Bodily symptoms are common in community samples, but not all people consult for medical advice about such symptoms. Medically unexplained symptoms (MUS) refer to persistent bodily complaints for which adequate examination (including investigation) does not reveal sufficiently explanatory structural or other specified pathology.1 MUS are common, with a spectrum of severity, and patients are found everywhere within the healthcare system.2 It has been estimated that MUS account for up to 45% of all general practice consultations, 3 while a study based in secondary care indicated that about 50% of patients had no clear diagnosis at 3 months. 2 WHAT ARE THE COSTS OF MUS?The annual NHS cost for MUS in adults of working age in England was estimated to be £2.89 billion in 2008/2009 (11% of total NHS spend), while sickness absence and decreased quality of life for people with MUS was estimated as costing over £14 billion per annum to the UK economy.

ObjectiveTo investigate the effectiveness of combining mirtazapine with serotonin-noradrenaline reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRI) antidepressants for treatment resistant depression in primary care.DesignTwo parallel group multicentre phase III randomised placebo controlled trial.Setting106 general practices in four UK sites; Bristol, Exeter, Hull, and Keele/North Staffs, August 2013 to October 2015.Participants480 adults aged 18 or more years who scored 14 or more on the Beck depression inventory, second revision, fulfilled ICD-10 (international classification of diseases, 10th revision) criteria for depression, and had used an SSRI or SNRI for at least six weeks but were still depressed. 241 were randomised to mirtazapine and 239 to placebo, both given in addition to usual SSRI or SNRI treatment. Participants were stratified by centre and minimised by baseline Beck depression inventory score, sex, and current psychological therapy. They were followed up at 12, 24, and 52 weeks. 431 (89.8%) were included in the (primary) 12 week follow-up.Main outcome measuresDepressive symptoms at 12 weeks after randomisation, measured using the Beck depression inventory II score as a continuous variable. Secondary outcomes included measures of anxiety, quality of life, and adverse effects at 12, 24, and 52 weeks.ResultsBeck depression inventory II scores at 12 weeks were lower in the mirtazapine group after adjustment for baseline scores and minimisation or stratification variables, although the confidence interval included the null (mean (SD) scores at 12 weeks: 18.0 (12.3) in the mirtazapine group, 19.7 (12.4) in the placebo group; adjusted difference between means −1.83 (95% confidence interval −3.92 to 0.27); P=0.09). Adverse effects were more common in the mirtazapine group and were associated with the participants stopping the trial drug.ConclusionThis study did not find evidence of a clinically important benefit for mirtazapine in addition to an SSRI or SNRI over placebo in a treatment resistant group of primary care patients with depression. This remains an area of important unmet need where evidence of effective treatment options is limited.Trial registrationCurrent Controlled Trials ISRCTN06653773.

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Monozygotic (MZ) and dizygotic (DZ) twins participate in research that partitions variance in health, disease, and behavior into genetic and environmental components. However, there are other innovative roles for twins in medical research. One such way is involving MZ and/or DZ twins in co-twin control-designed randomized controlled trials (RCTs). To our knowledge, no reviews have been conducted that summarizes the involvement of twins in RCTs. Therefore, we conducted a systematic literature search using the U.S. Clinical Trials Database, NHS electronic databases, MEDLINE, EMBASE, and PsychINFO for RCTs on publications involving MZ and/or DZ twins as RCT participants. Out of the 186,027 clinical trials registered in the U.S. clinical trial register ClinicaTrails.gov, only six RCTs used twins as participants. From 1,598 articles identified in our search, 50 peer-reviewed English language publications met our pre-defined inclusion criteria. Sample sizes for RCTs have ranged from a total number of participants from 2 to 1,162; however, 32 (64%) studies had a sample size of 100 or less, and of those, 12 (24%) had fewer than 10. Both MZ and DZ twins have been recruited to the RCTs. In most instances (33/50) each twin from a pair were assigned to different study arms. Most of those studies included MZ twins only. Despite the methodological advantages, the use of MZ and DZ twins as participants in interventional RCTs appeared limited. The continuous development of innovative twin designs, especially RCTs, indicates that twin research can extend beyond the more widely recognized heritability estimates.

Background The prevention of self-harm is an international public health priority. It is vital to identify at-risk populations, particularly as self-harm is a risk factor for suicide. This study aims to examine the risk of self-harm in people with vertebral fractures. Methods Retrospective cohort study. Patients with vertebral fracture were identified within the Clinical Practice Research Datalink and matched to patients without fracture by sex and age. Incident self-harm was defined by primary care record codes following vertebral fracture. Overall incidence rates (per 10,000 person-years (PY)) were reported. Cox regression analysis determined risk (hazard ratios (HR), 95 % confidence interval (CI)) of self-harm compared to the matched unexposed cohort. Initial crude analysis was subsequently adjusted and stratified by median age and sex. Results The number of cases of vertebral fracture was 16,293, with a matched unexposed cohort of the same size. Patients were predominantly female (70.1 %), median age was 76.3 years. Overall incidence of self-harm in the cohort with vertebral fracture was 12.2 (10.1, 14.8) /10,000 PY. There was an initial crude association between vertebral fracture and self-harm, which remained after adjustment (HR 2.4 (95 %CI 1.5, 3.6). Greatest risk of self-harm was found in those with vertebral fractures who were aged below 76.3 years (3.2(1.8, 5.7)) and male (3.9(1.8, 8.5)). Conclusions Primary care patients with vertebral fracture are at increased risk of self-harm compared to people without these fractures. Male patients aged below 76 years of age appear to be at greatest risk of self-harm. Clinicians need to be aware of the potential for self-harm in this patient group.