MAGIC (maternal glucose in pregnancy) understanding the glycemic profile of pregnancy, intensive CGM glucose profiling and its relationship to fetal growth: an observational study protocol.

BACKGROUND: Continuous glucose monitoring (CGM) provides the most objective method of assessing glucose in daily life. Although there have been small, short-term physiologic studies of glucose metabolism in 'healthy' pregnant women a comprehensive, longitudinal description of changes in glucose over the course of pregnancy and how glucose dysregulation earlier in pregnancy relates to traditional third trimester screening for gestational diabetes, fetal growth and pregnancy outcomes is lacking. This study aims to characterise longitudinal changes in glycemia across gestation using CGM, in order to understand the evolution of dysglycemia and its relationship to fetal growth. METHOD/DESIGN: A multi-centre, prospective, observational, cohort study of 500 healthy pregnant women, recruited in the first trimester of pregnancy. Masked CGM will be performed for a 14-day period on five occasions across pregnancy at ~ 10-12, 18-20, 26-28, 34-36 weeks gestation and postnatally. Routinely collected anthropometric and sociodemographic information will be recorded at each visit including: weight, height, blood pressure, current medication. Age, parity, ethnicity, smoking will be recorded. Blood samples will be taken at each visit for HbA1c and a sample stored. Details on fetal growth from ultrasound scans and the OGTT results will be recorded. Maternal and neonatal outcomes will be collected. CGM glucose profiling is the exposure of interest, and will be performed using standard summary statistics, functional data analysis and glucotyping. The primary maternal outcome is clinical diagnosis of GDM. The primary neonatal outcome is large for gestational age (LGA) (> 90th centile defined by customised birthweight centile). The relationship of glucose to key secondary maternal and neonatal outcomes will be explored. DISCUSSION: This study will ascertain the relationship of maternal dysglycemia to fetal growth and outcomes. It will explore whether CGM glucose profiling can detect GDM before the OGTT; or indeed whether CGM glucose profiling may be more useful than the OGTT at detecting LGA and other perinatal outcomes. TRIAL REGISTRATION: ISRCTN 15,706,303 https://www.isrctn.com/ISRCTN15706303 Registration date: 13th March 2023.

Real-world annualized relapse rates from contemporary multiple sclerosis clinics in the UK: a retrospective multicentre cohort study.

BACKGROUND: Annualized relapse rate (ARR) is used as an outcome measure in multiple sclerosis (MS) clinical trials. Previous studies demonstrated that ARR has reduced in placebo groups between 1990 and 2012. This study aimed to estimate real-world ARRs from contemporary MS clinics in the UK, in order to improve the feasibility estimations for clinical trials and facilitate MS service planning. METHODS: A multicentre observational, retrospective study of patients with MS from 5 tertiary neuroscience centres in the UK. We included all adult patients with a diagnosis of MS that had a relapse between 01/04/2020 and 30/06/2020. RESULTS: One hundred thirteen out of 8783 patients had a relapse during the 3-month study period. Seventy-nine percent of the patients with a relapse were female, the mean age was 39 years, and the median disease duration was 4.5 years; 36% of the patients that had a relapse were on disease-modifying treatment. The ARR from all study sites was estimated at 0.05. The ARR for relapsing remitting MS (RRMS) was estimated at 0.08, while the ARR for secondary progressive MS (SPMS) was 0.01. CONCLUSIONS: We report a lower ARR compared to previously reported rates in MS.

The effect of specific learning difficulties on general practice written and clinical assessments.

BACKGROUND: Substantial numbers of medical students and doctors have specific learning difficulties (SpLDs) and failure to accommodate their needs can disadvantage them academically. Evidence about how SpLDs affect performance during postgraduate general practice (GP) specialty training across the different licencing assessments is lacking. We aimed to investigate the performance of doctors with SpLDs across the range of licencing assessments. METHODS: We adopted the social model of disability as a conceptual framework arguing that problems of disability are societal and that barriers that restrict life choices for people with disabilities need to be addressed. We used a longitudinal design linking Multi-Specialty Assessment (MSRA) records from 2016 and 2017 with their Applied Knowledge Test (AKT), Clinical Skills Assessment (CSA), Recorded Consultation Assessment (RCA) and Workplace Based Assessment (WPBA) outcomes up to 2021. Multivariable logistic regression models accounting for prior attainment and demographics were used to determine the SpLD doctors' likelihood of passing licencing assessments. RESULTS: The sample included 2070 doctors, with 214 (10.34%) declaring a SpLD. Candidates declaring a SpLD were significantly less likely to pass the CSA (OR 0.43, 95% CI 0.26, 0.71, p = 0.001) but not the AKT (OR 0.96, 95% CI 0.44, 2.09, p = 0.913) or RCA (OR 0.81, 95% CI 0.35, 1.85, p = 0.615). Importantly, they were significantly more likely to have difficulties with WPBA (OR 0.28, 95% CI 0.20, 0.40, p < 0.001). When looking at licencing tests subdomains, doctors with SpLD performed significantly less well on the CSA Interpersonal Skills (B = -0.70, 95% CI -1.2, -0.19, p = 0.007) and the RCA Clinical Management Skills (B = -1.68, 95% CI -3.24, -0.13, p = 0.034). CONCLUSIONS: Candidates with SpLDs encounter difficulties in multiple domains of the licencing tests and during their training. More adjustments tailored to their needs should be put in place for the applied clinical skills tests and during their training.

Examiner perceptions of the MRCGP recorded consultation assessment for general practice licensing during COVID-19: cross-sectional study.

BACKGROUND: The Recorded Consultation Assessment (RCA) was developed rapidly during the COVID-19 pandemic to replace the Clinical Skills Assessment (CSA) for UK general practice licensing. Our aim was to evaluate examiner perceptions of the RCA. METHODS: We employed a cross-sectional design using a questionnaire survey of RCA examiners with attitudinal (relating to examiners thoughts and perceptions of the RCA) and free text response options. We conducted statistical descriptive and factor analysis of quantitative data with qualitative thematic analysis of free text responses. RESULTS: Overall, 182 of 260 (70%) examiners completed the questionnaire. Responders felt that consultations submitted were representative of the work of a typical GP during the pandemic and provided a good sample across the curriculum. They were also generally positive about the logistic, advisory and other support provided as well as the digital platform. Despite responders generally agreeing there was sufficient information available in video or audio consultations to judge candidates' data gathering, clinical management, and interpersonal skills, they were less confident about their ability to make judgments of candidates' performance compared with the CSA. The qualitative analysis of free text responses detailed the problems of case selection and content, explained examiners' difficulties when making judgments, and detailed the generally positive views about support, training and information technology. Responders also provided helpful recommendations for improving the assessment. CONCLUSION: The RCA was considered by examiners to be feasible and broadly acceptable, although they experienced challenges from candidate case selection, case content and judgments leading to suggested areas for improvement.

Mental health of people with multiple sclerosis during the COVID-19 outbreak: A prospective cohort and cross-sectional case-control study of the UK MS Register.

BACKGROUND: People with MS (pwMS) have had higher rates of anxiety and depression than the general population before the COVID-19 pandemic, placing them at higher risk of experiencing poor psychological wellbeing during the pandemic. OBJECTIVE: To assess mental health and its social/lifestyle determinants in pwMS during the first wave of the outbreak in the United Kingdom. METHODS: This is a community-based, prospective longitudinal cohort and cross-sectional case-control online questionnaire study. It includes 2010 pwMS from the UK MS Register and 380 people without MS. RESULTS: The Hospital Anxiety and Depression Scale scores of pwMS for anxiety and depression during the outbreak did not change from the previous year. PwMS were more likely to have anxiety (using General Anxiety Disorder-7) and/or depression (using Patient Health Questionnaire-9) than controls during the outbreak (OR: 2.14, 95% CI: 1.58-2.91). PwMS felt lonelier (OR: 1.37, 95% CI: 1.04-1.80) reported worse social support (OR: 1.90, 95% CI: 1.18-3.07) and reported worsened exercise habits (OR: 1.65, 95% CI: 1.18-2.32) during the outbreak than controls. CONCLUSION: Early in the pandemic, pwMS remained at higher risk of experiencing anxiety and depression than the general population. It is important that multidisciplinary teams improve their support for the wellbeing of pwMS, who are vulnerable to the negative effects of the pandemic on their lifestyle and social support.

People with diabetes and ambulance staff perceptions of a booklet-based intervention for diabetic hypoglycaemia, "Hypos can strike twice": a mixed methods process evaluation.

BACKGROUND: Hypoglycaemia is a potentially serious condition, characterised by lower-than-normal blood glucose levels, common in people with diabetes (PWD). It can be prevented and self-managed if expert support, such as education on lifestyle and treatment, is provided. Our aim was to conduct a process evaluation to investigate how ambulance staff and PWD perceived the "Hypos can strike twice" booklet-based ambulance clinician intervention, including acceptability, understandability, usefulness, positive or negative effects, and facilitators or barriers to implementation. METHODS: We used an explanatory sequential design with a self-administered questionnaire study followed by interviews of people with diabetes and ambulance staff. We followed the Medical Research Council framework for process evaluations of complex interventions to guide data collection and analysis. Following descriptive analysis (PWD and staff surveys), exploratory factor analysis was conducted to identify staff questionnaire subscales and multiple regression models were fitted to identify demographic predictors of overall and subscale scores. RESULTS: 113 ambulance staff members and 46 PWD completed the survey. We conducted interviews with four ambulance staff members and five PWD who had been attended by an ambulance for a hypoglycaemic event. Based on surveys and interviews, there were positive attitudes to the intervention from both ambulance staff and PWD. Although the intervention was not always implemented, most staff members and PWD found the booklet informative, easy to read and to use or explain. PWD who completed the survey reported that receiving the booklet reminded and/or encouraged them to test their blood glucose more often, adjust their diet, and have a discussion/check up with their diabetes consultant. Interviewed PWD felt that the booklet intervention would be more valuable to less experienced patients or those who cannot manage their diabetes well. Overall, participants felt that the intervention could be beneficial, but were uncertain about whether it might help prevent a second hypoglycaemic event and/or reduce the number of repeat ambulance attendances. CONCLUSIONS: The 'Hypos may strike twice' intervention, which had demonstrable reductions in repeat attendances, was found to be feasible, acceptable to PWD and staff, prompting reported behaviour change and help-seeking from primary care. TRIAL REGISTRATION: Registered with ClinicalTrials.gov: NCT04243200 on 27 January 2020.

Candidate perceptions of the UK Recorded Consultation Assessment: cross-sectional data linkage study.

The Recorded Consultation Assessment (RCA) was rapidly developed to replace the Clinical Skills Assessment (CSA) for UK general practice licencing during COVID-19. We aimed to evaluate candidate perceptions of the RCA and relationships with performance. We conducted a cross-sectional survey of RCA candidates with attitudinal, demographic, and free text response options, undertaking descriptive and factor analysis of quantitative data with qualitative thematic analysis of free text. Binomial regression was used to estimate associations between RCA pass, candidate characteristics and questionnaire responses.645 of 1551 (41.6%) candidates completed a questionnaire; 364 (56.4%) responders permitted linkage with performance and demographic data. Responders and non-responders were similar in exam performance, gender and declared disability but were significantly more likely to be UK graduates (UKG) or white compared with international medical (IMG) or ethnic minority graduates. Responders were positive about the digital platform and support resources. A small overall majority regarded the RCA as a fair assessment; a larger majority reported difficulty collecting, selecting, and submitting cases or felt rushed during recording.Logistic regression showed that ethnicity (white vs minority ethnic: odds ratio [OR] 2.99,95% confidence interval [CI] 1.23, 7.30, p = 0.016), training (UK vs IMG: OR 6.88, 95% CI 2.79, 16.95, p < 0.001), and English as first language (OR 5.11, 0% CI 2.08, 12.56, p < 0.001) were associated with exam success but questionnaire subscales, consultation type submitted, or extent of trainer review were not. The RCA was broadly acceptable but experiences were variable. Candidates experienced challenges and suggested areas for improvement.

The effects of a leaflet-based intervention, 'Hypos can strike twice', on recurrent hypoglycaemic attendances by ambulance services: A non-randomised stepped wedge study.

AIMS: We aimed to investigate the effect of an intervention in which ambulance personnel provided advice supported by a booklet-'Hypos can strike twice'-issued following a hypoglycaemic event to prevent future ambulance attendances. METHODS: We used a non-randomised stepped wedge-controlled design. The intervention was introduced at different times (steps) in different areas (clusters) of operation within East Midlands Ambulance Service NHS Trust (EMAS). During the first step (T0), no clusters were exposed to the intervention, and during the last step (T3), all clusters were exposed. Data were analysed using a general linear mixed model (GLMM) and an interrupted-time series analysis (ITSA). RESULTS: The study included 4825 patients (mean age 65.42 years, SD 19.42; 2,166 females) experiencing hypoglycaemic events attended by EMAS. GLMM indicated a reduction in the number of unsuccessful attendances (i.e., attendance followed by a repeat attendance) in the final step of the intervention when compared to the first (odds ratio OR: 0.50, 95%CI: 0.33-0.76, p = 0.001). ITSA indicated a significant decrease in repeat ambulance attendances for hypoglycaemia-relative to the pre-intervention trend (p = 0.008). Furthermore, the hypoglycaemia care bundle was delivered in 66% of attendances during the intervention period, demonstrating a significant level of practice change (p < 0.001). CONCLUSION: The 'Hypos can strike twice' intervention had a positive effect on reducing numbers of repeat attendances for hypoglycaemia and in achieving the care bundle. The study supports the use of information booklets by ambulance clinicians to prevent future attendances for recurrent hypoglycaemic events.

Incidence of Bloodstream Infections, Length of Hospital Stay, and Survival in Patients With Recurrent Clostridioides difficile Infection Treated With Fecal Microbiota Transplantation or Antibiotics: A Prospective Cohort Study.

Background: Clostridioides difficile infection (CDI) is a risk factor for bloodstream infection (BSI). Fecal microbiota transplantation (FMT) is more effective than antibiotics in treating recurrent CDI, but its efficacy in preventing CDI-related BSI is uncertain. Objective: To assess incidence of primary BSI in patients with recurrent CDI treated with FMT versus antibiotics. Design: Prospective cohort study. Patients treated with FMT and those treated with antibiotics were matched on propensity score. Setting: Single academic medical center. Patients: 290 inpatients with recurrent CDI (57 patients per treatment in matched cohort). Intervention: FMT or antibiotics. Measurements: The primary outcome was primary BSI within 90 days. Secondary outcomes were length of hospitalization and overall survival (OS) at 90 days. Results: Of the 290 patients, 109 were treated with FMT and 181 received antibiotics. Five patients in the FMT group and 40 in the antibiotic group developed BSI. Because of differences in the patients treated with FMT versus antibiotics in many baseline characteristics, including number of recurrences and CDI severity, comparative analyses were limited to the matched cohort. Risk for BSI was 23 percentage points (95% CI, 10 to 35 percentage points) lower in the FMT group; the FMT group also had 14 fewer days of hospitalization (CI, 9 to 20 fewer days) and a 32-percentage point increase in OS (CI, 16 to 47 percentage points) compared with the antibiotic group. Limitation: Nonrandomized study with potential for unmeasured or residual confounding; limited generalizability of the propensity score-matched cohort. Conclusion: In a propensity score-matched cohort, patients with recurrent CDI treated with FMT were less likely to develop primary BSI. Primary Funding Source: None.

Myocardial Scar and Mortality in Severe Aortic Stenosis.

BACKGROUND: Aortic valve replacement (AVR) for aortic stenosis is timed primarily on the development of symptoms, but late surgery can result in irreversible myocardial dysfunction and additional risk. The aim of this study was to determine whether the presence of focal myocardial scar preoperatively was associated with long-term mortality. METHODS: In a longitudinal observational outcome study, survival analysis was performed in patients with severe aortic stenosis listed for valve intervention at 6 UK cardiothoracic centers. Patients underwent preprocedural echocardiography (for valve severity assessment) and cardiovascular magnetic resonance for ventricular volumes, function and scar quantification between January 2003 and May 2015. Myocardial scar was categorized into 3 patterns (none, infarct, or noninfarct patterns) and quantified with the full width at half-maximum method as percentage of the left ventricle. All-cause mortality and cardiovascular mortality were tracked for a minimum of 2 years. RESULTS: Six hundred seventy-four patients with severe aortic stenosis (age, 75±14 years; 63% male; aortic valve area, 0.38±0.14 cm2/m2; mean gradient, 46±18 mm Hg; left ventricular ejection fraction, 61.0±16.7%) were included. Scar was present in 51% (18% infarct pattern, 33% noninfarct). Management was surgical AVR (n=399) or transcatheter AVR (n=275). During follow-up (median, 3.6 years), 145 patients (21.5%) died (52 after surgical AVR, 93 after transcatheter AVR). In multivariable analysis, the factors independently associated with all-cause mortality were age (hazard ratio [HR], 1.50; 95% CI, 1.11-2.04; P=0.009, scaled by epochs of 10 years), Society of Thoracic Surgeons score (HR, 1.12; 95% CI, 1.03-1.22; P=0.007), and scar presence (HR, 2.39; 95% CI, 1.40-4.05; P=0.001). Scar independently predicted all-cause (26.4% versus 12.9%; P<0.001) and cardiovascular (15.0% versus 4.8%; P<0.001) mortality, regardless of intervention (transcatheter AVR, P=0.002; surgical AVR, P=0.026 [all-cause mortality]). Every 1% increase in left ventricular myocardial scar burden was associated with 11% higher all-cause mortality hazard (HR, 1.11; 95% CI, 1.05-1.17; P<0.001) and 8% higher cardiovascular mortality hazard (HR, 1.08; 95% CI, 1.01-1.17; P<0.001). CONCLUSIONS: In patients with severe aortic stenosis, late gadolinium enhancement on cardiovascular magnetic resonance was independently associated with mortality; its presence was associated with a 2-fold higher late mortality.