Differential associations of risk factors with severe and non-severe hypoglycaemia: the Hypoglycaemia Assessment Tool prospective observational study in people with insulin-treated type 1 diabetes and type 2 diabetes.

AIM: To assess the differential association of risk factors with severe and non-severe hypoglycaemia. MATERIALS AND METHODS: The Hypoglycaemia Assessment Tool study evaluated the risk of hypoglycaemia over a 4-week period in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) on insulin in 24 countries. Negative binomial regressions were applied to examine the associations of several risk factors with severe and non-severe hypoglycaemia. RESULTS: The median age was 41 years in 5949 patients with T1D and 62 years in 12 914 patients with T2D. The 4-week rates of non-severe hypoglycaemic were 5.57 and 1.40 episodes per person in T1D and T2D, respectively; the corresponding rates for severe hypoglycaemia were 0.94 and 0.30. The excess risk was 42% higher for severe than non-severe hypoglycaemia in females versus males with T2D; 27% higher in patients with T2D with versus without a continuous glucose monitoring (CGM); and 47% lower in patients with T1D with versus without an insulin pump. The excess risk also differed across geographical areas and was marginally lower for severe than non-severe hypoglycaemia for higher values of HbA1c in patients with T2D. Associations with severity of hypoglycaemia were not different for age, diabetes and insulin therapy duration, previous hypoglycaemic episodes and insulin regimen. CONCLUSIONS: The risk of severe versus non-severe hypoglycaemia differs in patients with T1D and T2D; sex, the use of a CGM and insulin pump, and geographical areas were differently associated with one type of hypoglycaemia than the other.

Identifying subtypes of type 2 diabetes mellitus with machine learning: development, internal validation, prognostic validation and medication burden in linked electronic health records in 420 448 individuals.

INTRODUCTION: None of the studies of type 2 diabetes (T2D) subtyping to date have used linked population-level data for incident and prevalent T2D, incorporating a diverse set of variables, explainable methods for cluster characterization, or adhered to an established framework. We aimed to develop and validate machine learning (ML)-informed subtypes for type 2 diabetes mellitus (T2D) using nationally representative data. RESEARCH DESIGN AND METHODS: In population-based electronic health records (2006-2020; Clinical Practice Research Datalink) in individuals ≥18 years with incident T2D (n=420 448), we included factors (n=3787), including demography, history, examination, biomarkers and medications. Using a published framework, we identified subtypes through nine unsupervised ML methods (K-means, K-means++, K-mode, K-prototype, mini-batch, agglomerative hierarchical clustering, Birch, Gaussian mixture models, and consensus clustering). We characterized clusters using intracluster distributions and explainable artificial intelligence (AI) techniques. We evaluated subtypes for (1) internal validity (within dataset; across methods); (2) prognostic validity (prediction for 5-year all-cause mortality, hospitalization and new chronic diseases); and (3) medication burden. RESULTS: Development: We identified four T2D subtypes: metabolic, early onset, late onset and cardiometabolic. Internal validity: Subtypes were predicted with high accuracy (F1 score >0.98). Prognostic validity: 5-year all-cause mortality, hospitalization, new chronic disease incidence and medication burden differed across T2D subtypes. Compared with the metabolic subtype, 5-year risks of mortality and hospitalization in incident T2D were highest in late-onset subtype (HR 1.95, 1.85-2.05 and 1.66, 1.58-1.75) and lowest in early-onset subtype (1.18, 1.11-1.27 and 0.85, 0.80-0.90). Incidence of chronic diseases was highest in late-onset subtype and lowest in early-onset subtype. Medications: Compared with the metabolic subtype, after adjusting for age, sex, and pre-T2D medications, late-onset subtype (1.31, 1.28-1.35) and early-onset subtype (0.83, 0.81-0.85) were most and least likely, respectively, to be prescribed medications within 5 years following T2D onset. CONCLUSIONS: In the largest study using ML to date in incident T2D, we identified four distinct subtypes, with potential future implications for etiology, therapeutics, and risk prediction.

Multiple Long-Term Conditions and Disability are Independently Associated with Higher Risk of Fall Among Community Adults: a Cross-Sectional Study.

Background: Previous studies have suggested an association between falls and the presence of Multiple Long-Term Conditions (MLTC) or disabilities. However, there is limited understanding of how these factors independently or collectively contribute to the risk of falls and fear of falling among community-dwelling adults. Objective: This study examined the independent association between MLTC and the presence of disability with the risk of falls among community adults. Methods: A cross-sectional study included 324 adults (age ≥ 50). Demographic and clinical data included age, sex, body mass index (BMI), MLTC (≥ two chronic diseases) risk of fall (ie, history of fall in the previous 12-months, number of falls, and recurrent falls). The Barthel Index and Falls Efficacy Scale-International (FES-I) were used to assess disability and fear of fall, respectively. Results: MLTC (Odds Ratio (OR) 2.50, 95% Confidence Interval (CI) [1.26, 4.95], p=0.009), and disability (OR 1.71, 95% CI [1.04, 2.79], p = 0.034) were independently associated with history of falls. MLTC (Incidence Rate Ratio (IRR) 2.87, 95% CI [1.93, 4.29], p < 0.001) and disability (IRR 1.86 95% CI [1.46, 2.36], p < 0.001) were independently associated with an increased number of falls. MLTC (OR 4.50, 95% CI [1.78, 11.36], p = 0.001) and disability (OR 2.82, 95% CI [1.58, 5.05], p < 0.001) were independently associated with recurrent falls. MLTC (B = 6.45, p < 0.001) and disability (B = 3.05, p = 0.025) were independently associated with increased fear of falling. Conclusion: This study indicated that both MLTC and disability are independently associated with falls, number of falls and fear of falling in this population.

Polygenic risk score adds to a clinical risk score in the prediction of cardiovascular disease in a clinical setting.

BACKGROUND AND AIMS: A cardiovascular disease polygenic risk score (CVD-PRS) can stratify individuals into different categories of cardiovascular risk, but whether the addition of a CVD-PRS to clinical risk scores improves the identification of individuals at increased risk in a real-world clinical setting is unknown. METHODS: The Genetics and the Vascular Health Check Study (GENVASC) was embedded within the UK National Health Service Health Check (NHSHC) programme which invites individuals between 40-74 years of age without known CVD to attend an assessment in a UK general practice where CVD risk factors are measured and a CVD risk score (QRISK2) is calculated. Between 2012-2020, 44,141 individuals (55.7% females, 15.8% non-white) who attended an NHSHC in 147 participating practices across two counties in England were recruited and followed. When 195 individuals (cases) had suffered a major CVD event (CVD death, myocardial infarction or acute coronary syndrome, coronary revascularisation, stroke), 396 propensity-matched controls with a similar risk profile were identified, and a nested case-control genetic study undertaken to see if the addition of a CVD-PRS to QRISK2 in the form of an integrated risk tool (IRT) combined with QRISK2 would have identified more individuals at the time of their NHSHC as at high risk (QRISK2 10-year CVD risk of ≥10%), compared with QRISK2 alone. RESULTS: The distribution of the standardised CVD-PRS was significantly different in cases compared with controls (cases mean score .32; controls, -.18, P = 8.28×10-9). QRISK2 identified 61.5% (95% confidence interval [CI]: 54.3%-68.4%) of individuals who subsequently developed a major CVD event as being at high risk at their NHSHC, while the combination of QRISK2 and IRT identified 68.7% (95% CI: 61.7%-75.2%), a relative increase of 11.7% (P = 1×10-4). The odds ratio (OR) of being up-classified was 2.41 (95% CI: 1.03-5.64, P = .031) for cases compared with controls. In individuals aged 40-54 years, QRISK2 identified 26.0% (95% CI: 16.5%-37.6%) of those who developed a major CVD event, while the combination of QRISK2 and IRT identified 38.4% (95% CI: 27.2%-50.5%), indicating a stronger relative increase of 47.7% in the younger age group (P = .001). The combination of QRISK2 and IRT increased the proportion of additional cases identified similarly in women as in men, and in non-white ethnicities compared with white ethnicity. The findings were similar when the CVD-PRS was added to the atherosclerotic cardiovascular disease pooled cohort equations (ASCVD-PCE) or SCORE2 clinical scores. CONCLUSIONS: In a clinical setting, the addition of genetic information to clinical risk assessment significantly improved the identification of individuals who went on to have a major CVD event as being at high risk, especially among younger individuals. The findings provide important real-world evidence of the potential value of implementing a CVD-PRS into health systems.

Towards the standardisation of adult person-reported outcome domains in diabetes research: A Consensus Statement development panel.

Diabetes is unique among chronic diseases because clinical outcomes are intimately tied to how the person living with diabetes reacts to and implements treatment recommendations. It is further characterised by widespread social stigma, judgement and paternalism. This physical, social and psychological burden collectively influences self-management behaviours. It is widely recognised that the individual's perspective about the impact of trying to manage the disease and the burden that self-management confers must be addressed to achieve optimal health outcomes. Standardised, rigorous assessment of mental and behavioural health status, in interaction with physical health outcomes is crucial to aid understanding of person-reported outcomes (PROs). Whilst tempting to conceptualise PROs as an issue of perceived quality of life (QoL), in fact health-related QoL is multi-dimensional and covers indicators of physical or functional health status, psychological and social well-being. This complexity is illuminated by the large number of person reported outcome measures (PROMs) that have been developed across multiple psychosocial domains. Often measures are used inappropriately or because they have been used in the scientific literature rather than based on methodological or outcome assessment rigour. Given the broad nature of psychosocial functioning/mental health, it is important to broadly define PROs that are evaluated in the context of therapeutic interventions, real-life and observational studies. This report summarises the central themes and lessons derived in the assessment and use of PROMs amongst adults with diabetes. Effective assessment of PROMs routinely in clinical research is crucial to understanding the true impact of any intervention. Selecting appropriate measures, relevant to the specific factors of PROs important in the research study will provide valuable data alongside physical health data.

Prediabetes, participation in the English National Health Service Diabetes Prevention Programme, and associations with COVID-19-related mortality: A whole population study.

AIMS: To assess the effects of non-diabetic hyperglycaemia (NDH, also known as pre-diabetes), including the impact of the NHS Diabetes Prevention Programme (NHS DPP), on COVID-19-related mortality during the pandemic. METHODS: This study included all 61,438,225 individuals registered with General Practices in England and alive on 1st March 2020. We assessed COVID-19-related mortality in the 2,290,280(3.7 %) individuals with diagnosed NDH between March 2020 and February 2022 compared to those without diagnosed NDH or diabetes using Cox regression to adjust for demographic factors and cardiovascular comorbidities. Individuals with diagnosed NDH were further sub-categorised based on their contact with the NHS DPP (N = 376,590). Analyses were stratified by age (years) (<50, 50-69 and ≥ 70). RESULTS: There were 158,070 COVID-19 deaths; 17,280(11 %) for people with diagnosed NDH. The adjusted hazard ratio (HR) was 0.95(0.93-0.96),p < 0.001 for those with diagnosed NDH compared to those without diagnosed diabetes or NDH. By age (years), HRs were, 2.53(2.23-2.88),p < 0.001 for < 50, 1.29(1.24-1.35),p < 0.001 for 50-69 and 0.87(0.85-0.89),p < 0.001 for ≥ 70. NHS DPP attendance was associated with lower COVID-19 mortality with a dose-response relationship with engagement. CONCLUSIONS: Younger people with diagnosed NDH were at higher relative risk of COVID-19 mortality. Attendance at the NHS DPP was associated with significantly lower COVID-19-related mortality.

Long COVID and cardiovascular disease: a prospective cohort study.

BACKGROUND: Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known. OBJECTIVES: To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors. METHODS: In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health. RESULTS: From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86). CONCLUSION: Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need. TRAIL REGISTRATION NUMBER: ISRCTN10980107.

Comparative effectiveness of second line oral antidiabetic treatments among people with type 2 diabetes mellitus: emulation of a target trial using routinely collected health data.

OBJECTIVE: To compare the effectiveness of three commonly prescribed oral antidiabetic drugs added to metformin for people with type 2 diabetes mellitus requiring second line treatment in routine clinical practice. DESIGN: Cohort study emulating a comparative effectiveness trial (target trial). SETTING: Linked primary care, hospital, and death data in England, 2015-21. PARTICIPANTS: 75 739 adults with type 2 diabetes mellitus who initiated second line oral antidiabetic treatment with a sulfonylurea, DPP-4 inhibitor, or SGLT-2 inhibitor added to metformin. MAIN OUTCOME MEASURES: Primary outcome was absolute change in glycated haemoglobin A1c (HbA1c) between baseline and one year follow-up. Secondary outcomes were change in body mass index (BMI), systolic blood pressure, and estimated glomerular filtration rate (eGFR) at one year and two years, change in HbA1c at two years, and time to ≥40% decline in eGFR, major adverse kidney event, hospital admission for heart failure, major adverse cardiovascular event (MACE), and all cause mortality. Instrumental variable analysis was used to reduce the risk of confounding due to unobserved baseline measures. RESULTS: 75 739 people initiated second line oral antidiabetic treatment with sulfonylureas (n=25 693, 33.9%), DPP-4 inhibitors (n=34 464 ,45.5%), or SGLT-2 inhibitors (n=15 582, 20.6%). SGLT-2 inhibitors were more effective than DPP-4 inhibitors or sulfonylureas in reducing mean HbA1c values between baseline and one year. After the instrumental variable analysis, the mean differences in HbA1c change between baseline and one year were -2.5 mmol/mol (95% confidence interval (CI) -3.7 to -1.3) for SGLT-2 inhibitors versus sulfonylureas and -3.2 mmol/mol (-4.6 to -1.8) for SGLT-2 inhibitors versus DPP-4 inhibitors. SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in reducing BMI and systolic blood pressure. For some secondary endpoints, evidence for SGLT-2 inhibitors being more effective was lacking-the hazard ratio for MACE, for example, was 0.99 (95% CI 0.61 to 1.62) versus sulfonylureas and 0.91 (0.51 to 1.63) versus DPP-4 inhibitors. SGLT-2 inhibitors had reduced hazards of hospital admission for heart failure compared with DPP-4 inhibitors (0.32, 0.12 to 0.90) and sulfonylureas (0.46, 0.20 to 1.05). The hazard ratio for a ≥40% decline in eGFR indicated a protective effect versus sulfonylureas (0.42, 0.22 to 0.82), with high uncertainty in the estimated hazard ratio versus DPP-4 inhibitors (0.64, 0.29 to 1.43). CONCLUSIONS: This emulation study of a target trial found that SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in lowering mean HbA1c, BMI, and systolic blood pressure and in reducing the hazards of hospital admission for heart failure (v DPP-4 inhibitors) and kidney disease progression (v sulfonylureas), with no evidence of differences in other clinical endpoints.

Indirect effects of the COVID-19 pandemic on diagnosing, monitoring, and prescribing in people with diabetes and strategies for diabetes service recovery internationally.

The COVID-19 pandemic has caused major disruptions in clinical services for people with chronic long-term conditions. In this narrative review, we assess the indirect impacts of the COVID-19 pandemic on diabetes services globally and the resulting adverse effects on rates of diagnosing, monitoring, and prescribing in people with type 2 diabetes. We summarise potential practical approaches that could address these issues and improve clinical services and outcomes for people living with diabetes during the recovery phase of the pandemic.

Impact of the COVID-19 pandemic on hospital episodes for falls and fractures associated with new-onset disability and frailty in England: a national cohort study.

BACKGROUND: Older people with frailty are at risk of harm from immobility or isolation, yet data about how COVID-19 lockdowns affected them are limited. Falls and fractures are easily measurable adverse outcomes correlated with frailty. We investigated whether English hospital admission rates for falls and fractures varied from the expected trajectory during the COVID-19 pandemic, and how these varied by frailty status. METHODS: NHS England Hospital Episode Statistics Admitted Patient Care data were analysed for observed versus predicted outcome rates for 24 January 2020 to 31 December 2021. An auto-regressive integrated moving average time-series model was trained using falls and fracture incidence data from 2013 to 2018 and validated using data from 2019. Models included national and age-, sex- and region-stratified forecasts. Outcome measures were hospital admissions for falls, fractures, and falls and fractures combined. Frailty was defined using the Hospital Frailty Risk Score. RESULTS: 144,148,915 pre-pandemic hospital admissions were compared with 42,267,318 admissions after pandemic onset. For the whole population, falls and fracture rates were below predicted for the first period of national lockdown, followed by a rapid return to rates close to predicted. Thereafter, rates followed expected trends. For people living with frailty, however, falls and fractures increased above expected rates during periods of national lockdown and remained elevated throughout the study period. Effects of frailty were independent of age. CONCLUSIONS: People living with frailty experienced increased fall and fracture rates above expected during and following periods of national lockdown. These remained persistently elevated throughout the study period.

Reporting and representation of underserved groups in intervention studies for patients with multiple long-term conditions: a systematic review.

OBJECTIVES: Globally, there is a growing number of people who are living with multiple long-term conditions (MLTCs). Due to complex management needs, it is imperative that research consists of participants who may benefit most from interventions. It is well documented that ethnic minority groups and lower socioeconomic status (SES) groups are at an increased risk of developing MLTCs. Therefore, the aim of this systematic review was to determine the level of reporting and representation of underserved groups (ethnic minority and low SES) in intervention studies addressing MLTCs. DESIGN: Systematic review. Four databases including Cochrane Library, MEDLINE, CINAHL and Scopus were searched for intervention studies from North America or Europe published between January 1990 and July 2023. SETTING: Hospital and community-based interventions. We included interventional studies focusing on improving MLTC-related outcomes. PARTICIPANTS: Patients with MLTCs. MAIN OUTCOME MEASURES: Total number of studies reporting on ethnicity and SES. Number and proportion of studies reporting by ethnic/SES group. RESULTS: Thirteen studies met the inclusion criteria. Only 4 of 13 studies (31%) recorded and reported ethnicity information. Of these four studies that reported on ethnicity, three studies consisted of primarily White participants. Ethnic minority groups were underrepresented, but one study included a majority of African American participants. Moreover, 12 of 13 studies (92%) reported on SES with income and educational level being the primary measures used. SES representation of higher deprivation groups was varied due to limited data. CONCLUSIONS: For ethnicity, there was a lack of reporting, and ethnic minority groups were underrepresented in intervention studies. For SES, there was a high level of reporting but the proportion of study samples from across the spectrum of SES varied due to the variety of SES measures used. Findings highlight a need to improve the reporting and representation of ethnic minority groups and provide more detailed information for SES through using consistent measures (e.g. education, income and employment) to accurately determine the distribution of SES groups in intervention studies of people with MLTCs.

Uptake of self-management education programmes for people with type 2 diabetes in primary care through the embedding package: a cluster randomised control trial and ethnographic study.

BACKGROUND: Self-management education programmes are cost-effective in helping people with type 2 diabetes manage their diabetes, but referral and attendance rates are low. This study reports on the effectiveness of the Embedding Package, a programme designed to increase type 2 diabetes self-management programme attendance in primary care. METHODS: Using a cluster randomised design, 66 practices were randomised to: (1) a wait-list group that provided usual care for nine months before receiving the Embedding Package for nine months, or (2) an immediate group that received the Embedding Package for 18 months. 'Embedders' supported practices and self-management programme providers to embed programme referral into routine practice, and an online 'toolkit' contained embedding support resources. Patient-level HbA1c (primary outcome), programme referral and attendance data, and clinical data from 92,977 patients with type 2 diabetes were collected at baseline (months - 3-0), step one (months 1-9), step 2 (months 10-18), and 12 months post-intervention. An integrated ethnographic study including observations, interviews, and document analysis was conducted using interpretive thematic analysis and Normalisation Process Theory. RESULTS: No significant difference was found in HbA1c between intervention and control conditions (adjusted mean difference [95% confidence interval]: -0.10 [-0.38, 0.18] mmol/mol; -0.01 [-0.03, 0.02] %). Statistically but not clinically significantly lower levels of HbA1c were found in people of ethnic minority groups compared with non-ethnic minority groups during the intervention condition (-0.64 [-1.08, -0.20] mmol/mol; -0.06% [-0.10, -0.02], p = 0.004), but not greater self-management programme attendance. Twelve months post-intervention data showed statistically but not clinically significantly lower HbA1c (-0.56 [95% confidence interval: -0.71, -0.42] mmol/mol; -0.05 [-0.06, -0.04] %; p < 0.001), and higher self-management programme attendance (adjusted odds ratio: 1.13; 95% confidence interval: 1.02, 1.25; p = 0.017) during intervention conditions. Themes identified through the ethnographic study included challenges for Embedders in making and sustaining contact with practices and providers, and around practices' interactions with the toolkit. CONCLUSIONS: Barriers to implementing the Embedding Package may have compromised its effectiveness. Statistically but not clinically significantly improved HbA1c among ethnic minority groups and in longer-term follow-up suggest that future research exploring methods of embedding diabetes self-management programmes into routine care is warranted. TRIAL REGISTRATION: ISRCTN23474120, registered 05/04/2018.

Incorporating polygenic risk into the Leicester Risk Assessment score for 10-year risk prediction of type 2 diabetes.

AIMS: We evaluated whether incorporating information on ethnic background and polygenic risk enhanced the Leicester Risk Assessment (LRA) score for predicting 10-year risk of type 2 diabetes. METHODS: The sample included 202,529 UK Biobank participants aged 40-69 years. We computed the LRA score, and developed two new risk scores using training data (80% sample): LRArev, which incorporated additional information on ethnic background, and LRAprs, which incorporated polygenic risk for type 2 diabetes. We assessed discriminative and reclassification performance in a test set (20% sample). Type 2 diabetes was ascertained using primary care, hospital inpatient and death registry records. RESULTS: Over 10 years, 7,476 participants developed type 2 diabetes. The Harrell's C indexes were 0.796 (95% Confidence Interval [CI] 0.785, 0.806), 0.802 (95% CI 0.792, 0.813), and 0.829 (95% CI 0.820, 0.839) for the LRA, LRArev and LRAprs scores, respectively. The LRAprs score significantly improved the overall reclassification compared to the LRA (net reclassification index [NRI] = 0.033, 95% CI 0.015, 0.049) and LRArev (NRI = 0.040, 95% CI 0.024, 0.055) scores. CONCLUSIONS: Polygenic risk moderately improved the performance of the existing LRA score for 10-year risk prediction of type 2 diabetes.

Association of ethnicity and socioeconomic status with health outcomes in women with gestational diabetes: Clinical practice research datalink cohort study.

AIMS: To investigate in women with prior gestational diabetes mellitus (GDM), differences by ethnicity and socioeconomic status in the incidence of recurrent GDM, type 2 diabetes (T2D), hypertension, and depression. METHODS: This was a retrospective cohort study including 10,868 women diagnosed with GDM in the Clinical Practice Research Datalink (CPRD GOLD) between January 01, 2000 and November 05, 2018. Linked data were obtained for Hospital Episode Statistics and the Index of Multiple Deprivation. We estimated incidence rates and hazard ratios, by ethnicity and socioeconomic status. RESULTS: During a follow-up of 58,479 person years (mean (SD): 5.38 (3.67) years), the crude incidence was 9.67 (95 % confidence interval: 9.30-10.00) per 100 person years for recurrent GDM, 3.86 (3.70-4.02) for depression, 2.15 (2.03-2.27) for T2D and 0.89 (0.81-0.97) for hypertension. South Asian ethnicity was associated with an increased risk of T2D compared to White (adjusted hazard ratio: 1.65; 1.34-2.05) and Black ethnicity was associated with a greater risk of hypertension (2.93; 1.93-4.46). Black and South Asian ethnicity were associated with a reduced risk of depression compared to White: 0.23 (0.13-0.39) and 0.37 (0.29-0.46), respectively. Incidence rates were higher for all conditions with increasing deprivation level. CONCLUSIONS: The risk of health complications in women with a prior history of GDM differs by ethnicity and socio-economic status, suggesting the opportunity for targeted assessment in the years following pregnancy. These findings may inform future guidelines on screening for health outcomes in women with GDM.

Beliefs, practices, perceptions and motivations of healthcare professionals on medication deprescribing during end-of-life care: A systematic review.

AIM: Conduct a systematic review to investigate current beliefs, practices, perceptions, and motivations towards deprescribing practices from the healthcare professional perspective in older adults residing in long term care facilities with cardiometabolic conditions, using a narrative approach. METHODS: Studies were identified using a literature search of MEDLINE, CINAHL and Web of Science from inception to June 2023 Two reviewers (EH and AA) independently extracted data from each selected study using a standardised self-developed data extraction proforma. Studies reviewed included cross-sectional and observational studies. Data was extracted on baseline characteristics, motivations and beliefs and was discussed using a narrative approach. RESULTS: Eight studies were identified for inclusion. Deprescribing approaches included complete withdrawal, dose reduction, or switching to an alternative medication, for at least one preventive medication. Most healthcare professionals were willing to initiate deprescribing strategies and stated the importance of such interventions, however many felt inexperienced and lacked the required knowledge to feel comfortable doing so. CONCLUSION: Deprescribing is a key strategy when managing older people with cardiometabolic and multiple long term conditions (MLTC). Overall, HCPs including specialists, were happy to explore deprescribing strategies if provided with the relevant training and development to do so. Barriers that still exist include communication and consultation skills, a lack of evidence-based guidance and trust based policies, and a lack of MDT communications and involvement. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022335106.

Cost-effectiveness analysis of two interventions to promote physical activity in a multiethnic population at high risk of diabetes: an economic evaluation of the 48-month PROPELS randomized controlled trial.

INTRODUCTION: Physical activity (PA) is protective against type 2 diabetes (T2D). However, data on pragmatic long-term interventions to reduce the risk of developing T2D via increased PA are lacking. This study investigated the cost-effectiveness of a pragmatic PA intervention in a multiethnic population at high risk of T2D. MATERIALS AND METHODS: We adapted the School for Public Health Research diabetes prevention model, using the PROPELS trial data and analyses of the NAVIGATOR trial. Lifetime costs, lifetime quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each intervention (Walking Away (WA) and Walking Away Plus (WA+)) versus usual care and compared with National Institute for Health and Care Excellence's willingness-to-pay of £20 000-£30 000 per QALY gained. We conducted scenario analyses on the outcomes of the PROPELS trial data and a threshold analysis to determine the change in step count that would be needed for the interventions to be cost-effective. RESULTS: Estimated lifetime costs for usual care, WA, and WA+ were £22 598, £23 018, and £22 945, respectively. Estimated QALYs were 9.323, 9.312, and 9.330, respectively. WA+ was estimated to be more effective and cheaper than WA. WA+ had an ICER of £49 273 per QALY gained versus usual care. In none of our scenario analyses did either WA or WA+ have an ICER below £20 000 per QALY gained. Our threshold analysis suggested that a PA intervention costing the same as WA+ would have an ICER below £20 000/QALY if it were to achieve an increase in step count of 500 steps per day which was 100% maintained at 4 years. CONCLUSIONS: We found that neither WA nor WA+ was cost-effective at a limit of £20 000 per QALY gained. Our threshold analysis showed that interventions to increase step count can be cost-effective at this limit if they achieve greater long-term maintenance of effect. TRIAL REGISTRATION NUMBER: ISRCTN registration: ISRCTN83465245: The PRomotion Of Physical activity through structuredEducation with differing Levels of ongoing Support for those with pre-diabetes (PROPELS)https://doi.org/10.1186/ISRCTN83465245.

Prevalence of mental health conditions and brain fog in people with long COVID: A systematic review and meta-analysis.

OBJECTIVE: Long COVID can include impaired cognition ('brain fog'; a term encompassing multiple symptoms) and mental health conditions. We performed a systematic review and meta-analysis to estimate their prevalence and to explore relevant factors associated with the incidence of impaired cognition and mental health conditions. METHODS: Searches were conducted in Medline and PsycINFO to cover the start of the pandemic until August 2023. Included studies reported prevalence of mental health conditions and brain fog in adults with long COVID after clinically-diagnosed or PCR-confirmed SARS-CoV-2 infection. FINDINGS: 17 studies were included, reporting 41,249 long COVID patients. Across all timepoints (3-24 months), the combined prevalence of mental health conditions and brain fog was 20·4% (95% CI 11·1%-34·4%), being lower among those previously hospitalised than in community-managed patients(19·5 vs 29·7% respectively; p = 0·047). The odds of mental health conditions and brain fog increased over time and when validated instruments were used. Odds of brain fog significantly decreased with increasing vaccination rates (p = ·000). CONCLUSIONS: Given the increasing prevalence of mental health conditions and brain fog over time, preventive interventions and treatments are needed. Research is needed to explore underlying mechanisms that could inform further research in development of effective treatments. The reduced risk of brain fog associated with vaccination emphasizes the need for ongoing vaccination programs.

Nasal Glucagon Reverses Insulin-induced Hypoglycemia With Less Rebound Hyperglycemia: Pooled Analysis of Clinical Trials.

Background: Rebound hyperglycemia may occur following glucagon treatment for severe hypoglycemia. We assessed rebound hyperglycemia occurrence after nasal glucagon (NG) or injectable glucagon (IG) administration in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D). Methods: This was a pooled analysis of 3 multicenter, randomized, open-label studies (NCT03339453, NCT03421379, NCT01994746) in patients ≥18 years with T1D or T2D with induced hypoglycemia. Proportions of patients achieving treatment success [blood glucose (BG) increase to ≥70 mg/dL or increase of ≥20 mg/dL from nadir within 15 and 30 minutes]; BG ≥70 mg/dL within 15 minutes; in-range BG (70-180 mg/dL) 1 to 2 and 1 to 4 hours postdose; and BG >180 mg/dL 1 to 2 and 1 to 4 hours postdose were compared. Incremental area under curve (iAUC) of BG >180 mg/dL and area under curve (AUC) of observed BG values postdose were analyzed. Safety was assessed in all studies. Results: Higher proportions of patients had in-range BG with NG vs IG (1-2 hours: P = .0047; 1-4 hours: P = .0034). Lower proportions of patients had at least 1 BG value >180 mg/dL with NG vs IG (1-2 hours: P = .0034; 1-4 hours: P = .0068). iAUC and AUC were lower with NG vs IG (P = .025 and P < .0001). As expected, similar proportions of patients receiving NG or IG achieved treatment success at 15 and 30 minutes (97-100%). Most patients had BG ≥70 mg/dL within 15 minutes (93-96%). The safety profile was consistent with previous studies. Conclusion: This study demonstrated lower rebound hyperglycemia risk after NG treatment compared with IG. Clinical Trial Registration: NCT03421379, NCT03339453, NCT01994746.