Showing papers by "Leicester General Hospital published in 2020"

Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

Abstract: The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication and surgical interventions, are recommended. With regards to medication management, for patients with clinical cardiovascular disease, a sodium–glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) receptor agonist with proven cardiovascular benefit is recommended. For patients with chronic kidney disease or clinical heart failure and atherosclerotic cardiovascular disease, an SGLT2 inhibitor with proven benefit is recommended. GLP-1 receptor agonists are generally recommended as the first injectable medication.

Is ethnicity linked to incidence or outcomes of covid-19?

Abstract: Preliminary signals must be explored urgently

Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and meta-analysis

Abstract: Objective To estimate and compare progression rates to type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) and healthy controls. Design Systematic review and meta-analysis. Data sources Medline and Embase between January 2000 and December 2019, studies published in English and conducted on humans. Eligibility criteria for selecting studies Observational studies investigating progression to T2DM. Inclusion criteria were postpartum follow-up for at least 12 months, incident physician based diagnosis of diabetes, T2DM reported as a separate outcome rather than combined with impaired fasting glucose or impaired glucose tolerance, and studies with both a group of patients with GDM and a control group. Results This meta-analysis of 20 studies assessed a total of 1 332 373 individuals (67 956 women with GDM and 1 264 417 controls). Data were pooled by random effects meta-analysis models, and heterogeneity was assessed by use of the I2 statistic. The pooled relative risk for the incidence of T2DM between participants with GDM and controls was estimated. Reasons for heterogeneity between studies were investigated by prespecified subgroup and meta-regression analyses. Publication bias was assessed by funnel plots and, overall, studies were deemed to have a low risk of bias (P=0.58 and P=0.90). The overall relative risk for T2DM was almost 10 times higher in women with previous GDM than in healthy controls (9.51, 95% confidence interval 7.14 to 12.67, P Conclusions Women with a history of GDM appear to have a nearly 10-fold higher risk of developing T2DM than those with a normoglycaemic pregnancy. The magnitude of this risk highlights the importance of intervening to prevent the onset of T2DM, particularly in the early years after pregnancy. Systematic review registration PROSPERO CRD42019123079.

Impact of COVID-19 on routine care for chronic diseases: A global survey of views from healthcare professionals.

Abstract: Routine care for chronic disease is an ongoing major challenge We aimed to evaluate the global impact of COVID-19 on routine care for chronic diseases An online survey was posted 31 March to 23 April 2020 targeted at healthcare professionals 202 from 47 countries responded Most reported change in routine care to virtual communication Diabetes, chronic obstructive pulmonary disease, and hypertension were the most impacted conditions due to reduction in access to care 80% reported the mental health of their patients worsened during COVID-19 It is important routine care continues in spite of the pandemic, to avoid a rise in non-COVID-19-related morbidity and mortality

Healthy lifestyle and life expectancy in people with multimorbidity in the UK Biobank: A longitudinal cohort study.

Abstract: Background Whether a healthy lifestyle impacts longevity in the presence of multimorbidity is unclear. We investigated the associations between healthy lifestyle and life expectancy in people with and without multimorbidity. Methods and findings A total of 480,940 middle-aged adults (median age of 58 years [range 38–73], 46% male, 95% white) were analysed in the UK Biobank; this longitudinal study collected data between 2006 and 2010, and participants were followed up until 2016. We extracted 36 chronic conditions and defined multimorbidity as 2 or more conditions. Four lifestyle factors, based on national guidelines, were used: leisure-time physical activity, smoking, diet, and alcohol consumption. A combined weighted score was developed and grouped participants into 4 categories: very unhealthy, unhealthy, healthy, and very healthy. Survival models were applied to predict life expectancy, adjusting for ethnicity, working status, deprivation, body mass index, and sedentary time. A total of 93,746 (19.5%) participants had multimorbidity. During a mean follow-up of 7 (range 2–9) years, 11,006 deaths occurred. At 45 years, in men with multimorbidity an unhealthy score was associated with a gain of 1.5 (95% confidence interval [CI] −0.3 to 3.3; P = 0.102) additional life years compared to very unhealthy score, though the association was not significant, whilst a healthy score was significantly associated with a gain of 4.5 (3.3 to 5.7; P < 0.001) life years and a very healthy score with 6.3 (5.0 to 7.7; P < 0.001) years. Corresponding estimates in women were 3.5 (95% CI 0.7 to 6.3; P = 0.016), 6.4 (4.8 to 7.9; P < 0.001), and 7.6 (6.0 to 9.2; P < 0.001) years. Results were consistent in those without multimorbidity and in several sensitivity analyses. For individual lifestyle factors, no current smoking was associated with the largest survival benefit. The main limitations were that we could not explore the consistency of our results using a more restrictive definition of multimorbidity including only cardiometabolic conditions, and participants were not representative of the UK as a whole. Conclusions In this analysis of data from the UK Biobank, we found that regardless of the presence of multimorbidity, engaging in a healthier lifestyle was associated with up to 6.3 years longer life for men and 7.6 years for women; however, not all lifestyle risk factors equally correlated with life expectancy, with smoking being significantly worse than others.

Effect of Flash Glucose Monitoring on Glycemic Control, Hypoglycemia, Diabetes-Related Distress, and Resource Utilization in the Association of British Clinical Diabetologists (ABCD) Nationwide Audit.

Abstract: OBJECTIVE The FreeStyle Libre (FSL) flash glucose-monitoring device was made available on the U.K. National Health Service (NHS) drug tariff in 2017. This study aims to explore the U.K. real-world experience of FSL and the impact on glycemic control, hypoglycemia, diabetes-related distress, and hospital admissions. RESEARCH DESIGN AND METHODS Clinicians from 102 NHS hospitals in the U.K. submitted FSL user data, collected during routine clinical care, to a secure web-based tool held within the NHS N3 network. The t and Mann-Whitney U tests were used to compare the baseline and follow-up HbA1c and other baseline demographic characteristics. Linear regression analysis was used to identify predictors of change in HbA1c following the use of FSL. Within-person variations of HbA1c were calculated using . RESULTS Data were available for 10,370 FSL users (97% with type 1 diabetes), age 38.0 (±18.8) years, 51% female, diabetes duration 16.0 (±49.9) years, and BMI of 25.2 (±16.5) kg/m2 (mean [±SD]). FSL users demonstrated a −5.2 mmol/mol change in HbA1c, reducing from 67.5 (±20.9) mmol/mol (8.3%) at baseline to 62.3 (±18.5) mmol/mol (7.8%) after 7.5 (interquartile range 3.4–7.8) months of follow-up (n = 3,182) (P 8.5%), reducing from 85.5 (±16.1) mmol/mol (10%) to 73.1 (±15.8) mmol/mol (8.8%) (P CONCLUSIONS We show that the use of FSL was associated with significantly improved glycemic control and hypoglycemia awareness and a reduction in hospital admissions.

Recommendations for management of diabetes during Ramadan: update 2020, applying the principles of the ADA/EASD consensus

Abstract: Fasting the Holy month of Ramadan constitutes one of the five pillars of the Muslim faith. Although there is some evidence that intermittent fasting during Ramadan may be of benefit in losing weight and cardiometabolic risk factors, there is no strong evidence these benefits apply to people with diabetes. The American Diabetes Association/European Association for the Study of Diabetes consensus recommendations emphasize the importance of patient factors and comorbidities when choosing diabetes medications including the presence of comorbidities, atherosclerotic cardiovascular disease, heart failure, chronic kidney disease, hypoglycemia risk, weight issues and costs. Structured education and pre-Ramadan counseing are key components to successful management of patients with diabetes. These should cover important aspects like glycemic targets, self-monitoring of blood glucose, diet, physical activity including Taraweeh prayers, medication and dose adjustment, side effects and when to break the fast. The decision cycle adapted for the specific situation of Ramadan provides an aid for such an assessment. Children with type 1 diabetes should strongly be advised not to fast due to the high risk of acute complications such as hypoglycemia and probably diabetic ketoacidosis (DKA), although there is very little evidence that DKA is increased in Ramadan. Pregnant women with diabetes or gestational diabetes should be advised to avoid fasting because of possible negative maternal and fetal outcomes. Hypoglycemia is a common concern during Ramadan fasting. To prevent hypoglycemic and hyperglycemic events, we recommend the adoption of diabetes self-management education and support principles. The use of the emerging technology and continuous glucose monitoring during Ramadan could help to recognize hypoglycemic and hyperglycemic complications related to omission and/or medication adjustment during fasting; however, the cost represents a significant barrier.

New global guidelines on sedentary behaviour and health for adults: broadening the behavioural targets

Abstract: In 2018, the World Health Organisation (WHO) commenced a program of work to update the 2010 Global Recommendations on Physical Activity for Health, for the first-time providing population-based guidelines on sedentary behaviour. This paper briefly summarizes and highlights the scientific evidence behind the new sedentary behaviour guidelines for all adults and discusses its strengths and limitations, including evidence gaps/research needs and potential implications for public health practice. An overview of the scope and methods used to update the evidence is provided, along with quality assessment and grading methods for the eligible new systematic reviews. The literature search update was conducted for WHO by an external team and reviewers used the AMSTAR 2 (Assessment of Multiple Systematic Reviews) tool for critical appraisal of the systematic reviews under consideration for inclusion. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was used to rate the certainty (i.e. very low to high) of the evidence. The updated systematic review identified 22 new reviews published from 2017 up to August 2019, 14 of which were incorporated into the final evidence profiles. Overall, there was moderate certainty evidence that higher amounts of sedentary behaviour increase the risk for all-cause, cardiovascular disease (CVD) and cancer mortality, as well as incidence of CVD, cancer, and type 2 diabetes. However, evidence was deemed insufficient at present to set quantified (time-based) recommendations for sedentary time. Moderate certainty evidence also showed that associations between sedentary behaviour and all-cause, CVD and cancer mortality vary by level of moderate-to-vigorous physical activity (MVPA), which underpinned additional guidance around MVPA in the context of high sedentary time. Finally, there was insufficient or low-certainty systematic review evidence on the type or domain of sedentary behaviour, or the frequency and/or duration of bouts or breaks in sedentary behaviour, to make specific recommendations for the health outcomes examined. The WHO 2020 guidelines are based on the latest evidence on sedentary behaviour and health, along with interactions between sedentary behaviour and MVPA, and support implementing public health programmes and policies aimed at increasing MVPA and limiting sedentary behaviour. Important evidence gaps and research opportunities are identified.

Diabetic retinopathy and diabetic macular oedema pathways and management: UK Consensus Working Group.

Abstract: The management of diabetic retinopathy (DR) has evolved considerably over the past decade, with the availability of new technologies (diagnostic and therapeutic). As such, the existing Royal College of Ophthalmologists DR Guidelines (2013) are outdated, and to the best of our knowledge are not under revision at present. Furthermore, there are no other UK guidelines covering all available treatments, and there seems to be significant variation around the UK in the management of diabetic macular oedema (DMO). This manuscript provides a summary of reviews the pathogenesis of DR and DMO, including role of vascular endothelial growth factor (VEGF) and non-VEGF cytokines, clinical grading/classification of DMO vis a vis current terminology (of centre-involving [CI-DMO], or non-centre involving [nCI-DMO], systemic risks and their management). The excellent UK DR Screening (DRS) service has continued to evolve and remains world-leading. However, challenges remain, as there are significant variations in equipment used, and reproducible standards of DMO screening nationally. The interphase between DRS and the hospital eye service can only be strengthened with further improvements. The role of modern technology including optical coherence tomography (OCT) and wide-field imaging, and working practices including virtual clinics and their potential in increasing clinic capacity and improving patient experiences and outcomes are discussed. Similarly, potential roles of home monitoring in diabetic eyes in the future are explored. The role of pharmacological (intravitreal injections [IVT] of anti-VEGFs and steroids) and laser therapies are summarised. Generally, IVT anti-VEGF are offered as first line pharmacologic therapy. As requirements of diabetic patients in particular patient groups may vary, including pregnant women, children, and persons with learning difficulties, it is important that DR management is personalised in such particular patient groups. First choice therapy needs to be individualised in these cases and may be intravitreal steroids rather than the standard choice of anti-VEGF agents. Some of these, but not all, are discussed in this document.

Association of Type 2 Diabetes With Cancer: A Meta-analysis With Bias Analysis for Unmeasured Confounding in 151 Cohorts Comprising 32 Million People

Abstract: BACKGROUND AND PURPOSE Whether the association between type 2 diabetes (T2D) and cancer is causal remains controversial. The goal of this work is to assess the robustness of the observational associations between T2D and cancer to unmeasured confounding. DATA SOURCES AND STUDY SELECTION PubMed, Web of Science, and the Cochrane library were systematically searched on 10 January 2019 for observational studies investigating associations between T2D and cancer incidence or mortality. DATA EXTRACTION AND DATA SYNTHESIS Cohort-level relative risk (RR) was extracted. RRs were combined in random-effects meta-analyses and pooled estimates used in bias analyses. A total of 151 cohorts (over 32 million people, 1.1 million cancer cases, and 150,000 cancer deaths) were included. In meta-analyses, T2D was associated with incidence of several cancers, from prostate (RR 0.83; 95% CI 0.79, 0.88) to liver (2.23; 1.99, 2.49), and with mortality from pancreatic cancer (1.67; 1.30, 2.14). In bias analyses, assuming an unmeasured confounding associated with both T2D and cancer with a RR of 1.5, the proportion of studies with a true effect size larger than a RR of 1.1 (i.e., 10% increased risk in individuals with T2D) was nearly 100% for liver, pancreatic, and endometrial, 86% for gallbladder, 67% for kidney, 64% for colon, 62% for colorectal, and LIMITATIONS Biases other than unmeasured confounding were not analytically assessed. CONCLUSIONS Our findings strongly suggest a causal association between T2D and liver, pancreatic, and endometrial cancer incidence, and pancreatic cancer mortality. Conversely, associations with other cancers were less robust to unmeasured confounding.

Is there long-term value of pathology scoring in immunoglobulin A nephropathy? A validation study of the Oxford Classification for IgA Nephropathy (VALIGA) update

Abstract: BACKGROUND: It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up. METHODS: In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1-10.8)]. RESULTS: In this extended analysis, M1, S1 and T1-T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P < 0.01), and there was no effect modification by age for these associations, suggesting that they may be valid in children and in adults as well. Only T lesions were associated with the rate of eGFR loss in the whole cohort, whereas C showed this association only in patients not treated with immunosuppression. In separate prognostic analyses, the whole set of pathology lesions provided a gain in discrimination power over the clinical variables alone, which was similar at 5 years (+2.0%) and for the whole follow-up (+1.8%). A similar benefit was observed for risk reclassification analyses (+2.7% and +2.4%). CONCLUSION: Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.

Demographic and occupational determinants of anti-SARS-CoV-2 IgG seropositivity in hospital staff.

Abstract: Background Although evidence suggests that demographic characteristics including minority ethnicity increase the risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), it is unclear whether these characteristics, together with occupational factors, influence anti-SARS-CoV-2 IgG seroprevalence in hospital staff. Methods We conducted cross-sectional surveillance examining seroprevalence of anti-SARS-CoV-2 IgG amongst staff at University Hospitals of Leicester (UHL) NHS Trust. We quantified seroprevalence stratified by ethnicity, occupation and seniority of practitioner and used logistic regression to examine demographic and occupational factors associated with seropositivity. Results A total of 1148/10662 (10.8%) hospital staff members were seropositive. Compared to White staff (seroprevalence 9.1%), seroprevalence was higher in South Asian (12.3%) and Black (21.2%) staff. The occupations and department with the highest seroprevalence were nurses/healthcare assistants (13.7%) and the Emergency Department (ED)/Acute Medicine (17.5%), respectively. Seroprevalence decreased with seniority in medical/nursing practitioners. Minority ethnicity was associated with seropositivity on an adjusted analysis (South Asian: aOR 1.26; 95%CI: 1.07-1.49 and Black: 2.42; 1.90-3.09). Anaesthetics/ICU staff members were less likely to be seropositive than ED/Acute medicine staff (0.41; 0.27-0.61). Conclusions Ethnicity and occupational factors, including specialty and seniority, are associated with seropositivity for anti-SARS-Cov-2 IgG. These findings could be used to inform occupational risk assessments for front-line healthcare workers.

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

Abstract: 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.

Identifying Outcomes Important to Patients with Glomerular Disease and Their Caregivers.

Abstract: Background and objectives Shared decision making in patients with glomerular disease remains challenging because outcomes important to patients remain largely unknown. We aimed to identify and prioritize outcomes important to patients and caregivers and to describe reasons for their choices. Design, setting, participants, & measurements We purposively sampled adult patients with glomerular disease and their caregivers from Australia, Hong Kong, the United Kingdom, and the United States. Participants identified, discussed, and ranked outcomes in focus groups using the nominal group technique; a relative importance score (between zero and one) was calculated. Qualitative data were analyzed thematically. Results Across 16 focus groups, 134 participants (range, 19–85 years old; 51% women), including 101 patients and 33 caregivers, identified 58 outcomes. The ten highest-ranked outcomes were kidney function (importance score of 0.42), mortality (0.29), need for dialysis or transplant (0.22), life participation (0.18), fatigue (0.17), anxiety (0.13), family impact (0.12), infection and immunity (0.12), ability to work (0.11), and BP (0.11). Three themes explained the reasons for these rankings: constraining day-to-day experience, impaired agency and control over health, and threats to future health and family. Conclusions Patients with glomerular disease and their caregivers highly prioritize kidney health and survival, but they also prioritize life participation, fatigue, anxiety, and family impact.

Covid-19 and ethnic minorities: an urgent agenda for overdue action.

Abstract: The government’s report falls seriously short on commitment

Prognostic Relevance of Cardiorespiratory Fitness as Assessed by Submaximal Exercise Testing for All-Cause Mortality: A UK Biobank Prospective Study.

Abstract: Objective To investigate whether the inverse associations of cardiorespiratory fitness (CRF) with all-cause and cardiovascular mortality in the general population vary among individuals who are at different levels of pretest risk. Patients and Methods Cardiorespiratory fitness was assessed through submaximal bicycle tests in 58,892 participants aged 40 to 69 years who completed baseline questionnaires between January 1, 2006, and December 31, 2010, in the UK Biobank Prospective Study. Participants were categorized into risk categories, which determined allocation to an individualized bicycle protocol. The groups at minimal risk (category 1), small risk (category 2), and medium risk (category 3) were tested at 50%, 35% of the predicted maximal workload, and constant level, respectively. We investigated associations of CRF with mortality across different levels of pretest risk and determined whether CRF improves risk prediction. Results During a median follow-up of 5.8 years, 936 deaths occurred. Cardiorespiratory fitness was linearly associated with mortality risk. Comparing extreme fifths of CRF, the multivariable-adjusted hazard ratios (95% CIs) for mortality were 0.63 (0.52-0.77), 0.54 (0.36-0.82), 0.81 (0.46-1.43), and 0.58 (0.48-0.69) in categories 1, 2, and 3 and overall population, respectively. The addition of CRF to a 5-year mortality risk score containing established risk factors was associated with a C-index change (0.0012; P=.49), integrated discrimination improvement (0.0005; P Conclusion Cardiorespiratory fitness, assessed by submaximal exercise testing, improves mortality risk prediction beyond conventional risk factors and its prognostic relevance varies across cardiovascular risk levels.

Recommendations for management of diabetes during Ramadan: update 2020, applying the principles of the ADA/EASD consensus

Abstract: Fasting the Holy month of Ramadan constitutes one of the five pillars of the Muslim faith. Although there is some evidence that intermittent fasting during Ramadan may be of benefit in losing weight and cardiometabolic risk factors, there is no strong evidence these benefits apply to people with diabetes. The American Diabetes Association/European Association for the Study of Diabetes consensus recommendations emphasize the importance of patient factors and comorbidities when choosing diabetes medications including the presence of comorbidities, atherosclerotic cardiovascular disease, heart failure, chronic kidney disease, hypoglycemia risk, weight issues and costs. Structured education and pre-Ramadan counseing are key components to successful management of patients with diabetes. These should cover important aspects like glycemic targets, self-monitoring of blood glucose, diet, physical activity including Taraweeh prayers, medication and dose adjustment, side effects and when to break the fast. The decision cycle adapted for the specific situation of Ramadan provides an aid for such an assessment. Children with type 1 diabetes should strongly be advised not to fast due to the high risk of acute complications such as hypoglycemia and probably diabetic ketoacidosis (DKA), although there is very little evidence that DKA is increased in Ramadan. Pregnant women with diabetes or gestational diabetes should be advised to avoid fasting because of possible negative maternal and fetal outcomes. Hypoglycemia is a common concern during Ramadan fasting. To prevent hypoglycemic and hyperglycemic events, we recommend the adoption of diabetes self-management education and support principles. The use of the emerging technology and continuous glucose monitoring during Ramadan could help to recognize hypoglycemic and hyperglycemic complications related to omission and/or medication adjustment during fasting; however, the cost represents a significant barrier.

Short-term and Long-term Feasibility, Safety, and Efficacy of High-Intensity Interval Training in Cardiac Rehabilitation: The FITR Heart Study Randomized Clinical Trial

Abstract: Importance High-intensity interval training (HIIT) is recognized as a potent stimulus for improving cardiorespiratory fitness (volume of oxygen consumption [VO2] peak) in patients with coronary artery disease (CAD). However, the feasibility, safety, and long-term effects of HIIT in this population are unclear. Objective To compare HIIT with moderate-intensity continuous training (MICT) for feasibility, safety, adherence, and efficacy of improving VO2peak in patients with CAD. Design, Setting, and Participants In this single-center randomized clinical trial, participants underwent 4 weeks of supervised training in a private hospital cardiac rehabilitation program, with subsequent home-based training and follow-up over 12 months. A total of 96 participants with angiographically proven CAD aged 18 to 80 years were enrolled, and 93 participants were medically cleared for participation following a cardiopulmonary exercise test. Data were collected from May 2016 to December 2018, and data were analyzed from December 2018 to August 2019. Interventions A 4 × 4-minute HIIT program or a 40-minute MICT program (usual care). Patients completed 3 sessions per week (2 supervised and 1 home-based session) for 4 weeks and 3 home-based sessions per week thereafter for 48 weeks. Main Outcomes and Measures The primary outcome was change in VO2peak during the cardiopulmonary exercise test from baseline to 4 weeks. Further testing occurred at 3, 6, and 12 months. Secondary outcomes were feasibility, safety, adherence, cardiovascular risk factors, and quality of life. Results Of 93 randomized participants, 78 (84%) were male, the mean (SD) age was 65 (8) years, and 46 were randomized to HIIT and 47 to MICT. A total of 86 participants completed testing at 4 weeks for the primary outcome, including 43 in the HIIT group and 43 in the MICT group; 69 completed testing at 12 months for VO2peak, including 32 in the HIIT group and 37 in the MICT group. After 4 weeks, HIIT improved VO2peak by 10% compared with 4% in the MICT group (mean [SD] oxygen uptake: HIIT, 2.9 [3.4] mL/kg/min; MICT, 1.2 [3.4] mL/kg/min;P = .02). After 12 months, there were similar improvements from baseline between groups, with a 10% improvement in the HIIT group and a 7% improvement in the MICT group (mean [SD] oxygen uptake: HIIT, 2.9 [4.5] mL/kg/min; MICT, 1.8 [4.3] mL/kg/min;P = .30). Both groups had high feasibility scores and low rates of withdrawal due to serious adverse events (3 participants in the HIIT group and 1 participant in the MICT group). One event occurred following exercise (hypotension) in the HIIT group. Over 12 months, both home-based HIIT and MICT had low rates of adherence (HIIT, 18 of 34 [53%]; MICT, 15 of 37 [41%];P = .35) compared with the supervised stage (HIIT, 39 of 44 [91%]; MICT, 39 of 43 [91%];P > .99). Conclusions and Relevance In this randomized clinical trial, a 4-week HIIT program improved VO2peak compared with MICT in patients with CAD attending cardiac rehabilitation. However, improvements in VO2peak at 12 months were similar for both groups. HIIT was feasible and safe, with similar adherence to MICT over 12-month follow-up. These findings support inclusion of HIIT in cardiac rehabilitation programs as an adjunct or alternative modality to moderate-intensity exercise. Trial Registration Australian New Zealand Clinical Trials Registry Identifier:ACTRN12615001292561

Uses and Limitations of the Restricted Mean Survival Time: Illustrative Examples From Cardiovascular Outcomes and Mortality Trials in Type 2 Diabetes.

Abstract: This article describes an alternative to the hazard ratio for reporting effects of interventions in trials: the restricted mean survival time. By presenting examples from trials with cardiovascular...

Application of normalisation process theory in understanding implementation processes in primary care settings in the UK: A systematic review

Abstract: Normalisation Process Theory (NPT) provides a framework to understand how interventions are implemented, embedded, and integrated in healthcare settings. Previous reviews of published literature have examined the application of NPT across international healthcare and reports its benefits. However, given the distinctive clinical function, organisational arrangements and the increasing management of people with a wide variety of conditions in primary care settings in the United Kingdom, it is important to understand how and why authors utilise and reflect on NPT in such settings to inform and evaluate implementation processes. A systematic review of peer-reviewed literature using NPT in primary care settings in the United Kingdom (UK) was conducted. Eight electronic databases were searched using replicable methods to identify articles published between January 2012 and April 2018. Data were analysed using a framework approach. Thirty-one articles met the inclusion criteria. Researchers utilised NPT to explore the implementation of interventions, targeting a wide range of health services and conditions, within primary care settings in the UK. NPT was mostly applied qualitatively; however, a small number of researchers have moved towards mixed and quantitative methods. Some variation was observed in the use of NPT constructs and sub-constructs, and whether and how researchers undertook modification to make them more relevant to the implementation process and multiple stakeholder perspectives. NPT provides a flexible framework for the development and evaluation of complex healthcare interventions in UK primary care settings. This review updates the literature on NPT use and indicates that its application is well suited to these environments, particularly in supporting patients with long-term conditions and co-morbidities. We recommend future research explores the receipt of interventions by multiple stakeholders and suggest that authors reflect on justifications for using NPT in their reporting.

Assessing the cost-effectiveness of sodium–glucose cotransporter-2 inhibitors in type 2 diabetes mellitus: A comprehensive economic evaluation using clinical trial and real-world evidence

Abstract: Aims The economic burden of diabetes is driven by the management of vascular complications. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated reductions in cardiovascular and renal complications, including hospitalization for heart failure (HHF) and renal disease progression, in randomized clinical trials. The objective of this study was to evaluate the cost-effectiveness of the SGLT2i class versus standard of care in type 2 diabetes mellitus (T2DM), using evidence from both clinical trial and real-world studies. Methods An established T2DM model was adapted to use contemporary outcomes evidence from real-world studies and randomized controlled trial evaluations of SGLT2i, and extrapolated over a lifetime for HHF, myocardial infarction, stroke, end-stage renal disease and all-cause mortality. The economic analysis considered adults with T2DM, with and without established cardiovascular disease, and was conducted over a lifetime from the perspective of the health care payer in the United Kingdom, United States and China, discounted at country-specific rates. Results SGLT2i were consistently associated with increased treatment costs, reduced complication costs and gains in quality-adjusted life years driven by differences in projected life expectancy, cardiovascular and microvascular morbidity and weight loss. SGLT2i were estimated to be cost-saving or cost-effective at relevant thresholds for the overall population in the United Kingdom, United States and China, with cost-effectiveness being the greatest in higher risk subgroups. Conclusions The findings highlight the need to take into account cost savings from reducing common, morbid and preventable T2DM complications when considering the cost of diabetes medications.

The Exclusion of Patients with CKD in Prospectively Registered Interventional Trials for COVID-19-a Rapid Review of International Registry Data.

Abstract: The exclusion of patients with CKD from clinical trials has been a barrier to therapeutic advancement in CKD for the last two decades.1 These inequities were highlighted by the Kidney Disease Improving Global Outcomes Controversies Conference, with the ambition of ensuring that individuals with CKD are included in relevant clinical trials.2 The coronavirus disease 2019 (COVID-19) pandemic’s global effect has led to rapid clinical trial registration and commencement in search of effective treatments. Individuals with CKD are at higher risk of COVID-19–related mortality.3 It is unclear, however, if these individuals have equitable access to clinical trial recruitment. Therefore, we aimed to assess the CKD-related inclusion and exclusion criteria for COVID-19 trials.