Patient preference as a predictor of outcomes in a pilot trial of person-centred counselling versus low-intensity cognitive behavioural therapy for persistent sub-threshold and mild depression

The aim of this analysis was to explore whether pre-treatment intervention preferences were related to outcomes for patients with persistent sub-threshold and mild depression who received one of two treatment types. Thirty-six patients took part in a two-arm, parallel group, pilot randomized controlled trial that compared short term (3 month and 6 month) outcomes of person-centred counselling (PCC) compared with low-intensity, CBT-based guided self-help (LICBT). Patient preferences for the two interventions were assessed at baseline assessment, and analysed as two independent linear variables (pro-PCC, pro-LICBT). Eight out of 30 interactions between baseline treatment preferences and treatment type were found to be significant at the p < .05 level. All were in the predicted direction, with patients who showed a stronger preference for a treatment achieving better outcomes in that treatment compared with the alternative. However, pro-LICBT was a stronger predictor of outcomes than pro-PCC. The findings provide preliminary support that treatment preferences should be taken into account when providing interventions for patients with persistent sub-threshold and mild depression. It is recommended that further research analyses preferences for different treatment types as independent variables, and examines preferences for format of treatment (e.g. guided self-help vs. face-to-face)

Randomised, double-blind, placebo-controlled trials of non-individualised homeopathic treatment: systematic review and meta-analysis

Background: A rigorous systematic review and meta-analysis focused on randomised controlled trials (RCTs) of non-individualised homeopathic treatment has not previously been reported. We tested the null hypothesis that the main outcome of treatment using a non-individualised (standardised) homeopathic medicine is indistinguishable from that of placebo. An additional aim was to quantify any condition-specific effects of non-individualised homeopathic treatment. Methods: Literature search strategy, data extraction and statistical analysis all followed the methods described in a pre-published protocol. A trial comprised ‘reliable evidence’ if its risk of bias was low or it was unclear in one specified domain of assessment. ‘Effect size’ was reported as standardised mean difference (SMD), with arithmetic transformation for dichotomous data carried out as required; a negative SMD indicated an effect favouring homeopathy. Results: Forty-eight different clinical conditions were represented in 75 eligible RCTs. Forty-nine trials were classed as ‘high risk of bias’ and 23 as ‘uncertain risk of bias’; the remaining three, clinically heterogeneous, trials displayed sufficiently low risk of bias to be designated reliable evidence. Fifty-four trials had extractable data: pooled SMD was –0.33 (95% confidence interval (CI) –0.44, –0.21), which was attenuated to –0.16 (95% CI –0.31, –0.02) after adjustment for publication bias. The three trials with reliable evidence yielded a non-significant pooled SMD: –0.18 (95% CI –0.46, 0.09). There was no single clinical condition for which meta-analysis included reliable evidence. Conclusions: The quality of the body of evidence is low. A meta-analysis of all extractable data leads to rejection of our null hypothesis, but analysis of a small sub-group of reliable evidence does not support that rejection. Reliable evidence is lacking in condition-specific meta-analyses, precluding relevant conclusions. Better designed and more rigorous RCTs are needed in order to develop an evidence base that can decisively provide reliable effect estimates of non-individualised homeopathic treatment

ECG in suspected pulmonary embolism

Objective: To establish the diagnostic value of prespecified ECG changes in suspected pulmonary embolism (PE). Methods: Retrospective case–control study in a district general hospital setting. We identified 189 consecutive patients with suspected PE whose CT pulmonary angiogram (CTPA) was positive for a first PE and for whom an ECG taken at the time of presentation was available. We matched these for age±3 years with 189 controls with suspected PE whose CTPA was negative. We considered those with large (n=76) and small (n=113) clot load separately. We scored each ECG for the presence or absence of eight features that have been reported to occur more commonly in PE. Results: 20%–25% of patients with PE, including those with large clot load, had normal ECGs. The most common ECG abnormality in patients with PE was sinus tachycardia (28%). S1Q3T3 (3.7%), P pulmonale (0.5%) and right axis deviation (4.2%) were infrequent findings. Right bundle branch block (9.0%), atrial dysrhythmias (10.1%) and clockwise rotation (20.1%) occurred more frequently but were also common in controls. Right ventricular (RV) strain pattern was significantly more commonly in patients than controls, 11.1% vs 2.6% (sensitivity 11.1%, specificity 97.4%; OR 4.58, 95% CI 1.63 to 15.91; p=0.002), particularly in those with large clot load, 17.1% vs 2.6% (sensitivity 17.1%, specificity 97.4%; OR 7.55, 95% CI 1.62 to 71.58; p=0.005). Conclusion: An ECG showing RV strain in a breathless patient is highly suggestive of PE. Many of the other ECG changes that have been described in PE occur too infrequently to be of predictive value

Excessive age-related decline in functional ovarian reserve in infertile women: prospective cohort of 15,500 women

Context: Whether infertile women exhibit accelerated ovarian aging and whether a low ovarian reserve is overrepresented in infertility populations is not known. Objective: To compare the age-related decline in antral follicle count (AFC), a biomarker of the ovarian reserve, in fertile and infertile women. Design: Cross-sectional data from a large prospective cohort study conducted from January 2013 to December 2014. Setting: Thirteen fertility centers across Spain. Patients or Other Participants: Consecutive women aged 18 to 45 years of age attending the fertility centers either seeking fertility treatment or as fertile women wishing to act as potential oocyte donors. Intervention(s): Standardized AFC assessment on day 2 to 4 of the cycle. Main Outcome Measure(s): Age-related decline of AFC for both fertile and infertile women. Results: A total of 15 500 women, of whom 5722 were potential donors and 9778 were patients seeking fertility treatment, participated in the study. Average AFC was greater in potential oocyte donors than in infertile women (20 [interquartile range, 16–24] vs 10 [interquartile range, 6–15], respectively; P < .001), a difference that was maintained after adjustment for age (P < .001) in a model predicting log(AFC) from donor vs infertility, adjusting for 2-year age bands. The age-related decline in AFC was much steeper in infertile women compared with that of potential oocyte donors, with an increased prevalence of a low ovarian reserve (AFC < 5) at all ages in infertile women. Conclusions: The age-related decline in AFC was substantially greater in infertility patients than potential oocyte donors. Overrepresentation in infertility populations of women with low ovarian reserve may be an additional functional cause of infertility

Autism and attachment disorder symptoms in the general population : Prevalence, overlap, and burden

Acknowledgements: This work was supported by the Chief Scientist Office of the Scottish Government (CZG/2/565) and the Gillberg Neuropsychiatry Centre. We are grateful to all of the participants and to the Growing up in Scotland team for their support with this study. Funding: The author(s) received no financial support for the research, authorship, and/or publication of this articlePeer reviewedPublisher PD

Within-trial cost and 1-year cost-effectiveness of the DiRECT/Counterweight-Plus weight-management programme to achieve remission of type 2 diabetes

No abstract available

Study protocol for COVID-RV: a multicentre prospective observational cohort study of right ventricular dysfunction in ventilated patients with COVID-19

Introduction: COVID-19 can cause severe acute respiratory failure requiring management in intensive care unit with invasive ventilation and a 40% mortality rate. Cardiovascular manifestations are common and studies have shown an increase in right ventricular (RV) dysfunction associated with mortality. These studies, however, comprise heterogeneous patient groups with few requiring invasive ventilation. This study will investigate the prevalence and prognostic significance of RV dysfunction in ventilated patients with COVID-19 which may lead to targeted interventions to improve patient outcomes. Methods and analysis: This prospective multicentre observational cohort study will perform transthoracic echocardiography (TTE) in 150 patients with COVID-19 requiring invasive ventilation for more than 48 hours. RV dysfunction will be defined as TTE evidence of RV dilatation along with the presence of septal flattening. Baseline demographics, disease severity data and clinical information relating to proposed aetiological mechanisms of RV dysfunction (acute respiratory distress syndrome (ARDS), disordered coagulation, direct myocardial injury and ventilation) will be collected and analysed. Primary outcome measures include the prevalence of RV dysfunction and its association with 30-day mortality. Exploratory outcome measures will investigate the association of the proposed aetiological mechanisms of RV dysfunction to the primary outcomes. Prevalence of RV dysfunction will be determined along with 95% Clopper-Pearson CIs and 30-day survival will be analysed using logistic regression adjusting for patient demographics, phase of disease and baseline severity of illness. The role of potential aetiological factors (ARDS, disordered coagulation, direct myocardial injury and ventilation) in relation to the primary outcomes will be analysed using logistic regression. Ethics and dissemination: Approval was gained from Scotland A Research Ethics Committee (REC reference 20/SS/0059). Findings will be disseminated by various methods including webinars, international presentations and publication in peer-reviewed journals

Association between GDF-15 levels and changes in vascular and physical function in older patients with hypertension

Background: Growth differentiation factor-15 (GDF-15) may be a biomarker of disease, protective response and/or prognosis, in older people with hypertension. Aims: To correlate baseline GDF-15 levels with physical and vascular health data in this population. Methods: Baseline blood samples were analysed using a GDF-15 ELISA assay kit. Correlations with baseline and 12-month outcome data, including measures of physical and vascular function, were performed. Results: A total of 147 individuals, mean age 76.8 ± 4.7 years, were included. 77 (52 %) were male. Baseline log10GDF-15 showed significant correlations with age (r = 0.37, p < 0.001), total cholesterol (r = −0.33, p < 0.001) and 6-min walking distance (r = −0.37, p < 0.001). Age remained significantly associated with log10GDF-15 in multivariable analysis (beta = −0.29, p = 0.001). Baseline log10GDF-15 was significantly associated with decline in 6-min walk distance over 12 months (beta = −0.27, p = 0.01) in multivariable models. No significant correlations were seen with changes in vascular function over 12 months. Conclusion: Baseline GDF-15 predicts declining physical, but not vascular, function in our population

The Best Services Trial (BeST?) : a cluster randomised controlled trial comparing the clinical and cost-effectiveness of New Orleans Intervention Model with services as usual (SAU) for infants and young children entering care

Funding Information: The definitive RCT is funded by the National Institute for Health Research (PHR ref 12/211/54). Other funders include the Chief Scientist’s Office, The National Society for the Prevention of Cruelty to Children, and the Department of Health and Social Care. The funding body approved the design of the study, will approve any substantial amendments to data collection and will be involved in reviewing major outputs.Peer reviewedPublisher PD

Type 2 diabetes remission: 2 year within-trial and lifetime-horizon cost-effectiveness of the Diabetes Remission Clinical Trial (DiRECT)/Counterweight-Plus weight management programme.

AIMS/HYPOTHESIS: Approximately 10% of total healthcare budgets worldwide are spent on treating diabetes and its complications, and budgets are increasing globally because of ageing populations and more expensive second-line medications. The aims of the study were to estimate the within-trial and lifetime cost-effectiveness of the weight management programme, which achieved 46% remissions of type 2 diabetes at year 1 and 36% at year 2 in the Diabetes Remission Clinical Trial (DiRECT). METHODS: Within-trial analysis assessed costs of the Counterweight-Plus intervention in DiRECT (including training, programme materials, practitioner appointments and low-energy diet), along with glucose-lowering and antihypertensive medications, and all routine healthcare contacts. Lifetime cost per quality-adjusted life-year (QALY) was estimated according to projected durations of remissions, assuming continued relapse rates as seen in year 2 of DiRECT and consequent life expectancy, quality of life and healthcare costs. RESULTS: Mean total 2 year healthcare costs for the intervention and control groups were £3036 and £2420, respectively: an incremental cost of £616 (95% CI -£45, £1269). Intervention costs (£1411; 95% CI £1308, £1511) were partially offset by lower other healthcare costs (£796; 95% CI £150, £1465), including reduced oral glucose-lowering medications by £231 (95% CI £148, £314). Net remission at 2 years was 32.3% (95% CI 23.5%, 40.3%), and cost per remission achieved was £1907 (lower 95% CI: intervention dominates; upper 95% CI: £4212). Over a lifetime horizon, the intervention was modelled to achieve a mean 0.06 (95% CI 0.04, 0.09) QALY gain for the DiRECT population and mean total lifetime cost savings per participant of £1337 (95% CI £674, £2081), with the intervention becoming cost-saving within 6 years. CONCLUSIONS/INTERPRETATION: Incorporating the lifetime healthcare cost savings due to periods of remission from diabetes and its complications, the DiRECT intervention is predicted to be both more effective (QALY gain) and cost-saving in adults with type 2 diabetes compared with standard care. This conclusion appears robust to various less favourable model scenarios, providing strong evidence that resources could be shifted cost-effectively to support achieving remissions with the DiRECT intervention. TRIAL REGISTRATION: ISRCTN03267836 Graphical abstract