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.

The impact of COVID-19 lockdowns on the body mass index of people living with obesity: A UK retrospective cohort study using the UK Clinical Practice Research Datalink.

BACKGROUND: Restrictions implemented by governments during the coronavirus disease 2019 (COVID-19) pandemic affected people's eating habits and physical activity. We investigated the effect of COVID-19 lockdowns and restrictions on body mass index (BMI) and weight in a UK population, according to BMI class, sex, age and ethnicity. METHODS: This retrospective observational cohort study used the Clinical Practice Research Datalink AURUM database. Baseline spanned from 22 March 2017-22 March 2020, and the follow-up lockdown period was from 23 March 2020 (start of the lockdown in the UK) to 13 March 2021. The descriptive analysis included individuals with ≥ 1 valid BMI/weight measurements during both the baseline and follow-up periods, while the model-based analysis comprised individuals with ≥ 1 valid measurement(s) during baseline. Results were stratified by baseline BMI category, sex, age and ethnicity. RESULTS: In the descriptive analysis (n = 273,529), most individuals did not change BMI category post-lockdown (66.4-83.3%). A greater proportion of women (12.6%) than men (9.5%) moved up BMI categories post-lockdown. Compared with older groups, a higher proportion of individuals < 45 years old increased post-lockdown BMI category. The model-based analysis (n = 938,150) revealed consistent trends, where changes in body weight and BMI trajectories pre- and post-lockdown were observed for women and for individuals < 45 years. CONCLUSION: During COVID-19 restrictions, women and young individuals were more likely than other groups to increase BMI category and weight post-lockdown.

Age at Type 2 Diabetes Diagnosis and Cause-Specific Mortality: Observational Study of Primary Care Patients in England.

OBJECTIVE: To examine the associations between age at type 2 diabetes diagnosis and the relative and absolute risk of all-cause and cause-specific mortality in England. RESEARCH DESIGN AND METHODS: In this cohort study using primary care data from the Clinical Practice Research Datalink, we identified 108,061 individuals with newly diagnosed type 2 diabetes (16-50 years of age), matched to 829,946 individuals without type 2 diabetes. We estimated all-cause and cause-specific mortality (cancer, cardiorenal, other [noncancer or cardiorenal]) by age at diagnosis, using competing-risk survival analyses adjusted for key confounders. RESULTS: Comparing individuals with versus without type 2 diabetes, the relative risk of death decreased with an older age at diagnosis: the hazard ratio for all-cause mortality was 4.32 (95% CI 3.35-5.58) in individuals diagnosed at ages 16-27 years compared with 1.53 (95% CI 1.46-1.60) at ages 48-50 years. Smaller relative risks by increasing age at diagnosis were also observed for cancer, cardiorenal, and noncancer or cardiorenal death. Irrespective of age at diagnosis, the 10-year absolute risk of all-cause and cause-specific mortality were higher in individuals with type 2 diabetes; yet, the absolute differences were small. CONCLUSIONS: Although the relative risk of death in individuals with versus without type 2 was higher at younger ages, the 10-year absolute risk of all investigated causes of death was small and similar in the two groups. Further multidecade studies could help estimate the long-term risk of complications and death in individuals with early-onset type 2 diabetes.

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.

Socioeconomic inequalities of Long COVID: a retrospective population-based cohort study in the United Kingdom.

OBJECTIVES: To estimate the risk of Long COVID by socioeconomic deprivation and to further examine the inequality by sex and occupation. DESIGN: We conducted a retrospective population-based cohort study using data from the ONS COVID-19 Infection Survey between 26 April 2020 and 31 January 2022. This is the largest nationally representative survey of COVID-19 in the UK with longitudinal data on occupation, COVID-19 exposure and Long COVID. SETTING: Community-based survey in the UK. PARTICIPANTS: A total of 201,799 participants aged 16 to 64 years and with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MAIN OUTCOME MEASURES: The risk of Long COVID at least 4 weeks after SARS-CoV-2 infection by index of multiple deprivation (IMD) and the modifying effects of socioeconomic deprivation by sex and occupation. RESULTS: Nearly 10% (n = 19,315) of participants reported having Long COVID. Multivariable logistic regression models, adjusted for a range of variables (demographic, co-morbidity and time), showed that participants in the most deprived decile had a higher risk of Long COVID (11.4% vs. 8.2%; adjusted odds ratio (aOR): 1.46; 95% confidence interval (CI): 1.34, 1.59) compared to the least deprived decile. Significantly higher inequalities (most vs. least deprived decile) in Long COVID existed in healthcare and patient-facing roles (aOR: 1.76; 95% CI: 1.27, 2.44), in the education sector (aOR: 1.68; 95% CI: 1.31, 2.16) and in women (aOR: 1.56; 95% CI: 1.40, 1.73) than men (aOR: 1.32; 95% CI: 1.15, 1.51). CONCLUSIONS: This study provides insights into the heterogeneous degree of inequality in Long COVID by deprivation, sex and occupation. These findings will help inform public health policies and interventions in incorporating a social justice and health inequality lens.

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.

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.

Predictors of hypertension detection in English general practices: a cross sectional study.

BACKGROUND: Worldwide, high systolic blood pressure is the leading risk factor for deaths and disability-adjusted life-years but has been historically under-detected. This study aimed to quantify differences between estimated and practice-detected prevalences of hypertension across English general practices, and to determine how variations in detected prevalence could be explained by population-level and service-level factors. METHODS: Descriptive statistics, pair wise correlations between the independent variables and a multivariable regression analysis were undertaken. In the regression model, the outcome was detected hypertension prevalence, adjusted for estimated prevalence, person-related and disease-related determinants of illness and characteristics of general practices. RESULTS: Detected prevalence was substantially lower than estimated prevalence (mean difference 16.23%; standard deviation 2.88%). Higher detected prevalence was associated with increased deprivation, increased non-white ethnicity and urban location. Lower detected prevalence was associated with larger list sizes, more general practitioners and being located in the South outside London. The final multivariable model's adjusted R2 value was 0.75. CONCLUSIONS: Substantial under-detection of hypertension is widespread across England. Independent of estimated prevalence, factors associated with greater morbidity and population density predicted higher detected prevalence. Identifying patients with undetected hypertension and coordinating care for these patients will require further resources and logistical support in community settings.

Social inequality and the syndemic of chronic disease and COVID-19: county-level analysis in the USA.

BACKGROUND: Given the effect of chronic diseases on risk of severe COVID-19 infection, the present pandemic may have a particularly profound impact on socially disadvantaged counties. METHODS: Counties in the USA were categorised into five groups by level of social vulnerability, using the Social Vulnerability Index (a widely used measure of social disadvantage) developed by the US Centers for Disease Control and Prevention. The incidence and mortality from COVID-19, and the prevalence of major chronic conditions were calculated relative to the least vulnerable quintile using Poisson regression models. RESULTS: Among 3141 counties, there were 5 010 496 cases and 161 058 deaths from COVID-19 by 10 August 2020. Relative to the least vulnerable quintile, counties in the most vulnerable quintile had twice the rates of COVID-19 cases and deaths (rate ratios 2.11 (95% CI 1.97 to 2.26) and 2.42 (95% CI 2.22 to 2.64), respectively). Similarly, the prevalence of major chronic conditions was 24%-41% higher in the most vulnerable counties. Geographical clustering of counties with high COVID-19 mortality, high chronic disease prevalence and high social vulnerability was found, especially in southern USA. CONCLUSION: Some counties are experiencing a confluence of epidemics from COVID-19 and chronic diseases in the context of social disadvantage. Such counties are likely to require enhanced public health and social support.

COVID-19 and climatic factors: A global analysis.

BACKGROUND: It is unknown if COVID-19 will exhibit seasonal pattern as other diseases e.g., seasonal influenza. Similarly, some environmental factors (e.g., temperature, humidity) have been shown to be associated with transmission of SARS-CoV and MERS-CoV, but global data on their association with COVID-19 are scarce. OBJECTIVE: To examine the association between climatic factors and COVID-19. METHODS: We used multilevel mixed-effects (two-level random-intercepts) negative binomial regression models to examine the association between 7- and 14-day-lagged temperature, humidity (relative and absolute), wind speed and UV index and COVID-19 cases, adjusting for Gross Domestic Products, Global Health Security Index, cloud cover (%), precipitation (mm), sea-level air-pressure (mb), and daytime length. The effects estimates are reported as adjusted rate ratio (aRR) and their corresponding 95% confidence interval (CI). RESULTS: Data from 206 countries/regions (until April 20, 2020) with ≥100 reported cases showed no association between COVID-19 cases and 7-day-lagged temperature, relative humidity, UV index, and wind speed, after adjusting for potential confounders, but a positive association with 14-day-lagged temperature and a negative association with 14-day-lagged wind speed. Compared to an absolute humidity of <5 g/m3, an absolute humidity of 5-10 g/m3 was associated with a 23% (95% CI: 6-42%) higher rate of COVID-19 cases, while absolute humidity >10 g/m3 did not have a significant effect. These findings were robust in the 14-day-lagged analysis. CONCLUSION: Our results of higher COVID-19 cases (through April 20) at absolute humidity of 5-10 g/m3 may be suggestive of a 'sweet point' for viral transmission, however only controlled laboratory experiments can decisively prove it.

Physical distancing interventions and incidence of coronavirus disease 2019: natural experiment in 149 countries.

OBJECTIVE: To evaluate the association between physical distancing interventions and incidence of coronavirus disease 2019 (covid-19) globally. DESIGN: Natural experiment using interrupted time series analysis, with results synthesised using meta-analysis. SETTING: 149 countries or regions, with data on daily reported cases of covid-19 from the European Centre for Disease Prevention and Control and data on the physical distancing policies from the Oxford covid-19 Government Response Tracker. PARTICIPANTS: Individual countries or regions that implemented one of the five physical distancing interventions (closures of schools, workplaces, and public transport, restrictions on mass gatherings and public events, and restrictions on movement (lockdowns)) between 1 January and 30 May 2020. MAIN OUTCOME MEASURE: Incidence rate ratios (IRRs) of covid-19 before and after implementation of physical distancing interventions, estimated using data to 30 May 2020 or 30 days post-intervention, whichever occurred first. IRRs were synthesised across countries using random effects meta-analysis. RESULTS: On average, implementation of any physical distancing intervention was associated with an overall reduction in covid-19 incidence of 13% (IRR 0.87, 95% confidence interval 0.85 to 0.89; n=149 countries). Closure of public transport was not associated with any additional reduction in covid-19 incidence when the other four physical distancing interventions were in place (pooled IRR with and without public transport closure was 0.85, 0.82 to 0.88; n=72, and 0.87, 0.84 to 0.91; n=32, respectively). Data from 11 countries also suggested similar overall effectiveness (pooled IRR 0.85, 0.81 to 0.89) when school closures, workplace closures, and restrictions on mass gatherings were in place. In terms of sequence of interventions, earlier implementation of lockdown was associated with a larger reduction in covid-19 incidence (pooled IRR 0.86, 0.84 to 0.89; n=105) compared with a delayed implementation of lockdown after other physical distancing interventions were in place (pooled IRR 0.90, 0.87 to 0.94; n=41). CONCLUSIONS: Physical distancing interventions were associated with reductions in the incidence of covid-19 globally. No evidence was found of an additional effect of public transport closure when the other four physical distancing measures were in place. Earlier implementation of lockdown was associated with a larger reduction in the incidence of covid-19. These findings might support policy decisions as countries prepare to impose or lift physical distancing measures in current or future epidemic waves.

Reactive Molecular Dynamics Simulations and Quantum Chemistry Calculations To Investigate Soot-Relevant Reaction Pathways for Hexylamine Isomers.

Sooting tendencies of a series of nitrogen-containing hydrocarbons (NHCs) have been recently characterized experimentally using the yield sooting index (YSI) methodology. This work aims to identify soot-relevant reaction pathways for three selected C6H15N amines, namely, dipropylamine (DPA), diisopropylamine (DIPA), and 3,3-dimethylbutylamine (DMBA) using ReaxFF molecular dynamics (MD) simulations and quantum mechanical (QM) calculations and to interpret the experimentally observed trends. ReaxFF MD simulations are performed to determine the important intermediate species and radicals involved in the fuel decomposition and soot formation processes. QM calculations are employed to extensively search for chemical reactions involving these species and radicals based on the ReaxFF MD results and also to quantitatively characterize the potential energy surfaces. Specifically, ReaxFF simulations are carried out in the NVT ensemble at 1400, 1600, and 1800 K, where soot has been identified to form in the YSI experiment. These simulations account for the interactions among test fuel molecules and pre-existing radicals and intermediate species generated from rich methane combustion, using a recently proposed simulation framework. ReaxFF simulations predict that the reactivity of the amines decrease in the order DIPA > DPA > DMBA, independent of temperature. Both QM calculations and ReaxFF simulations predict that C2H4, C3H6, and C4H8 are the main nonaromatic soot precursors formed during the decomposition of DPA, DIPA, and DMBA, respectively, and the associated reaction pathways are identified for each amine. Both theoretical methods predict that sooting tendency increases in the order DPA, DIPA, and DMBA, consistent with the experimentally measured trend in YSI. This work demonstrates that sooting tendencies and soot-relevant reaction pathways of fuels with unknown chemical kinetics can be identified efficiently through combined ReaxFF and QM simulations. Overall, predictions from ReaxFF simulations and QM calculations are consistent, in terms of fuel reactivity, major intermediates, and major nonaromatic soot precursors.

Evaluation of the effect of nickel clusters on the formation of incipient soot particles from polycyclic aromatic hydrocarbons via ReaxFF molecular dynamics simulations.

In the present study, the ReaxFF reactive molecular dynamics simulation method was applied to investigate the effect of a small nickel cluster (Ni13) on the formation of nascent soot from polycyclic aromatic hydrocarbon (PAH) precursors. A series of NVT simulations was performed for systems of a Ni13 cluster and various PAH monomers, namely, naphthalene, anthracene, pyrene, coronene, ovalene, and circumcoronene, at temperatures from 400 to 2500 K. At low temperatures, the PAHs form soot particles via binding and stacking around nickel clusters. Larger soot particles are formed due to the early initiation of clustering provided by nickel compared to those observed in homogenous PAH systems. At 1200-1600 K, the PAH monomers show a chemisorption tendency onto the nickel surface, which results in incipient soot particles. Chemical nucleation was observed at 2000 K where nickel-assisted dehydrogenation and chemisorption of PAH led to the growth of stable soot particles, which did not occur in the absence of Ni-clusters. At a high temperature (2500 K), nickel significantly accelerates the ring-opening and graphitization of PAH molecules and increases the size of the fullerene-type soot as compared to that of homogenous systems.