The bi-factor structure of the 17-item Hamilton Depression Rating Scale in persistent major depression; dimensional measurement of outcome

Background:The 17-item Hamilton Depression Rating Scale (HDRS17) is used world-wide as an observer-rated measure of depression in randomised controlled trials (RCTs) despite continued uncertainty regarding its factor structure. This study investigated the dimensionality of HDRS17 for patients undergoing treatment in UK mental health settings with moderate to severe persistent major depressive disorder (PMDD).Methods:Exploratory Structural Equational Modelling (ESEM) was performed to examine the HDRS17 factor structure for adult PMDD patients with HDRS17 score ≥16. Participants (n = 187) were drawn from a multicentre RCT conducted in UK community mental health settings evaluating the outcomes of a depression service comprising CBT and psychopharmacology within a collaborative care model, against treatment as usual (TAU). The construct stability across a 12-month follow-up was examined through a measurement equivalence/invariance (ME/I) procedure via ESEM.Results:ESEM showed HDRS17 had a bi-factor structure for PMDD patients (baseline mean (sd) HDRS17 22.6 (5.2); 87% PMDD >1 year) with an overall depression factor and two group factors: vegetative-worry and retardation-agitation, further complicated by negative item loading. This bi-factor structure was stable over 12 months follow up. Analysis of the HDRS6 showed it had a unidimensional structure, with positive item loading also stable over 12 months.Conclusions:In this cohort of moderate-severe PMDD the HDRS17 had a bi-factor structure stable across 12 months with negative item loading on domain specific factors, indicating that it may be more appropriate to multidimensional assessment of settled clinical states, with shorter unidimensional subscales such as the HDRS6 used as measures of change

Biological vulnerability to depression: Linked structural and functional brain network findings

Background: Patients in recovery following episodes of major depressive disorder (MDD) remain highly vulnerable to future recurrence. Although psychological determinants of this risk are well established, little is known about associated biological mechanisms. Recent work has implicated the default mode network (DMN) in this vulnerability but specific hypotheses remain untested within the high risk, recovered state of MDD. Aims: To test the hypothesis that there is excessive DMN functional connectivity during task performance within recovered-state MDD and to test for connected DMN cortical gyrification abnormalities. Method: A multimodal structural and functional magnetic resonance imaging (fMRI) study, including task-based functional connectivity and cortical folding analysis, comparing 20 recoveredstate patients with MDD with 20 matched healthy controls. Results: The MDD group showed significant task-based DMN hyperconnectivity, associated with hypogyrification of key DMN regions (bilateral precuneus). Conclusions: This is the first evidence of connected structural and functional DMN abnormalities in recovered-state MDD, supporting recent hypotheses on biological-level vulnerability

Exploring access to support services for medical students: recommendations for enhancing wellbeing support

BackgroundMedical students have reported facing unique challenges in their academic journey that can have a significant impact on their mental health and wellbeing; therefore, their access to support services and wellbeing resources has been deemed crucial for dealing effectively with the various challenges they tend to face. While previous research has highlighted certain barriers affecting medical students’ help-seeking and access to wellbeing support more generally, there is a pressing need for more in-depth research into the factors that may hinder or facilitate medical students’ acceptability and uptake of the wellbeing resources available to them within institutional contexts. The current study aims to explore students’ perceptions and utilization of wellbeing interventions and welfare resources within a medical school setting, as well as the factors influencing their help-seeking attitudes or behaviours. Additionally, it seeks to instigate medical students’ deeper reflections on potential enhancements that could be applied to wellbeing resources so that they are better suited to address their needs. MethodsThis study employed a qualitative design, involving semi-structured interviews and a series of focus groups with medical students at the University of Nottingham (UK). Post-interview, focus groups were deemed necessary to gain deeper insights into emerging findings from the interviews regarding students’ views on wellbeing support services. Qualitative data from the interviews was subjected to thematic analysis while a hybrid thematic analytic approach was applied for the focus group data in order to allow for both pre-defined themes from the interviews and newly emerging patterns to be identified and analysed in a combined manner. ResultsTwenty-five participants took part in the semi-structured interviews and twenty-two participants were recruited in a total of seven focus groups. Thematic analysis findings identified several key barriers to medical students’ accessing wellbeing resources, including difficulties in finding relevant information, lengthy processes and difficulties receiving prompt help in urgent situations, learning environment issues, confidentiality concerns, and stigma around mental health. Student suggestions for the enhancement of wellbeing provision were centered around proposed improvements in the format that the relevant information was presented and in the structure underlying the delivery of support services. ConclusionThe study findings shed light on multi-faceted factors contributing to medical students’ challenges in accessing support services; and provided a deeper understanding of medical students’ wellbeing needs through a consolidation of their recommendations for the implementation of practical steps to address these needs. These steps can potentially inform key medical education stakeholders so that they can actively and proactively foster more supportive environments that may help improve medical students’ help-seeking, as well as their acceptability and uptake of wellbeing services

Standardisation of data from real-time quantitative PCR methods – evaluation of outliers and comparison of calibration curves

BACKGROUND: As real-time quantitative PCR (RT-QPCR) is increasingly being relied upon for the enforcement of legislation and regulations dependent upon the trace detection of DNA, focus has increased on the quality issues related to the technique. Recent work has focused on the identification of factors that contribute towards significant measurement uncertainty in the real-time quantitative PCR technique, through investigation of the experimental design and operating procedure. However, measurement uncertainty contributions made during the data analysis procedure have not been studied in detail. This paper presents two additional approaches for standardising data analysis through the novel application of statistical methods to RT-QPCR, in order to minimise potential uncertainty in results. RESULTS: Experimental data was generated in order to develop the two aspects of data handling and analysis that can contribute towards measurement uncertainty in results. This paper describes preliminary aspects in standardising data through the application of statistical techniques to the area of RT-QPCR. The first aspect concerns the statistical identification and subsequent handling of outlying values arising from RT-QPCR, and discusses the implementation of ISO guidelines in relation to acceptance or rejection of outlying values. The second aspect relates to the development of an objective statistical test for the comparison of calibration curves. CONCLUSION: The preliminary statistical tests for outlying values and comparisons between calibration curves can be applied using basic functions found in standard spreadsheet software. These two aspects emphasise that the comparability of results arising from RT-QPCR needs further refinement and development at the data-handling phase. The implementation of standardised approaches to data analysis should further help minimise variation due to subjective judgements. The aspects described in this paper will help contribute towards the development of a set of best practice guidelines regarding standardising handling and interpretation of data arising from RT-QPCR experiments

Generating groups using hypergraphs

To a set B of 4-subsets of a set Ω of size n, we introduce an invariant called the ‘hole stabilizer’ which generalizes a construction of Conway, Elkies and Martin of the Mathieu group M12 based on Lloyd's ‘15-puzzle’. It is shown that hole stabilizers may be regarded as objects inside an objective partial group (in the sense of Chermak). We classify pairs (Ω,B) with a trivial hole stabilizer, and determine all hole stabilizers associated to 2-(n,4,λ) designs with λ⩽2⁠

The EX-FRAIL CKD Trial: a study protocol for a pilot randomised controlled trial of a home-based EXercise programme for pre-FRAIL and FRAIL, older adults with Chronic Kidney Disease

Introduction Frailty is highly prevalent in adults with chronic kidney disease (CKD) and is associated with adverse health outcomes including falls, poorer health-related quality of life (HRQOL), hospitalisation and mortality. Low physical activity and muscle wasting are important contributors to physical frailty in adults with CKD. Exercise training may improve physical function and frailty status leading to associated improvements in health outcomes, including HRQOL. The EX-FRAIL CKD trial aims to inform the design of a definitive randomised controlled trial (RCT) that investigates the effectiveness of a progressive, multi-component home-based exercise programme in pre-frail and frail older adults with CKD. Methods and Analysis The EX-FRAIL CKD trial is a two-arm parallel group pilot RCT. Participants categorised as pre-frail or frail, following Frailty Phenotype assessment, will be randomised to receive exercise or usual care. Participants randomised to the intervention arm will receive a tailored 12-week exercise programme, which includes weekly telephone calls to advise on exercise progression. Primary feasibility outcome measures include rate of recruitment, intervention adherence, outcome measure completion and participant attrition. Semi-structured interviews with a purposively selected group of participants will inform the feasibility of the randomisation procedures, outcome measures and intervention. Secondary outcome measures include physical function (walking speed and Short Physical Performance Battery), frailty status (Frailty Phenotype), fall concern (Falls Efficacy Scale-International tool), activities of daily living (Barthel Index), symptom-burden (Palliative Care Outcome Scale-Symptoms RENAL) and HRQOL (Short Form-12v2). Ethics and Dissemination Ethical approval was granted by a National Health Service (NHS) Regional Ethics Committee and the NHS Health Research Authority. The study team aim to publish findings in a peer-reviewed journal and present the results at relevant national and international conferences. A summary of findings will be provided to participants, a local kidney patient charity and the funding body

Diagnostic Accuracy of Frailty Screening Methods in Advanced Chronic Kidney Disease

BACKGROUND/AIMS: Frail patients with chronic kidney disease (CKD) have an increased hospitalisation and mortality rate. However, many popular frailty screening methods have not been validated in patients with CKD. This study evaluates the diagnostic accuracy of several frailty screening methods in patients with CKD G4-5 and those established on haemodialysis (G5D). METHODS: Ninety participants with CKD G4-5D were recruited from Nephrology Outpatient Clinics and 2 Haemodialysis Units between December 2016 and December 2017. Frailty was diagnosed using the Fried Frailty Phenotype. The following frailty screening tests were evaluated: Clinical Frailty Scale, PRISMA-7, CKD Frailty Index, CKD FI-LAB, walking speed, hand grip strength and Short Physical Performance Battery. RESULTS: The mean age of participants was 69 years (SD ±13). One-third of participants were dialysis-dependent. Nineteen (21%) patients were categorised as frail, 42 (47%) as pre-frail and 29 (32%) as robust. Overall, walking speed was the most discriminative measure (AUC 0.97 [95% CI 0.93-1.00], sensitivity 0.84 [95% CI 0.62-0.94], specificity 0.96 [95% CI 0.88-0.99]). The Clinical Frailty Scale had the best performance of the non-physical assessment frailty screening methods (AUC 0.90 [95% CI 0.84-0.97], sensitivity 0.79 [95% CI 0.57-0.91], specificity 0.87 [95% CI 0.78-0.93]). CONCLUSIONS: Walking speed can be used to accurately screen for frailty in CKD populations. If it is not practical to perform a physical assessment to screen for frailty, the Clinical Frailty Scale is a useful alternative