Dr Caroline Jenkinson

Background. The role of GPs in recruiting or excluding participants critically underpins the feasibility, external validity and generalizability of primary care research. A better understanding of this role is needed. Aim. To investigate why GPs excluded potentially eligible participants from a large scale randomized controlled trial (RCT), to determine the proportion of patients excluded on account of trial eligibility compared with other reasons, and to explore the impact of such exclusions on the management and generalizability of RCTs. Design and setting. Secondary analysis of data from the CoBalT study, a multi-centre general-practice-based RCT investigating cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression. Method. GPs were asked to screen patient lists generated from computerized record searches for trial eligibility and to provide narrative reasons for excluding patients. These reasons were coded independently by two researchers, with a third researcher resolving discrepancies. Results. Thirty-one percent (4750/15 379) of patients were excluded at the GP screening stage, including 663 on patient lists that remained unscreened. Of the 4087 actively excluded patients, 67% were excluded on account of trial exclusion criteria, 20% for other criteria (half of which were comorbid conditions) and 13% without reason. Conclusion. Clear, comprehensive criteria, particularly with regards to comorbidities, are required for GPs to confidently screen patients for potential participation in research. Future studies should promote inclusivity and encourage GPs to adopt a liberal approach when screening patient lists. This would enhance the validity and generalizability of primary care research and encourage greater patient autonomy.

OBJECTIVE To 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. DESIGN Two parallel group multicentre phase III randomised placebo controlled trial. SETTING 106 general practices in four UK sites; Bristol, Exeter, Hull, and Keele/North Staffs, August 2013 to October 2015. PARTICIPANTS 480 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 MEASURES Depressive 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. RESULTS Beck 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. CONCLUSION This 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.

The NHS Cardiovascular Health Check (NHSHC) programme was introduced in England in 2009 to reduce cardiovascular disease mortality and morbidity for all patients aged 40 to 74 years old. Programme cost-effectiveness was based on an assumed uptake of 75% but current estimates of uptake in primary care are less than 50%. The purpose of this study was to identify factors influencing patients' willingness to attend an NHSHC. For those who attended, their views, experiences and their future willingness to engage in the programme were explored. Telephone or face-to-face interviews were conducted with patients who had recently been invited for an NHSHC by a letter from four general practices in Torbay, England. Patients were purposefully sampled (by gender, age, attendance status). Interviews were audio recorded, transcribed verbatim and analysed thematically. 17 attendees and 10 non-attendees were interviewed. Patients who attended an NHSHC viewed it as worthwhile. Proactive attitudes towards their health, a desire to prevent disease before they developed symptoms, and a willingness to accept screening and health check invitations motivated many individuals to attend. Non-attendees cited not seeing the NHSHC as a priority, or how it differed from regular monitoring already received for other conditions as barriers to attendance. Some non-attendees actively avoided GP practices when feeling well, while others did not want to waste health professionals' time. Misunderstandings of what the NHSHC involved and negative views of what the likely outcome might be were common. While a minority of non-attendees simply had made an informed choice not to have an NHSHC, improving the clarity and brevity of invitational materials, better advertising, and simple administrative interventions such as sending reminder letters, have considerable potential to improve NHSHC uptake.

Introduction Pharmaceutical treatment options for patients with type 2 diabetes mellitus (T2DM) have increased to include multiple classes of oral glucose-lowering agents but without accompanying guidance on which of these may most benefit individual patients. Clinicians lack information for treatment intensification after first-line metformin therapy. Stratifying patients by simple clinical characteristics may improve care by targeting treatment options to those in whom they are most effective. This academically designed and run three-way crossover trial aims to test a stratification approach using three standard oral glucose-lowering agents. Methods and analysis TriMaster is a randomised, double-blind, crossover trial taking place at up to 25 clinical sites across England, Scotland and Wales. 520 patients with T2DM treated with either metformin alone, or metformin and a sulfonylurea who have glycated haemoglobin (HbA(1c)) >58 mmol/mol will be randomised to receive 16 weeks each of a dipeptidyl peptidase-4 inhibitor, sodium-glucose co-transporter-2 inhibitor and thiazolidinedione in random order. Participants will be assessed at the end of each treatment period, providing clinical and biochemical data, and their experience of side effects. Participant preference will be assessed on completion of all three treatments. The primary endpoint is HbA(1c) after 4 months of therapy (allowing a range of 12-18 weeks for analysis). Secondary endpoints include participant-reported preference between the three treatments, tolerability and prevalence of side effects. Ethical approval This study was approved by National Health Service Health Research Authority Research Ethics Committee South Central-Oxford A, study 16/SC/0147. Written informed consent will be obtained from all participants. Results will be submitted to a peer-reviewed journal and presented at relevant scientific meetings. A lay summary of results will be made available to all participants.

Coronary heart disease (CHD) is the most common cause of death globally, although mortality rates are falling. Psychological symptoms are prevalent for people with CHD, and many psychological treatments are offered following cardiac events or procedures with the aim of improving health and outcomes. This is an update of a Cochrane systematic review previously published in 2011. To assess the effectiveness of psychological interventions (alone or with cardiac rehabilitation) compared with usual care (including cardiac rehabilitation where available) for people with CHD on total mortality and cardiac mortality; cardiac morbidity; and participant-reported psychological outcomes of levels of depression, anxiety, and stress; and to explore potential study-level predictors of the effectiveness of psychological interventions in this population. We updated the previous Cochrane Review searches by searching the following databases on 27 April 2016: CENTRAL in the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid), and CINAHL (EBSCO). We included randomised controlled trials (RCTs) of psychological interventions compared to usual care, administered by trained staff, and delivered to adults with a specific diagnosis of CHD. We selected only studies estimating the independent effect of the psychological component, and with a minimum follow-up of six months. The study population comprised of adults after: a myocardial infarction (MI), a revascularisation procedure (coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI)), and adults with angina or angiographically defined coronary artery disease (CAD). RCTs had to report at least one of the following outcomes: mortality (total- or cardiac-related); cardiac morbidity (MI, revascularisation procedures); or participant-reported levels of depression, anxiety, or stress. Two review authors independently screened titles and abstracts of all references for eligibility. A lead review author extracted study data, which a second review author checked. We contacted study authors to obtain missing information. This review included 35 studies which randomised 10,703 people with CHD (14 trials and 2577 participants added to this update). The population included mainly men (median 77.0%) and people post-MI (mean 65.7%) or after undergoing a revascularisation procedure (mean 27.4%). The mean age of participants within trials ranged from 53 to 67 years. Overall trial reporting was poor, with around a half omitting descriptions of randomisation sequence generation, allocation concealment procedures, or the blinding of outcome assessments. The length of follow-up ranged from six months to 10.7 years (median 12 months). Most studies (23/35) evaluated multifactorial interventions, which included therapies with multiple therapeutic components. Ten studies examined psychological interventions targeted at people with a confirmed psychopathology at baseline and two trials recruited people with a psychopathology or another selecting criterion (or both). Of the remaining 23 trials, nine studies recruited unselected participants from cardiac populations reporting some level of psychopathology (3.8% to 53% with depressive symptoms, 32% to 53% with anxiety), 10 studies did not report these characteristics, and only three studies excluded people with psychopathology.Moderate quality evidence showed no risk reduction for total mortality (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.77 to 1.05; participants = 7776; studies = 23) or revascularisation procedures (RR 0.94, 95% CI 0.81 to 1.11) with psychological therapies compared to usual care. Low quality evidence found no risk reduction for non-fatal MI (RR 0.82, 95% CI 0.64 to 1.05), although there was a 21% reduction in cardiac mortality (RR 0.79, 95% CI 0.63 to 0.98). There was also low or very low quality evidence that psychological interventions improved participant-reported levels of depressive symptoms (standardised mean difference (SMD) -0.27, 95% CI -0.39 to -0.15; GRADE = low), anxiety (SMD -0.24, 95% CI -0.38 to -0.09; GRADE = low), and stress (SMD -0.56, 95% CI -0.88 to -0.24; GRADE = very low).There was substantial statistical heterogeneity for all psychological outcomes but not clinical outcomes, and there was evidence of small-study bias for one clinical outcome (cardiac mortality: Egger test P = 0.04) and one psychological outcome (anxiety: Egger test P = 0.012). Meta-regression exploring a limited number of intervention characteristics found no significant predictors of intervention effects for total mortality and cardiac mortality. For depression, psychological interventions combined with adjunct pharmacology (where deemed appropriate) for an underlying psychological disorder appeared to be more effective than interventions that did not (β = -0.51, P = 0.003). For anxiety, interventions recruiting participants with an underlying psychological disorder appeared more effective than those delivered to unselected populations (β = -0.28, P = 0.03). This updated Cochrane Review found that for people with CHD, there was no evidence that psychological treatments had an effect on total mortality, the risk of revascularisation procedures, or on the rate of non-fatal MI, although the rate of cardiac mortality was reduced and psychological symptoms (depression, anxiety, or stress) were alleviated; however, the GRADE assessments suggest considerable uncertainty surrounding these effects. Considerable uncertainty also remains regarding the people who would benefit most from treatment (i.e. people with or without psychological disorders at baseline) and the specific components of successful interventions. Future large-scale trials testing the effectiveness of psychological therapies are required due to the uncertainty within the evidence. Future trials would benefit from testing the impact of specific (rather than multifactorial) psychological interventions for participants with CHD, and testing the targeting of interventions on different populations (i.e. people with CHD, with or without psychopathologies).

ObjectivesThis mixed-methods study evaluated the feasibility, acceptability and preliminary effectiveness of an interactive digital training programme for non-specialist supporters providing a guided self-help intervention for postnatal depression (PND).MethodsA total of 49 non-specialist trainees participated. Six digital training modules were flexibly delivered over a 5-week period. Training included a chatroom, moderated by a supervised assistant psychologist. Quantitatively, feasibility was assessed via participation and retention levels; acceptability was examined using course evaluation questionnaires; and effectiveness was measured pre-test-post-test quantitatively using a self-report questionnaire and pre-post using scenario questions. Participant focus groups explored feasibility, acceptability and effectiveness.ResultsThe training was feasible; 41 completed the course and 42 were assessed at follow-up. Quantitative course evaluation and thematic analysis of focus group feedback demonstrated high training acceptability. RANOVAs indicated training significantly improved knowledge and confidence pre- to post-test. There were demonstrable increases in specific skills at post-test as assessed via clinical scenarios.ConclusionThis training is a feasible, acceptable and effective way to upskill non-specialists in supporting treatment for PND, however supervised practice is recommended to ensure participants embed knowledge competently into practice. The training offers an effective first step in upskilling non-specialist supporters to support women with PND treatment at scale.

Background Although psychological interventions are recommended for the management of coronary heart disease (CHD), there remains considerable uncertainty regarding their effectiveness. Design Systematic review and meta-analysis of randomised controlled trials (RCTs) of psychological interventions for CHD. Methods The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL and PsycINFO were searched to April 2016. Retrieved papers, systematic reviews and trial registries were hand-searched. We included RCTs with at least 6 months of follow-up, comparing the direct effects of psychological interventions to usual care for patients following myocardial infarction or revascularisation or with a diagnosis of angina pectoris or CHD defined by angiography. Two authors screened titles for inclusion, extracted data and assessed risk of bias. Studies were pooled using random effects meta-analysis and meta-regression was used to explore study-level predictors. Results Thirty-five studies with 10,703 participants (median follow-up 12 months) were included. Psychological interventions led to a reduction in cardiovascular mortality (rfcelative risk 0.79, 95% confidence interval [CI] 0.63 to 0.98), although no effects were observed for total mortality, myocardial infarction or revascularisation. Psychological interventions improved depressive symptoms (standardised mean difference [SMD] -0.27, 95% CI -0.39 to -0.15), anxiety (SMD -0.24, 95% CI -0.38 to -0.09) and stress (SMD -0.56, 95% CI -0.88 to -0.24) compared with controls. Conclusions We found that psychological intervention improved psychological symptoms and reduced cardiac mortality for people with CHD. However, there remains considerable uncertainty regarding the magnitude of these effects and the specific techniques most likely to benefit people with different presentations of CHD.