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Bariatric surgery, lifestyle interventions and orlistat for severe obesity: the REBALANCE mixed-methods systematic review and economic evaluation.

Background: Adults with severe obesity [body mass index (BMI) of ≥ 35 kg/m2] have an increased risk of comorbidities and psychological, social and economic consequences. Objectives: Systematically review bariatric surgery, weight-management programmes (WMPs) and orlistat pharmacotherapy for adults with severe obesity, and evaluate the feasibility, acceptability, clinical effectiveness and cost-effectiveness of treatment. Data sources: Electronic databases including MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials and the NHS Economic Evaluation Database were searched (last searched in May 2017). Review methods: Four systematic reviews evaluated clinical effectiveness, cost-effectiveness and qualitative evidence for adults with a BMI of ≥ 35 kg/m2. Data from meta-analyses populated a microsimulation model predicting costs, outcomes and cost-effectiveness of Roux-en-Y gastric bypass (RYGB) surgery and the most effective lifestyle WMPs over a 30-year time horizon from a NHS perspective, compared with current UK population obesity trends. Interventions were cost-effective if the additional cost of achieving a quality-adjusted life-year is < £20,000-30,000. Results: A total of 131 randomised controlled trials (RCTs), 26 UK studies, 33 qualitative studies and 46 cost-effectiveness studies were included. From RCTs, RYGB produced the greatest long-term weight change [-20.23 kg, 95% confidence interval (CI) -23.75 to -16.71 kg, at 60 months]. WMPs with very low-calorie diets (VLCDs) produced the greatest weight loss at 12 months compared with no WMPs. Adding a VLCD to a WMP gave an additional mean weight change of -4.41 kg (95% CI -5.93 to -2.88 kg) at 12 months. The intensive Look AHEAD WMP produced mean long-term weight loss of 6% in people with type 2 diabetes mellitus (at a median of 9.6 years). The microsimulation model found that WMPs were generally cost-effective compared with population obesity trends. Long-term WMP weight regain was very uncertain, apart from Look AHEAD. The addition of a VLCD to a WMP was not cost-effective compared with a WMP alone. RYGB was cost-effective compared with no surgery and WMPs, but the model did not replicate long-term cost savings found in previous studies. Qualitative data suggested that participants could be attracted to take part in WMPs through endorsement by their health-care provider or through perceiving innovative activities, with WMPs being delivered to groups. Features improving long-term weight loss included having group support, additional behavioural support, a physical activity programme to attend, a prescribed calorie diet or a calorie deficit. Limitations: Reviewed studies often lacked generalisability to UK settings in terms of participants and resources for implementation, and usually lacked long-term follow-up (particularly for complications for surgery), leading to unrealistic weight regain assumptions. The views of potential and actual users of services were rarely reported to contribute to service design. This study may have failed to identify unpublished UK evaluations. Dual, blinded numerical data extraction was not undertaken. Conclusions: Roux-en-Y gastric bypass was costly to deliver, but it was the most cost-effective intervention. Adding a VLCD to a WMP was not cost-effective compared with a WMP alone. Most WMPs were cost-effective compared with current population obesity trends. Future work: Improved reporting of WMPs is needed to allow replication, translation and further research. Qualitative research is needed with adults who are potential users of, or who fail to engage with or drop out from, WMPs. RCTs and economic evaluations in UK settings (e.g. Tier 3, commercial programmes or primary care) should evaluate VLCDs with long-term follow-up (≥ 5 years). Decision models should incorporate relevant costs, disease states and evidence-based weight regain assumptions. Study registration: This study is registered as PROSPERO CRD42016040190. Funding: The National Institute for Health Research Health Technology Assessment programme. The Health Services Research Unit and Health Economics Research Unit are core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate.

Health technology assessment (Winchester, England) · meta-analysis · 68 citationsread the source →

Alzheimer's pathology targets distinct memory networks in the ageing brain.

Alzheimer's disease researchers have been intrigued by the selective regional vulnerability of the brain to amyloid-β plaques and tau neurofibrillary tangles. Post-mortem studies indicate that in ageing and Alzheimer's disease tau tangles deposit early in the transentorhinal cortex, a region located in the anterior-temporal lobe that is critical for object memory. In contrast, amyloid-β pathology seems to target a posterior-medial network that subserves spatial memory. In the current study, we tested whether anterior-temporal and posterior-medial brain regions are selectively vulnerable to tau and amyloid-β deposition in the progression from ageing to Alzheimer's disease and whether this is reflected in domain-specific behavioural deficits and neural dysfunction. 11C-PiB PET and 18F-flortaucipir uptake was quantified in a sample of 131 cognitively normal adults (age: 20-93 years; 47 amyloid-β-positive) and 20 amyloid-β-positive patients with mild cognitive impairment or Alzheimer's disease dementia (65-95 years). Tau burden was relatively higher in anterior-temporal regions in normal ageing and this difference was further pronounced in the presence of amyloid-β and cognitive impairment, indicating exacerbation of ageing-related processes in Alzheimer's disease. In contrast, amyloid-β deposition dominated in posterior-medial regions. A subsample of 50 cognitively normal older (26 amyloid-β-positive) and 25 young adults performed an object and scene memory task while functional MRI data were acquired. Group comparisons showed that tau-positive (n = 18) compared to tau-negative (n = 32) older adults showed lower mnemonic discrimination of object relative to scene images [t(48) = -3.2, P = 0.002]. In a multiple regression model including regional measures of both pathologies, higher anterior-temporal flortaucipir (tau) was related to relatively worse object performance (P = 0.010, r = -0.376), whereas higher posterior-medial PiB (amyloid-β) was related to worse scene performance (P = 0.037, r = 0.309). The functional MRI data revealed that tau burden (but not amyloid-β) was associated with increased task activation in both systems and a loss of functional specificity, or dedifferentiation, in posterior-medial regions. The loss of functional specificity was related to worse memory. Our study shows a regional dissociation of Alzheimer's disease pathologies to distinct memory networks. While our data are cross-sectional, they indicate that with ageing, tau deposits mainly in the anterior-temporal system, which results in deficits in mnemonic object discrimination. As Alzheimer's disease develops, amyloid-β deposits preferentially in posterior-medial regions additionally compromising scene discrimination and anterior-temporal tau deposition worsens further. Finally, our findings propose that the progression of tau pathology is linked to aberrant activation and dedifferentiation of specialized memory networks that is detrimental to memory function.

Brain : a journal of neurology · 180 citationsread the source →

Video feedback for parental sensitivity and attachment security in children under five years

BACKGROUND: Children who are securely attached to at least one parent are able to be comforted by that parent when they are distressed and explore the world confidently by using that parent as a 'secure base'. Research suggests that a secure attachment enables children to function better across all aspects of their development. Promoting secure attachment, therefore, is a goal of many early interventions. Attachment is mediated through parental sensitivity to signals of distress from the child. One means of improving parental sensitivity is through video feedback, which involves showing a parent brief moments of their interaction with their child, to strengthen their sensitivity and responsiveness to their child's signals. OBJECTIVES: To assess the effects of video feedback on parental sensitivity and attachment security in children aged under five years who are at risk for poor attachment outcomes. SEARCH METHODS: In November 2018 we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, nine other databases and two trials registers. We also handsearched the reference lists of included studies, relevant systematic reviews, and several relevant websites SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs that assessed the effects of video feedback versus no treatment, inactive alternative intervention, or treatment as usual for parental sensitivity, parental reflective functioning, attachment security and adverse effects in children aged from birth to four years 11 months. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: This review includes 22 studies from seven countries in Europe and two countries in North America, with a total of 1889 randomised parent-child dyads or family units. Interventions targeted parents of children aged under five years, experiencing a wide range of difficulties (such as deafness or prematurity), or facing challenges that put them at risk of attachment issues (for example, parental depression). Nearly all studies reported some form of external funding, from a charitable organisation (n = 7) or public body, or both (n = 18). We considered most studies as being at low or unclear risk of bias across the majority of domains, with the exception of blinding of participants and personnel, where we assessed all studies as being at high risk of performance bias. For outcomes where self-report measures were used, such as parental stress and anxiety, we rated all studies at high risk of bias for blinding of outcome assessors. Parental sensitivity. A meta-analysis of 20 studies (1757 parent-child dyads) reported evidence of that video feedback improved parental sensitivity compared with a control or no intervention from postintervention to six months' follow-up (standardised mean difference (SMD) 0.34, 95% confidence interval (CI) 0.20 to 0.49, moderate-certainty evidence). The size of the observed impact compares favourably to other, similar interventions. Parental reflective functioning. No studies reported this outcome. Attachment security. A meta-analysis of two studies (166 parent-child dyads) indicated that video feedback increased the odds of being securely attached, measured using the Strange Situation Procedure, at postintervention (odds ratio 3.04, 95% CI 1.39 to 6.67, very low-certainty evidence). A second meta-analysis of two studies (131 parent-child dyads) that assessed attachment security using a different measure (Attachment Q-sort) found no effect of video feedback compared with the comparator groups (SMD 0.02, 95% CI -0.33 to 0.38, very low-certainty evidence). Adverse events. Eight studies (537 parent-child dyads) contributed data at postintervention or short-term follow-up to a meta-analysis of parental stress, and two studies (311 parent-child dyads) contributed short-term follow-up data to a meta-analysis of parental anxiety. There was no difference between intervention and comparator groups for either outcome. For parental stress the SMD between video feedback and control was -0.09 (95% CI -0.26 to 0.09, low-certainty evidence), while for parental anxiety the SMD was -0.28 (95% CI -0.87 to 0.31, very low-certainty evidence). Child behaviour. A meta-analysis of two studies (119 parent-child dyads) at long-term follow-up found no evidence of the effectiveness of video feedback on child behaviour (SMD 0.04, 95% CI -0.33 to 0.42, very low-certainty evidence). A moderator analysis found no evidence of an effect for the three prespecified variables (intervention type, number of feedback sessions and participating carer) when jointly tested. However, parent gender (both parents versus only mothers or only fathers) potentially has a statistically significant negative moderation effect, though only at α (alpha) = 0.1 AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that video feedback may improve sensitivity in parents of children who are at risk for poor attachment outcomes due to a range of difficulties. There is currently only little, very low-certainty evidence regarding the impact of video feedback on attachment security, compared with control: results differed based on the type of measure used, and follow-up was limited in duration. There is no evidence that video feedback has an impact on parental stress or anxiety (low- and very low-certainty evidence, respectively). Further evidence is needed regarding the longer-term impact of video feedback on attachment and more distal outcomes such as children's behaviour (very low-certainty evidence). Further research is needed on the impact of video-feedback on paternal sensitivity and parental reflective functioning, as no study measured these outcomes. This review is limited by the fact that the majority of included parents were mothers.

Cochrane Database of Systematic Reviews · meta-analysis · 58 citationsread the source →

Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia: A Randomized Clinical Trial.

Importance: A significant need exists for new antipsychotic medications with different mechanisms of action, greater efficacy, and better tolerability than existing agents. Xanomeline is a dual M1/M4 preferring muscarinic receptor agonist with no direct D2 dopamine receptor blocking activity. KarXT combines xanomeline with the peripheral muscarinic receptor antagonist trospium chloride with the goal of reducing adverse events due to xanomeline-related peripheral muscarinic receptor activation. In prior trials, xanomeline-trospium chloride was effective in reducing symptoms of psychosis and generally well tolerated in people with schizophrenia. Objective: To evaluate the efficacy and safety of xanomeline-trospium vs placebo in adults with schizophrenia. Design, setting, and participants: EMERGENT-3 (NCT04738123) was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 5-week trial of xanomeline-trospium in people with schizophrenia experiencing acute psychosis, conducted between April 1, 2021, and December 7, 2022, at 30 inpatient sites in the US and Ukraine. Data were analyzed from February to June 2023. Interventions: Participants were randomized 1:1 to receive xanomeline-trospium chloride (maximum dose xanomeline 125 mg/trospium 30 mg) or placebo for 5 weeks. Main outcomes and measures: The prespecified primary end point was change from baseline to week 5 in Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcome measures were change from baseline to week 5 in PANSS positive subscale score, PANSS negative subscale score, PANSS Marder negative factor score, Clinical Global Impression-Severity score, and proportion of participants with at least a 30% reduction in PANSS total score. Safety and tolerability were also evaluated. Results: A total of 256 participants (mean [SD] age, 43.1 [11.8] years; 191 men [74.6%]; 156 of 256 participants [60.9%] were Black or African American, 98 [38.3%] were White, and 1 [0.4%] was Asian) were randomized (125 in xanomeline-trospium group and 131 in placebo group). At week 5, xanomeline-trospium significantly reduced PANSS total score compared with placebo (xanomeline-trospium , -20.6; placebo, -12.2; least squares mean difference, -8.4; 95% CI, -12.4 to -4.3; P < .001; Cohen d effect size, 0.60). Discontinuation rates due to treatment-emergent adverse events (TEAEs) were similar between the xanomeline-trospium (8 participants [6.4%]) and placebo (7 participants [5.5%]) groups. The most common TEAEs in the xanomeline-trospium vs placebo group were nausea (24 participants [19.2%] vs 2 participants [1.6%]), dyspepsia (20 participants [16.0%] vs 2 participants [1.6%]), vomiting (20 participants [16.0%] vs 1 participant [0.8%]), and constipation (16 participants [12.8%] vs 5 participants [3.9%]). Measures of extrapyramidal symptoms, weight gain, and somnolence were similar between treatment groups. Conclusions and relevance: Xanomeline-trospium was efficacious and well tolerated in people with schizophrenia experiencing acute psychosis. These findings, together with the previously reported and consistent results from the EMERGENT-1 and EMERGENT-2 trials, support the potential of xanomeline-trospium to be the first in a putative new class of antipsychotic medications without D2 dopamine receptor blocking activity. Trial registration: ClinicalTrials.gov Identifier: NCT04738123.

JAMA psychiatry · randomised controlled trial · 128 citationsread the source →

Effect of Varenicline Combined With Medical Management on Alcohol Use Disorder With Comorbid Cigarette Smoking: A Randomized Clinical Trial.

Importance: Individuals with alcohol use disorder have high rates of cigarette smoking. Varenicline tartrate, an approved treatment for smoking cessation, may reduce both drinking and smoking. Objectives: To test the efficacy of varenicline with medical management for patients with alcohol use disorder and comorbid smoking seeking alcohol treatment, and to evaluate the secondary effects on smoking abstinence. Design, setting, and participants: This phase 2, randomized, double-blind, parallel group, placebo-controlled trial was conducted at 2 outpatient clinics from September 19, 2012, to August 31, 2015. Eligible participants met alcohol-dependence criteria and reported heavy drinking (≥5 drinks for men and ≥4 drinks for women) 2 or more times per week and smoking 2 or more times per week; 131 participants were randomized to either varenicline or placebo stratified by sex and site. All analyses were of the intention-to-treat type. Data analysis was conducted from February 5, 2016, to September 29, 2017. Interventions: Varenicline tartrate, 1 mg twice daily, and matching placebo pills for 16 weeks. Medical management emphasized medication adherence for 4 weeks followed by support for changing drinking. Main outcomes and measures: Percentage of heavy drinking days (PHDD) weeks 9 to 16, no heavy drinking days (NHDD) weeks 9 to 16, and prolonged smoking abstinence weeks 13 to 16. Results: Of 131 participants, 39 (29.8%) were women and 92 (70.2%) were men, the mean (SD) age was 42.7 (11.7) years, and the race/ethnicity self-identified by most respondents was black (69 [52.7%]). Sixty-four participants were randomized to receive varenicline, and 67 to receive placebo. Mean change in PHDD between varenicline and placebo across sex and site was not significantly different. However, a significant treatment by sex by time interaction for PHDD (F1,106 = 4.66; P = .03) revealed that varenicline compared with placebo resulted in a larger decrease in log-transformed PHDD in men (least square [LS] mean difference in change from baseline, 0.54; 95% CI, -0.09 to 1.18; P = .09; Cohen d = 0.45) but a smaller decrease in women (LS mean difference, -0.69; 95% CI, -1.63 to 0.25; P = .15; Cohen d = -0.53). Thirteen of 45 men (29%) had NHDD taking varenicline compared with 3 of 47 men (6%) taking placebo (Cohen h = 0.64; 95% CI, 0.22-1.03), whereas 1 of 19 women (5%) had NHDD compared with 5 of 20 women (25%) taking placebo (Cohen h = -0.60; 95% CI, -1.21 to 0.04). Taking varenicline, 8 of 64 participants (13%) achieved prolonged smoking abstinence; no one (0 of 67) quit smoking taking placebo (P = .003; Cohen h = 0.72; 95% CI, 0.38-1.07). Conclusions and relevance: Varenicline with medical management resulted in decreased heavy drinking among men and increased smoking abstinence in the overall sample. Varenicline could be considered to promote improvements in men with these dual behavioral health risks. Trial registration: clinicaltrials.gov Identifier: NCT01553136.

JAMA psychiatry · randomised controlled trial · 77 citationsread the source →

Behavioural intervention for weight loss maintenance versus standard weight advice in adults with obesity: A randomised controlled trial in the UK (NULevel Trial).

Background: Scalable weight loss maintenance (WLM) interventions for adults with obesity are lacking but vital for the health and economic benefits of weight loss to be fully realised. We examined the effectiveness and cost-effectiveness of a low-intensity technology-mediated behavioural intervention to support WLM in adults with obesity after clinically significant weight loss (≥5%) compared to standard lifestyle advice. Methods and findings: The NULevel trial was an open-label randomised controlled superiority trial in 288 adults recruited April 2014 to May 2015 with weight loss of ≥5% within the previous 12 months, from a pre-weight loss BMI of ≥30 kg/m2. Participants were self-selected, and the majority self-certified previous weight loss. We used a web-based randomisation system to assign participants to either standard lifestyle advice via newsletter (control arm) or a technology-mediated low-intensity behavioural WLM programme (intervention arm). The intervention comprised a single face-to-face goal-setting meeting, self-monitoring, and remote feedback on weight, diet, and physical activity via links embedded in short message service (SMS). All participants were provided with wirelessly connected weighing scales, but only participants in the intervention arm were instructed to weigh themselves daily and told that they would receive feedback on their weight. After 12 months, we measured the primary outcome, weight (kilograms), as well as frequency of self-weighing, objective physical activity (via accelerometry), psychological variables, and cost-effectiveness. The study was powered to detect a between-group weight difference of ±2.5 kg at follow-up. Overall, 264 participants (92%) completed the trial. Mean weight gain from baseline to 12 months was 1.8 kg (95% CI 0.5-3.1) in the intervention group (n = 131) and 1.8 kg (95% CI 0.6-3.0) in the control group (n = 133). There was no evidence of an effect on weight at 12 months (difference in adjusted mean weight change from baseline: -0.07 [95% CI 1.7 to -1.9], p = 0.9). Intervention participants weighed themselves more frequently than control participants and were more physically active. Intervention participants reported greater satisfaction with weight outcomes, more planning for dietary and physical activity goals and for managing lapses, and greater confidence for healthy eating, weight loss, and WLM. Potential limitations, such as the use of connected weighing study in both trial arms, the absence of a measurement of energy intake, and the recruitment from one region of the United Kingdom, are discussed. Conclusions: There was no difference in the WLM of participants who received the NULevel intervention compared to participants who received standard lifestyle advice via newsletter. The intervention affected some, but not all, process-related secondary outcomes of the trial. Trial registration: This trial is registered with the ISRCTN registry (ISRCTN 14657176; registration date 20 March 2014).

PLoS medicine · randomised controlled trial · 36 citationsread the source →

Elevated C-reactive protein levels, psychological distress, and depression in 73, 131 individuals.

CONTEXT The pathogenesis of depression is not fully understood, but studies suggest that low-grade systemic inflammation contributes to the development of depression. OBJECTIVE To test whether elevated plasma levels of C-reactive protein (CRP) are associated with psychological distress and depression. DESIGN We performed cross-sectional and prospective analyses of CRP levels in 4 clinically relevant categories using data from 2 general population studies. SETTING The Copenhagen General Population and the Copenhagen City Heart studies. PARTICIPANTS We examined 73 131 men and women aged 20 to 100 years. MAIN OUTCOME MEASURES We ascertained psychological distress with 2 single-item self-reports and depression using self-reported antidepressant use, register-based prescription of antidepressants, and register-based hospitalization with depression. RESULTS In cross-sectional analyses, increasing CRP levels were associated with increasing risk for psychological distress and depression (P = 3 × 10-8 to P = 4 × 10-105 for trend). For self-reported use of antidepressants, the odds ratio was 1.38 (95% CI, 1.23-1.55) for CRP levels of 1.01 to 3.00 mg/L, 2.02 (1.77-2.30) for 3.01 to 10.00 mg/L, and 2.70 (2.25-3.25) for greater than 10.00 mg/L compared with 0.01 to 1.00 mg/L. For prescription of antidepressants, the corresponding odds ratios were 1.08 (95% CI, 0.99-1.17), 1.47 (1.33-1.62), and 1.77 (1.52-2.05), respectively; for hospitalization with depression, 1.30 (1.01-1.67), 1.84 (1.39-2.43), and 2.27 (1.54-3.32), respectively. In prospective analyses, increasing CRP levels were also associated with increasing risk for hospitalization with depression (P = 4 × 10-8 for trend). CONCLUSIONS Elevated levels of CRP are associated with increased risk for psychological distress and depression in the general population.

JAMA psychiatry · 350 citationsread the source →

Substance use and abuse in first-episode psychosis: prevalence before and after early intervention.

Unlabelled: Despite the high prevalence of substance abuse among first-episode psychosis (FEP) populations, few studies examine whether early intervention (EI) improves substance abuse. Objective: To examine the prevalence and pattern of substance use and abuse among an FEP sample over 12 months. Methods: All the participants were diagnosed with a first episode of a schizophrenia spectrum disorder. The participants were followed prospectively. The prevalence rates of substance use and abuse from this sample were compared before and after 12 months of EI services and were compared with rates observed in a sample from the general population. Results: A total of 200 participants (80.0% males; mean age 24 years) entered the study: 183 participants completed all the assessments at baseline, 131 participants completed all the assessments at 12 months. At baseline, the findings showed similar prevalence rates between the FEP sample and the general sample for lifetime cannabis use (60% vs 55%, respectively) and hazardous alcohol use (26% vs 21%) but significantly different prevalence rates for lifetime hallucinogen (29% vs 15%; P < .001) and cocaine use (20% vs 14%; P < .001). At 12 months, the prevalence rates for drug abuse (P < .01), hazardous alcohol use (P < .01), and concurrent drug abuse and hazardous alcohol use (P < .05) were significantly lower than at baseline. Conclusion: Substance use and abuse decreased significantly after 12 months of EI services; EI services may be able to detect and to reduce substance use among FEP patients before it becomes a more serious disorder.

Schizophrenia bulletin · cohort or longitudinal · 74 citationsread the source →

Voluntary work for the physical and mental health of older volunteers: A systematic review.

Background: The increasing imbalance between the number of older adults not working and the number of adults in the age range of labour force participation (age range 20-64) has long been a fundamental public policy challenge in the Organization for Economic Co-operation and Development member countries. At a societal level, this growing imbalance raises serious concerns about the viability and funding of social security, pensions and health programmes. At an individual level, the concern is probably more that of aging well with the prospect of many years in retirement. Some research suggests that retiring for some carries the risk of a fast decline in health. Volunteering can play a significant role in people's lives as they transition from work to retirement, as it offers a "structured" means of making a meaningful contribution in society once the opportunity to do so through work has been cut off. Some older people consider voluntary work as a way to replicate aspects of paid work lost upon retirement, such as organisational structure and time discipline. In many countries, volunteering of the older adults is increasing and programmes designed specifically for this subpopulation are emerging. Volunteering may contribute to both individuals aging well and society aging well, as volunteering by the older adults at the same time relieves the societal burden if it helps maintain health and functionality for those who volunteer. It thus remains to be established to what extent volunteering impacts on the physical and mental health of those who volunteer. Objectives: The main objective of this review is to answer the following research question: what are the effects of volunteering on the physical and mental health of people aged 65 years or older? Search strategy: Relevant studies were identified through electronic searches of bibliographic databases, governmental and grey literature repositories, hand search in specific targeted journals, citation tracking, contact to international experts and internet search engines. The database searches were carried out to December 2018 and other resources were searched in September 2019 and October 2019. We searched to identify both published and unpublished literature. The searches were international in scope. Reference lists of included studies and relevant reviews were also searched. Selection criteria: The intervention of interest was formal volunteering which can be described as voluntary, on-going, planned, helping behaviour that intend to increase the well-being of strangers, offers no monetary compensation and typically occurs within an organisational context. We included older people aged 65 or over who are engaged in formal voluntary work. The primary focus was on measures of physical and mental health. All study designs that used a well-defined control group were eligible for inclusion. Studies that utilised qualitative approaches were not included. Data collection and analysis: The total number of potential relevant studies constituted 17,046 hits. A total of 90 studies, met the inclusion criteria and were critically appraised by the review authors. The 90 studies analysed 47 different populations. Only 26 studies (analysing 19 different populations) could be used in the data synthesis. Forty-six studies could not be used in the data synthesis as they were judged to have too high risk of bias and, in accordance with the protocol, were excluded from the meta-analysis on the basis that they would be more likely to mislead than inform. Eighteen studies did not provide enough information enabling us to calculate an effects size and standard error or did not provide results in a form enabling us to use it in the data synthesis. Finally, of the 26 studies that could be used in the data synthesis, two pairs of studies used the same two data sets and reported on the same outcome(s), thus in addition two studies were not used in the data synthesis. Meta-analysis of both physical health outcomes and mental health outcomes were conducted on each metric separately. All analyses were inverse variance weighted using random effects statistical models that incorporate both the sampling variance and between study variance components into the study level weights. Random effects weighted mean effect sizes were calculated using 95% confidence intervals (CIs).Sensitivity analysis was carried out by restricting the meta-analysis to a subset of all studies included in the original meta-analysis and was used to evaluate whether the pooled effect sizes were robust across components of risk of bias. Results: The 24 studies (analysing 19 different populations), used for meta analysis were from Australia, Ireland, Israel, Japan, Korea and United States, three were a randomised controlled trial and 21 were NRS. The baseline time period (the year the voluntary work that was analysed was measured) spanned by the included studies is 30 years, from 1984 to 2014 and on average the baseline year was 2001. On average the number of follow up years was 5, although with great variation from 0 to 25 years. The average number of volunteers analysed (not reported in four studies) was 2,369, ranging from 15 to 27,131 and the average number of controls was 13,581, ranging from 13 to 217.297. In total the average number of participants analysed was 14,566, ranging from 28 to 244.428.Ten studies analysed the effect of voluntary work on mortality, however, eight studies reported a hazard ratio and two studies reported an odds ratio. We analysed these two types of effect sizes separately. A hazard ratio <1 indicates that the treated, the volunteers is favoured. That is, the conditional mortality rate is lower for volunteers. All reported results indicated an effect favouring the volunteers, primary study effect sizes lied in the range 0.67-0.91. The random effects weighted mean hazard ratio was 0.76 (95% CI, 0.72-0.80) and statistically significant. The two studies that reported odds ratios of mortality supported this result. There was no heterogeneity between the studies in either of the meta analyses. Three studies analysed the effect of voluntary work on incident functional disability, using a hazard ratio as effect measure. All reported results indicated an effect favouring the volunteers, primary study effect sizes lied in the range 0.70-0.99. The random effects weighted mean hazard ratio was 0.83 (95% CI, 0.72-0.97) and statistically significant. There was a small amount of heterogeneity between the studies. Two studies analysed the effect of voluntary work on decline in instrumental activities of daily living, using an odds ratio as effect measure. Both reported results indicated an effect favouring the volunteers (0.63 and 0.83). The random effects weighted mean odds ratio was 0.73 (95% CI, 0.53-1.01) and not statistically significant. There is no heterogeneity between the two studies. Three studies analysed the effect of voluntary work on maintenance of functional competence, using an odds ratio as effect measure. All reported results indicated an effect favouring the volunteers, primary study effect sizes lied in the range 0.67-0.83. The random effects weighted mean odds ratio was 0.81 (95% CI, 0.70-0.94) and statistically significant. There is no heterogeneity between the studies. In addition a number of other physical outcomes were reported in a single study only. Three studies analysed the effect of voluntary work on depression, and reported results that enabled the calculation of standardised mean difference (SMD) and variance. The effect sizes are measured such that a positive effect size favours the volunteers. All reported results indicated an effect favouring the volunteers, primary study effect sizes lied in the range 0.05-0.66. The random effects weighted SMD was 0.12 (95% CI, 0.00-0.23) and statistically significant. There is a very small amount of heterogeneity between the studies. In addition, a number of other mental health outcomes were reported in a single study only. We did not find any adverse effects. There were no appreciable changes in the results across components of risk of bias as indicated by the sensitivity analysis. Authors' conclusions: The review aimed to examine effects on all types of physical and mental health outcomes. With the exception of mortality, there was insufficient evidence available. The available evidence, however, does suggest that there is an effect on the mortality of volunteers, although the effect is small. We found evidence that voluntary work reduces the mortality hazard of the volunteers aged 65 and above. The effect corresponds to a 43% chance of the volunteers dying first which should be compared to a fifty-fifty chance (50%) of dying first if the intervention had no effect. The evidence seems robust in the sense that we did not find any heterogeneity between the studies. As the intervention, unlike most other interventions in the social welfare area, is not costly, it could be prescribed to more older adults. In fact as the intervention in contrary to carrying a cost is a productive activity contributing directly to community well-being and has a positive effect on the volunteers it probably should be prescribed universally. However, due to the very nature of the intervention, it is voluntary and it cannot be prescribed. But more people could be encouraged to take up voluntary work if the opportunity was immediately available and visible.

Campbell systematic reviews · review · 33 citationsread the source →

Physical exercise training interventions for children and young adults during and after treatment for childhood cancer.

Background: A decreased physical fitness and impaired social functioning has been reported in patients and survivors of childhood cancer. This is influenced by the negative effects of disease and treatment of childhood cancer and by behavioural and social elements. Exercise training for adults during or after cancer therapy has frequently been reported to improve physical fitness and social functioning. More recently, literature on this subject became available for children and young adults with cancer, both during and after treatment. Objectives: This review aimed to evaluate the effect of a physical exercise training intervention (at home, at a physical therapy centre, or hospital based) on the physical fitness of children with cancer, in comparison with the physical fitness in a care as usual control group. The intervention needed to be offered within the first five years from diagnosis. The second aim was to assess the effects of a physical exercise training intervention in this population on fatigue, anxiety, depression, self efficacy, and health-related quality of life and to assess the adverse effects of the intervention. Search methods: For this review the electronic databases of CENTRAL, MEDLINE, EMBASE, CINAHL, PEDro, and ongoing trial registries were searched on 6 September 2011. In addition, a handsearch of reference lists and conference proceedings was performed in that same month. Selection criteria: The review included randomised controlled trials (RCTs) and clinical controlled trials (CCTs) that compared the effects of physical exercise training with no training, in people who were within the first five years of their diagnosis of childhood cancer. Data collection and analysis: By the use of standardised forms two review authors independently identified studies meeting the inclusion criteria, performed the data extraction, and assessed the risk of bias. Quality of the studies was rated by using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria. Main results: Five articles were included in this review: four RCTs (14, 14, 28, and 51 participants) and one CCT (24 participants). In total 131 participants (74 boys, 54 girls, three unknown) were included in the analysis, all being treated for childhood acute lymphoblastic leukaemia (ALL). The study interventions were all implemented during chemotherapy treatment. The duration of the training sessions ranged from 15 to 60 minutes per session. Both the type of intervention, as well as the intervention period, which ranged from 10 weeks to two years, varied in all the included studies. In all included studies the control group received care as usual. All studies had methodological limitations, such as small numbers of participants, unclear randomisation methods, and single-blind study designs in case of an RCT.Cardiorespiratory fitness was studied by the use of the nine-minute run-walk test, the timed up-and-down stairs test, and the 20-m shuttle run test. Only the up-and-down stairs test showed significant differences between the intervention and the control group, in favour of the intervention group (P value = 0.05, no further information available).Bone mineral density was assessed in one study, in which a statistically significant difference in favour of the exercise group was identified (standardised mean difference (SMD) 1.07; 95% confidence interval (CI) 0.48 to 1.66; P value < 0.001). Body mass index was assessed in two studies. The pooled data on this item did not show a statistically significant difference between the intervention and control study group. Flexibility was assessed in three studies. In one study the active ankle dorsiflexion method was used to assess flexibility and the second study they used the passive ankle dorsiflexion test. No statistically significant difference between the intervention and control group was identified with the active ankle dorsiflexion test, whereas with the passive test method a statistically significant difference in favour of the exercise group was found (SMD 0.69; 95% CI 0.12 to 1.25; P value = 0.02). The third study assessed body flexibility by the use of the sit-and-reach distance test; no statistically significant difference between the intervention and control group was identified. One study assessed the effects of an inspiratory muscle training programme aimed to train the lung muscles and increase physical fitness. This study reported no significant effect on either inspiratory or expiratory muscle strength. Two other studies using either knee and ankle strength changes by hand-held dynamometry or the number of completed push-ups (with knees on the ground) and a peripheral quantitative computed tomography of the tibia to determine the muscle mass did not identify statistically significant differences in muscle strength/endurance. The level of daily activity, health-related quality of life, fatigue, and adverse events were assessed in one study only; for all these items no statistically significant differences between the intervention and control group were found. None of the included studies evaluated the outcomes activity energy expenditure, time spent exercising, anxiety and depression, or self efficacy. Authors' conclusions: The effects of physical exercise training interventions for childhood cancer participants are not yet convincing due to small numbers of participants and insufficient study methodology. Despite that, first results show a trend towards an improved physical fitness in the intervention group compared to the control group. Changes in physical fitness were seen by improved body composition, flexibility, and cardiorespiratory fitness. However, the evidence is limited and these positive effects were not found for the other assessed outcomes, such as muscle strength/endurance, the level of daily activity, health-related quality of life, and fatigue. There is a need for more studies with comparable aims and interventions, using higher numbers of participants and for studies with another childhood cancer population than ALL only.

The Cochrane database of systematic reviews · meta-analysis · 52 citationsread the source →

Young@Heart clinic: a feasibility study of an undergraduate pharmacy student-led blood pressure and healthy lifestyle clinic.

Objectives: Student-led clinics offer a work-based learning (WBL) opportunity for undergraduate healthcare students to engage with professional activities in a real-life setting. Participation is posited to provide experiential learning and prepare students for clinical practice. This study aims to assess the feasibility of establishing and engaging undergraduate students in one such initiative through the collaboration between one School of Pharmacy and local authority. Methods: The clinic was developed using a logic model and delivered in 2019-2020. A service specification and training were developed and provided to volunteering undergraduate pharmacy students. Anonymised service data were collected and process outcomes around student and public engagement were recorded to assess feasibility for longer-term embedding into the undergraduate programme. Key findings: The clinic was operational for 20 days from November 2019 to February 2020. Student volunteers (n = 43, 36.7%) were trained and provided blood pressure screening and healthy living advice to 131 members of the public. Student drop-out occurred due to the voluntary nature of the initiative. Conclusions: Collaborative working with the local authority facilitated this WBL experience outside conventional clinical environments. The study demonstrated the potential for students to participate in service provision. This offers value to the local population through a health prevention service when a structured approach to the design and delivery of the educational experience is undertaken. The study provides insight into how the WBL can work, what it requires (e.g. resource, preparation), and learning to inform the wider implementation of this WBL into the undergraduate curriculum.

The International journal of pharmacy practice · 2 citationsread the source →

Initial psychometric evaluation of the Moral Injury Questionnaire--Military version.

Unlabelled: Moral injury is an emerging construct related to negative consequences associated with war-zone stressors that transgress military veterans' deeply held values/beliefs. Given the newness of the construct, there is a need for instrumentation that might assess morally injurious experiences (MIEs) in this population. Drawing on a community sample of 131 Iraq and/or Afghanistan Veterans and clinical sample of 82 returning Veterans, we conducted an initial psychometric evaluation of the newly developed Moral Injury Questionnaire-Military version (MIQ-M)-a 20-item self-report measure for assessing MIEs. Possibly due to low rates of reporting, an item assessing sexual trauma did not yield favourable psychometric properties and was excluded from analyses. Veterans in the clinical sample endorsed significantly higher scores across MIQ-M items. Factor analytic results for the final 19 items supported a unidimensional structure, and convergent validity analyses revealed that higher scores (indicative of more MIEs) were correlated with greater general combat exposure, impairments in work/social functioning, posttraumatic stress and depression in the community sample. In addition, when controlling for demographics, deployment-related factors and exposure to life threat stressors associated with combat, tests of incremental validity indicated that MIQ-M scores were also uniquely linked with suicide risk and other mental health outcomes. These findings provide preliminary evidence for the validity of the MIQ-M and support the applicability of this measure for further research and clinical work with Veterans. Key practitioner message: Military service can confront service members with experiences that undermine their core sense of humanity and violate global values and beliefs. These types of experiences increase the risk for posttraumatic maladjustment in this population, even when accounting for rates of exposure to life threat traumas. Moral injury is an emerging construct to more fully capture the many possible psychological, ethical, and spiritual/existential challenges among persons who served in modern wars and other trauma-exposed professional groups. There is currently a need for psychometrically sound instrumentation for assessing morally injurious experiences (MIEs). The Moral Injury Questionnaire - Military Version (MIQ-M) was developed to provide a tool for assessing possible MIEs among military populations. This study provides preliminary evidence of the validity - including factorial, concurrent, and incremental - and clinical utility of the MIQ-M for further applications in clinical and research contexts.

Clinical psychology & psychotherapy · 104 citationsread the source →

Effective Strategies to Recruit Young Adults Into the TXT2BFiT mHealth Randomized Controlled Trial for Weight Gain Prevention.

Background: Younger adults are difficult to engage in preventive health, yet in Australia they are gaining more weight and increasing in waist circumference faster than middle-to-older adults. A further challenge to engaging 18- to 35-year-olds in interventions is the limited reporting of outcomes of recruitment strategies. Objective: This paper describes the outcomes of strategies used to recruit young adults to a randomized controlled trial (RCT), healthy lifestyle mHealth program, TXT2BFiT, for prevention of weight gain. The progression from enquiry through eligibility check to randomization into the trial and the costs of recruitment strategies are reported. Factors associated with nonparticipation are explored. Methods: Participants were recruited either via letters of invitation from general practitioners (GPs) or via electronic or print advertisements, including Facebook and Google-social media and advertising-university electronic newsletters, printed posters, mailbox drops, and newspapers. Participants recruited from GP invitation letters had an appointment booked with their GP for eligibility screening. Those recruited from other methods were sent an information pack to seek approval to participate from their own GP. The total number and source of enquiries were categorized according to eligibility and subsequent completion of steps to enrolment. Cost data and details of recruitment strategies were recorded. Results: From 1181 enquiries in total from all strategies, 250 (21.17%) participants were randomized. A total of 5311 invitation letters were sent from 12 GP practices-16 participating GPs. A total of 131 patients enquired with 68 participants randomized (68/74 of those eligible, 92%). The other recruitment methods yielded the remaining 182 randomized participants. Enrolment from print media was 26% of enquiries, from electronic media was 20%, and from other methods was 3%. Across all strategies the average cost of recruitment was Australian Dollar (AUD) $139 per person. The least expensive modality was electronic (AUD $37), largely due to a free feature story on one university Web home page, despite Facebook advertising costing AUD $945 per enrolment. The most expensive was print media at AUD $213 and GP letters at AUD $145 per enrolment. Conclusions: The research indicated that free electronic media was the most cost-effective strategy, with GP letters the least expensive of the paid strategies in comparison to the other strategies. This study is an important contribution for future research into efficacy, translation, and implementation of cost-effective programs for the prevention of weight gain in young adults. Procedural frameworks for recruitment protocols are required, along with systematic reporting of recruitment strategies to reduce unnecessary expenditure and allow for valuable public health prevention programs to go beyond the research setting. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12612000924853; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362872 (Archived by WebCite at http://www.webcitation.org/6YpNfv1gI).

JMIR research protocols · 40 citationsread the source →

Night shift work at specific age ranges and chronic disease risk factors.

Objectives: We examined the association of night shift work history and age when night shift work was performed with cancer and cardiovascular disease risk factors among 54 724 women in the Nurses' Health Study (NHS) II. Methods: We calculated age-adjusted and socioeconomic status-adjusted means and percentages for cancer and cardiovascular risk factors in 2009 across categories of night shift work history. We used multivariable-adjusted logistic regression to estimate odds ratios (ORs) and 95% CIs for key risk factors among 54 724 participants (72% ever shift workers). We further examined these associations by age (20-25, 26-35, 36-45 and 46+ years) at which shift work was performed. Results: Ever night shift workers had increased odds of obesity (body mass index ≥30 kg/m(2); OR=1.37, 95% CI 1.31 to 1.43); higher caffeine intake (≥131 mg/day; OR=1.16, 95% CI 1.12 to 1.22) and total calorie intake (≥1715 kcal/day; OR=1.09, 95% CI 1.04 to 1.13); current smoking (OR=1.30, 95% CI 1.19 to 1.42); and shorter sleep durations (≤7 h of sleep/day; OR=1.19, 95% CI 1.15 to 1.24) compared to never night shift workers. These estimates varied depending on age at which night work was performed, with a suggestion that night shift work before age 25 was associated with fewer risk factors compared to night shift work at older ages. Conclusions: Our results indicate that night shift work may contribute to an adverse chronic disease risk profile, and that risk factors may vary depending on the age at which night shift work was performed.

Occupational and environmental medicine · 150 citationsread the source →

Atypical Antipsychotics: CATIE Study, Drug-Induced Movement Disorder and Resulting Iatrogenic Psychiatric-Like Symptoms, Supersensitivity Rebound Psychosis and Withdrawal Discontinuation Syndromes

Chronic illness can result in chronicity of clinical practice. As we have moved away from prescribing classical antipsychotics and tricyclic antidepressants, issues remain with the use of atypical antipsychotics and second-generation antidepressants that need to be addressed, namely, iatrogenic discontinuation syndromes and supersensitivity psychiatric symptoms. An optimal maintenance drug treatment consists of regular attempts to reduce the dose by finding a minimal therapeutic dose, regularly asking the question of when to reduce or withdraw treatment and for which patients, and moreover, why it is difficult to decrease a given drug treatment. Recently, Falloon [1] proposed that maintenance pharmacotherapy in schizophrenia will depend on finally finding minimally effective doses through ‘extensive training in stress management’. In the long-term treatment of major depression, Fava [2] has hypothesized that antidepressants can aggravate the course of depressive illness. Lambert [3] recently suggested that ‘antipsychotic-switching syndromes’, which include discontinuation syndromes, are a ‘major barrier’ to adjusting antipsychotic treatment. In this paper, we propose that to achieve optimal maintenance treatment with antipsychotics, and to reduce or withdraw antipsychotics effectively, we must distinguish syndromes associated with discontinuing antipsychotics, such as supersensitivity psychosis, from true relapse. While the prevalence and incidence of drug-induced movement disorder(s) (DIMD) has continuously decreased with atypical antipsychotics, DIMD persist as do psychiatric and psychiatric-like symptoms associated with DIMD, and these must also be identified and evaluated. Persistent DIMD have been found to be a predictor of the later emergence of tardive dyskinesia (TD) and supersensitivity psychosis [4]. At present, we need to determine the relative risk of iatrogenic discontinuation syndromes, DIMD and DIMD psychiatric symptoms resulting from atypical antipsychotics. Although atypical antipsychotics are now most commonly prescribed, a debate has emerged on the differences between classical and atypical antipsychotics following the results of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study [5]. The question that comes to the forefront is why recent studies are no longer finding well-established differences between these two generations in terms of efficacy and DIMD. Reasons to explain why recent schizophrenia studies have found reduced drug and placebo differences were examined at the International Society for CNS Clinical Trials and Methodology Annual Mid-Year Conference [6]. While the fact must be considered that patients included in recent studies have less severe illness with symptoms that are better controlled than in past studies (likely due to earlier treatment), the issue that psychiatric symptoms specific to schizophrenia are not being adequately measured nor differentiated from psychiatric and psychiatric-like symptoms associated with DIMD is crucial to answering this question. For example, it is hard to believe that in a recent review of psychomotor slowing in schizophrenia, the authors, when evaluating its effect on measurement and treatment research to improve cognition in schizophrenia (MATRICS), nearly completely ignored the influence of akinesia and DIMD on neuropsychological tests in schizophrenia and the importance of accurate DIMD measurements [7]. As we pursue this ongoing discussion, we recommend the discontinuation of all classical antipsychotics due to their neurotoxic association with a high prevalence of DIMD and increases in basal ganglia volumes [8], and now address how to prescribe atypical antipsychotics most effectively, by taking into account DIMD-associated psychiatric symptoms and iatrogenic discontinuation syndromes. The first widely prescribed atypical antipsychotic, risperidone, was first approved in Canada in 1993 following the publication of the Canadian Multicenter Risperidone Study, which reported clear advantages of risperidone over haloperidol and the placebo, and significantly less appearance of DIMD with risperidone than haloperidol [9]. DIMD includes the 4 types of movement disorders induced by antipsychotics: parkinsonism, dystonia, dyskinesia and akathisia [10]. These findings were confirmed by the American Risperidone Study [11] and several other studies reporting greater efficacy of risperidone over classical antipsychotics in terms of cost-efficiency [12] and the clinical management of patients with schizophrenia [13,14,15,16,17]. However, the CATIE study [5] challenged these results. The CATIE study found that of the 4 atypical antipsychotics studied, olanzapine was the only atypical to be more efficacious than the classical antipsychotic perphenazine, and to be highly superior to risperidone for discontinuation of treatment, due to lack of efficacy [5]. Olanzapine is known to produce less DIMD compared to risperidone, therefore one would expect psychiatric symptoms caused by DIMD to be less frequent with olanzapine than risperidone. The expected higher rate of DIMD-induced emergent psychiatric symptoms associated with risperidone would explain the CATIE results, showing risperidone to be significantly less efficacious than olanzapine [5], despite risperidone being known to be at least as efficacious as olanzapine for true schizophrenic symptoms. Furthermore, the rating scales used to measure DIMD did not find the well-established differences between the 5 antipsychotics for DIMD rates [5]. Thus, we propose that DIMD and DIMD-induced psychiatric symptoms were confounded with true schizophrenic symptoms in the CATIE study. DIMD-associated psychiatric symptoms could be classified into 3 types: (1) emergent psychiatric symptoms caused by DIMD, such as akinesia inducing depression, akathisia inducing anxiety; (2) iatrogenic psychiatric-like symptoms resulting from confounding DIMD with psychiatric symptoms, such as akinesia confounded with psychomotor retardation, akathisia with agitation; (3) supersensitivity psychosis symptoms associated with DIMD. In the CATIE study, quetiapine (mean dose = 543.4 mg/day), which shares a low rate of DIMD with olanzapine, was also found to be significantly less efficacious compared to olanzapine, but in contrast to risperidone, this lack of efficacy could be due to psychiatric symptoms related to supersensitivity psychosis explained by quetiapine’s loose binding properties at the D2 receptor [18]. Patients taking quetiapine had a completion rate of 18% out of 329 patients, whereas in our 3-year prospective study of quetiapine monotherapy with a lower mean dose of 487 mg/day (thus less likely to develop therapeutic tolerance), the completion rate was 21.7% out of 23 patients; 6 of 7 patients who relapsed, after a minimum 3 months of stabilized quetiapine treatment, met the criteria for supersensitivity psychosis [19]. Without distinguishing these DIMD-associated psychiatric symptoms from symptoms due to the original illness, the major impact of atypical antipsychotics is on the reduction of DIMD and TD [10, 20,] and their beneficial effects on psychosis are masked by DIMD emergent psychiatric symptoms, including supersensitivity psychosis. We will review 4 multicenter trials, which include a total of 14,497 patients, to illustrate how psychiatric and schizophrenic symptoms are confounded with DIMD-associated psychiatric symptoms.TD epidemiology has changed significantly since the introduction of atypical antipsychotics, with a constant decline in its prevalence [10]. TD, classified as a DIMD, is a hyperkinetic, involuntary and purposeless movement disorder [10, 20]. Considered as the most significant side effect of classical antipsychotics, TD has been associated with antipsychotics and gastrointestinal neuroleptics, and usually occurs after several years of treatment. Persistent TD can also occur after short-term exposure to classical antipsychotics and gastrointestinal neuroleptics even at low doses and for as few as 2 months [8,21,22,23], while reversible and withdrawal dyskinesias share properties with levodopa-induced dyskinesia [24]. We conducted several epidemiological studies of TD [4,25,26,27] and in 1975, using the National Institute of Mental Health (NIMH) psychopharmacology criteria, we found a 31% prevalence of TD in 261 outpatients with schizophrenia [25]. We also evaluated these patients according to the Schooler and Kane research diagnostic criteria and found a 22% prevalence of TD. This variability of findings related to defining criteria complicates comparisons across studies [10]. In a 5-year follow-up study of 169 of the same patients [4, 25], 45% met the research diagnostic criteria for TD. In 1975, 131 of the 261 patients did not meet the research diagnostic for TD, and in 1980 treatment-emergent TD was found in 46 of the patients who did not have it in 1975, for a 5-year cumulative incidence rate of 35% and a mean annual incidence rate of 8.4%. When corrected for remissions, the mean annual incidence rate decreased to 2.9%. This incidence rate, which includes both patients who developed and remitted from TD over time, is similar to results found by other studies during the same time period [28, 29]. The cumulative incidence of treatment-emergent TD in the study by Kane et al. [29] was 12% after 4 years and 40% after 8 years of neuroleptic exposure, which is similar to our finding of an annual incidence rate (corrected for remissions) of 3% for classical antipsychotics. In a study carried out in 130 lithium-treated affective disorder patients previously, but less, exposed to antipsychotics, we found a TD prevalence of 9.2% [26], which was a quarter of the incidence reported in our previous studies on patients with schizophrenia who had greater exposure to antipsychotics. In this time period of classical antipsychotics, 2 meta-analyses (including mostly patients with schizophrenia) reported mean TD prevalences of 23% [30] and 20% [31]. In view of the fact that 58% of patients treated with classical antipsychotics will develop treatment-emergent TD after 10–15 years of treatment [4], and the known beneficial neuroprotective effects of atypical antipsychotics on TD [32] and on increased basal ganglia volumes induced by classical antipsychotics [8], we recommend the discontinuation of all classical antipsychotics due to their neurotoxic effects. In the time period of both classical and atypical antipsychotics, the following multicenter studies (n = 3,753) evaluated the incidence and prevalence of TD, using the same definitions, Extrapyramidal Symptom Rating Scale [20] and training videotapes as in the previous time period. In the first study, an annual TD incidence of 0.68% was reported prospectively in 725 patients with schizophrenia, treated with the long-acting injectable atypical antipsychotic risperidone [27, 33]. Treatment-emergent TD was found in 12 of 587 patients without dyskinesia at the baseline [33]; however, expert case assessment determined 7 cases (1.19%) of withdrawal dyskinesia (3 cases resolved, 4 cases unchanged), 1 case (0.17%) of reversible dyskinesia and 4 cases (0.68%) of persistent treatment-emergent TD. Of the patients with baseline dyskinesia, 28.4% improved, no longer met TD criteria and maintained this response [33]. This annual treatment-emergent TD incidence of 0.68% with atypical antipsychotics is only 22% of the annual incidence of 3% reported with classical antipsychotics [4]. In the second study, the Schizophrenia International Suicide Prevention Trial (67 centers in 11 countries) [34], 980 patients with schizophrenia, or schizoaffective disorders, taking an atypical alone (25.6%), a classical alone (31.5%) or both a classical and an atypical antipsychotic (42.9%) were included from March 19, 1998, to February 14, 1999, and TD was found at the baseline in 115 (12%) patients [27, 35]. Thus, after 10 years in the time period of both classical and atypical antipsychotics, the overall prevalence of TD decreased by at least twofold compared to our previous 1979–1988 studies with classical antipsychotics [4, 25], using the same definitions, Extrapyramidal Symptom Rating Scale and training videotapes. In the third study (baseline data from three Ris-Consta multicenter studies) [27, 36] carried out 1 year later, 2,048 patients were included from March 21, 1999, to December 15, 2000, and TD was found at the baseline in 209 patients (10.2%), using the same methodology. This study showed a further decrease in the prevalence of TD after an additional year of atypical use. This changing epidemiology of TD with atypical antipsychotics is confirmed by Correll et al. [37] in a systematic review of 1-year prospective studies with atypical antipsychotics, and by Jeste et al. [38] in a 1-year study of elderly patients treated with risperidone. In conclusion, following the introduction of atypical antipsychotics, the prevalence and incidence of TD have significantly decreased. However, the risk for TD still exists with both atypical and classical antipsychotics, and there is a need for continued surveillance of emerging cases of TD in patients taking antipsychotics [39], especially as the current debate continues on the differences in efficacy between these two generations of antipsychotics following results from studies such as the CATIE [5, 39]. Furthermore, Kane [39] has pointed out that newly trained clinicians using mostly atypical antipsychotics may not have had the same exposure to TD as previously trained clinicians.A high prevalence of all 4 types of DIMD (parkinsonism, dystonia, dyskinesia and akathisia) remains. In the Schizophrenia International Suicide Prevention Trial (n = 980), a prevalence of 57.5% of DIMD (n = 551 patients) was found [27, 35]. In the Ris-Consta studies (n = 2,048) [27, 36], 970 patients (47.4%) had DIMD at the baseline, which consisted of 778 patients with parkinsonism (38.0%), 285 patients with akathisia (14%) and 209 patients with TD (10.2%). Thus, nearly 1 patient out of 2 had a definite DIMD in this time period of classical and atypical antipsychotics. In addition, DIMD have been consistently associated with significant psychiatric symptoms as measured by the positive and negative syndrome scale (PANSS) [40, 41]. In the InterSept study (n = 980), which included patients with schizophrenia and schizoaffective disorder who were at risk of suicide, suicidality was associated at baseline with DIMD, parkinsonism, TD and akathisia, and depression was associated with TD and akathisia [27, 35]. Based on these results, we recommend routinely assessing DIMD in patients with schizophrenia with suicidal and depressive symptoms. In the Ris-Consta studies (n = 2,048), baseline DIMD were also significantly associated with the PANSS total score, positive, negative and anxiety/depression symptoms [27, 36]. Greater anxiety and depression were seen in patients with severer DIMD, akathisia and parkinsonism. Higher PANSS negative symptom rating was associated with parkinsonism and higher PANSS total scores were associated with akathisia. In this time period, these last two studies (n = 3,028) show that DIMD persists with atypical antipsychotics, and that patients with DIMD have significantly higher PANSS scores compared to patients without DIMD.These results are in agreement with findings from 2 other multicenter studies: the American CATIE study [5] and the European Schizophrenia Outpatient Health Outcomes (SOHO) study [42]. In the CATIE baseline data, patients with TD (n = 212) were found to have significantly more psychopathology than patients without TD (n = 1,098) as measured by the PANSS total score and PANSS general psychopathology subscale [43]. In the 3-year prospective SOHO study, emergent cases of TD were associated with greater overall psychopathology. An increase in clinical global impression overall symptom severity was longitudinally associated with cases of TD in patients without TD at the baseline (n = The SOHO and the CATIE studies have also examined other for TD. the CATIE and SOHO studies found that other DIMD were associated with TD the CATIE study showed that patients with TD had more parkinsonism akathisia while the SOHO study found that baseline symptoms TD our findings in a prospective study of TD [4]. In to reporting that the incidence of TD was lower in patients taking atypical compared to classical antipsychotics after 6 months the SOHO study showed that the incidence of TD was associated with the incidence of of drug-induced in is crucial to that there is a of DIMD with atypical antipsychotics, which are not and confounded with psychiatric symptoms rating scales used routinely in clinical to DIMD do not DIMD from psychiatric symptoms from the 4 multicenter (n = 14,497 patients) into this the CATIE the [27, the Ris-Consta [27, 36] and the SOHO studies have all confirmed the association of DIMD with psychiatric symptoms. most of the studies included in this measure psychiatric symptoms according to the we propose the following of PANSS psychiatric symptoms associated with emergent psychiatric symptoms caused by DIMD, such as depression and suicidality example, akinesia is known to produce depression, psychomotor and suicidal while akathisia psychomotor and suicidal and TD is also associated with suicidal iatrogenic psychiatric-like symptoms resulting from confounding and DIMD with psychiatric symptoms, such as confounding and with and retardation, akathisia with anxiety and and and dyskinesias with and schizophrenic psychiatric schizophrenic symptoms associated with DIMD caused by supersensitivity psychosis, which we are now to first reported drug-induced associated with TD a in and increased receptor after long-term treatment with classical antipsychotics, and we this supersensitivity psychosis. We that TD and supersensitivity psychosis with the decrease or withdrawal of an antipsychotic, given risk not and at the same The debate continues on how to most withdraw antipsychotic [1] and and psychiatric syndromes associated with types of syndromes have been with the discontinuation of (1) withdrawal syndromes and major (2) syndromes anxiety and which have been reported with and (3) supersensitivity syndromes such as TD and supersensitivity psychosis These discontinuation syndromes all produce psychiatric symptoms that can be confounded with true of the original illness. In a recent review of the on psychosis the importance of between antipsychotic withdrawal effects related to the course of the original illness and drug-induced effects such as supersensitivity psychosis. due to the discontinuation of a drug can be differentiated from the course of original illness and more long-term maintenance treatment could be reduced and in patients The long-term maintenance with second-generation antidepressants and of a major depressive disorder is of the in and during long-term maintenance treatment. The has also recently been to produce a persistent disorder following withdrawal to be related to supersensitivity When discontinuing antipsychotics and antidepressants, the of supersensitivity syndromes and other iatrogenic discontinuation syndromes must be to high doses or of outpatients and with schizophrenia treated with a classical antipsychotic treatment also included 1 but no antidepressants, no and no showed a prevalence of 22% for supersensitivity psychosis The prevalence of TD using Schooler and Kane criteria, was that found for supersensitivity psychosis. cases of supersensitivity psychosis increased the prevalence of supersensitivity psychosis to psychosis was associated with a higher maintenance dose of classical antipsychotics, high and schizophrenia with a The higher antipsychotic dose and higher associated with supersensitivity psychosis to the of supersensitivity and these results that lower doses of antipsychotics could the appearance of supersensitivity psychosis. In this study, there was no found between TD and supersensitivity psychosis, due to TD being associated with schizophrenia and supersensitivity psychosis with higher antipsychotic dose was not to be a risk for TD, whereas increased was associated with TD but not associated with supersensitivity psychosis. is that most patients in this study were treated with which has a high for the D2 which could to both a high incidence of supersensitivity psychosis and DIMD as the drug is known to produce a high incidence of symptoms psychosis, in its masked and withdrawal is known to occur 6 following the decrease or withdrawal of an antipsychotic or 3 months for a long-acting injectable We have proposed that TD and supersensitivity psychosis can result from the of in the caused by following in D2 with high for The of supersensitivity psychosis and TD share can both occur after long-term use of antipsychotics and can and difficult to with of the antipsychotic stress both TD and supersensitivity psychosis and both can be by and by and TD was to be the predictor of supersensitivity psychosis in our and follow-up study of supersensitivity psychosis [4, TD and supersensitivity psychosis may or may not occur in the same time but TD is associated with supersensitivity psychosis when it occurs during withdrawal of antipsychotics These two supersensitivity syndromes have been difficult to study due to the fact that antipsychotics can their appearance further with supersensitivity psychosis is that symptoms the original illness and true however, supersensitivity psychosis can be as it more after of the antipsychotic than true occurs with high doses of antipsychotics and not with antipsychotic treatment and therapeutic to antipsychotic treatment after drug response time, as therapeutic there is further of supersensitivity and further syndromes, TD, can (1) or (2) persistent or (3) reversible or symptoms can persist for several months or years and can still be reversible or When persistent and supersensitivity symptoms symptoms, being severer than the original symptoms, but these supersensitivity symptoms persist in contrast to symptoms and may include symptoms atypical antipsychotics, it has been proposed that supersensitivity psychosis occurs more with antipsychotics with from the D2 receptor The 2 atypical antipsychotics most associated with supersensitivity psychosis are quetiapine and which both have loose binding properties at the D2 receptor An additional which and severe in the withdrawal of is its effect as an receptor Thus, for the withdrawal would be by the receptor following of at this drug in the of the a and psychosis results cases of supersensitivity psychosis have also been reported with olanzapine psychosis was found to be associated with quetiapine in our 3-year study of quetiapine in 23 outpatients with schizophrenia and schizoaffective disorder who had previously been treated with classical antipsychotics risperidone, and had symptoms and of side effects [19]. As in our of the CATIE study, 7 patients after a minimum of 3 months of stabilized treatment and 6 of these patients met the criteria for supersensitivity psychosis [19]. the 11 of patients with baseline TD relapsed, the that TD to supersensitivity psychosis and have been to be efficacious in of patients with supersensitivity psychosis We also recommend the use of in supersensitivity and anxiety disorder induced by the discontinuation of the An can be used in with an antipsychotic or an in to more decrease or withdraw these and find the minimal therapeutic dose for patients who still need long-term treatment. a minimal therapeutic dose with an has an additional for a drug olanzapine, as the dose will significant side In in the of Mental Health psychiatric 35% of patients with a of schizophrenia and For severe cases of schizophrenia, the use of or is in to drug to antipsychotic While is less than or it is superior to for anxiety and the of optimal minimal maintenance drug treatment. proposed the beneficial results of treatment in schizophrenia is their effect We have also related their beneficial effects to an of a We recommend treatment as a first for from treatment, can also be prescribed as with as it has a In a and that and had than other in addition, emerging that may improve DIMD has also been to be effective as an to antipsychotic monotherapy in patients with schizophrenia who treatment We that of cases of schizophrenia can be related to supersensitivity psychosis. In patients for maintenance treatment is a minimal therapeutic dose can be with the use of an that will patients from antipsychotic or conclusion, DIMD-induced psychiatric symptoms and supersensitivity syndromes will to to results such as found in the CATIE study which show that olanzapine is the only atypical antipsychotic more efficacious than a classical The proposed for psychiatric and psychiatric-like symptoms associated with DIMD may to the of all classical antipsychotics and the use of higher doses and longer than of atypical antipsychotics. research is in to develop to distinguish between true and iatrogenic discontinuation syndromes and to to more withdraw antipsychotics and antidepressants by and supersensitivity syndromes, for the antipsychotics and quetiapine and for the may to further of DIMD, TD and supersensitivity psychosis as we to more differences in the of As most of antipsychotics and second-generation antidepressants are not routinely or for more differences in drug will also to prescribe minimal therapeutic doses of antipsychotics and antidepressants for greater efficacy and better in the maintenance has and the last 3 years from and

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