent health · 46 citationsread the source →

Impact of the COVID-19 pandemic and lockdown restrictions on psychosocial and behavioural outcomes among Australian adults with type 2 diabetes: Findings from the PREDICT cohort study.

Aim: To examine psychosocial and behavioural impacts of the novel coronavirus disease 2019 (COVID-19) pandemic and lockdown restrictions among adults with type 2 diabetes. Methods: Participants enrolled in the PRogrEssion of DIabetic ComplicaTions (PREDICT) cohort study in Melbourne, Australia (n = 489 with a baseline assessment pre-2020) were invited to complete a phone/online follow-up assessment in mid-2020 (i.e., amidst COVID-19 lockdown restrictions). Repeated assessments that were compared with pre-COVID-19 baseline levels included anxiety symptoms (7-item Generalised Anxiety Disorder scale [GAD-7]), depressive symptoms (8-item Patient Health Questionnaire [PHQ-8]), diabetes distress (Problem Areas in Diabetes scale [PAID]), physical activity/sedentary behaviour, alcohol consumption and diabetes self-management behaviours. Additional once-off measures at follow-up included COVID-19-specific worry, quality of life (QoL), and healthcare appointment changes (telehealth engagement and appointment cancellations/avoidance). Results: Among 470 respondents (96%; aged 66 ± 9 years, 69% men), at least 'moderate' worry about COVID-19 infection was reported by 31%, and 29%-73% reported negative impacts on QoL dimensions (greatest for: leisure activities, feelings about the future, emotional well-being). Younger participants reported more negative impacts (p < 0.05). Overall, anxiety/depressive symptoms were similar at follow-up compared with pre-COVID-19, but diabetes distress reduced (p < 0.001). Worse trajectories of anxiety/depressive symptoms were observed among those who reported COVID-19-specific worry or negative QoL impacts (p < 0.05). Physical activity trended lower (~10%), but sitting time, alcohol consumption and glucose-monitoring frequency remained unchanged. 73% of participants used telehealth, but 43% cancelled a healthcare appointment and 39% avoided new appointments despite perceived need. Conclusions: COVID-19 lockdown restrictions negatively impacted QoL, some behavioural risk factors and healthcare utilisation in adults with type 2 diabetes. However, generalised anxiety and depressive symptoms remained relatively stable.

Diabetic medicine : a journal of the British Diabetic Association · 50 citationsread the source →

Combat sports and wellbeing: advancing health and inclusion in athletes and practitioners. An opinion paper

Historically, combat sports have been predominantly conceptualized within the framework of elite competition, emphasizing physical aptitude, technical proficiency, and strategic execution (1-3). Despite their traditional and peculiar constitutions and developments, disciplines such as judo, karate, taekwondo, wrestling, fencing, boxing, and mixed martial arts have commonly been associated with high-performance athletes striving for competitive excellence on national and international stages (1, 4-6). However, contemporary discourse increasingly recognizes their expansive role in contributing to physical and psychological well-being, and social inclusion of the practitioners (7, 8). This paradigmatic shift underscores the capacity of combat sports to function as inclusive and accessible modalities for fostering multidimensional health benefits across diverse populations, including individuals with disabilities and other marginalized groups (9-13).The interdisciplinary exploration of physical activity and health highlights the intricate interrelationship between structured sports engagement and holistic well-being (14). Whilst conventional team and individual sports have long been acknowledged for their physiological and psychosocial benefits, combat sports exhibit distinct characteristics that might amplify these advantages (15, 16). Within combat sports, the synergistic interplay of rigorous physical conditioning, the cognitive engagement, adherence to rules, competition dynamics, respect, externalizing emotions regulation, are intertwined with pedagogical and philosophical values, thus presenting a unique framework for enhancing psychological resilience, cognitive adaptability, and emotional control. Consequently, the systematic practice of combat sports has been increasingly examined as a way of promoting mental health, stress modulation, and social cohesion (17, 18).The inclusive nature of many combat sports programmes further accentuates their relevance in dismantling stereotypes, facilitating integration, and fostering equity and social integration (19-21). In fact, they demonstrated significant adaptability to accommodate individuals with disabilities (e.g., physical impairments, developmental, emotional, intellectual disorders), thereby ensuring equitable access and fostering empowerment (9, 22). Adapted judo, para-taekwondo, and other modified combat disciplines provide individuals with disabilities a structured platform to engage in physical activity, cultivate self-efficacy, and develop meaningful social connections within a supportive and adaptive environment (23). From a public health perspective, the integration of combat sports within community-based health initiatives offers a compelling opportunity to engage populations that may not traditionally participate in structured physical activity programmes (7, 8, 19). The distinctive accessibility of combat sports, which cater to practitioners of all skill levels (e.g., from novices to elite athletes) sets them apart from many other sports. While their structured progression, adaptability, and emphasis on holistic development make them a viable option for lifelong and intergenerational participation (19, 24, 25), the mentorship and pedagogical frameworks cultivate positive role modeling, discipline, and intrinsic motivation, which are integral for sustaining long-term adherence to health-promoting behaviors (8).Furthermore, the intersection between combat sports and mental health has increasingly emerged as a focal point within academic and clinical research (17) with empirical evidence suggesting an association between participation and enhanced self-regulation and self-efficacy, and reduction in anxiety and depressive symptomatology (8, 26, 27). In necessitating sustained focus, adaptability, and emotional equilibrium, combat sports inherently require cognitive and affective demands, which align closely with established psychological frameworks that underpin mental well-being (28, 29). Moreover, the integration of mindfulness techniques, stress management strategies, and resilience-building paradigms within combat sports training substantiates their potential as a non-pharmacological intervention for addressing various mental health challenges (e.g., autism spectrum and oppositional defiant disorders) (30, 31).Despite these advantages, the discourse surrounding combat sports and well-being necessitates a critical examination of inherent risks and potential challenges. Issues related to injury risk, hypercompetitive environments, eating disorders, sexual harassment, and the psychological stressors associated with high-intensity training warrant careful scrutiny (32-36). The implementation of evidence-based injury prevention protocols, the establishment of ethically responsible coaching methodologies, and the promotion of safe training environments are imperative to ensure that the benefits of combat sports are maximized while minimizing adverse outcomes. Against this backdrop, this opinion paper seeks to examine the role of combat sports in advancing health and social inclusion among athletes and practitioners. Through a synthesis of contemporary empirical findings, theoretical paradigms, and applied insights, this paper aims to contribute to the evolving discourse on the potential of combat sports as a catalyst for holistic well-being. By delineating the multidimensional impact of combat sports on physical, psychological, and social health, this paper endeavors to underscore their transformative potential as an instrument for fostering individual and community well-being within different populations. DiscussionWhilst an expanding body of research and an evolution in scholarly discourse is recognizing the combat sports’ broader implications for holistic well-being (30, 37), a rigorous evaluation of the investigation methodologies, the validity of hypotheses, and the translational potential of recent findings is necessary to contextualize their significance within the sports and public health sciences, considering their strengths, weaknesses, opportunities, and threats (Figure 1).----------------------------------------ADD FIGURE 1 ABOUT HERE----------------------------------------Empirical evidence robustly shows the positive impact of combat sports on physical fitness, motor coordination, and cardiovascular health (3, 38). These benefits are attributed to the high-intensity, intermittent nature of combat sports training, which enhances aerobic and anaerobic endurance, muscular strength, and neuromuscular control (39). However, concerns regarding injury risk, particularly in striking and contact-intensive disciplines such as boxing, taekwondo, and mixed martial arts, necessitate continued research into injury mitigation strategies, particularly those targeting concussion and repetitive head trauma (6, 35, 40, 41). Moreover, many combat sports have developed styles with reduced or simulated contact to minimize injury risk. For example, the French "boxe éducative" emphasizing technique and control, penalizing any violent behaviors (42) and the value and application of kata (i.e., forms; prearranged, pattern practices) to learning and adopting judo technique in a safe way educating the athlete culturally, to enrich her/him as a person (43).Beyond physical health, recent studies highlight the psychological benefits of combat sports, including reductions in anxiety and depression and improvements in self-efficacy, emotional regulation, resilience, and stress management (27, 44-47). Therefore, combat sports-based interventions for individuals with mental health conditions have yielded promising outcomes (23). Despite these encouraging findings, variability in study designs, participant demographics, and intervention protocols limits their external validity, underscoring the need for further rigorously controlled investigations. Furthermore, some authors claimed that combat sport athletes might present symptoms of low energy availability and high anxiety levels associated with competition- and injury-related psychological stressors, deficits in executive functions and neuropsychological impairments associated with occurrence of concussions, disordered eating and eating disorders associated with weight-loss, and might suffer offensive, frightening, hostile, degrading, humiliating experiences, or sexual harassment, which urge safeguarding actions (32-36).The role of combat sports in fostering social inclusion has gained empirical support, particularly in programmes aimed at individuals with disabilities and marginalized communities (25, 48). For instance, a recent systematic review shows that judo interventions adapted for intellectual disabilities help improve social integration and self-perception and enhance participants' quality of life (49). The development of para-combat sports demonstrates enhanced physical and motor abilities while providing psychosocial benefits to various populations with different disabilities, promoting social integration, self-perception, and community belonging (50, 51). However, longitudinal research is needed to assess the long-term retention rates and sustainability of these benefits. Furthermore, there is a need of studies focused on the most appropriate adapted rules to achieve a fairer competition for ensuring a sense of success in individuals with physical, emotional, mental, hearing or visual impairments participating in adapted sports competitions at local, national, and international levels. Methodological approaches in combat sports research encompass experimental, longitudinal, qualitative, and systematic review designs. While randomized controlled trials remain the gold standard for establishing causality, their application in combat sports research is constrained by ethical concerns, logistical challenges, and the inherently dynamic nature of training environments (52, 53). Consequently, many studies rely on observational designs, which, despite their value in identifying associations, are susceptible to confounding variables and biases (24, 54).Qualitative methodologies have provided critical insights into the lived experiences of combat sports practitioners, offering perspectives on psychological and social dimensions that are often overlooked in quantitative studies (28). Ethnographic research has been particularly instrumental in elucidating the role of combat sports in shaping identity, discipline, and personal development (55). However, limitations in reproducibility and generalizability highlight the need for mixed-methods approaches to generate a more comprehensive understanding of combat sports' impact (25, 56).Additionally, the incorporation of biometric and neurocognitive assessments, such as heart rate variability analysis, functional MRI, and salivary cortisol measurements, has advanced our understanding of the physiological and psychological mechanisms underlying combat sports participation (47, 57, 58). Despite their objective precision, these techniques often face challenges related to cost, accessibility, and limited sample sizes, necessitating the development of scalable and cost-effective methodologies for broader research application. Finally, recent studies show that virtual reality (VR) technology and digital platforms are increasingly becoming part of combat sports training methods. Due to COVID-19 restrictions, martial arts schools and organizations implemented hybrid or online training models, which allowed athletes to stay engaged. VR boxing programmes provide users with virtual sparring simulations to enhance their motor skills without needing physical interaction. Initial results indicate that VR training enhances response behavior in karate athletes (59). Digital adaptations offer great potential, especially for people with limited mobility or remote locations. However, further studies are necessary to prove their enduring effects on physical health and psychological and social aspects (59-61).Strengths and Weaknesses of Scientific HypothesesThe hypothesis that combat sports confer multidimensional health benefits is strongly supported by empirical evidence spanning physiological, psychological, and social domains (8, 62-64). The integration of physical exertion, cognitive engagement, and structured discipline inherent in combat sports aligns with established theories of exercise psychology, neuroplasticity, and social identity formation (65, 66). This multidimensional perspective provides a robust theoretical foundation for advocating combat sports as a health-promoting activity. Nevertheless, several limitations warrant consideration. The heterogeneity of disciplines, which vary highly in intensity, contact level, and training methodologies, is often inadequately addressed in research, leading to overgeneralized conclusions (17, 39). Often underexamined, individual differences in personality, motivation, and previous trauma history may strongly moderate the psychological outcomes of combat sports participation (35, 67, 68).Additionally, a research focus is needed on concerns regarding the potential for adverse psychological effects (e.g., anxiety, depression, disordered eating behaviors, burnout, and decreased self-esteem), particularly in competitive environments where performance pressure, extreme weight-cutting practices, and aggressive coaching styles are prevalent (69, 70). Indeed, a balanced perspective that considers both benefits and risks is essential for the development of evidence-based recommendations (10, 71).Future DirectionsTo enhance the field, future research should prioritize well-structured longitudinal studies that assess the long-term impact of combat sports participation on physical, psychological, and social health. Standardization of outcome measures, intervention protocols, and participant demographics would facilitate cross-study comparisons and strengthen the reliability of findings (72, 73). Moreover, interdisciplinary collaborations incorporating sports science, psychology, and sociology could provide a more holistic perspective on combat sports' broader implications on practitioners (74).From a policy perspective, to yield valuable insights into combat sports’ practical applications research should investigate their efficacy within public health, educational, and rehabilitation initiatives, particularly for underserved and vulnerable populations (23, 75, 76).Furthermore, while safety remains a primary concern, advancements in protective equipment, training methodologies, education for athletes, coaches, referees and tournament directors, and regulatory frameworks should be continually evaluated to optimize benefits while mitigating risks (40, 41, 58, 77, 78). Ethical considerations, particularly concerning athlete well-being and inclusive participation, should remain a central focus in both research and practical implementation (17, 34, 36).Therefore, key research challenges to be addressed are: 1. Injury risk and safety: a need for injury prevention strategies, especially for concussions and head trauma in striking sports. 2. Psychological wellbeing: risks of stress, anxiety, burnout, and negative self-perception in competitive environments. 3. Inclusion and accessibility: a need for more research on long-term social and psychological benefits for marginalized groups and individuals with disabilities. 4. Methodological limitations: lack of standardized protocols, variability in study designs, and limited reproducibility of findings. 5. Ethical and regulatory issues: concerns over coaching practices, extreme weight-cutting, and athlete wellbeing in high-pressure environments. 6. Technological innovations: more research required on the effectiveness of VR and digital training tools in combat sports. 7. Public health and policy: exploration of combat sports' role in health initiatives, rehabilitation, and educational programs. ConclusionThe evolving discourse on combat sports highlights their potential as a multidimensional tool for well-being promotion. While a substantial body of evidence supports their benefits, a critical examination of methodological limitations, scientific hypotheses, and practical applications is essential for further refine our understanding and enhance their effectiveness. Finally, this article makes a significant contribution not only to the field of martial arts but also to public health and sports psychology. Its interdisciplinary approach calls for scientific collaboration and methodological rigor, reinforces the need for evidence-based policies and can serve as a valuable guide for researchers and policymakers looking to integrate combat sports into strategies for promoting health and social inclusion.

Frontiers in Psychology · 12 citationsread the source →

Are Mindfulness and Self-Compassion Associated with Sleep and Resilience in Health Professionals?

Objectives: To describe the relationship between trainable qualities (mindfulness and self-compassion), with factors conceptually related to burnout and quality of care (sleep and resilience) in young health professionals and trainees. Design: Cross-sectional survey. Setting: Large Midwestern academic health center. Participants: 213 clinicians and trainees. Outcome measures: Sleep and resilience were assessed by using the 8-item PROMIS Sleep scale and the 6-item Brief Resilience Scale. Mindfulness and self-compassion were assessed using the 10-item Cognitive and Affective Mindfulness Scale, Revised and the 12-item Self-Compassion Scale. Health was assessed with Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health measures, and stress was assessed with the 10-item Perceived Stress Scale. After examination of descriptive statistics and Pearson correlations, multiple regression analyses were done to determine whether mindfulness and self-compassion were associated with better sleep and resilience. Results: Respondents had an average age of 28 years; 73% were female. Professions included dieticians (11%), nurses (14%), physicians (38%), social workers (24%), and other (12%). Univariate analyses showed normative values for all variables. Sleep disturbances were significantly and most strongly correlated with perceived stress and poorer health, but also with less mindfulness and self-compassion. Resilience was strongly and significantly correlated with less stress and better mental health, more mindfulness, and more self-compassion. Conclusions: In these young health professionals and trainees, sleep and resilience are correlated with both mindfulness and self-compassion. Prospective studies are needed to determine whether training to increase mindfulness and self-compassion can improve clinicians' sleep and resilience or whether decreasing sleep disturbances and building resilience improves mindfulness and compassion.

Journal of alternative and complementary medicine (New York, N.Y.) · 120 citationsread the source →

Exceptional longevity in men: modifiable factors associated with survival and function to age 90 years.

Background: Prospective data on nongenetic determinants of exceptional longevity are limited, and information on long-lived men and their functional status is particularly sparse. We examined modifiable factors associated with a life span of 90 or more years and late-life function in men. Methods: In this prospective cohort study of 2357 healthy men (mean age, 72 years) within the Physicians' Health Study (1981-2006), biological and lifestyle factors and comorbid conditions were assessed by self-report with baseline and annual questionnaires. Mortality and incidence of major diseases were confirmed by medical record review. Late-life function was assessed 16 years after baseline by the Medical Outcomes Study 36-Item Short-Form Health Survey. Results: A total of 970 men (41%) survived to at least age 90 years. Smoking was associated with increased risk of mortality before age 90 years (hazard ratio [HR]; 2.10; 95% confidence interval [CI], 1.75-2.51), and similar associations were observed with diabetes (HR, 1.86; 95% CI, 1.52-2.26), obesity (HR, 1.44; 95% CI, 1.10-1.90), and hypertension (HR, 1.28; 95% CI, 1.15-1.43). Regular exercise was associated with a nearly 30% lower mortality risk (HR, 0.72; 95% CI, 0.62-0.83). The probability of a 90-year life span at age 70 years was 54% in the absence of smoking, diabetes, obesity, hypertension, or sedentary lifestyle. It ranged from 36% to 22% with 2 adverse factors and was negligible (4%) with 5. Compared with nonsurvivors, men with exceptional longevity had a healthier lifestyle (67% vs 53% had <or=1 adverse factor), had a lower incidence of chronic diseases, and were 3 to 5 years older at disease onset. They had better late-life physical function (mean +/- SD score [maximum 100], 73 +/- 23 vs 62 +/- 30; P < .001) and mental well-being (mean score, 84 +/- 14 vs 81 +/- 17; P = .03). More than 68% (vs 45%) rated their late-life health as excellent or very good, and less than 8% (vs 22%) reported fair or poor health (P < .001 for trend). Regular exercise was associated with significantly better-and smoking and overweight with significantly worse-late-life physical function. Smoking also was associated with a significant decrement in mental function. Conclusion: Modifiable healthy behaviors during early elderly years, including smoking abstinence, weight management, blood pressure control, and regular exercise, are associated not only with enhanced life span in men but also with good health and function during older age.

Archives of internal medicine · editorial or comment · 143 citationsread the source →

PATHOPHYSIOLOGY OF DEPRESSION: DO WE HAVE ANY SOLID EVIDENCE OF INTEREST TO CLINICIANS?

Major depressive disorder (MDD) is a common and costly disorder which is usually associated with severe and persistent symptoms leading to important social role impairment and increased mortality 1,2. It is one of the most important causes of disability worldwide 3. The high rate of inadequate treatment of the disorder remains a serious concern 1. This review is aimed at summarizing the solid evidence on the etiology and pathophysiology of MDD that is likely relevant for clinical psychiatry. Neurobiological findings are regarded as solid when they are consistent and convergent, i.e., they have been confirmed by several studies using the same method and fit into results from studies using different methodological approaches. Family, twin, and adoption studies provide very solid and consistent evidence that MDD is a familial disorder and that this familiality is mostly or entirely due to genetic factors 4. This important finding suggests that parental social behavior and other familial environmental risk factors are not as important in the pathogenesis of MDD as previously assumed and should not be the major focus of the treatment of the disorder. The above-mentioned studies consistently show that the influence of genetic factors is around 30–40% 4. Non-genetic factors, explaining the remaining 60–70% of the variance in susceptibility to MDD, are individual-specific environmental effects (including measurement error effects and gene-environment interactions). These effects are mostly adverse events in childhood and ongoing or recent stress due to interpersonal adversities, including childhood sexual abuse, other lifetime trauma, low social support, marital problems, and divorce 5,6. These results suggest that there is a huge potential in the prevention of MDD by means of psychosocial interventions (e.g., in schools, at workplace). In addition, these results mirror the clinical practice of empirically validated psychotherapies to treat depression 7,8,9, including interpersonal, psychodynamic and cognitive behavioral psychotherapies and cognitive behavioural analysis system of psychotherapy, which all focus directly or indirectly on interpersonal difficulties and skills. This does not exclude the fact that unidentified non-genetic, non-psychosocial risk factors may also play important roles in some patients (e.g., climatic change, medical conditions). Stress sensitivity in depression is partly gender-specific. While men and women are, in general, equally sensitive to the depressogenic effects of stressful life events, their responses vary depending upon the type of stressor. Specifically, men are more likely to have depressive episodes following divorce, separation, and work difficulties, whereas women are more sensitive to events in their proximal social network, such as difficulty getting along with an individual, serious illness, or death 10. These findings point to the importance of gender-sensitive psychosocial approaches in the prevention and treatment of MDD. In contrast to the very solid evidence from epidemiological studies on broad risk factor domains, there is no solid evidence for specific genes and specific gene-by-environment interactions in the pathogenesis of MDD. Genome-wide association studies have indicated that many genes with small effects are involved in complex diseases, increasing the difficulty in identifying such genes 11. While there has been progress in the search for risk genes for several complex diseases despite this methodological problem 12, psychiatric conditions have turned out to be very resistant to robust gene identification. For example, based on a community-based prospective study, it has been proposed that a specific genetic variation in the promoter region of the serotonin transporter (a target of antidepressant drugs) interacts with stressful life events in the pathogenesis of depression 13. Although there is high clinical and neurobiological plausibility of this interaction, a recent meta-analysis yielded no evidence that the serotonin transporter gene alone or in interaction with psychological stress was associated with the risk of depression 14. The limited success of genetic studies of depression has been related to use of current classification schemas including ICD-10 and DSM-IV. These diagnostic manuals are based on clusters of symptoms and characteristics of clinical course that do not necessarily describe homogenous disorders but instead reflect common final pathways of different pathophysiolgical processes 15,16. The clinician should be aware that family history will continue to be the most solid source of information to estimate the genetic risk of MDD. Corticotropin-releasing hormone (CRH) is released from the hypothalamus in response to the perception of psychological stress by cortical brain regions. This hormone induces the secretion of pituitary corticotropin, which stimulates the adrenal gland to release cortisol into the plasma. The physiologic response to stress is partly gender-specific: women show generally greater stress responsiveness than men, which is consistent with the greater incidence of major depression in women 17. Moreover, men show greater cortisol responses to achievement challenges, whereas women show greater cortisol responses to social rejection challenges 18. Although MDD is considered as a stress disorder, most subjects treated for MDD have no evidence of dysfunctions of the hypothalamic-pituitary-adrenal axis (HPA) 19. However, some subjects with MDD do show abnormalities of that axis and of the extrahypothalamic CRH system 20. Altered stress hormone secretion appeared to be most prominent in depressed subjects with a history of childhood trauma 21. Elevated cortisol may act as a mediator between major depression and its physical long-term consequences such as coronary heart disease, type II diabetes, and osteoporosis 22. The importance of HPA axis dysfunction for the efficacy of antidepressants is a matter of debate 23. This axis is regulated through a dual system of mineralocorticoid (MR) and glucocorticoid (GR) receptors. Decreased limbic GR receptor function 24,25 and increased functional activity of the MR system 26 suggest an imbalance in the MR/GR ratio in stress-related conditions such as MDD. Epigenetic regulation of the glucocorticoid receptors has been associated with childhood abuse 27. Such environmental programming of gene expression may represent one possible mechanism that links early life stress to abnormal HPA axis function and increased risk of MDD in adults. While the CRH stimulation test (dex/CRH test) 28 is a sensitive measure of the HPA axis dysfunction in depression, the specificity of this test for MDD is low. However, non-suppression in the dex/CRH test has consistently predicted increased risk for depressive relapse during clinical remission 23. Additionally, the measurement of waking salivary cortisol concentration has been shown to be a simple and sensitive test for HPA axis hyperactivity in depression 29. Hypercortisolemia is almost exclusively found in subjects with severe and psychotic depression, in whom glucocorticoid antagonists may have some therapeutic effect 30. There is convergent evidence for CRH to play a major role in the pathogenesis of certain types of depression. Levels of CRH in the cerebrospinal fluid are elevated in some depressed subjects 31. Post-mortem studies reported an increased number of CRH secreting neurons in limbic brain regions in depression 32, likely reflecting a compensatory response to increased CRH concentrations 33. In addition, CRH produces a number of physiological and behavioral alterations that resemble the symptoms of major depression, including decreased appetite, disrupted sleep, decreased libido, and psychomotor alterations 34. There is also preliminary evidence that CRH1 receptor antagonists reduce symptoms of depression and anxiety 35. “Sickness behavior” as a result of an activation of the inflammatory response system shares many symptoms with depression, including fatigue, anhedonia, psychomotor retardation, and cognitive impairment. Sickness is mediated by pro-inflammatory cytokines such as interleukin-1α, tumor necrosis factor-α, and interleukin-6, which activate the HPA axis and impair the central serotonin system 36. The prevalence of depression as an unwanted effect of recombinant interferons is around 30% 37. In animals, blocking pro-inflammatory cytokine-mediated signaling produces antidepressant-like effects 38. Clinical data suggest that cytokines may play a role in the pathophysiology of a subgroup of depressed subjects, particularly those with comorbid physical conditions 36. The antidepressant enhancing effect of acetylsalicylic acid 39 points to the possible clinical relevance of psychoneuroimmunology in clinical depression research. Taken together, the laboratory tests with the highest potential to be clinically useful in the care of depressed individuals are based on abnormalities of the neuroendocrine and neuroimmune systems. Despite the large amount of basic science data suggesting that the HPA axis is importantly involved in the pathophysiology of depression, the effect of pharmacological modulation of this neuroendocrine system as antidepressant therapy has been disappointing. The link between childhood trauma and a permanently altered physiologic stress system points to the use of specific psychotherapies in the treatment of depressed patients with a history of early life trauma 40. Most of the serotonergic, noradrenergic and dopaminergic neurons are located in midbrain and brainstem nuclei and project to large areas of the entire brain. This anatomy suggests that monoaminergic systems are involved in the regulation of a broad range of brain functions, including mood, attention, reward processing, sleep, appetite, and cognition. Almost every compound that inhibits monoamine reuptake, leading to an increased concentration of monoamines in the synaptic cleft, has been proven to be a clinically effective antidepressant 19. Inhibiting the enzyme monoamine oxidase, which induces an increased availability of monoamines in presynaptic neurons, also has antidepressant effects. These observations led to the pharmacologically most relevant theory of depression, referred to as the monoamine-deficiency hypothesis. The monoamine-deficiency theory posits that the underlying pathophysiological basis of depression is a depletion of the neurotransmitters serotonin, norepinephrine or dopamine in the central nervous system. Serotonin is the most extensively studied neurotransmitter in depression. The most direct evidence for an abnormally reduced function of central serotonergic system comes from studies using tryptophan depletion, which reduces central serotonin synthesis. Such a reduction leads to the development of depressive symptoms in subjects at increased risk of depression (subjects with MDD in full remission, healthy subjects with a family history of depression) 41,42, possibly mediated by increased brain metabolism in the ventromedial prefrontal cortex and subcortical brain regions 42. Experimentally reduced central serotonin has been associated with mood congruent memory bias, altered reward-related behaviors, and disruption of inhibitory affective processing 16, all of which add to the clinical plausibility of the serotonin deficiency hypothesis. There is also evidence for abnormalities of serotonin receptors in depression, with the most solid evidence pointing to the serotonin-1A receptor, which regulates serotonin function. Decreased availability of this receptor has been found in multiple brain areas of patients with MDD 43, although this abnormality is not highly specific for MDD and has been found in patients with panic disorder 44 and temporal lobe epilepsy 45, possibly contributing to the considerable comorbidity among these conditions. However, there is no explanation for the mechanism of serotonin loss in depressed patients, and studies of serotonin metabolites in plasma, urine and cerebrospinal fluid, as well as post-mortem research on the serotonergic system in depression, have yielded inconsistent results. There is preliminary evidence that an increased availability of the brain monoamine oxidase, which metabolizes serotonin, may cause serotonin deficiency 46. In addition, loss-of-function mutations in the gene coding for the brain-specific enzyme tryptophan hydroxylase-2 may explain the loss of serotonin production as a rare risk factor for depression 47. Dysfunction of the central noradrenergic system has been hypothesized to play a role in the pathophysiology of MDD, based upon evidence of decreased norepinephrine metabolism, increased activity of tyrosine hydroxylase, and decreased density of norepinephrine transporter in the locus coeruleus in depressed patients 48. In addition, decreased neuronal counts in the locus coeruleus, increased alpha-2 adrenergic receptor density, and decreased alpha-1 adrenergic receptor density have been found in the brains of depressed suicide victims post-mortem 49. Since there is no method to selectively deplete central norepinephrine and no imaging tool to study the central norepinephrine system, solid evidence for abnormalities of this system in depression is lacking. While the classical theories of the neurobiology of depression mainly focused on serotonin and norepinephrine, there is increasing interest in the role of dopamine 50. Dopamine reuptake inhibitors (e.g., nomifensine) and dopamine receptor agonists (e.g., pramipexole) had antidepressant effects in placebo-controlled studies of MDD 51. In the cerebrospinal fluid and jugular vein plasma, levels of dopamine metabolites were consistently reduced in depression, suggesting decreased dopamine turnover 52. Striatal dopamine transporter binding and dopamine uptake were reduced in MDD, consistent with a reduction in dopamine neurotransmission 53. Degeneration of dopamine projections to the striatum in Parkinson's disease was associated with a major depressive syndrome in about one half of cases, which usually preceded the appearance of motor signs 54. Experimentally reduced dopaminergic transmission into the accumbens has been associated with anhedonic symptoms and performance deficits on a reward processing task in subjects at increased risk of depression 55,56. These findings are consistent with the clinical observation that depressed patients have a blunted reaction to positive reinforcers and an abnormal response to negative feedback 57. Almost all established antidepressants target the monoamine systems 58. However, full and partial resistance to these drugs and their delayed onset of action suggest that dysfunctions of monoaminergic neurotransmitter systems found in MDD represent the downstream effects of other, more primary abnormalities. Despite this limitation, the monoamine-deficiency hypothesis has proved to be the most clinically relevant neurobiological theory of depression. New findings on the role of dopamine in depression emphasize the scientific potential of this theory, and promising reports of antidepressant effects of drugs that modulate the dopaminergic system (e.g., pramipexole, modafinil) in difficult-to-treat depression underline its clinical relevance 51,59. Although many historical attempts to localize mental functions have failed, they have considerably contributed to a modern neuroscientific understanding of mental disorders 60. The development of neuroimaging techniques has opened up the potential to investigate structural and functional abnormalities in living depressed patients. Unfortunately, the diversity of imaging techniques used, the relatively small and heterogeneous study samples studied, and the limited overlap of results across imaging paradigms 61 make it difficult to reliably identify neuronal regions or networks with consistently abnormal structure or function in MDD. Functional imaging studies have provided the most limited overlap of findings. This may be due to methodological limitations and/or the complexity of neurocircuitry involved in MDD. A recent meta-analytic study found the best evidence for abnormal brain activity in MDD in lateral frontal and temporal cortices, insula, and cerebellum. In these brain regions activity was decreased at rest, they showed a relative lack of activation during induction of negative emotions, and an increase in activity following treatment with serotonin reuptake inhibitors. Opposite changes may exist in ventromedial frontal areas, striatum and possibly other subcortical brain regions 61. More solid evidence has been provided by structural imaging and post-mortem studies. A recent meta-analytic study on brain volume abnormalities in MDD revealed relatively large volume reductions in the ventromedial prefrontal cortex, particularly in the left anterior cingulate and in the orbitofrontal cortex. Moderate volume reductions were found in the lateral prefrontal cortex, hippocampus and striatum 62. Post-mortem studies consistently identified a reduction in glia cell density in dorsal, orbital and subgenual prefrontal cortices, as well as in the amygdala 63,64. Overall, functional, structural and post-mortem studies suggest that structural and functional abnormalities in the left subgenual cingulate cortex are the most solid neuroanatomical finding in MDD. Volume reduction in this region was found early in illness and in young adults at high familial risk for MDD 65, suggesting a primary neurobiological abnormality associated with the etiology of the illness. Humans with lesions that include the subgenual prefrontal cortex showed abnormal autonomic responses to social stimuli 66, and rats with left-sided lesions in this region had increased sympathetic arousal and corticosterone responses to restraint stress 67. Most importantly, chronic deep brain stimulation to reduce the potentially elevated activity in the subgenual cingulated cortex produced clinical benefits in patients with treatment-resistant depression 68. In summary, despite the considerable heterogeneity of findings from neuroimaging studies, there is convergent evidence for the presence of abnormalities in the subgenual prefrontal cortex in some patients with MDD. Neuroanatomical research in depression is of great clinical interest, since novel antidepressant treatments such as deep brain stimulation can target specific brain regions. In addition, there are promising leads for neuroimaging findings to predict the likelihood of responses to specific treatments 69. Risk factors for depressive episodes change during the course of the illness. The first depressive episode is usually “reactive”, i.e., triggered by important psychosocial stressors, while subsequent episodes become increasingly “endogenous”, i.e., triggered by minor stressors or occurring spontaneously 70. There is consistent evidence that the volume loss of the hippocampus and other brain regions is related to the duration of depression 71, suggesting that untreated depression leads to hippocampal volume loss, possibly resulting in increased stress sensitivity 72 and increased risk of recurrence 73. Glucocorticoid neurotoxicity, glutamatergic toxicity, decreased neurotrophic factors, and decreased neurogenesis have been proposed as possible mechanisms explaining brain volume loss in depression. There is no solid evidence on of these since there are no imaging to directly and neurotrophic processes in neurotrophic factor has considerable Specifically, studies have shown between and in hippocampal as well as expression of following antidepressant treatment The clinician should be aware of the potentially effect of depression and treat depressed patients as early and as A of studies consistently showed reductions in acid concentrations in the prefrontal and cortex in depression This may reflect stress since psychological stress to presynaptic of prefrontal neurotransmission low concentration may reflect reduction in the density and of In addition, chronic stress may reduce receptor possibly through changes in evidence of the hypothesis of depression the lack of effects of drugs on depressive symptoms and prefrontal concentration in subjects with MDD of evidence suggest a dysfunction of the neurotransmitter system in a of the receptor produced and large antidepressant effects in patients with treatment-resistant MDD inhibitors of release (e.g., antidepressant abnormal levels were found in depressed subjects as by and there is evidence for abnormal signaling in post-mortem Since is the major neurotransmitter involved in almost every brain the of the specific role of in depression (e.g., there are promising leads that the receptor is involved in MDD and are diagnostic for MDD, suggesting regulation in depressed patients. In addition, some depressive symptoms may show psychomotor of of positive and negative and a subgroup of patients with MDD may have a disorder In healthy young subjects, changes in the of the had specific effects on subsequent mood In depressed patients, of can have antidepressant on these abnormalities have been hypothesized to be associated with MDD The association between of the and in cortisol in some subjects with and the effect of antidepressants on of and to the of this hypothesis Despite of the many promising the and genetic of this hypothesis are It remains to be antidepressant effects of such as directly to of on these abnormalities have been hypothesized to be associated with MDD The association between of the and in cortisol in some subjects with and the effect of antidepressants on of and to the of this hypothesis Despite of the many promising the and genetic of this hypothesis are It remains to be antidepressant effects of such as directly to of The and of the neurobiological of depression are in 1. The many theories of depression and the relatively low response rate of all antidepressant treatments a hypothesis of and suggest that depression is a clinically and heterogeneous disorder. This research on of the response to therapeutic interventions using such as neuroimaging and neuroendocrine tests in with for with to stress sensitivity and antidepressant The of of therapeutic will for the development of that has the potential to interventions and to up pathways in the of novel therapeutic approaches.

World Psychiatry · editorial or comment · 607 citationsread the source →

Spirituality and mental health

INTRODUCTION All along, the majority position of Psychiatry has been that Psychiatry has nothing to do with religion and spirituality. Religious beliefs and practices have long been thought to have a pathological basis, and psychiatrists over a century have understood them in this light. Religion was considered as a symptom of mental illness. Jean Charcot and Sigmund Freud linked religion with neurosis. DSM3 portrayed religion negatively by suggesting that religious and spiritual experiences are examples of psychopathology. But recent research reports strongly suggest that to many patients, religion and spirituality are resources that help them to cope with the stresses in life, including those of their illness. Many psychiatrists now believe that religion and spirituality are important in the life of their patients. The importance of spirituality in mental health is now widely accepted. As John Turbott[1] puts it, rapprochement between religion and psychiatry is essential for psychiatric practice to be effective. The Royal College of Psychiatrists, London, has a special group on Psychiatry and Spirituality. The American College of Graduate Medical Education mandates in its special requirements for residency training in Psychiatry, that all programs must provide training in religious and spiritual factors that can influence mental health. The World Psychiatric Association recently established a section on psychiatry and religion. Lukoff et al.[2] proposed that the diagnostic entities of religious and psychospiritual problems should be incorporated in DSM4 which has been accepted. DSM4, V 62.89 includes three categories—normal religious and spiritual experiences; religious and spiritual problems leading to mental disturbances; and mental disturbances with a religious and spiritual context. I understand that the Indian Psychiatric Society has formed a task force on spirituality and mental health which is urging the Medical council of India to include taking the spiritual history as part of psychiatric evaluation. Even so the importance of religion and spirituality are not sufficiently recognized by the psychiatric community. Religion does not have a place in most of the psychiatry text books. Only very few psychiatrists make use of religion and spirituality in the therapeutic situation. This paper makes an attempt to bring out the importance of spirituality in mental health. WHAT IS SPIRITUALITY? Spirituality is a globally acknowledged concept. It involves belief and obedience to an all powerful force usually called God, who controls the universe and the destiny of man. It involves the ways in which people fulfill what they hold to be the purpose of their lives, a search for the meaning of life and a sense of connectedness to the universe. The universality of spirituality extends across creed and culture. At the same time, spirituality is very much personal and unique to each person. It is a sacred realm of human experience. Spirituality produces in man qualities such as love, honesty, patience, tolerance, compassion, a sense of detachment, faith, and hope. Of late, there are some reports which suggest that some areas of the brain, mainly the nondominant one, are involved in the appreciation and fulfillment of spiritual values and experiences.[3–5] SPIRITUALITY AND RELIGION Religion is institutionized spirituality. Thus, there are several religions having different sets of beliefs, traditions, and doctrines. They have different types of community-based worship programs. Spirituality is the common factor in all these religions. It is possible that religions can lose their spirituality when they become institutions of oppression instead of agents of goodwill, peace and harmony. They can become divisive instead of unifying. History will tell us that this had happened from time to time. It has been said that more blood has been shed in the cause of religion than any other cause. The medieval holy wars of Europe; the religion-based terrorism and conflicts of modern times are examples. We must remember that the institutions of religion are supposed to help us to practice spirituality in our lives. They need periodical revivals to put spirituality in place. SPIRITUAL DIMENSION IS IMPORTANT IN MENTAL HEALTH Mental health has two dimensions—absence of mental illness and presence of a well-adjusted personality that contributes effectively to the life of the community. Ability to take responsibility for one's own actions, flexibility, high frustration tolerance, acceptance of uncertainty, involvement in activities of social interest, courage to take risks, serenity to accept the things which we cannot change, courage to change the things which we can change, the wisdom to know the difference between the above, acceptance of handicaps, tempered self-control, harmonious relationships to self, others, including Nature and God, are the essential features of mental health. Spirituality is an important aspect of mental health. St. Augustine prayed “O God, thou created us in thy image and our hearts will be restless until they find their rest in Thee.” Though Sigmund Freud looked upon religion as an illusion and neurosis, Carl Jung considered the psyche as a carrier of truth, powerfully rooted in the unconscious mind. Religion is important, directly and indirectly, in the etiology, diagnosis, symptomatology, treatment and prognosis of psychiatric disturbances. Lack of spirituality can interfere with interpersonal relationships, which can contribute to the genesis of psychiatric disturbance. Psychiatric symptoms can have a religious content. For example, the loss of interest in religious activities is a common symptom of depression. Too much and distorted religious practices are common in schizophrenia. It is well recognized that some religious states and experiences are misdiagnosed as symptoms of psychiatric illness. Visions and possession states are examples. The spiritual background of the patient will help in the diagnosis of psychiatric disturbance. They are important in the treatment of psychiatric disturbance because spiritual matters can be profitably incorporated in psychotherapy. Spirituality is important in the prognosis of psychiatric conditions. In the spiritual perspective, a differentiation must be made between cure and healing. Cure is the removal of symptoms. Healing is the healing of the whole person. Adversity often produces maturity. Hence in psychotherapy, the patient must be helped to accept the handicap and transform the handicap to a life of usefulness. SOME SIGNIFICANT CLINICAL AND RESEARCH FINDINGS Recent studies show that religious beliefs and practices are supportive to cope with stresses in life and are beneficial to mental health. Thomas Ashby Wills,[6] Professor of Epidemiology and population health at Albert Einstein College of Medicine developed a scale that determines how important is religion to people. This was administered to 1182 children in New York. It was found that religiosity kept children from smoking, drinking and drug abuse by buffering the impact of life stresses. Gene H. Brody,[7] a research professor of child and family development at the University of Georgia, Athens, found that parents who were more involved in church activities were more likely to have harmonious marital relationships and better parenting skills. That in turn enhanced children's competence, self-regulation, psychosocial adjustment and school performance. Miller et al.[8] made a 10-year follow up study on depressed mothers and their offsprings and reported that maternal religiosity and mother-child concordance in religiosity were protective against depression in the offspring. They also reported that low level of religiosity was associated with substance abuse in the offsprings.[9] J. Scott Tonigan,[10] a research professor of psychiatry at the University of New Mexico, followed up 226 patients of alcohol dependence and reported that spirituality predicts behavior such as honesty and responsibility which in turn promoted alcohol abstinence. Wagner and King[11] conducted a study involving three groups—one group of patients who had psychotic illness, one group of formal care givers, and a third group of informal caregivers. The existential needs were the most important for the patient group, while the other groups considered material needs such as housing and work as more important. Neeleman and King[12] surveyed the psychiatric practices of 231 psychiatrists in London. 73% had no religious affiliation, 28% had belief in God, 61% believed that religion can protect against mental illness, and 48% asked patients about their religious practices. Baetz et al.[13] surveyed 1204 psychiatrists and 157 psychiatric patients in Canada. 54% of psychiatrists believed in God, 47% asked patients regarding their religious beliefs, and 55% consulted clergy for the management of patients. Among the patients, 71% believed in God, and 24% preferred psychiatrists who were religious. In an Australian survey, a large majority of patients with psychiatric illness wanted their therapists to be aware of their spiritual beliefs and needs and believed that their spiritual practices helped them to cope better.[14] Mathai and North[15] constructed a questionnaire, consisting of 5 questions and gave it to 70 parents of children attending child and adolescent mental health clinic. They reported that majority of the parents believed that spiritual concerns were important and that therapists should consider their spiritual beliefs in the management of the problems of the children. In USA, Curlin et al.[16] conducted a study of psychiatrists and compared them with physicians from other specialities in their religious affiliations and found that psychiatrists showed less religious affiliations. Several empirical studies on psychiatrists' religious characteristics have indicated that psychiatrists are significantly less religious than the general population, their patients and other physicians.[17],[18] In a 12-year follow up of all articles appearing in American Journal of Psychiatry and Archives of General Psychiatry, 72% of the religious commitment variables were beneficial to mental health; participation in religious services, social support, prayer and relationship with God were beneficial in 92% of citations.[19] Similar findings were reported in a review of the Journal of Family Practice.[20] In a British epidemiological study, church going and active religion were found to be protective to vulnerability for depression by Brown and Prudo.[21] In a detailed study on suicide in Netherlands, Kerkoff [quoted by Sims[22]] reported that there was a decline in suicidal rate, which was concurrent with a religious revival. A study on the factors in the course and outcome of schizophrenia was conducted in the Department of psychiatry, Christian Medical College, Vellore.. It was a collaborative study among three centers—Vellore, Madras and Lucknow. A two-year and five-year follow up showed that those patients who spent more time in religious activities tended to have a better prognosis.[23],[24] The above reports strongly suggest that religious beliefs and practices of psychiatric patients should be given importance. The sense of hope and spiritual support that patients get by discussing religious matters help them to cope better. They also suggest that the importance of religion and spirituality is not sufficiently recognized by the psychiatric community. Mental health workers must take it seriously since psychiatry cannot afford to ignore the importance of spirituality and religion in psychiatry. Sims[22] gives two case histories which drives home this fact. One is the case of Jim who suffered from Korsakov's psychosis. He was so deteriorated that he mistook his wife for a hat. In the ward, others considered him as desolate individual. But his behavior in the chapel was normal. In absolute concentration and attention, he would partake Holy Communion. He did not forget anything nor did he show any signs of Korsakov's psychosis. The other patient had chronic schizophrenia. He used to hear a voice commanding him to jump out of the window. His simple devout mother had taught him to resist the voice by praying to God. His mind was destroyed, but the capacity for spiritual life was present. Unfortunately, on the final occasion, he was too late to pray and he lost his life. Sims makes a comment, “It is unfortunate that we as psychiatrists can be so crass as to neglect this area of life which is clearly important to many of our patients.” Andresen,[25] in an editorial, has pointed out that our civilization's “loss of soul” may cause psychiatric symptoms such as depression, obsessions, addictions, and violence. She has suggested that it is the responsibility of psychiatrists to remind the medical fraternity the necessity of putting back the soul in medical ethics and the fact that spirituality is of vital importance for the mental health of people. WHAT CAN WE DO? As pointed out earlier, spiritual values and religious practices are important in the lives of our patients. Many of their problems may centre round existential preoccupations. It is therefore important that we incorporate spirituality and religious practices in our treatment protocol. We must propagate the Bio-psycho-socio-spiritual model in our approach in psychiatry. Harold Koening,[26] in his paper Religion and Mental health: what should psychiatrists do?, has made some suggestions in this area. Psychiatric history should be catered to the patients' spiritual orientation and religious practices. When we take psychiatric history, we usually ask for the denomination the patient belongs. We do not try to find out how the patient experiences religion. What does religion and spirituality mean to the patient. The psychiatric history should gather information about patient's religious background and experiences in the past and what role religion plays in coping with life stresses. Has patient had any past negative religious experiences? Has he got spiritual and social support from the congregation which he attends? How active is he in the religious congregation? Some religious beliefs can be in conflict with the proposed treatment. Some religious groups are against any type of treatment. Some religious conflicts and frustrations may be contributing to the present psychiatric problem. Sexual abuse by religious workers, traumatic events which turned the patient away from religious beliefs and activities, unanswered prayers, etc. are examples. There are some questionnaires that can be used to take a history of spirituality and religious experiences.[152728] Discussion with the patient on spiritual matters and religious experiences will strengthen the therapeutic relationship. It can also lead to reversal effect of a personal growth of the therapist. We should respect and support patients' religious beliefs if these help them to cope better or do not adversely affect their mental health. For example, if a patient says that his discipline of fasting and prayer helps him to cope better, then this has to be encouraged. We should also challenge the beliefs that can adversely affect mental health. This has to be done very tactfully. It is better to be neutral till we understand the patients and the issues involved well and a good therapeutic relationship is formed. Patients may wish to discuss with the therapist regarding their subjective experiences and existential needs. We should spend time in listening to them. Partnership with the religious workers is an useful area. Leavy and King[29] in their paper, The devil in the detail: partnership between psychiatry and faith based organizations, brings out the importance of such a partnership. They have reported that in UK, the clergy continue to have a central role in several communities and the utility of their involvement in the care of people with mental health problems is increasing. They have argued the importance of examining the form and parameters of partnership between the mental health team and the faith-based communities. For this partnership to be effective, the mental health workers must be spiritually oriented and the religious workers must be better informed about mental health and illness. As referred to earlier, some religious experiences are often misdiagnosed as symptoms of mental illness and vice versa, some psychiatric symptoms are explained as spiritual experiences. According to Sims,[22] phenomena such as faith, prayer and magic can lend themselves to description and definition using Jasperian phenomenology which can lead to a clear differentiation of normal and pathological religious experiences. This emphasizes the importance of psycho-pastoral partnership. One example of such a partnership is the Bangalore psycho-pastoral association, which runs a very efficient half-way home for psychiatric patients. Recognizing the importance of this, the World Council of Churches has formed an Advisory group on mental health and faith communities, which has been active in the exploration of strategies for an effective partnership between mental health services and faith communities. There can be problems in such a partnership. The religious workers may be reluctant to get involved in secular programs, leaving their spiritual fortress. Some of them can have incorrect ideas about the causes of mental illness, which can interfere with the treatment program. Some others can be against medical treatment. Mental health workers can also be prejudiced against the patients' religious beliefs and practices. As referred to earlier, research findings suggest that majority of psychiatrists do not give importance to the spiritual and religious experiences of patients. According to Neelman and Persaud,[30] this may be due to the following factors. Psychiatrists are by and large less religious than other physicians; psychiatrists often come to know of spirituality through the pathological religious symptoms of patients, which make them prejudiced against spirituality; psychiatrists tend to have a biological approach to mental illness, which ignores spiritual dimension; and psychiatrists may think that religion and spirituality cause dependence and guilt feelings. All these can be minimized with dialogue and periodical orientation programs. As John Turbott[31] puts it, psychiatry as a whole can only benefit if the concepts and vocabulary of religion and spirituality are more widely known and discussed among its practitioners. It is also true that conflicts and problems arise more with religious experiences and not with spirituality Praying with the patient is a controversial area. Many psychiatrists will argue that it is a dangerous ground upon which to tread. If at all it is done, it should be done only after a strong therapeutic relationship is established and only if the patient asks for it. Praying for the patient can be beneficial. Research. Although there is substantial body of literature that describes the connection between mental health and spirituality, we must develop theoretical models to understand their relationship in practice. The statistical findings reported earlier were mainly the results of surveys. High-quality evidence-based research is required to make the clinical applications more objective and effective. There are ample opportunities to do research in this area. Phenomena such as meditation, religious faith, and concepts are all What are their to normal life and psychiatric What are the which influence spiritual experiences? If spirituality is to mental health and if religious beliefs and experiences are important in the life of the psychiatric it is only that we should include religious concepts in psychotherapy. For example, some and can be profitably used to help the patient to cope with life situation. The spiritual concepts are incorporated in the treatment of out of the to spirituality. describes a which is called This is a treatment spiritual values to behavior which was developed and promoted at the University of areas are meaning and purpose and The patient is through to meaning and This with examining the of life such as and the patient to the patient is to the of of and in life. The the patient's that and and The involves a on after examining and one's in life. meaning is by meaning for each This is by and factors life and illness The are of and The use of meditation, and with of beliefs and on symptoms form the of the treatment. When the patient negative is the treatment about each about The are depression and adolescent show that produces

Indian Journal of Psychiatry · editorial or comment · 106 citationsread the source →

Relationship between vagal tone, cortisol, TNF-alpha, epinephrine and negative affects in Crohn's disease and irritable bowel syndrome.

Crohn's disease (CD) and irritable bowel syndrome (IBS) involve brain-gut dysfunctions where vagus nerve is an important component. The aim of this work was to study the association between vagal tone and markers of stress and inflammation in patients with CD or IBS compared to healthy subjects (controls). The study was performed in 73 subjects (26 controls, 21 CD in remission and 26 IBS patients). The day prior to the experiment, salivary cortisol was measured at 8:00 AM and 10:00 PM. The day of the experiment, subjects completed questionnaires for anxiety (STAI) and depressive symptoms (CES-D). After 30 min of rest, ECG was recorded for heart rate variability (HRV) analysis. Plasma cortisol, epinephrine, norepinephrine, TNF-alpha and IL-6 were measured in blood samples taken at the end of ECG recording. Compared with controls, CD and IBS patients had higher scores of state-anxiety and depressive symptomatology. A subgroup classification based on HRV-normalized high frequency band (HFnu) as a marker of vagal tone, showed that control subjects with high vagal tone had significantly lower evening salivary cortisol levels than subjects with low vagal tone. Such an effect was not observed in CD and IBS patients. Moreover, an inverse association (r =  -0.48; p<0.05) was observed between the vagal tone and TNF-alpha level in CD patients exclusively. In contrast, in IBS patients, vagal tone was inversely correlated with plasma epinephrine (r =  -0.39; p<0.05). No relationship was observed between vagal tone and IL-6, norepinephrine or negative affects (anxiety and depressive symptomatology) in any group. In conclusion, these data argue for an imbalance between the hypothalamus-pituitary-adrenal axis and the vagal tone in CD and IBS patients. Furthermore, they highlight the specific homeostatic link between vagal tone and TNF-alpha in CD and epinephrine in IBS and argue for the relevance of vagus nerve reinforcement interventions in those diseases.

PloS one · 165 citationsread the source →

Childhood eating disorders: British national surveillance study.

Background: The incidence of eating disorders appears stable overall, but may be increasing in younger age groups. Data on incidence, clinical features and outcome of early-onset eating disorders are sparse. Aims: To identify new cases of early-onset eating disorders (<13 years) presenting to secondary care over 1 year and to describe clinical features, management and 1-year outcomes. Method: Surveillance over 14 months through the established British Paediatric Surveillance System, and a novel child and adolescent psychiatry surveillance system set up for this purpose. Results: Overall incidence was 3.01/100,000 (208 individuals). In total, 37% met criteria for anorexia nervosa; 1.4% for bulimia nervosa; and 43% for eating disorder not otherwise specified. Nineteen per cent showed determined food avoidance and underweight without weight/shape concerns. Rates of comorbidity were 41%; family history of psychiatric disorder 44%; and early feeding difficulties 21%. Time to presentation was >8 months. A total of 50% were admitted to hospital, typically soon after diagnosis. Outcome data were available for 76% of individuals. At 1 year, 73% were reported improved, 6% worse and 10% unchanged (11% unknown). Most were still in treatment, and seven were hospital in-patients for most of the year. Conclusions: Childhood eating disorders represent a significant clinical burden to paediatric and mental health services. Efforts to improve early detection are needed. These data provide a baseline to monitor changing trends in incidence.

The British journal of psychiatry : the journal of mental science · 174 citationsread the source →

Bullying and ostracism experiences in children with special health care needs.

Objective: Bullying experiences are becoming increasingly common in children and can have devastating consequences. Ostracism threatens a child's need for self-esteem, sense of belonging, sense of control, and meaningful existence. Recent literature suggests that children with special health care needs may be at risk for these negative events and consequences. This study compares bullying and ostracism experiences in children with and without various special health care needs. Methods: Participants aged 8 to 17 years completed questionnaires during a routine primary care or subspecialty clinic visit. Children with learning disabilities (N = 34), attention deficit or hyperactivity disorder (N = 100), autism spectrum disorders (N = 32), behavioral or mental health disorders (N = 33), and cystic fibrosis (CF, N = 22) were compared with 73 control children with no diagnosis on Reynolds' Bully-Victimization Scale scores and a 15-item pilot ostracism scale. Results: Compared with the control group, children in the learning disabilities, autism spectrum disorders, and attention deficit or hyperactivity disorder groups exhibited significant victimization scores on the Bully-Victimization Scale, whereas the behavioral or mental health disorders group had increased mean victimization scores. The learning disabilities group also reported clinically significant bullying. The CF group did not report involvement as bullies or victims. All children with special health care needs groups had increased mean frequency of threats to basic needs related to ostracism, and children with attention deficit or hyperactivity disorder and autism spectrum disorders were at higher risk for ostracism experiences. Conclusion: Children with special health care needs may be at higher risk for bullying, victimization, and ostracism. Further research is needed to explore this relationship, especially as it relates to child adjustment. Children with special health care needs should be asked about bullying and ostracism experiences and potential effects as part of mental health screening.

Journal of developmental and behavioral pediatrics : JDBP · 77 citationsread the source →

Fostering Resilience: Protective Agents, Resources, and Mechanisms for Adolescent Refugees' Psychosocial Well-Being.

Background: Adolescent refugees face many challenges but also have the potential to become resilient. The purpose of this study was to identify and characterize the protective agents, resources, and mechanisms that promote their psychosocial well-being. Methods: Participants included a purposively sampled group of 73 Burundian and Liberian refugee adolescents and their families who had recently resettled in Boston and Chicago. The adolescents, families, and their service providers participated in a two-year longitudinal study using ethnographic methods and grounded theory analysis with Atlas/ti software. A grounded theory model was developed which describes those persons or entities who act to protect adolescents (Protective Agents), their capacities for doing so (Protective Resources), and how they do it (Protective Mechanisms). Protective agents are the individuals, groups, organizations, and systems that can contribute either directly or indirectly to promoting adolescent refugees' psychosocial well-being. Protective resources are the family and community capacities that can promote psychosocial well-being in adolescent refugees. Protective mechanisms are the processes fostering adolescent refugees' competencies and behaviors that can promote their psychosocial well-being. Results: Eight family and community capacities were identified that appeared to promote psychosocial well-being in the adolescent refugees. These included 1) finances for necessities; 2) English proficiency; 3) social support networks; 4) engaged parenting; 5) family cohesion; 6) cultural adherence and guidance; 7) educational support; and 8) faith and religious involvement. Nine protective mechanisms identified were identified and grouped into three categories: 1) Relational (supporting, connecting, belonging); 2) Informational (informing, preparing), and; 3) Developmental (defending, promoting, adapting). Conclusions: To further promote the psychosocial well-being of adolescent refugees, targeted prevention focused policies and programs are needed to enhance the identified protective agents, resources, and mechanisms. Because resilience works through protective mechanisms, greater attention should be paid to understanding how to enhance them through new programs and practices, especially informational and developmental protective mechanisms.

Adolescent psychiatry (Hilversum, Netherlands) · 34 citationsread the source →

Physical activity and depressive symptoms in adolescents: a prospective study.

Background: The frequency of mental illness amongst adolescents and its potential long-term consequences make it an important topic to research in relation to risk and protective factors. Research on the relationship between physical activity and depressive symptoms in adolescents is limited. There is a particular lack of evidence from longitudinal studies. This study examines the relationship between depression and physical activity using the Research with East London Adolescents: Community Health Survey (RELACHS). Methods: This was a prospective cohort study. Participants were recruited from three Local Education Authority boroughs in East London in 2001 from year 7 (aged 11-12) and year 9 (aged 13-14) and were followed-up in 2003. All pupils in the 28 schools that took part were eligible for the study. Of the total 3,322 pupils eligible for the survey the overall response rate was 84% (2,789 pupils). A total of 2,093 (75%) pupils were also followed-up in 2003. The sample was multiethnic (73% of respondents were non-white) and deprived. Just under half of the sample was male (49%). Depressive symptoms were measured using the Short Moods and Feelings Questionnaire (SMFQ). Logistic regression analyses were used to examine the association between physical activity and depressive symptoms both cross-sectionally and longitudinally. Results: After adjustments, there was evidence for a cross-sectional association between physical activity and depressive symptoms for both boys and girls at baseline, with a decrease in the odds of depressive symptoms of about 8% for each additional hour of exercise undertaken per week (boys: odds ratio (OR) = 0.92, 95% CI 0.85 to 0.99; girls: OR = 0.92, 95% CI 0.85 to 1.00). There was no evidence for an association between a change in physical activity from baseline to follow-up and depressive symptoms at follow-up. Conclusions: This study provides some evidence for an association between level of physical activity and decreased depressive symptoms in adolescents. Further longitudinal research of these associations is required before physical activity can be recommended as an intervention for depression in adolescents.

BMC medicine · 105 citationsread the source →

Development and validation of the Eating Pathology Symptoms Inventory (EPSI).

Many current measures of eating disorder (ED) symptoms have 1 or more serious limitations, such as inconsistent factor structures or poor discriminant validity. The goal of this study was to overcome these limitations through the development of a comprehensive multidimensional measure of eating pathology. An initial pool of 160 items was developed to assess 20 dimensions of eating pathology. The initial item pool was administered to a student sample (N = 433) and community sample (N = 407) to determine the preliminary structure of the measure using exploratory and confirmatory factor analyses. The revised measure was administered to independent samples of patients recruited from specialty ED treatment centers (N = 158), outpatient psychiatric clinics (N = 303), and students (N = 227). Analyses revealed an 8-factor structure characterized by Body Dissatisfaction, Binge Eating, Cognitive Restraint, Excessive Exercise, Restricting, Purging, Muscle Building, and Negative Attitudes Toward Obesity. Scale scores showed excellent convergent and discriminant validity; other analyses demonstrated that the majority of scales were invariant across sex and weight categories. Eating Pathology Symptoms Inventory scale scores had excellent internal consistency (median coefficient alphas ranged from .84-.89) and reliability over a 2- to 4-week period (mean retest r = .73). The current study represents one of the most comprehensive scale development projects ever conducted in the field of EDs and will enhance future basic and treatment research focused on EDs.

Psychological assessment · 339 citationsread the source →