Recent Submissions

  • Core outcomes and factors influencing the experience of care for children with severe acute exacerbations of asthma: a qualitative study

    Roland, Damian (2023-11)
    Objective: To identify the outcomes considered important, and factors influencing the patient experience, for parents and caregivers of children presenting to hospital with a severe acute exacerbation of asthma. This work contributes to the outcome-identification process in developing a core outcome set (COS) for future clinical trials in children with severe acute asthma. Design: A qualitative study involving semistructured interviews with parents and caregivers of children who presented to hospital with a severe acute exacerbation of asthma. Setting: Hospitals in 12 countries associated with the global Pediatric Emergency Research Networks, including high-income and middle-income countries. Interviews were conducted face-to-face, by teleconference/video-call, or by phone. Findings: Overall, there were 54 interviews with parents and caregivers; 2 interviews also involved the child. Hospital length of stay, intensive care unit or high-dependency unit (HDU) admission, and treatment costs were highlighted as important outcomes influencing the patient and family experience. Other potential clinical trial outcomes included work of breathing, speed of recovery and side effects. In addition, the patient and family experience was impacted by decision-making leading up to seeking hospital care, transit to hospital, waiting times and the use of intravenous treatment. Satisfaction of care was related to communication with clinicians and frequent reassessment. Conclusions: This study provides insight into the outcomes that parents and caregivers believe to be the most important to be considered in the process of developing a COS for the treatment of acute severe exacerbations of asthma.
  • Clinical Frailty Scale at presentation to the emergency department: interrater reliability and use of algorithm-assisted assessment

    Banerjee, Jay (2023-11-16)
    Purpose: The Clinical Frailty Scale (CFS) allows health care providers to quickly stratify older patients, to support clinical decision-making. However, few studies have evaluated the CFS interrater reliability (IRR) in Emergency Departments (EDs), and the freely available smartphone application for CFS assessment was never tested for reliability. This study aimed to evaluate the interrater reliability of the Clinical Frailty Scale (CFS) ratings between experienced and unexperienced staff (ED clinicians and a study team (ST) of medical students supported by a smartphone application to assess the CFS), and to determine the feasibility of CFS assignment in patients aged 65 or older at triage. Methods: Cross-sectional study using consecutive sampling of ED patients aged 65 or older. We compared assessments by ED clinicians (Triage Clinicians (TC) and geriatric ED trained nurses (geriED-TN)) and a study team (ST) of medical students using a smartphone application for CFS scoring. The study is registered on (NCT05400707). Results: We included 1349 patients aged 65 and older. Quadratic-weighted kappa values for ordinal CFS levels showed a good IRR between TC and ST (ϰ = 0.73, 95% CI 0.69-0.76), similarly to that between TC and geriED-TN (ϰ = 0.75, 95% CI 0.66-0.82) and between the ST and geriED-TN (ϰ = 0.74, 95% CI 0.63-0.81). A CFS rating was assigned to 972 (70.2%) patients at triage. Conclusion: We found good IRR in the assessment of frailty with the CFS in different ED providers and a team using a smartphone application to support rating. A CFS assessment occurred in more than two-thirds (70.2%) of patients at triage.
  • Sustaining interventions in care homes initiated by quality improvement projects: a qualitative study

    Banerjee, Jaydip (2023-11)
    Introduction: Inadequate and varied quality of care in care homes has led to a proliferation of quality improvement (QI) projects. This study examined the sustainability of interventions initiated by such projects. Method: This qualitative study explored the sustainability of seven interventions initiated by three QI projects between 2016 and 2018 in UK care homes and explored the perceived influences to the sustainability of interventions. QI projects were followed up in 2019. Staff leading QI projects (n=9) and care home (n=21, from 13 care homes) and healthcare (n=2) staff took part in semi-structured interviews. Interventions were classified as sustained if the intervention was continued at the point of the study. Thematic analysis of interview data was performed, drawing on the Consolidated Framework for Sustainability (CFS), a 40-construct model of sustainability of interventions. Results: Three interventions were sustained and four interventions were not. Seven themes described perceptions around what influenced sustainability: monitoring outcomes and regular check-in; access to replacement intervention materials; staff willingness to dedicate time and effort towards interventions; continuity of staff and thorough handover/inductions in place for new staff; ongoing communication and awareness raising; perceived effectiveness; and addressing care home priorities. All study themes fell within 18 of the 40 CFS constructs. Discussion: Our findings resonate with the CFS and are also consistent with implementation theories, suggesting sustainability is best addressed during implementation rather than treated as a separate process which follows implementation. Commissioning and funding QI projects should address these considerations early on, during implementation.
  • Response to a low-energy meal replacement plan on glycometabolic profile and reverse cardiac remodelling in type 2 diabetes: a comparison between South Asians and White Europeans

    Athithan, Lavanya; Brady, Emer; Davies, Melanie J; Gulsin, Guarav S; Henson, Joseph; McCann, Gerry; Parke, Kelly (2023-10-06)
    Background: South Asians (SA) constitute a quarter of the global population and are disproportionally affected by both type 2 diabetes (T2D) and heart failure. There remains limited data of the acceptability and efficacy of low-energy meal replacement plans to induce remission of T2D in SA. Objectives: The objective of this exploratory secondary analysis of the DIASTOLIC study was to determine if there was a differential uptake, glycometabolic and cardiovascular response to a low-energy meal replacement plan (MRP) between SA and White European (WE) people with T2D. Methods: Obese adults with T2D without symptomatic cardiovascular disease were allocated a low-energy (~810 kcal/day) MRP as part of the DIASTOLIC study (NCT02590822). Comprehensive multiparametric cardiovascular magnetic resonance imaging, echocardiography, cardiopulmonary exercise testing and metabolic profiling were undertaken at baseline and 12 weeks. A comparison of change at 12 weeks between groups with baseline adjustment was undertaken. Results: Fifteen WE and 12 SAs were allocated the MRP. All WE participants completed the MRP versus 8/12 (66%) SAs. The degree of concentric left ventricular remodelling was similar between ethnicities. Despite similar weight loss and reduction in liver fat percentage, SA had a lower reduction in Homeostatic Model Assessment for Insulin Resistance [-5.7 (95% CI: -7.3, -4.2) versus -8.6 (-9.7, -7.6), p = 0.005] and visceral adiposity compared to WE [-0.43% (-0.61, -0.25) versus -0.80% (-0.91, -0.68), p = 0.002]. Exercise capacity increased in WE with no change observed in SA. There was a trend towards more reverse remodelling in WE compared to SAs. Conclusions: Compliance to the MRP was lower in SA versus WE. Overall, those completing the MRP saw improvements in weight, body composition and indices of glycaemic control irrespective of ethnicity. Whilst improvements in VAT and insulin resistance appear to be dampened in SA versus WE, given the small sample, larger studies are required to confirm or challenge this potential ethnic disparity.
  • Effect of delay in treatment intensification in people with type 2 diabetes and suboptimal glycaemia after basal insulin initiation: A real-world observational study

    Davies, Melanie J; Webb, David R; Zaccardi, Francesco (2023-10-19)
    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.
  • Effect of conventional lifestyle interventions on Type 2 Diabetes incidence by glucose-defined prediabetes phenotype: an individual participant data meta-analysis of randomized controlled trials

    Davies, Melanie J (2023-11-01)
    Objective: To examine whether the effect of conventional lifestyle interventions on type 2 diabetes incidence differs by glucose-defined prediabetes phenotype. Research design and methods: We searched multiple databases until 1 April 2023 for randomized controlled trials that recruited people with isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), and impaired fasting glucose plus impaired glucose tolerance (IFG+IGT). Individual participant data were pooled from relevant trials and analyzed through random-effects models with use of the within-trial interactions approach. Results: Four trials with 2,794 participants (mean age 53.0 years, 60.7% men) were included: 1,240 (44.4%), 796 (28.5%), and 758 (27.1%) had i-IFG, i-IGT, and IFG+IGT, respectively. After a median of 2.5 years, the pooled hazard ratio for diabetes incidence in i-IFG was 0.97 (95% CI 0.66, 1.44), i-IGT 0.65 (0.44, 0.96), and IFG+IGT 0.51 (0.38, 0.68; Pinteraction = 0.01). Conclusions: Conventional lifestyle interventions reduced diabetes incidence in people with IGT (with or without IFG) but not in those with i-IFG.
  • The cardiovascular effects of novel weight loss therapies

    Davies, Melanie (2023-11-15)
    The prevalence of overweight and obesity has reached pandemic proportions. Obesity is known to increase the risk for Type 2 diabetes and hypertension, as well as the risk for overt cardiovascular (CV) disease, including myocardial infarction, heart failure, and stroke. The rising prevalence of obesity may counteract the recent advances in primary and secondary prevention of CV disease. Overweight and obesity are common in patients with CV disease; however, cardiologists face several challenges in managing body weight in this population. Many may not consider obesity as a therapeutic target probably because there were no previous highly effective and safe pharmacologic interventions to consider. In addition, they may not have the expertise or resources to implement lifestyle interventions and may have limited familiarity with obesity pharmacotherapy. Moreover, the long-term CV effects of obesity pharmacotherapy remain uncertain due to limited CV outcome data with weight loss as the primary intervention. Although current CV guidelines recognize the importance of weight loss, they primarily focus on lifestyle modifications, with fewer details on strategies to utilize obesity pharmacotherapy and surgery. However, the recent 2022 American Diabetes Association/European Association for the Study of Diabetes consensus on the management of Type 2 diabetes has moved up weight management to the front of the treatment algorithm, by prioritizing the use of pharmacologic interventions such as glucagon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists, which have potent weight-lowering effects, in addition to glucose-lowering effects. This review appraises the current evidence regarding the CV effects of weight-loss interventions. Considering this evidence, practical guidance is provided to assist cardiologists in developing and implementing treatment plans, which may allow optimal weight management while maximizing CV benefits and minimizing side effects to improve the overall well-being of people with CV disease.
  • The potential blunting effect of metformin and/or statin therapy on physical activity-induced associations with HbA1c in type 2 diabetes

    Brady, Emer; Davies, Melanie J; Henson, Joseph; Redman, Emma; Sargeant, Jack (2023-11-14)
    Highlights Our analysis indicates a potential blunting effect of metformin and/or statin therapy on physical activity-induced associations with HbA1c. The benefit of daily physical activity on glycemic control in people with type 2 diabetes is potentially more apparent in those prescribed neither metformin nor statin therapy. As physical activity is rarely prescribed in isolation of other background medications used to manage type 2 diabetes, the results of this analysis may help to maximize interventions delivered through routine clinical care, while allowing for personalization in prescribed physical activity and pharmacotherapy.
  • Relapse after cessation of weekly tocilizumab for giant cell arteritis: a multicentre service evaluation in England

    Doddami, Parveen; Kinder, Alison (2023-11-11)
    Objectives: The National Health Service in England funds 12 months of weekly subcutaneous tocilizumab (qwTCZ) for patients with relapsing or refractory giant cell arteritis (GCA). During the COVID-19 pandemic, some patients were allowed longer treatment. We sought to describe what happened to patients after cessation of qwTCZ. Methods: Multicentre service evaluation of relapse after stopping qwTCZ for GCA. The log-rank test was used to identify significant differences in time to relapse. Results: 336 GCA patients were analysed from 40 centres, treated with qwTCZ for a median (interquartile range, IQR) of 12 (12-17) months. At time of stopping qwTCZ, median (IQR) prednisolone dose was 2 (0-5) mg/day. By 6, 12 and 24 months after stopping qwTCZ, 21.4%, 35.4% and 48.6% respectively had relapsed, requiring an increase in prednisolone dose to a median (IQR) of 20 (10-40) mg/day. 33.6% of relapsers had a major relapse as defined by EULAR. Time to relapse was shorter in those that had previously also relapsed during qwTCZ treatment (P = 0.0017); in those not in remission at qwTCZ cessation (P = 0.0036); and in those with large vessel involvement on imaging (P = 0.0296). Age ≥65, gender, GCA-related sight loss, qwTCZ treatment duration, TCZ taper, prednisolone dosing, and conventional synthetic DMARD use were not associated with time to relapse. Conclusion: Up to half our patients with GCA relapsed after stopping qwTCZ, often requiring a substantial increase in prednisolone dose. One third of relapsers had a major relapse. Extended use of TCZ or repeat treatment for relapse should be considered for these patients.
  • Diabetes specialist intervention in general practices in areas of deprivation and ethnic diversity: A qualitative evaluation (QUAL-ECLIPSE)

    Patel, Shweta (2023-11-03)
    Aim: To assess patients' and healthcare professionals' perspectives of a specialist-led Diabetes Risk-based Assessment Clinic (DIRAC) for people with diabetes at high risk of complications (PWDHRC) in areas of deprivation in Coventry, UK. Methods: A qualitative evaluation of a pilot trial, comprising a specialist team intervention (DIRAC), was undertaken in seven GP practices through observations of weekly virtual or occasional face-to-face patient consultations and monthly interventionists' meetings. Semi-structured interviews were carried out post-intervention, with PWDHRC, primary care clinicians and diabetes specialists (interventionists). Thematic analyses of observations and interviews were undertaken. Key findings: Over 12 months, 28 DIRAC clinics comprising 154 patient consultations and five interventionists' meetings, were observed. 19 interviews were undertaken, PWDHRC experienced 'culturally-sensitive care from a specialist-led clinic intervention encompassing integrated care. This model of care was recommended at GP practice level, all participants (PWDHRC, primary care clinicians and diabetes specialist interventionists) felt upskilled to deal with complex diabetes care. The EMIS and ECLIPSE technologies utilised during the intervention were perceived to positively contribute to diabetes management of PWDHRC despite reservations around cost and database. Conclusion: The specialist-led DIRACs were largely appreciated by study participants. These qualitative data support the trial progressing to a full-service evaluation.
  • Investigating the impact of financial concerns on symptoms of depression in UK healthcare workers: data from the UK-REACH nationwide cohort study

    Martin, Christopher A; Batson, Megan; Pan, Daniel; Pareek, Manish (2023-07-12)
    Background: Exploration of the association between financial concerns and depression in UK healthcare workers (HCWs) is paramount given the current 'cost of living crisis', ongoing strike action and recruitment/retention problems in the National Health Service. Aims: To assess the impact of financial concerns on the risk of depression in HCWs, how these concerns have changed over time and what factors might predict financial concerns. Method: We used longitudinal survey data from a UK-wide cohort of HCWs to determine whether financial concerns at baseline (December 2020 to March 2021) were associated with depression (measured with the Public Health Questionnaire-2) at follow-up (June to October 2022). We used logistic regression to examine the association between financial concerns and depression, and ordinal logistic regression to establish predictors of developing financial concerns. Results: A total of 3521 HCWs were included. Those concerned about their financial situation at baseline had higher odds of developing depressive symptoms at follow-up. Financial concerns increased in 43.8% of HCWs and decreased in 9%. Those in nursing, midwifery and other nursing roles had over twice the odds of developing financial concerns compared with those in medical roles. Conclusions: Financial concerns are increasing in prevalence and predict the later development of depressive symptoms in UK HCWs. Those in nursing, midwifery and other allied nursing roles may have been disproportionately affected. Our results are concerning given the potential effects on sickness absence and staff retention. Policy makers should act to alleviate financial concerns to reduce the impact this may have on a discontent workforce plagued by understaffing.
  • Accelerometer-Assessed Physical Activity in People with Type 2 Diabetes: Accounting for Sleep when Determining Associations with Markers of Health Authors

    Brady, Emer M; Davies, Melanie J; Henson, Joseph (2023-06-07)
    High physical activity levels during wake are beneficial for health, while high movement levels during sleep are detrimental to health. Our aim was to compare the associations of accelerometer-assessed physical activity and sleep disruption with adiposity and fitness using standardized and individualized wake and sleep windows. People (N = 609) with type 2 diabetes wore an accelerometer for up to 8 days. Waist circumference, body fat percentage, Short Physical Performance Battery (SPPB) test score, sit-to-stands, and resting heart rate were assessed. Physical activity was assessed via the average acceleration and intensity distribution (intensity gradient) over standardized (most active 16 continuous hours (M16h)) and individualized wake windows. Sleep disruption was assessed via the average acceleration over standardized (least active 8 continuous hours (L8h)) and individualized sleep windows. Average acceleration and intensity distribution during the wake window were beneficially associated with adiposity and fitness, while average acceleration during the sleep window was detrimentally associated with adiposity and fitness. Point estimates for the associations were slightly stronger for the standardized than for individualized wake/sleep windows. In conclusion, standardized wake and sleep windows may have stronger associations with health due to capturing variations in sleep durations across individuals, while individualized windows represent a purer measure of wake/sleep behaviors.
  • UK Kidney Association Clinical Practice Guideline: Sodium-Glucose Co-transporter-2 (SGLT-2) inhibition in adults with kidney disease 2023 UPDATE

    Webb, David; Kuverji, Apexa; Burton, James O (2023-10-25)
    Large placebo-controlled trials have demonstrated kidney and cardiovascular clinical benefits of SGLT-2 inhibitors. Data from the EMPA-KIDNEY and DELIVER trials and associated meta-analyses triggered an update to the UK Kidney Association Clinical Practice Guideline on Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibition in Adults with Kidney Disease. We provide a summary of the full guideline and highlight the rationale for recent updates. The use of SGLT-2 inhibitors in people with specific medical conditions, including type 1 diabetes, kidney transplants, and people admitted to hospital with heart failure is also considered, along with Recommendations for future research and Recommendations for implementation. A full "lay" summary of the guidelines is provided as an appendix to ensure that these guidelines are accessible and understandable to people who are not medical professionals.
  • Provision of dietary education in UK-based cardiac rehabilitation: a cross-sectional survey conducted in conjunction with the British Association for Cardiovascular Prevention and Rehabilitation

    James, Emily (2023-10-23)
    Dietary education is a core component of cardiac rehabilitation (CR). It is unknown how or what dietary education is delivered across the United Kingdom (UK). We aimed to characterise practitioners who deliver dietary education in UK CR and determine the format and content of the education sessions. A 54-item survey was approved by the British Association for Cardiovascular Prevention and Rehabilitation (BACPR) committee and circulated between July and October 2021 via two emails to the BACPR mailing list and on social media. Practitioners providing dietary education within CR programmes were eligible to respond. Survey questions encompassed: practitioner job title and qualifications, resources, and the format, content and individual tailoring of diet education. Forty-nine different centres responded. Nurses (65.1%) and dietitians (55.3%) frequently provided dietary education. Practitioners had no nutrition-related qualifications in 46.9% of services. Most services used credible resources to support their education, and 24.5% used BACPR core competencies. CR programmes were mostly community-based (40.8%), lasting 8-weeks (range: 2-25) and included 2 (range: 1-7) diet sessions. Dietary history was assessed at the start (79.6%) and followed-up (83.7%) by most centres; barriers to completing assessment were insufficient time, staffing, or other priorities. Services mainly focused on the Mediterranean diet whilst topics such as malnutrition and protein intake were lower priority topics. Service improvement should focus on increasing qualifications of practitioners, standardisation of dietary assessment, and improvement in protein and malnutrition screening and assessment.
  • Impact of Coronary CT Angiography-derived Fractional Flow Reserve on Downstream Management and Clinical Outcomes in Individuals with and without Diabetes

    Gulsin, Gaurav S (2023-10-19)
    Purpose: To compare the clinical use of coronary CT angiography (CCTA)-derived fractional flow reserve (FFR) in individuals with and without diabetes mellitus (DM). Materials and methods: This secondary analysis included participants (enrolled July 2015 to October 2017) from the prospective, multicenter, international The Assessing Diagnostic Value of Noninvasive CT-FFR in Coronary Care (ADVANCE) registry ( identifier, NCT02499679) who were evaluated for suspected coronary artery disease (CAD), with one or more coronary stenosis ≥30% on CCTA images, using CT-FFR. CCTA and CT-FFR findings, treatment strategies at 90 days, and clinical outcomes at 1-year follow-up were compared in participants with and without DM. Results: The study included 4290 participants (mean age, 66 years ± 10 [SD]; 66% male participants; 22% participants with DM). Participants with DM had more obstructive CAD (one or more coronary stenosis ≥50%; 78.8% vs 70.6%, P < .001), multivessel CAD (three-vessel obstructive CAD; 18.9% vs 11.2%, P < .001), and proportionally more vessels with CT-FFR ≤ 0.8 (74.3% vs 64.6%, P < .001). Treatment reclassification by CT-FFR occurred in two-thirds of participants which was consistent regardless of the presence of DM. There was a similar graded increase in coronary revascularization with declining CT-FFR in both groups. At 1 year, presence of DM was associated with higher rates of major adverse cardiovascular events (hazard ratio, 2.2; 95% CI: 1.2, 4.1; P = .01). However, no between group differences were observed when stratified by stenosis severity (<50% or ≥50%) or CT-FFR positivity. Conclusion: Both anatomic CCTA findings and CT-FFR demonstrated a more complex pattern of CAD in participants with versus without DM. Rates of treatment reclassification were similar regardless of the presence of DM, and DM was not an adverse prognostic indicator when adjusted for diameter stenosis and CT-FFR.Clinical trial registration no. NCT 02499679Keywords: Fractional Flow Reserve, CT Angiography, Diabetes Mellitus, Coronary Artery Disease Supplemental material is available for this article. See also the commentary by Ghoshhajra in this issue.© RSNA, 2023.
  • Sedentary behaviour and disease risk

    Henson, Joseph (2023-10-19)
    Sedentary behaviour has become the new reference of living, which has paralleled the increase in the prevalence of multiple chronic diseases. Here, we highlight the evidence to date and propose specific topics of interest for the Collection at BMC Public Health, titled "Sedentary behaviour and disease risk".
  • Future therapies for obesity

    Melson, Eka; Papamargaritis, Dimitris (2023-07)
    Obesity is a chronic disease associated with increased morbidity and mortality. Bariatric surgery can lead to sustained long-term weight loss (WL) and improvement in multiple obesity-related complications, but it is not scalable at the population level. Over the past few years, gut hormone-based pharmacotherapies for obesity and type 2 diabetes mellitus (T2DM) have rapidly evolved, and combinations of glucagon-like peptide 1 (GLP1) with other gut hormones (glucose-dependent insulinotropic polypeptide (GIP), glucagon, and amylin) as dual or triple agonists are under investigation to enhance and complement the effects of GLP1 on WL and obesity-related complications. Tirzepatide, a dual agonist of GLP1 and GIP receptors, marks a new era in obesity pharmacotherapy in which a combination of gut hormones could approach the WL achieved with bariatric surgery. In this review, we discuss emerging obesity treatments with a focus on gut hormone combinations and the concept of a multimodal approach for obesity management.
  • Intensive glucose control and recurrent cardiovascular events: 14-year follow-up investigation of the ACCORDION study

    Davies, Melanie; Zaccardi, Francesco (2023-07)
    Aims: While cardiovascular disease in patients with type 2 diabetes commonly progresses with the occurrence of repeated events, most trials consider the effect of glucose-lowering strategies only on the first event. We examined the Action to Control Cardiovascular Risk in Diabetes trial and its observational follow-up study (ACCORDION) to investigate the effect of intensive glucose control on multiple events and further identify any subgroup effects. Materials and methods: A recurrent events analysis, using a negative binomial regression model, was applied to estimate the treatment effect on different consecutive cardiovascular disease events, including non-fatal myocardial infarction, non-fatal stroke, hospitalisation from heart failure, and cardiovascular death. Interaction terms were used to identify potential effect modifiers. The robustness of the results was confirmed in sensitivity analyses using alternative models. Results: The median duration of follow-up was 7.7 years. Of the 5128 participants in the intensive and 5123 in the standard glucose control arm, respectively, 822 (16.0%) and 840 (16.4%) participants experienced a single event; 189 (3.7%) and 214 (4.2%) participants experienced two events; 52 (1.0%) and 40 (0.8%) experienced three events; and 1 (0.02%) and 1 (0.02%) experienced four events. There was no evidence of a treatment effect, with a rate difference of 0.0 (-0.3, 0.3) per 100 person-years comparing intensive versus standard intervention, although with non-significantly lower event rates in younger patients with HbA1c < 7% and higher event rates in older patients with HbA1c ≥ 9%. Discussion: Intensive glucose control may not affect cardiovascular disease progression except in select subgroups. Since time-to-first event analysis may miss beneficial or harmful effects of glucose control on the risk of cardiovascular disease, recurrent events analysis should be routinely analysed in cardiovascular outcome trials, particularly when investigating long-term treatment effects.
  • Factors associated with therapeutic inertia in individuals with type 2 diabetes mellitus started on basal insulin

    Davies, Melanie; Melson, Eka; Webb, David; Zaccardi, Francesco (2023-09)
    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.

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