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.

Glycaemic control and macrovascular and microvascular outcomes: A systematic review and meta-analysis of trials investigating intensive glucose-lowering strategies in people with type 2 diabetes.

AIM: We aimed to determine the macrovascular and microvascular outcomes of intensive versus standard glucose-lowering strategies in type 2 diabetes (T2D) and investigate the relationships between these outcomes and trial arm glycated haemoglobin (HbA1c) reduction. MATERIALS AND METHODS: In this systematic review and meta-analysis, we identified relevant trials from MEDLINE, Embase, the Cochrane Library, and bibliographies up to August 2023. Macrovascular and microvascular outcomes, along with safety outcomes, were evaluated. Pooled study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, and meta-regression was employed to analyse the relationships between outcomes and HbA1c reduction. RESULTS: We included 11 unique RCTs involving 51 469 patients with T2D (intensive therapy, N = 26 691; standard therapy, N = 24 778). Intensive versus standard therapy reduced the risk of non-fatal myocardial infarction (MI) (HR 0.84; 95% CI 0.75-0.94) with no difference in the risk of major adverse cardiovascular events (HR 0.97; 95% CI 0.92-1.03) and other adverse cardiovascular outcomes. Intensive versus standard therapy reduced the risk of retinopathy (HR 0.85; 0.78-0.93), nephropathy (HR 0.71; 0.58-0.87) and composite microvascular outcomes (HR 0.88; 0.77-1.00). Meta-regression analyses showed modest evidence of inverse linear relationships between HbA1c reduction and the outcomes of major adverse cardiovascular events, non-fatal MI, stroke and retinopathy, but these were not statistically significant. CONCLUSIONS: In people with T2D, intensive glucose control was associated with a reduced risk of non-fatal MI and several microvascular outcomes, particularly retinopathy and nephropathy. The lack of an effect of intensive glucose-lowering on most macrovascular outcomes calls for a more comprehensive approach to managing cardiovascular risk factors alongside glycaemic control.

Glycaemic control and macrovascular and microvascular outcomes in type 2 diabetes: Systematic review and meta-analysis of cardiovascular outcome trials of novel glucose-lowering agents.

AIM: Using a systematic review and meta-analysis of placebo-controlled cardiovascular outcome trials (CVOTs) of newer glucose-lowering agents [sodium-glucose cotransporter-2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase-4 inhibitors (DPP-4is)] in type 2 diabetes (T2D), we aimed to determine the macrovascular and microvascular outcomes of these agents and clarify the relationships between glycated haemoglobin (HbA1c) reduction and risk of these outcomes. MATERIALS AND METHODS: Randomized controlled trials were identified from MEDLINE, Embase and the Cochrane Library until September 2023. Study-specific hazard ratios with 95% confidence intervals (CIs) were pooled, and meta-regression was used to assess the relationships between outcomes and between trial arm HbA1c reductions. RESULTS: Twenty unique CVOTs (six SGLT-2is, nine GLP-1RAs, five DPP-4is), based on 169 513 participants with T2D, were eligible. Comparing SGLT-2is, GLP-1RAs and DPP-4is with placebo, the hazard ratios (95% CIs) for 3-point major adverse cardiovascular events were 0.88 (0.82-0.94), 0.85 (0.79-0.92) and 1.00 (0.94-1.06), respectively. SGLT-2is and GLP-1RAs consistently reduced the risk of several macrovascular and microvascular complications, particularly kidney events. DPP-4is showed no macrovascular benefits. There was potential evidence of an inverse linear relationship between HbA1c reduction and 3-point major adverse cardiovascular event risk (estimated risk per 1% reduction in HbA1c: 0.84, 95% CI 0.67-1.06; p = .14; R2 = 14.2%), which was driven by the component of non-fatal stroke (R2 = 100.0%; p = .094). There were non-significant inverse linear relationships between HbA1c reduction and the risk of several vascular outcomes. CONCLUSIONS: SGLT-2is and GLP-1RAs showed consistent risk reductions in macrovascular and microvascular outcomes. The vascular benefits of SGLT-2is and GLP-1RAs in patients with T2D extend beyond mere glycaemic control.

Deintensification of potentially inappropriate medications amongst older frail people with type 2 diabetes: Protocol for a cluster randomised controlled trial (D-MED study).

AIMS: Amongst elderly people with type 2 diabetes (T2D) over prescribing can result in emergency ambulance call-outs, falls and fractures and increased mortality, particularly in frail patients. Current clinical guidelines, however, remain focused on medication intensification rather than deintensification where appropriate. This study aims to evaluate the effectiveness of an electronic decision-support system and training for the deintensification of potentially inappropriate medications amongst older frail people with T2D, when compared to 'usual' care at 12-months. METHODS: This study is an open-label, multi-site, two-armed pragmatic cluster-randomised trial. GP practices randomised to the 'enhanced care' group have an electronic decision support system installed and receive training on the tool and de-intensification of diabetes medications. The system flags eligible patients for possible deintensification of diabetes medications, linking the health care professional to a clinical algorithm. The primary outcome will be the number of patients at 12-months who have had potentially inappropriate diabetes medications de-intensified. RESULTS: Study recruitment commenced in June 2022. Data collection commenced in January 2023. Baseline data have been extracted from 40 practices (3145 patients). CONCLUSIONS: Digital technology, involving computer decision systems, may have the potential to reduce inappropriate medications and aid the process of de-intensification. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN53221378. Available at: https://www.isrctn.com/ISRCTN53221378.

The Effect of Practitioner Empathy on Patient Satisfaction : A Systematic Review of Randomized Trials.

BACKGROUND: Practitioners who deliver enhanced empathy may improve patient satisfaction with care. Patient satisfaction is associated with positive patient outcomes ranging from medication adherence to survival. PURPOSE: To evaluate the effect of health care practitioner empathy on patient satisfaction, using a systematic review of randomized trials. DATA SOURCES: Ovid MEDLINE, CINAHL, PsycInfo, Cochrane Central Register of Controlled Trials, and Scopus to 23 October 2023. STUDY SELECTION: Randomized trials published in any language that evaluated the effect of empathy on improving patient satisfaction as measured on a validated patient satisfaction scale. DATA EXTRACTION: Data extraction, risk-of-bias assessments, and strength-of-evidence assessments were done by 2 independent reviewers. Disagreements were resolved through consensus. DATA SYNTHESIS: Fourteen eligible randomized trials (80 practitioners; 1986 patients) were included in the analysis. Five studies had high risk of bias, and 9 had some concerns about bias. The trials were heterogeneous in terms of geographic locations (North America, Europe, Asia, and Africa), settings (hospital and primary care), practitioner types (family and hospital physicians, anesthesiologists, nurses, psychologists, and caregivers), and type of randomization (individual patient or clustered by practitioner). Although all trials suggested a positive change in patient satisfaction, inadequate reporting hindered the ability to draw definitive conclusions about the overall effect size. LIMITATIONS: Heterogeneity in the way that empathy was delivered and patient satisfaction was measured and incomplete reporting leading to concerns about the certainty of the underpinning evidence. CONCLUSION: Various empathy interventions have been studied to improve patient satisfaction. Development, testing, and reporting of high-quality studies within well-defined contexts is needed to optimize empathy interventions that increase patient satisfaction. PRIMARY FUNDING SOURCE: Stoneygate Trust. (PROSPERO: CRD42023412981).

Effect of delay in treatment intensification in people with type 2 diabetes and suboptimal glycaemia after basal insulin initiation: A real-world observational study.

AIM: Despite global recommendations for type 2 diabetes mellitus treatment to maintain optimal glycaemic targets, a significant proportion of people remain in suboptimal glycaemic control. Our objective was to investigate the impact of intensification delay after basal insulin (BI) initiation on long-term complications in people with suboptimal glycaemia. MATERIALS AND METHODS: We conducted a retrospective cohort study in individuals with type 2 diabetes mellitus initiated on BI. Those with suboptimal glycaemia (glycated haemoglobin ≥7% or ≥53 mmol/mol) within 12 months of BI initiation were divided into early (treatment intensified within 5 years), or late (≥5 years) intensification groups. We estimated the age-stratified risks of micro- and macrovascular complications among these groups compared with those with optimal glycaemia (glycated haemoglobin <7%). RESULTS: Of the 13 916 people with suboptimal glycaemia, 52.5% (n = 7304) did not receive any treatment intensification. In those aged <65 years, compared with the optimal glycaemia group late intensification was associated with a 56% higher risk of macrovascular complications (adjusted hazard ratio 1.56; 95% confidence intervals 1.08, 2.26). In elderly people (≥65 years), late intensification was associated with a higher risk of cardiovascular-related death (1.62; 1.03, 2.54) and a lower risk of microvascular complications (0.26; 0.08, 0.83). CONCLUSIONS: Those who had late intensification were at an increased risk of cardiovascular death if they were ≥65 years and an increased risk of macrovascular complications if they were <65 years. These findings highlight the critical need for earlier intensification of treatment and adopting personalized treatment strategies to improve patient outcomes.

Factors associated with therapeutic inertia in individuals with type 2 diabetes mellitus started on basal insulin.

AIM: In this study we aim to identify the factors associated with treatment inertia in patients with type 2 diabetes mellitus (T2DM) who have been recently started on basal insulin (BI). METHODS: Using UK CPRD GOLD, we identified adults with T2DM with suboptimal glycaemia (HbA1c within 12 months of BI ≥ 7% (≥53 mmol/mol)). We used multivariable Cox regression model to describe the association between patient characteristics and the time to treatment intensification. RESULTS: A total of 12,556 patients were analysed. Compared to individuals aged < 65 years, those aged ≥ 65 years had lower risk of treatment intensification (HR: 0.69; 95% CI: 0.64-0.73). Other factors included being female (0.93, 0.89-0.99), longer T2DM duration (0.99, 0.98-0.99), living in the most deprived areas (0.90, 0.83-0.98), being a current smoker (0.91, 0.84-0.98), having one (0.91, 0.85-0.97) or more than one comorbidity (0.88, 0.82-0.94), and patients who were on metformin (0.71, 0.63-0.80), or 2nd generation sulphonylureas (0.85; 0.79-0.92) or DPP4 inhibitors (0.87, 0.82-0.93) compared to those who were not. CONCLUSION: Therapeutic inertia still remains a major barrier, with multiple factors associated with delay in intensification. Interventions to overcome therapeutic inertia need to be implemented at both patient and health care professional level.

Soluble Vascular Adhesion Protein 1 (sVAP-1) as a biomarker for pregnancy complications: A pilot study.

BACKGROUND: Vascular adhesion protein 1 (VAP-1) has been implicated in a wide range of clinical conditions. Moreover, serum levels are associated with disease prediction and progression in several clinical studies. There is a paucity of data on VAP-1 and pregnancy. Given the emerging role of VAP-1 in pregnancy, the aim of this study was to examine sVAP-1 as an early biomarker of pregnancy complications, especially hypertension during pregnancy. The objectives of the study are to associate sVAP-1 levels with other pregnancy complications, patient demographics and blood tests performed throughout pregnancy. METHODS: We conducted a pilot study in a cohort of pregnant women (gestational week lower than 20 at the time of recruitment) attending their first antenatal ultrasound scan at the Leicester Royal Infirmary (LRI, UK). Data were both prospectively generated (from blood sample analysis) and retrospectively collected (from hospital records). RESULTS: From July and October 2021, a total of 91 participants were enrolled. Using ELISA (enzyme-linked immunosorbent assay), we found reduced serum levels of sVAP-1 in pregnant women with either pregnancy induced hypertension (PIH) (310 ng/mL) or GDM (366.73 ng/mL) as compared to controls (427.44 ng/mL and 428.34 ng/mL, respectively). No significant difference was found between women with FGR compared to controls (424.32 ng/mL vs 424.52 ng/mL), and patients with any pregnancy complications compared to healthy pregnancies (421.28 ng/mL vs 428.34 ng/mL). CONCLUSION: Further studies are needed to establish whether or not sVAP-1 might be considered as an early, non-invasive, and affordable biomarker to screen women who will develop PIH or GDM. Our data will aid sample size calculations for such larger studies.

Effect of more versus less intensive blood pressure control on cardiovascular, renal and mortality outcomes in people with type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Currently, there is uncertainty as to whether blood pressure control in patients with type 2 diabetes should be treated to standard recommended levels or more intensively. METHODS: Medline, EMBASE, CENTRAL, and Clinicaltrials.gov were searched between January 1, 2000 and April 20th, 2023. Outcomes considered were all-cause mortality, stroke, heart failure, cardiovascular disease, albuminuria, coronary heart disease, and renal outcomes. Random-effects meta-analyses estimated pooled relative risks and mean differences. RESULTS: Nine trials enrolling 11,005 participants with type 2 diabetes were included. The pooled mean difference between the intensive and standard treatment groups at follow-up were -7.98 mmHg (95% CI: 12.19 to -3.76) in systolic blood pressure, and -5.08 mmHg (-7.00 to -3.17) in diastolic blood pressure; although between study heterogeneity was high for both meta-analyses (I2>85%). Intensive blood pressure lowering resulted in a reduction in risk of stroke (risk ratio 0.64; 0.52 to 0.79), and macro-albuminuria (0.77; 0.63 to 0.93). More intensive blood pressure control did not result in a statistically significant reduction in risk of all-cause mortality, heart failure, cardiovascular death, cardiovascular events, renal outcomes, and micro-albuminuria; although the direction of estimated effect was beneficial for all outcomes. CONCLUSIONS: The use of intensive compared with standard blood pressure targets resulted in a significant reduction in blood pressure, stroke, and macro-albuminuria in patients with type 2 diabetes. The post-treatment blood pressure level in the intensive group was 125/73 mmHg, suggesting the current recommendations of 130/80 mmHg blood pressure or lower if tolerated, could be reduced further.

Life expectancy following a cardiovascular event in individuals with and without type 2 diabetes: A UK multi-ethnic population-based observational study.

BACKGROUND AND AIMS: We aimed to evaluate the life expectancy following the first cardiovascular disease (CVD) event by type 2 diabetes (T2D) status and ethnicity. METHODS AND RESULTS: We used the Clinical Practice Research Datalink database in England (UK), linked to the Hospital Episode Statistics information, to identify individuals with and without T2D who survived a first CVD event between 1st Jan 2007 and 31st Dec 2017; subsequent death events were extracted from the Office for National Statistics database. Ethnicity was categorised as White, South Asian (SA), Black, or other. Flexible parametric survival models were used to estimate survival and predict life expectancy. 59,939 individuals with first CVD event were included: 7596 (12.7%) with T2D (60.9% men; mean age at event: 69.7 years [63.2 years in SA, 65.9 in Black, 70.2 in White]) and 52,343 without T2D (56.7% men; 65.9 years [54.7 in Black, 58.2 in SA, 66.3 in White]). Accounting for potential confounders (sex, deprivation, lipid-lowering medication, current smoking, and pre-existing hypertension), comparing individuals with vs without T2D the mortality rate was 53% higher in White (hazard ratio [HR]: 1.53 [95% CI: 1.44, 1.62]), corresponding to a potential loss of 3.87 (3.30, 4.44) life years at the age of 50 years in individuals with T2D. No evidence of a difference in life expectancy was observed in individuals of SA (HR: 0.82 [0.52, 1.29]; -1.36 [-4.58, 1.86] life years), Black (HR: 1.26 [0.59, 2.70]; 1.21 [-2.99, 5.41] life years); and other (HR: 1.64 [0.80, 3.39]; 3.89 [-2.28, 9.99] life years) ethnic group. CONCLUSION: Following a CVD event, T2D is associated with a different prognosis and life years lost among ethnic groups.

COVID-19 vaccination uptake amongst ethnic minority communities in England: a linked study exploring the drivers of differential vaccination rates.

BACKGROUND: Despite generally high coronavirus disease 2019 (COVID-19) vaccination rates in the UK, vaccination hesitancy and lower take-up rates have been reported in certain ethnic minority communities. METHODS: We used vaccination data from the National Immunisation Management System (NIMS) linked to the 2011 Census and individual health records for subjects aged ≥40 years (n = 24 094 186). We estimated age-standardized vaccination rates, stratified by ethnic group and key sociodemographic characteristics, such as religious affiliation, deprivation, educational attainment, geography, living conditions, country of birth, language skills and health status. To understand the association of ethnicity with lower vaccination rates, we conducted a logistic regression model adjusting for differences in geographic, sociodemographic and health characteristics. ResultsAll ethnic groups had lower age-standardized rates of vaccination compared with the white British population, whose vaccination rate of at least one dose was 94% (95% CI: 94%-94%). Black communities had the lowest rates, with 75% (74-75%) of black African and 66% (66-67%) of black Caribbean individuals having received at least one dose. The drivers of these lower rates were partly explained by accounting for sociodemographic differences. However, modelled estimates showed significant differences remained for all minority ethnic groups, compared with white British individuals. CONCLUSIONS: Lower COVID-19 vaccination rates are consistently observed amongst all ethnic minorities.

Variations in documentation of atrial fibrillation predicted by population and service level characteristics in primary health care in England.

BACKGROUND: Identifying features associated with atrial fibrillation (AF) documentation could inform screening. This study used published data to describe differences in documented and estimated AF prevalence in general practices, and explored predictors of variations in AF prevalence. METHODS: Cross-sectional study of 7318 general practices in England. Descriptive and inferential statistics were undertaken. Multiple linear regression was used to model the difference between estimated AF and documented AF, adjusted for population, practice and practice performance variables. RESULTS: Documented AF prevalence was lower than estimated (- 0.55% 95% confidence intervals, -1.89, 2.99). The proportion of variability accounted for in the final regression model was 0.25. Factors positively associated with AF documentation (increase in difference between estimated and documented), were patients 65-74 years, 75 years +, Black or South Asian ethnicity, diabetes mellitus and practices in East and Midlands of England. Eight variables (female patients, deprivation score, heart failure and peripheral artery disease, total patients per practice, full-time GPs and nurses; and location in South of England) were negatively associated with AF documentation (reduction in difference). CONCLUSION: Variations in AF documentation were predicted by several practice and population characteristics. Screening could target these sources of variation to decrease variation and improve AF documentation.

Blood biomarkers to predict the onset of pre-eclampsia: A systematic review and meta-analysis.

Pre-eclampsia is one of the most common pregnancy complications, and a major cause of fetal and maternal morbidity and mortality globally. Diagnosis currently takes place in the third trimester based on clinical symptoms. This systematic review and meta-analysis sought to determine the blood biomarkers that are associated with pre-eclampsia, and in particular, the biomarkers that could predict pre-eclampsia in early pregnancy. We searched the electronic databases (Medline, Embase, Cochrane Library) from inception up to March 2022. Prospective studies with 1000 or more participants that measured blood biomarkers to predict or diagnose pre-eclampsia have been included in this systematic review. Biomarkers' measurements were considered from the first up to the third trimester, but not during labor. Data concerning pre-eclampsia, biomarker measurements and study characteristics were extracted. Meta-analysis was performed when possible. We found a total of 43 studies (assessing 62 different biomarkers in 18,170 pregnancies, have been included in this systematic review, and a total of 6 studies (assessing 2 biomarkers have been included in the meta-analysis). Statistical analysis was performed for PlGF and sFlt-1. Mean difference in PlGF levels between pre-eclampsia and healthy pregnancies, appear to increase as the pregnancy progresses. Results of sFlt-1 meta-analysis were inconclusive. No significant publication bias was identified. This is the most comprehensive and up to date systematic review and meta-analysis on this important topic on blood biomarkers for the early prediction of pre-eclampsia. Further This research highlights the urgent needed for further discovery research to identify blood biomarkers that could predict the development of pre-eclampsia.

Are major lower extremity amputations well recorded in primary care electronic health records?: Insights from primary care electronic health records in England.

AIMS: Major lower extremity amputations (MLEAs) are understood to be well recorded in secondary care in England in the Hospital Episode Statistics (HES) database. It is unclear how well MLEAs are recorded in primary care databases. BACKGROUND: This study compared MLEA event case ascertainment in Clinical Practice Research Datalink (CPRD) to that in HES. METHODS: MLEA events were ascertained in CPRD and in HES linkage between 1 January 2010 and 31 December 2019. The number of MLEA events and the number of patients with at least one MLEA in each database were recorded and compared. Individual events were matched between the databases using varying date-matching windows. Reasons for differences in case ascertainment were explored. FINDINGS: In total 23 262 patients had at least one MLEA record, 8716 (37.5%) had an MLEA record in HES only, 5393 (23.2%) in CPRD only and 9153 (39.4%) in both. Out of a total of 75 221 events, 13 071 (62.4%) were recorded in HES only and 44 151 (81.3%) in CPRD only. 7874 (37.6%) of HES events were recorded in CPRD and 10 125 (18.6%) of CPRD events were recorded in HES when using the maximum date matching window of 28 days plus the time between admission and procedure. The main reasons for differences in case ascertainment included, re-recordings and miscoding in CPRD.Compared to HES, MLEAs are poorly recorded in CPRD predominantly due to re-recordings of events and miscoding procedures. CPRD data cannot solely be relied upon to ascertain cases of MLEA; however, HES linkage to CPRD may be useful to obtain medical history of diagnoses, medication and diagnostic tests.

Patterns of rates of mortality in the Clinical Practice Research Datalink.

The Clinical Practice Research Datalink (CPRD) is a widely used data resource, representative in demographic profile, with accurate death recordings but it is unclear if mortality rates within CPRD GOLD are similar to rates in the general population. Rates may additionally be affected by selection bias caused by the requirement that a cohort have a minimum lookback window, i.e. observation time prior to start of at-risk follow-up. Standardised Mortality Ratios (SMRs) were calculated incorporating published population reference rates from the Office for National Statistics (ONS), using Poisson regression with rates in CPRD GOLD contrasted to ONS rates, stratified by age, calendar year and sex. An overall SMR was estimated along with SMRs presented for cohorts with different lookback windows (1, 2, 5, 10 years). SMRs were stratified by calendar year, length of follow-up and age group. Mortality rates in a random sample of 1 million CPRD GOLD patients were slightly lower than the national population [SMR = 0.980 95% confidence interval (CI) (0.973, 0.987)]. Cohorts with observational lookback had SMRs below one [1 year of lookback; SMR = 0.905 (0.898, 0.912), 2 years; SMR = 0.881 (0.874, 0.888), 5 years; SMR = 0.849 (0.841, 0.857), 10 years; SMR = 0.837 (0.827, 0.847)]. Mortality rates in the first two years after patient entry into CPRD were higher than the general population, while SMRs dropped below one thereafter. Mortality rates in CPRD, using simple entry requirements, are similar to rates seen in the English population. The requirement of at least a single year of lookback results in lower mortality rates compared to national estimates.

Bayesian network meta-analysis methods for combining individual participant data and aggregate data from single arm trials and randomised controlled trials.

BACKGROUND: Increasingly in network meta-analysis (NMA), there is a need to incorporate non-randomised evidence to estimate relative treatment effects, and in particular in cases with limited randomised evidence, sometimes resulting in disconnected networks of treatments. When combining different sources of data, complex NMA methods are required to address issues associated with participant selection bias, incorporating single-arm trials (SATs), and synthesising a mixture of individual participant data (IPD) and aggregate data (AD). We develop NMA methods which synthesise data from SATs and randomised controlled trials (RCTs), using a mixture of IPD and AD, for a dichotomous outcome. METHODS: We propose methods under both contrast-based (CB) and arm-based (AB) parametrisations, and extend the methods to allow for both within- and across-trial adjustments for covariate effects. To illustrate the methods, we use an applied example investigating the effectiveness of biologic disease-modifying anti-rheumatic drugs for rheumatoid arthritis (RA). We applied the methods to a dataset obtained from a literature review consisting of 14 RCTs and an artificial dataset consisting of IPD from two SATs and AD from 12 RCTs, where the artificial dataset was created by removing the control arms from the only two trials assessing tocilizumab in the original dataset. RESULTS: Without adjustment for covariates, the CB method with independent baseline response parameters (CBunadjInd) underestimated the effectiveness of tocilizumab when applied to the artificial dataset compared to the original dataset, albeit with significant overlap in posterior distributions for treatment effect parameters. The CB method with exchangeable baseline response parameters produced effectiveness estimates in agreement with CBunadjInd, when the predicted baseline response estimates were similar to the observed baseline response. After adjustment for RA duration, there was a reduction in across-trial heterogeneity in baseline response but little change in treatment effect estimates. CONCLUSIONS: Our findings suggest incorporating SATs in NMA may be useful in some situations where a treatment is disconnected from a network of comparator treatments, due to a lack of comparative evidence, to estimate relative treatment effects. The reliability of effect estimates based on data from SATs may depend on adjustment for covariate effects, although further research is required to understand this in more detail.

Estimates of years of life lost depended on the method used: tutorial and comparative investigation.

OBJECTIVES: This review aims to summarize key methods for estimating years of life lost (YLL), highlighting their differences and how they can be implemented in current software, and applies them in a real-world example. STUDY DESIGN AND SETTING: We investigated the common YLL methods: (1) Years of potential life lost (YPLL); (2) Global Burden of Disease (GBD) approach; (3) Life tables; (4) Poisson regression; and (5) Flexible parametric Royston-Parmar regression. We used data from UK Biobank and multimorbidity as our example. RESULTS: For the YPLL and GBD method, the analytical procedures allow only to quantify the average YLL within each group (with and without multimorbidity) and, from them, their difference; conversely, for the other methods both the remaining life expectancy within each group and the YLL could be estimated. At 65 years, the YLL in those with vs. without multimorbidity was 1.8, 1.2, and 2.7 years using the life tables approach and the Poisson, and Royston-Parmar regression, respectively; corresponding values were -0.73 and -0.05 years for YPLL and using the GBD approach. CONCLUSION: While deciding among different methods to estimate YLL, researchers should consider the purpose of the research, the type of available data, and the flexibility of the model.

Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19.

OBJECTIVE: To investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications. RESEARCH DESIGN AND METHODS: In this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors. RESULTS: Cardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8-8.7) (120.6 mg/dL [104.4-156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age <69 years. Preexisting diabetes status had a similar modifying effect on odds of complications, but evidence was strongest for renal injury, cardiac ischemia, and any cardiovascular/renal complication. CONCLUSIONS: Increased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes.