A cross-sectional time series of cardiometabolic health education format preferences across sociodemographic groups.

AIMS: Health education is integral to cardiometabolic disease (CMD) management. This study aimed to assess whether and how education preferences have changed over time, and whether trends differ by sociodemographic characteristics (education status, age, ethnicity, and sex). METHODS: A cross-sectional questionnaire was deployed across five counties in the East Midlands, UK between 2017 and 2022 to adults with CMD (type 2 diabetes, cardiovascular disease or cerebrovascular disease). Respondent demographic data were collected alongside health education preferences. Statistical analyses ascertained whether demographic characteristics influenced preferences. The distribution of preferences over time was charted to identify trends. RESULTS: A total of 4301 eligible responses were collected. Face-to-face one-to-one education was preferred (first choice for 75.1% of participants) but popularity waned over the five-year period. Trends were similar amongst demographic groups. Online education showed a U-shaped trend: In 2017, 44% of respondents ranked it as acceptable, peaking at 53% in 2019, but declining again, to below base line, 43%, by 2022. This modality was more popular with participants aged younger than 65 years, but popularity in people older than 65 years increased over the study period. The popularity of printed information also declined over time across all demographic groups except those of South Asian ethnicity, for whom it remained static. CONCLUSIONS: The overwhelming preference for face-to-face one-to-one health education from a doctor or nurse highlights the importance of preserving access to this modality, even in the face of current NHS pressures and trends towards digitalisation. Trends are changing, and should continue to be monitored, including between different sociodemographic groups.

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.

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.

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.

Evaluation of quality of diabetic foot examination on YouTube.

INTRODUCTION: Foot ulcers and amputations are common conditions in people with diabetes and can considerably impact quality of life, necessitate a lengthy hospital stay and increase mortality. Preventative foot care and examination can prevent or delay ulceration, and individuals may seek information from publicly available social media resources such as YouTube. Therefore, the purpose of this study is to evaluate the educational quality and reliability of publicly available YouTube videos on diabetes foot examinations. METHOD: A YouTube search for "diabetic foot examination" was conducted, and the first 100 relevant English videos focused on examining the diabetic foot were included for evaluation. The Journal of the American Medical Association (JAMA) standards were used to measure video reliability. The Global Quality Score (GQS) and the Diabetes UK Annual Foot Check (DUK-C) checklist were used to assess video educational quality. Differences in JAMA, GQS, and DUK-C ratings were analysed after videos were sorted by topic and source. RESULTS: The mean number of views per video was 101,311.9 ± 348,383.6, and the mean video power index was 41.6 ± 170.0. The most common upload source was from physicians (28%) and, the most popular material category was diabetes foot examination (58 videos). In terms of video reliability, 36% of videos scored 0. According to the GQS standards, only 5% of the videos are of excellent quality, while 34% are of poor quality, with 24 videos scoring between 0 and 1 on the DUK-C scale. CONCLUSION: While foot care examination videos have a substantial audience, the majority are considered low in quality and reliability. Videos on comprehensive diabetic foot examination should be accessed on reputable sources that guarantee standardisations of video quality and take into account the simplification of information transmission in order to reach lay audiences.

Physical activity and risk of chronic kidney disease: systematic review and meta-analysis of 12 cohort studies involving 1,281,727 participants.

The role of regular physical activity in preventing vascular and non-vascular disease is well established. Chronic kidney disease (CKD) is a major cause of global morbidity and mortality and largely preventable, but it is uncertain if regular physical activity can reduce the risk of CKD. Using a systematic review and meta-analysis of published observational cohort studies in the general population, we sought to assess the association between physical activity and CKD risk. Relevant studies with at least one-year of follow-up were sought from inception until 02 May 2022 in MEDLINE, Embase, Web of Science, and manual search of relevant articles. Relative risks (RRs) with 95% confidence intervals (CIs) for the maximum versus the minimal amount of physical activity groups were pooled using random effects meta-analysis. The quality of the evidence was evaluated using the GRADE tool. A total of 12 observational cohort studies comprising 1,281,727 participants and 66,217 CKD events were eligible for the analysis. The pooled multivariable-adjusted RR (95% CI) of CKD comparing the most versus the least physically active groups was 0.91 (0.85-0.97). The association was consistent across several study level subgroups. Exclusion of any single study at a time from the meta-analysis did not change the direction or significance of the association. There was no evidence of small study effects among contributing studies. The GRADE quality of the evidence was low. In the general population, individuals who are most physically active have a lowered risk of CKD compared to those who are not or least physically active. CRD42022327640.

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.

Temporal trends in admissions for atrial fibrillation and severe bleeding in England: an 18-year longitudinal analysis.

Objective. Temporal trends in admissions for atrial fibrillation (AF) and severe bleeding associated with AF vary worldwide. We aimed to explore their temporal trends in England and their relation to the introduction of DOACs in 2014 in the UK. Design. This longitudinal ecological study utilised aggregated data that was extracted from the Hospital Episode Statistics database, which captured annual admissions for AF and severe bleeding associated with AF between 2001 and 2018. Trends in admissions over the study period and across age groups, gender and regions in England were assessed. Results. In total, there were 11,292,177 admissions for AF and 324,851 admissions for severe bleeding associated with AF. There was a steady rise in admissions for AF from 2001 to 2017 (204,808 to 1,109,295; p for trend<.001). A similar trend was observed for severe bleeding (4940 to 30,169; p for trend <.001), but the increase dropped slightly between 2013 and 2014 and continued thereafter. Conclusions. There was a rise in admissions for AF and severe bleeding in England between 2001 and 2018. There is little evidence that the slight drop in admissions for severe bleeding between 2013 and 2014 may have been caused by the introduction of DOACs in 2014. Contributors to these trends need urgent exploration.

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.

Consultation rates in people with type 2 diabetes with and without vascular complications: a retrospective analysis of 141,328 adults in England.

OBJECTIVE: To assess trends in primary and specialist care consultation rates and average length of consultation by cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), or cardiometabolic multimorbidity exposure status. METHODS: Observational, retrospective cohort study used linked Clinical Practice Research Datalink primary care data from 01/01/2000 to 31/12/2018 to assess consultation rates in 141,328 adults with newly diagnosed T2DM, with or without CVD. Patients who entered the study with either a diagnosis of T2DM or CVD and later developed the second condition during the study are classified as the cardiometabolic multimorbidity group. Face to face primary and specialist care consultations, with either a nurse or general practitioner, were assessed over time in subjects with T2DM, CVD, or cardiometabolic multimorbidity. Changes in the average length of consultation in each group were investigated. RESULTS: 696,255 (mean 4.9 years [95% CI, 2.02-7.66]) person years of follow up time, there were 10,221,798 primary and specialist care consultations. The crude rate of primary and specialist care consultations in patients with cardiometabolic multimorbidity (N = 11,881) was 18.5 (95% CI, 18.47-18.55) per person years, 13.5 (13.50, 13.52) in patients with T2DM only (N = 83,094) and 13.2 (13.18, 13.21) in those with CVD (N = 57,974). Patients with cardiometabolic multimorbidity had 28% (IRR 1.28; 95% CI: 1.27, 1.31) more consultations than those with only T2DM. Patients with cardiometabolic multimorbidity had primary care consultation rates decrease by 50.1% compared to a 45.0% decrease in consultations for those with T2DM from 2000 to 2018. Specialist care consultation rates in both groups increased from 2003 to 2018 by 33.3% and 54.4% in patients with cardiometabolic multimorbidity and T2DM, respectively. For patients with T2DM the average consultation duration increased by 36.0%, in patients with CVD it increased by 74.3%, and in those with cardiometabolic multimorbidity it increased by 37.3%. CONCLUSIONS: Annual primary care consultation rates for individuals with T2DM, CVD, or cardiometabolic multimorbidity have fallen since 2000, while specialist care consultations and average consultation length have both increased. Individuals with cardiometabolic multimorbidity have significantly more consultations than individuals with T2DM or CVD alone. Service redesign of health care delivery needs to be considered for people with cardiometabolic multimorbidity to reduce the burden and health care costs.

Attitudes of older adults and their carers towards de-prescribing: A systematic review.

AIM: The aim of this systematic review is to explore the attitudes of older adults (≥65 years old) and their carers towards de-prescribing. METHODS: We identified relevant studies from three databases; MEDLINE, CINAHL and Web of Science. Two reviewers (MS, SS) independently extracted data from each selected study using a standardised self-developed data extraction form. Main findings of the studies were summarised descriptively. RESULTS: A total of 35 studies were included in the review. Of them, 19 were questionnaire studies, 11 semi-structured interviews, 4 focus groups and 1 study used the nominal group technique approach. Most older adults and their carers were willing to have medication de-prescribed if told to do so by a healthcare professional (HCP). Other factors that increased willingness to de-prescribing included; trust in the HCP, side effects and inconvenience from medications as well as the prospect of follow-up and monitoring during de-prescribing. In contrast, perceived effectiveness, unawareness of lack of benefit, negative expectations of ageing and fear were factors preventing de-prescribing. CONCLUSION: De-prescribing is an important concept in older people given the harm associated with polypharmacy in this age group. Overall, older adults and their carers are willing to have medication de-prescribed if facilitated by their HCP. However, there remain a few barriers to de-prescribing which may need to be addressed in certain patients, through discussions between older adults/their carers and a HCP, to allow de-prescribing to be more effective.

Cardiovascular and renal outcomes of initial combination therapy with glucose-lowering agents versus a stepwise approach in newly diagnosed or treatment-naïve type 2 diabetes: A systematic review and meta-analysis.

AIM: To evaluate the efficacy and safety of the initial combination therapy versus a stepwise approach in newly diagnosed type 2 diabetes (T2D) by conducting a systematic review and meta-analysis of observational cohort studies and randomized controlled trials (RCTs). METHODS: Studies were identified from MEDLINE, Embase, the Cochrane Library, and through search of bibliographies to January 2022. Study-specific risk ratios (RRs) and mean differences with 95% confidence intervals (CIs) were pooled. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Eight articles including four unique RCTs (n = 5527 participants) and one observational cohort study (n = 200) that compared initial combination therapy versus stepwise therapy were included. The RR for myocardial infarction comparing initial combination therapy versus stepwise therapy was 1.21 (95% CI 0.74-2.00). Initial combination therapy reduced levels of fasting plasma glucose and glycated haemoglobin: mean differences -0.97 mmol/L (95% CI -1.41, -0.53) and -24.92 mmol/mol (95% CI -25.67, -24.27), respectively. Initial combination therapy versus stepwise therapy reduced lipid levels, blood pressure and intima media thickness, with no differences in body composition variables, neuropathy, retinopathy or adverse events. Single-study results showed that initial combination therapy reduced creatinine levels and urine albumin excretion rate. The quality of the evidence ranged from moderate to very low. CONCLUSIONS: Except for improving cardiometabolic and glycaemic variables, a limited number of studies characterized by small sample sizes show that initial combination therapy for newly diagnosed T2D may be similar in efficacy and safety to stepwise therapy with respect to cardio-renal outcomes. There is a lack of sufficient evidence to recommend initial combination therapy with glucose-lowering agents in newly diagnosed T2D with the aim of preventing cardio-renal outcomes. Definitive RCTs are warranted.

Obesity, walking pace and risk of severe COVID-19 and mortality: analysis of UK Biobank.

Obesity is an emerging risk factor for coronavirus disease-2019 (COVID-19). Simple measures of physical fitness, such as self-reported walking pace, may also be important risk markers. This analysis includes 412,596 UK Biobank participants with linked COVID-19 data (median age at linkage = 68 years, obese = 24%, median number of comorbidities = 1). As of August 24th 2020, there were 1001 cases of severe (in-hospital) disease and 336 COVID-19 deaths. Compared to normal weight individuals, the adjusted odds ratio (OR) of severe COVID-19 in overweight and obese individuals was 1.26 (1.07, 1.48) and 1.49 (1.25, 1.79), respectively. For COVID-19 mortality, the ORs were 1.19 (0.88, 161) and 1.82 (1.33, 2.49), respectively. Compared to those with a brisk walking pace, the OR of severe COVID-19 for steady/average and slow walkers was 1.13 (0.98, 1.31) and 1.88 (1.53, 2.31), respectively. For COVID-19 mortality, the ORs were 1.44 (1.10, 1.90) and 1.83 (1.26, 2.65), respectively. Slow walkers had the highest risk regardless of obesity status. For example, compared to normal weight brisk walkers, the OR of severe disease and COVID-19 mortality in normal weight slow walkers was 2.42 (1.53, 3.84) and 3.75 (1.61, 8.70), respectively. Self-reported slow walkers appear to be a high-risk group for severe COVID-19 outcomes independent of obesity.

Effectiveness of the Transformation model, a model of care that integrates diabetes services across primary, secondary and community care: A retrospective study.

AIMS: The primary aim was to evaluate the effectiveness of a model integrating diabetes services across primary, secondary and community care (Transformation model). The secondary aim was to understand whether changes resulted from the model. METHODS: The model was implemented In Leicester, Leicestershire and Rutland (UK) across three clinical commissioning groups, the acute trust and accompanying stakeholders. One clinical commissioning group (Leicester City) implemented the entire model and was the primary evaluation population. A quasi-experimental interrupted time series design was employed. The primary outcome was number of Type 2 diabetes-related bed-days per 1000 patients. RESULTS: In the primary population, the mean number of Type 2 diabetes-related bed-days per 1000 patients was increasing before model implementation by 0.33/month (95% confidence interval: -0.07, 0.72), whereas it was decreasing after implementation by a mean value of -0.14/month (-0.33, 0.06); a statistically significant difference (p = 0.04). Secondary analyses showed: nationally, there was no significant change between the pre- and post-periods so it is unlikely that large secular change drove the improvement; the other two Leicestershire clinical commissioning groups saw improvement or stability; underlying processes worked as hypothesised overall; diabetes biomedical markers deteriorated in the primary care population suggesting a change in case-mix due to moving some patients out of secondary care. CONCLUSIONS: Given that the initial aim was to shift services from secondary to primary care without causing harm, an improvement is better than expected. This observational evaluation cannot show conclusively that improvements were due to the Transformation model, but secondary analyses support this.

Ethnic, social and multimorbidity disparities in therapeutic inertia: A UK primary care observational study in patients newly diagnosed with type 2 diabetes.

AIM: To investigate factors associated with delays in receiving glucose-lowering therapy in patients newly diagnosed with type 2 diabetes mellitus (T2DM), and explore the preferential order and time of intensifications. MATERIALS AND METHODS: Retrospective cohort study including 120 409 adults with T2DM initiating first- to fourth-line glucose-lowering therapy in primary care between 2000 and 2018, using the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics, Office of National Statistics death registration, and 2007 Index of Multiple Deprivation data. Associations were investigated using time-to-event analysis. RESULTS: The longest delays to prescription of first-line therapy were observed in older patients, of black or other ethnicities, and with multimorbidity. People from the most deprived areas received earlier first-line treatment than those from the least deprived areas. The majority were treated with metformin (82.4%) as the first-line prescription, sulphonylurea (50.4%) as second-line, dipeptidyl peptidase-4 inhibitor (27.7%) as third-line, and insulin (28.0%) as fourth-line. In the past 5 years, there was an increase in prescriptions of dipeptidyl peptidase-4-inhibitor and sodium-glucose transport protein-2 inhibitor. The median time was 0.5 years for first-line prescription, 4.1 for second-line, 4.6 for third-line and 4.7 for fourth-line. After T2DM diagnosis, 25% of patients developed cardiovascular disease and non-cardiovascular disease complications within a median time of 12-14 years, and received intensification 5-6 years later. CONCLUSIONS: Within the complex challenges of managing blood glucose levels and risk of additional comorbidities, future health care research and guidelines should focus on overcoming therapeutic inertia particularly at an earlier stage for older patients, from ethnic minorities and with multimorbidities.

Patterns of multimorbidity and risk of severe SARS-CoV-2 infection: an observational study in the U.K.

BACKGROUND: Pre-existing comorbidities have been linked to SARS-CoV-2 infection but evidence is sparse on the importance and pattern of multimorbidity (2 or more conditions) and severity of infection indicated by hospitalisation or mortality. We aimed to use a multimorbidity index developed specifically for COVID-19 to investigate the association between multimorbidity and risk of severe SARS-CoV-2 infection. METHODS: We used data from the UK Biobank linked to laboratory confirmed test results for SARS-CoV-2 infection and mortality data from Public Health England between March 16 and July 26, 2020. By reviewing the current literature on COVID-19 we derived a multimorbidity index including: (1) angina; (2) asthma; (3) atrial fibrillation; (4) cancer; (5) chronic kidney disease; (6) chronic obstructive pulmonary disease; (7) diabetes mellitus; (8) heart failure; (9) hypertension; (10) myocardial infarction; (11) peripheral vascular disease; (12) stroke. Adjusted logistic regression models were used to assess the association between multimorbidity and risk of severe SARS-CoV-2 infection (hospitalisation/death). Potential effect modifiers of the association were assessed: age, sex, ethnicity, deprivation, smoking status, body mass index, air pollution, 25-hydroxyvitamin D, cardiorespiratory fitness, high sensitivity C-reactive protein. RESULTS: Among 360,283 participants, the median age was 68 [range 48-85] years, most were White (94.5%), and 1706 had severe SARS-CoV-2 infection. The prevalence of multimorbidity was more than double in those with severe SARS-CoV-2 infection (25%) compared to those without (11%), and clusters of several multimorbidities were more common in those with severe SARS-CoV-2 infection. The most common clusters with severe SARS-CoV-2 infection were stroke with hypertension (79% of those with stroke had hypertension); diabetes and hypertension (72%); and chronic kidney disease and hypertension (68%). Multimorbidity was independently associated with a greater risk of severe SARS-CoV-2 infection (adjusted odds ratio 1.91 [95% confidence interval 1.70, 2.15] compared to no multimorbidity). The risk remained consistent across potential effect modifiers, except for greater risk among older age. The highest risk of severe infection was strongly evidenced in those with CKD and diabetes (4.93 [95% CI 3.36, 7.22]). CONCLUSION: The multimorbidity index may help identify individuals at higher risk for severe COVID-19 outcomes and provide guidance for tailoring effective treatment.

Physical activity and risk of atrial fibrillation in the general population: meta-analysis of 23 cohort studies involving about 2 million participants.

Regular physical activity is well established to be associated with reduced risk of cardiovascular disease outcomes. Whether physical activity is associated with the future risk of atrial fibrillation (AF) remains a controversy. Using a systematic review and meta-analysis of published observational cohort studies in general populations with at least one-year of follow-up, we aimed to evaluate the association between regular physical activity and the risk of AF. Relevant studies were sought from inception until October 2020 in MEDLINE, Embase, Web of Science, and manual search of relevant articles. Extracted relative risks (RRs) with 95% confidence intervals (CIs) for the maximum versus the minimal amount of physical activity groups were pooled using random-effects meta-analysis. Quality of the evidence was assessed by GRADE. A total of 23 unique observational cohort studies comprising of 1,930,725 participants and 45,839 AF cases were eligible. The pooled multivariable-adjusted RR (95% CI) for AF comparing the most physically active versus the least physically active groups was 0.99 (0.93-1.05). This association was modified by sex: an increased risk was observed in men: 1.20 (1.02-1.42), with a decreased risk in women: 0.91 (0.84-0.99). The quality of the evidence ranged from low to moderate. Pooled observational cohort studies suggest that the absence of associations reported between regular physical activity and AF risk in previous general population studies and their aggregate analyses could be driven by a sex-specific difference in the associations - an increased risk in men and a decreased risk in women.Systematic review registration: PROSPERO 2020: CRD42020172814.

Therapeutic uncertainties in people with cardiometabolic diseases and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) has been declared a pandemic by the World Health Organization and sent all countries scrambling to review emergency healthcare provisions. There is global evidence of each nation struggling to effectively manage the number of people being diagnosed with the virus. These are testing times which have not been experienced in recent generations and there are a number of insecurities regarding the management of people with COVID-19 and cardiometabolic diseases. This review highlights the current concerns related to COVID-19 and provides advice in terms of the therapeutic uncertainty and potential adverse harms associated with therapy when managing people, particularly those with cardiometabolic diseases, who have contracted or are at increased risk of contracting COVID-19.

Comparative effectiveness of gliclazide modified release versus sitagliptin as second-line treatment after metformin monotherapy in patients with uncontrolled type 2 diabetes.

AIMS: To compare the effectiveness and safety of gliclazide modified release (MR) to sitagliptin as type 2 diabetes mellitus (T2D) treatments in a real-world patient population. MATERIALS AND METHODS: This retrospective cohort study used records from the UK Clinical Practice Research Datalink. The cohort consisted of adult patients with T2D newly treated with either gliclazide MR or sitagliptin as second-line treatment added to metformin and with a glycated haemoglobin (HbA1c) level of ≥7.0% (53 mmol/mol). Patients were 1:1 matched using high-dimensional propensity score matching and followed to determine the time taken to reach an HbA1c <7.0%. Secondary outcomes included time to HbA1c ≤6.5% (48 mmol/mol), time to ≥1% (11 mmol/mol) HbA1c reduction from baseline, treatment persistence and durability, and hypoglycaemic events. RESULTS: Among the 1986 patients included, those on gliclazide MR more likely achieved an HbA1c <7.0% [hazard ratio (HR): 1.35; 95% confidence interval (CI): 1.15-1.57], HbA1c ≤6.5% (HR: 1.51; 95% CI: 1.19-1.92) or had an HbA1c reduction ≥1% from baseline (HR: 1.11; 95% CI: 1.00-1.24) compared with patients on sitagliptin. Durability (log-rank P = .135) and persistence (P = .119) were similar between the two groups. Hypoglycaemic events were uncommon (23 total severe and non-severe events; incidence rate, 3.7 per 1000 patient years), with 4.7 and 2.6 events per 1000 patient years with gliclazide MR and sitagliptin treatment, respectively. CONCLUSIONS: In this real-world study, second-line gliclazide MR was more effective than sitagliptin in reducing HbA1c, with similar durability and persistence and low rates of hypoglycaemic events, in individuals with T2D on metformin treatment and HbA1c above the target of 7.0%.

Physical activity and risk of venous thromboembolism: systematic review and meta-analysis of prospective cohort studies.

The inverse association between physical activity and arterial thrombotic disease is well established. Evidence on the association between physical activity and venous thromboembolism (VTE) is divergent. We conducted a systematic review and meta-analysis of published observational prospective cohort studies evaluating the associations of physical activity with VTE risk. MEDLINE, Embase, Web of Science, and manual search of relevant bibliographies were systematically searched until 26 February 2019. Extracted relative risks (RRs) with 95% confidence intervals (CIs) for the maximum versus minimal amount of physical activity groups were pooled using random effects meta-analysis. Twelve articles based on 14 unique prospective cohort studies comprising of 1,286,295 participants and 23,753 VTE events were eligible. The pooled fully-adjusted RR (95% CI) of VTE comparing the most physically active versus the least physically active groups was 0.87 (0.79-0.95). In pooled analysis of 10 studies (288,043 participants and 7069 VTE events) that reported risk estimates not adjusted for body mass index (BMI), the RR (95% CI) of VTE was 0.81 (0.70-0.93). The associations did not vary by geographical location, age, sex, BMI, and methodological quality of studies. There was no evidence of publication bias among contributing studies. Pooled observational prospective cohort studies support an association between regular physical activity and low incidence of VTE. The relationship does not appear to be mediated or confounded by BMI.