Nonregistration, Discontinuation, and Nonpublication of Randomized Trials: A Systematic Review.

Importance: Previous work found that 25% to 30% of randomized clinical trials (RCTs) with protocols approved in 2012 or between 2000 and 2003 were discontinued prematurely, most commonly due to inadequate participant recruitment. To minimize research waste, RCTs should be registered and their results made available.

Objectives: To assess the fate of RCTs approved by ethics committees in 2016 in terms of nonregistration, discontinuation, and nonpublication, and to examine RCT characteristics associated with discontinuation due to poor recruitment and nonpublication of RCT results.

Association of Albuminuria With 1-Year Risk of Heart Failure and Other Adverse Outcomes in Atrial Fibrillation.

Background: Albuminuria is associated with increased stroke risk in atrial fibrillation (AF), but its relationship with heart failure (HF) and other adverse outcomes in AF is less well understood.

Methods: Using linked administrative databases, we conducted a retrospective cohort study of individuals aged ≥66 years who were newly diagnosed with AF between April 2009 and March 2019 in Ontario, Canada. Albuminuria was assessed using (1) urine albumin-to-creatinine ratio (UACR, mg/g) and (2) dipstick proteinuria (negative, trace, 1+, 2+, ≥3+).

Cholesterol Levels and Cardiovascular Outcomes Following Statin Initiation for Primary Prevention: A Cohort Study.

Background: Non-high-density lipoprotein cholesterol (HDL-C) is increasingly incorporated into guidelines along with low-density lipoprotein cholesterol (LDL-C) to guide lipid-lowering therapy decisions.

Objectives: The purpose of this study was to examine patterns of LDL-C and non-HDL-C levels after statin initiation for primary prevention and their association with incident cardiovascular events.

Methods: This was a population-based cohort study in Ontario, Canada, among persons aged ≥66 years starting a statin for primary prevention between January 1, 2012, and December 31, 2019.

Metaresearch on patient-reported outcomes in trial protocols and results publications suggested large outcome reporting bias.

Objectives: Patient-reported outcomes (PROs) provide crucial information for evaluating health-care interventions, but previous research in specific disease areas suggested infrequent use and incomplete reporting of PROs. We examined the prevalence and characteristics of PROs in randomized clinical trial (RCT) protocols across medical fields, their reporting quality, and the consistency between PROs specified in trial protocols and subsequent reporting in trial publications.

Study Design And Setting: We included 237 RCT protocols approved in 2012 and 251 approved in 2016, by ethics committees in Switzerland, Germany, and Canada.

Do peer reviewers comment on reporting items as instructed by the journal? A secondary analysis of two randomized trials.

Objectives: Two studies randomizing manuscripts submitted to biomedical journals have previously shown that reminding peer reviewers about key reporting items did not improve the reporting quality in published articles. Within this secondary analysis of peer reviewer reports we aimed to assess at what stage the intervention failed.

Study Design And Setting: We exploratively analyzed peer reviewer reports from two published randomized controlled trials (RCTs) conducted at biomedical journals.

SGLT2 Inhibitors and Risk for Hyperkalemia Among Individuals Receiving RAAS Inhibitors.

Importance: Hyperkalemia is a common complication of taking a renin-angiotensin-aldosterone system inhibitor (RAASi). Post hoc analyses of large randomized clinical trials suggested that the addition of sodium-glucose cotransporter 2 inhibitors (SGLT2i) may attenuate this risk. It is unknown if this observation extends to daily clinical practice.

Upcoming drug targets for kidney protective effects in chronic kidney disease.

Unlabelled: People with chronic kidney disease (CKD) are at a high risk of heart disease and end-stage kidney disease. This review describes how new medications, such as glucagon-like peptide-1 receptor agonists (GLP1RA), aldosterone synthase inhibitors (ASi), soluble guanylate cyclase (sGC) and endothelin receptor antagonists (ERA), can lower heart-kidney risk in people with CKD. GLP1RA are already recommended for managing blood sugar in people with CKD and type 2 diabetes and have been shown to lower the risk of developing end-stage kidney disease.

Efficacy and Safety of Sotagliflozin in Patients with Type 1 Diabetes and CKD.

Key Points: Poor glycemic control in type 1 diabetes and CKD is associated with a higher risk of CKD progression. In a subgroup of inTandem participants with type 1 diabetes and CKD, adding sotagliflozin to insulin reduced HbA1c, body weight, and systolic BP without increasing severe hypoglycemia, compared with adding placebo. In participants with type 1 diabetes and CKD, sotagliflozin did not significantly increase the risk of DKA, however, there were a small number of diabetic ketoacidosis events.

Effect of Qualifying Atherosclerotic Cardiovascular Disease Diagnosis Proximity on Cardiovascular Risk and Benefit of Empagliflozin in the EMPA-REG OUTCOME Trial.

Background: In patients with type 2 diabetes mellitus (T2DM), a history of an ischemic event is associated with increased risk for cardiovascular (CV) disease. Whether patients with T2DM and a recent atherothrombotic diagnosis benefit from early intervention with a sodium-glucose co-transporter 2 inhibitor is unknown.

Methods: This study is a secondary analysis of the gliflozin Cardiovascular Event Trial in Type 2 Diabetes Mellitus Patients-emoving xcess lucose (EMPA-REG OUTCOME), which compared empagliflozin to placebo in adults with T2DM and atherosclerotic CV disease (ASCVD).

Proximal versus distal diuretics in congestive heart failure.

Volume overload represents a hallmark clinical feature linked to the development and progression of heart failure (HF). Alleviating signs and symptoms of volume overload represents a foundational HF treatment target that is achieved using loop diuretics in the acute and chronic setting. Recent work has provided evidence to support guideline-directed medical therapies, such as sodium glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor (MR) antagonists, as important adjunct diuretics that may act synergistically when used with background loop diuretics in people with chronic HF.

Cardiovascular Risk in Patients With Glomerular Disease: A Narrative Review of the Epidemiology, Mechanisms, Management, and Patient Priorities.

Purpose Of Review: Cardiovascular (CV) disease is a major cause of morbidity and mortality for patients with glomerular disease. Despite the fact that mechanisms underpinning CV disease risk in this population are likely distinct from other forms of kidney disease, treatment and preventive strategies tend to be extrapolated from studies of patients with undifferentiated chronic kidney disease (CKD). There is an unmet need to delineate the pathophysiology of CV disease in patients with glomerular disease, establish unique risk factors, and identify novel therapeutic targets for disease prevention.

Integrated Care: A Person-Centered and Population Health Strategy for the COVID-19 Pandemic Recovery and Beyond.

The COVID-19 pandemic has mandated a re-imagination of how healthcare is administered and delivered, with a view towards focusing on person-centred care and advancing population health while increasing capacity, access and equity in the healthcare system. These goals can be achieved through healthcare integration. In 2019, the University Health Network (UHN), a consortium of four quaternary care hospitals in Ontario, Canada, established the first stage of a pilot program to increase healthcare integration at the institutional level and vertically with other primary, secondary and tertiary institutions in the Ontario healthcare system.

Biology and Clinical Use of Glucagon-Like Peptide-1 Receptor Agonists in Vascular Protection.

Glucagon-like peptide-1 receptor agonists (GLP1RA) are incretin agents initially designed for the treatment of type 2 diabetes mellitus but because of pleiotropic actions are now used to reduce cardiovascular disease in people with type 2 diabetes mellitus and in some instances as approved treatments for obesity. In this review we highlight the biology and pharmacology of GLP1RA. We review the evidence for clinical benefit on major adverse cardiovascular outcomes in addition to modulation of cardiometabolic risk factors including reductions in weight, blood pressure, improvement in lipid profiles, and effects on kidney function.

Reminding Peer Reviewers of Reporting Guideline Items to Improve Completeness in Published Articles: Primary Results of 2 Randomized Trials.

Importance: Numerous studies have shown that adherence to reporting guidelines is suboptimal.

Objective: To evaluate whether asking peer reviewers to check if specific reporting guideline items were adequately reported would improve adherence to reporting guidelines in published articles.

Design, Setting, And Participants: Two parallel-group, superiority randomized trials were performed using manuscripts submitted to 7 biomedical journals (5 from the BMJ Publishing Group and 2 from the Public Library of Science) as the unit of randomization, with peer reviewers allocated to the intervention or control group.

A longitudinal assessment of trial protocols approved by research ethics committees: The Adherance to SPIrit REcommendations in the UK (ASPIRE-UK) study.

Background: To assess the quality of reporting of RCT protocols approved by UK research ethics committees before and after the publication of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline.

Methods: We had access to RCT study protocols that received ethical approval in the UK in 2012 (n=103) and 2016 (n=108). From those, we assessed the adherence to the 33 SPIRIT items (i.

A meta-research study of randomized controlled trials found infrequent and delayed availability of protocols.

Objectives: Availability of randomized controlled trial (RCT) protocols is essential for the interpretation of trial results and research transparency.

Study Design And Setting: In this study, we determined the availability of RCT protocols approved in Switzerland, Canada, Germany, and the United Kingdom in 2012. For these RCTs, we searched PubMed, Google Scholar, Scopus, and trial registries for publicly available protocols and corresponding full-text publications of results.

Reporting quality of clinical trial protocols: a repeated cross-sectional study about the Adherence to SPIrit Recommendations in Switzerland, CAnada and GErmany (ASPIRE-SCAGE).

Objectives: Comprehensive protocols are key for the planning and conduct of randomised clinical trials (RCTs). Evidence of low reporting quality of RCT protocols led to the publication of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist in 2013. We aimed to examine the quality of reporting of RCT protocols from three countries before and after the publication of the SPIRIT checklist.

Nonregistration, discontinuation, and nonpublication of randomized trials: A repeated metaresearch analysis.

Background: We previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs.

Methods And Findings: We included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study.

Reliability of Trial Information Across Registries for Trials With Multiple Registrations: A Systematic Review.

Importance: Clinical trial registries are important for gaining an overview of ongoing research efforts and for deterring and identifying publication bias and selective outcome reporting. The reliability of the information in trial registries is uncertain.

Objective: To assess the reliability of information across registries for trials with multiple registrations.