Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis.

BACKGROUND: The benefits and safety of medications for attention-deficit hyperactivity disorder (ADHD) remain controversial, and guidelines are inconsistent on which medications are preferred across different age groups. We aimed to estimate the comparative efficacy and tolerability of oral medications for ADHD in children, adolescents, and adults. METHODS: We did a literature search for published and unpublished double-blind randomised controlled trials comparing amphetamines (including lisdexamfetamine), atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with each other or placebo. We systematically contacted study authors and drug manufacturers for additional information. Primary outcomes were efficacy (change in severity of ADHD core symptoms based on teachers' and clinicians' ratings) and tolerability (proportion of patients who dropped out of studies because of side-effects) at timepoints closest to 12 weeks, 26 weeks, and 52 weeks. We estimated summary odds ratios (ORs) and standardised mean differences (SMDs) using pairwise and network meta-analysis with random effects. We assessed the risk of bias of individual studies with the Cochrane risk of bias tool and confidence of estimates with the Grading of Recommendations Assessment, Development, and Evaluation approach for network meta-analyses. This study is registered with PROSPERO, number CRD42014008976. FINDINGS: 133 double-blind randomised controlled trials (81 in children and adolescents, 51 in adults, and one in both) were included. The analysis of efficacy closest to 12 weeks was based on 10 068 children and adolescents and 8131 adults; the analysis of tolerability was based on 11 018 children and adolescents and 5362 adults. The confidence of estimates varied from high or moderate (for some comparisons) to low or very low (for most indirect comparisons). For ADHD core symptoms rated by clinicians in children and adolescents closest to 12 weeks, all included drugs were superior to placebo (eg, SMD -1·02, 95% CI -1·19 to -0·85 for amphetamines, -0·78, -0·93 to -0·62 for methylphenidate, -0·56, -0·66 to -0·45 for atomoxetine). By contrast, for available comparisons based on teachers' ratings, only methylphenidate (SMD -0·82, 95% CI -1·16 to -0·48) and modafinil (-0·76, -1·15 to -0·37) were more efficacious than placebo. In adults (clinicians' ratings), amphetamines (SMD -0·79, 95% CI -0·99 to -0·58), methylphenidate (-0·49, -0·64 to -0·35), bupropion (-0·46, -0·85 to -0·07), and atomoxetine (-0·45, -0·58 to -0·32), but not modafinil (0·16, -0·28 to 0·59), were better than placebo. With respect to tolerability, amphetamines were inferior to placebo in both children and adolescents (odds ratio [OR] 2·30, 95% CI 1·36-3·89) and adults (3·26, 1·54-6·92); guanfacine was inferior to placebo in children and adolescents only (2·64, 1·20-5·81); and atomoxetine (2·33, 1·28-4·25), methylphenidate (2·39, 1·40-4·08), and modafinil (4·01, 1·42-11·33) were less well tolerated than placebo in adults only. In head-to-head comparisons, only differences in efficacy (clinicians' ratings) were found, favouring amphetamines over modafinil, atomoxetine, and methylphenidate in both children and adolescents (SMDs -0·46 to -0·24) and adults (-0·94 to -0·29). We did not find sufficient data for the 26-week and 52-week timepoints. INTERPRETATION: Our findings represent the most comprehensive available evidence base to inform patients, families, clinicians, guideline developers, and policymakers on the choice of ADHD medications across age groups. Taking into account both efficacy and safety, evidence from this meta-analysis supports methylphenidate in children and adolescents, and amphetamines in adults, as preferred first-choice medications for the short-term treatment of ADHD. New research should be funded urgently to assess long-term effects of these drugs. FUNDING: Stichting Eunethydis (European Network for Hyperkinetic Disorders), and the UK National Institute for Health Research Oxford Health Biomedical Research Centre.

Substance use disorders in prisoners: an updated systematic review and meta-regression analysis in recently incarcerated men and women.

AIMS: The aims were to (1) estimate the prevalence of alcohol and drug use disorders in prisoners on reception to prison and (2) estimate and test sources of between study heterogeneity. METHODS: Studies reporting the 12-month prevalence of alcohol and drug use disorders in prisoners on reception to prison from 1 January 1966 to 11 August 2015 were identified from seven bibliographic indexes. Primary studies involving clinical interviews or validated instruments leading to DSM or ICD diagnoses were included; self-report surveys and investigations that assessed individuals more than 3 months after arrival to prison were not. Random-effects meta-analysis and subgroup and meta-regression analyses were conducted. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: In total, 24 studies with a total of 18 388 prisoners across 10 countries were identified. The random-effects pooled prevalence estimate of alcohol use disorder was 24% [95% confidence interval (CI) = 21-27], with very high heterogeneity (I2  = 94%). These ranged from 16 to 51% in male and 10-30% in female prisoners. For drug use disorders, there was evidence of heterogeneity by sex, and the pooled prevalence estimate in male prisoners was 30% (95% CI = 22-38; I2  = 98%; 13 studies; range 10-61%) and, in female prisoners, was 51% (95% CI = 43-58; I2  = 95%; 10 studies; range 30-69%). On meta-regression, sources of heterogeneity included higher prevalence of drug use disorders in women, increasing rates of drug use disorders in recent decades, and participation rate. CONCLUSIONS: Substance use disorders are highly prevalent in prisoners. Approximately a quarter of newly incarcerated prisoners of both sexes had an alcohol use disorder, and the prevalence of a drug use disorder was at least as high in men, and higher in women.

Comparative efficacy and tolerability of pharmacological interventions for attention-deficit/hyperactivity disorder in children, adolescents and adults: protocol for a systematic review and network meta-analysis.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is a major public health issue. Pharmacological treatments play an important role in the multimodal treatment of ADHD. Currently, there is a lack of up-to-date and comprehensive evidence on how available ADHD drugs compare and rank in terms of efficacy and tolerability, in children or adolescents as well as in adults. We will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomised controlled trials (RCTs), to rank pharmacological treatments for ADHD according to their efficacy and tolerability profiles. METHODS AND ANALYSIS: We will search a broad range of electronic databases, including PubMed, MEDLINE, EMBASE, PsycINFO, ERIC and Web of Science, with no date or language restrictions. We will also search for unpublished studies using international clinical trial registries and contacting relevant drug companies. We will identify and include available parallel-group, cross-over and cluster randomised trials that compare methylphenidate, dexmethylphenidate, amphetamine derivatives (including lisdexamfetamine), atomoxetine, clonidine, guanfacine, bupropion or modafinil (as oral therapy) either with each other or to placebo, in children, adolescents or adults with ADHD. Primary outcomes will be efficacy (indicated by reduction in severity of ADHD core symptoms measured on a standardised scale) and tolerability (the proportion of patients who left a study early due to side effects). Secondary outcomes will be global functioning, acceptability (proportion of patients who left the study early by any cause) and changes in blood pressure and body weight. NMA will be conducted in STATA within a frequentist framework. The quality of RCTs will be evaluated using the Cochrane risk of bias tool, and the quality of the evidence will be assessed using the GRADE approach. Subgroup and sensitivity analyses will be conducted to assess the robustness of the findings. ETHICS AND DISSEMINATION: No ethical issues are foreseen. Results from this study will be published in a peer-reviewed journal and possibly presented at relevant national and international conferences. TRIAL REGISTRATION NUMBER: CRD42014008976.

Mental health of prisoners: prevalence, adverse outcomes, and interventions.

More than 10 million people are imprisoned worldwide, and the prevalence of all investigated mental disorders is higher in prisoners than in the general population. Although the extent to which prison increases the incidence of mental disorders is uncertain, considerable evidence suggests low rates of identification and treatment of psychiatric disorders. Prisoners are also at increased risk of all-cause mortality, suicide, self-harm, violence, and victimisation, and research has outlined some modifiable risk factors. Few high quality treatment trials have been done on psychiatric disorders in prisoners. Despite this lack of evidence, trial data have shown that opiate substitution treatments reduce substance misuse relapse and possibly reoffending. The mental health needs of women and older adults in prison are distinct, and national policies should be developed to meet these. In this Review, we present clinical, research, and policy recommendations to improve mental health care in prisons. National attempts to meet these recommendations should be annually surveyed.

Improving awareness of patient safety in a peer-led pilot educational programme for undergraduate medical students.

BACKGROUND: Patient safety is becoming an important but under-emphasised topic in medical education. Despite high-profile recommendations, it has not yet been ingrained in the medical undergraduate curriculum. We designed and evaluated an educational intervention on patient safety to pre-clinical undergraduate medical students, devised and run entirely by medical students in their clinical years. The aim was to raise awareness of patient safety, and provide the opportunity to practice specific skills useful as medical students and junior doctors. METHODS: We designed a two hour seminar consisting of a brief lecture on the principles of patient safety, followed by a carousel of interactive activities in small groups. Attendance was voluntary. The effects were evaluated by questionnaires addressing satisfaction, attitudes and self-efficacy completed before, after and six months following the seminar. RESULTS: A total of 86 students attended, with a reserve list of interested students in place. A total of 92% completed the pre- and post-evaluation, of whom 100% enjoyed the seminar, 99% recommended other students to take part and 92% thought it should be a mandatory part of the curriculum. A total of 64% completed follow-up questionnaires at six months and showed significant maintenance of skills taught. DISCUSSION: Student tutors can deliver effective and engaging teaching on patient safety and should be utilised as part of the existing medical curriculum. Patient safety should be taught at medical schools using interactive methodologies to promote interest.

Social and custodial needs of older adults in prison.

BACKGROUND: older prisoners are a fast-growing group but there is limited evidence for how well their needs are being met. OBJECTIVES: to quantify the social and custodial needs of older prisoners and suggest improvements for service provision. DESIGN: cross-sectional study. SETTING: twelve prisons holding adult males in North West England. SUBJECTS: two hundred and sixty-two prisoners; 97 aged between 50 and 59, 165 aged 60 and over. METHODS: interview and case-note review for issues of social and custodial need and quality of life in prison, including Forensic Camberwell Assessment of Need and Lubben Scale for social networks. RESULTS: many had problems mixing with younger prisoners, accommodation and activities, and limited contact with friends and family. A small group had personal care needs which were not well managed in prison. CONCLUSION: older prisoners have distinct social and custodial needs which need to be addressed by a national strategy for their care and management.

The health and social needs of older male prisoners.

OBJECTIVES: This study aimed to quantify the health and social needs of older male prisoners in the North West of England, to determine whether their needs were being met, and to explore an age cut-off for this group. METHODS: Data were collected by interview and case note review. Areas covered included physical health, mental health, personality disorder, cognitive impairment and social need. RESULTS: A total of 262 prisoners were included in the study. Over 90% had a physical health disorder, most commonly hypertension and osteoarthritis. A total of 61% had a mental disorder, most commonly major depressive disorder and alcohol misuse disorder. There were few differences within age bands for physical health problem or health/social need, but those aged 50-59 years had more mental disorder, including mental illness, substance misuse disorder and personality disorder. CONCLUSIONS: Older prisoners have a high level of health need and a different profile to the rest of the prison population. Fifty appears to be a useful age over which to define this group, and service provision should reflect this in a national management strategy.

Improvements to suicide prevention training for prison staff in England and Wales.

Suicide prevention training for the prison service in England and Wales has been criticized. STORM is a package emphasizing the practice and review of interactions with suicidal persons and was evaluated in a pilot study for use in prisons. Trainees completed questionnaires immediately before and after training and at 6 to 8 months follow-up. Training significantly improved attitudes, knowledge, and confidence, and improvements were maintained at follow-up. Satisfaction with training was very high. STORM was successfully adapted for prison settings, and showed good effects among staff trained. It should be provided to the wider prison estate, with regular refresher training.