Protocol for a multi-center randomized controlled trial to evaluate the benefits of exercise incentives and corticosteroid injections in osteoarthritis of the knee (MOVE-OK).

Background: Knee osteoarthritis (KOA) is a high-priority problem among the aging population. While exercise has been shown to be beneficial in management of the disease, scalable and low-cost interventions to improve exercise in this population are lacking. Recent controversy over the value of corticosteroid injections for palliation has also arisen.

Improving quality of hepatitis B care in the Veteran's Health Administration.

Content available: Audio Recording.

Substance use disorders and COVID-19: An analysis of nation-wide Veterans Health Administration electronic health records.

Background: Substance use disorders (SUD) elevate the risk for COVID-19 hospitalization, but studies are inconsistent on the relationship of SUD to COVID-19 mortality.

Methods: Veterans Health Administration (VHA) patients treated in 2019 and evaluated in 2020 for COVID-19 (n=5,556,315), of whom 62,303 (1.1%) tested positive for COVID-19 (COVID-19+).

Quantitative trait loci, G×E and G×G for glycemic traits: response to metformin and placebo in the Diabetes Prevention Program (DPP).

The complex genetic architecture of type-2-diabetes (T2D) includes gene-by-environment (G×E) and gene-by-gene (G×G) interactions. To identify G×E and G×G, we screened markers for patterns indicative of interactions (relationship loci [rQTL] and variance heterogeneity loci [vQTL]). rQTL exist when the correlation between multiple traits varies by genotype and vQTL occur when the variance of a trait differs by genotype (potentially flagging G×G and G×E).

Risk factors for adverse outcomes in emergency versus nonemergency open umbilical hernia repair and opportunities for elective repair in a national cohort of patients with cirrhosis.

Background: Whether to perform umbilical hernia repair in patients with cirrhosis is a common dilemma for surgeons. We aimed to determine the incidence, morbidity, and mortality associated with emergency and nonemergency umbilical hernia repair in patients with and without cirrhosis, and to explore opportunities for nonemergency repair.

Methods: Veterans diagnosed with cirrhosis between 2001 and 2014 and a frequency-matched sample of veterans without cirrhosis were followed through September 2017.

COVID-19 Vaccination Effectiveness Against Infection or Death in a National U.S. Health Care System : A Target Trial Emulation Study.

Background: Little is known about real-world COVID-19 vaccine effectiveness (VE) in racially and ethnically diverse, elderly populations with high comorbidity burden.

Objective: To determine the effectiveness of messenger RNA COVID-19 vaccines.

Design: Target trial emulation study comparing newly vaccinated persons with matched unvaccinated controls.

Concomitant Lung and Kidney Disorders in Critically Ill Patients: Core Curriculum 2022.

The lungs and kidneys are cooperative and interdependent organs that secure the homeostasis of the body. Volume and acid-base disorders sit at the nexus between these two systems. However, lung-kidney interactions affect the management of many other conditions, especially among critically ill patients.

Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial.

Background: We aimed to assess efficacy and safety, with a special focus on cardiovascular safety, of the novel dual GIP and GLP-1 receptor agonist tirzepatide versus insulin glargine in adults with type 2 diabetes and high cardiovascular risk inadequately controlled on oral glucose-lowering medications.

Methods: This open-label, parallel-group, phase 3 study was done in 187 sites in 14 countries on five continents. Eligible participants, aged 18 years or older, had type 2 diabetes treated with any combination of metformin, sulfonylurea, or sodium-glucose co-transporter-2 inhibitor, a baseline glycated haemoglobin (HbA) of 7·5-10·5% (58-91 mmol/mol), body-mass index of 25 kg/m or greater, and established cardiovascular disease or a high risk of cardiovascular events.

Acetazolamide prevents hypoxia-induced reactive oxygen species generation and calcium release in pulmonary arterial smooth muscle.

Upon sensing a reduction in local oxygen partial pressure, pulmonary vessels constrict, a phenomenon known as hypoxic pulmonary vasoconstriction. Excessive hypoxic pulmonary vasoconstriction can occur with ascent to high altitude and is a contributing factor to the development of high-altitude pulmonary edema. The carbonic anhydrase inhibitor, acetazolamide, attenuates hypoxic pulmonary vasoconstriction through stimulation of alveolar ventilation via modulation of acid-base homeostasis and by direct effects on pulmonary vascular smooth muscle.

COVID-19, Hyperglycemia, and New-Onset Diabetes.

Certain chronic comorbidities, including diabetes, are highly prevalent in people with coronavirus disease 2019 (COVID-19) and are associated with an increased risk of severe COVID-19 and mortality. Mild glucose elevations are also common in COVID-19 patients and associated with worse outcomes even in people without diabetes. Several studies have recently reported new-onset diabetes associated with COVID-19.

Risks of Opportunistic Infections in People With Human Immunodeficiency Virus With Cancers Treated With Chemotherapy.

Background: We ascertained incidence of opportunistic infections (OIs) in people with human immunodeficiency virus (PWH) with cancer undergoing chemotherapy with non-human immunodeficiency virus (HIV) comparators.

Methods: We identified 2106 PWH and 2981 uninfected Veterans with cancer who received at least 1 dose of chemotherapy between 1996 and 2017 from the Veterans Aging Cohort Study. We ascertained incident OIs within 6 months of chemotherapy amongst zoster, cytomegalovirus, tuberculosis, esophagitis, pneumonia (PCP), toxoplasmosis, Cryptococcosis, atypical infection, bacteremia, histoplasmosis, coccidioidomycosis, or progressive multifocal leukoencephalopathy.

Legacy of a 10-Year Multidomain Lifestyle Intervention on the Cognitive Trajectories of Individuals with Overweight/Obesity and Type 2 Diabetes Mellitus.

Introduction: Weight loss and increased physical activity interventions are commonly recommended for individuals with type 2 diabetes (T2D) and overweight or obesity. We examined the impact of randomization to an intensive lifestyle intervention (ILI) on trajectories of cognitive function over 10 years in a cohort of participants in a randomized clinical trial who had T2D and overweight/obesity at baseline.

Methods: Participants aged 45-76 years were enrolled in 2001-2004 and were randomized to the ILI or a diabetes support and education (DSE) condition.

Loss of apoptosis repressor with caspase recruitment domain (ARC) worsens high fat diet-induced hyperglycemia in mice.

Apoptosis repressor with caspase recruitment domain (ARC) is an endogenous inhibitor of cell death signaling that is expressed in insulin-producing β cells. ARC has been shown to reduce β-cell death in response to diabetogenic stimuli in vitro, but its role in maintaining glucose homeostasis in vivo has not been fully established. Here we examined whether loss of ARC in FVB background mice exacerbates high fat diet (HFD)-induced hyperglycemia in vivo over 24 weeks.

The β Cell in Diabetes: Integrating Biomarkers With Functional Measures.

The pathogenesis of hyperglycemia observed in most forms of diabetes is intimately tied to the islet β cell. Impairments in propeptide processing and secretory function, along with the loss of these vital cells, is demonstrable not only in those in whom the diagnosis is established but typically also in individuals who are at increased risk of developing the disease. Biomarkers are used to inform on the state of a biological process, pathological condition, or response to an intervention and are increasingly being used for predicting, diagnosing, and prognosticating disease.

Baseline Predictors of Glycemic Worsening in Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes in the Restoring Insulin Secretion (RISE) Study.

Objective: To identify predictors of glycemic worsening among youth and adults with impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes in the Restoring Insulin Secretion (RISE) Study.

Research Design And Methods: A total of 91 youth (10-19 years) were randomized 1:1 to 12 months of metformin (MET) or 3 months of glargine, followed by 9 months of metformin (G-MET), and 267 adults were randomized to MET, G-MET, liraglutide plus MET (LIRA+MET), or placebo for 12 months. All participants underwent a baseline hyperglycemic clamp and a 3-h oral glucose tolerance test (OGTT) at baseline, month 6, month 12, and off treatment at month 15 and month 21.

Virtual Interactive Case-Based Education (VICE): A Conference for Deliberate Practice of Diagnostic Reasoning.

Introduction: Current approaches to teaching diagnostic reasoning minimally address the need for deliberate practice. We developed an educational conference for internal medicine residents to practice diagnostic reasoning and examine how biases affect their differential diagnoses through cognitive autopsies.

Methods: We formatted the Virtual Interactive Case-Based Education (VICE) conference as a clinical problem-solving exercise, in which a facilitator presents a case to a single discussant selected from the audience.

Brief Report: Association Between Pain, Pulmonary Function, and Respiratory Symptoms in People With HIV.

Background: People with HIV (PWH) experience chronic pain and respiratory symptoms, which are closely related in the general population. Pain may affect the impaired pulmonary function seen in PWH beyond its association with HIV alone. Our objective was to investigate the relationship of pain severity to pulmonary function, respiratory symptoms, and sleep disturbance in PWH.

Sex-related differences in cognitive trajectories in older individuals with type 2 diabetes and overweight or obesity.

Introduction: It is unknown whether rates of cognitive decline differ between older women and men with type 2 diabetes (T2D) and overweight or obesity.

Methods: Two to four cognitive assessments were obtained across up to 10 years from 2799 adults (mean age 68 years; 62% women) with T2D who had been enrolled in a clinical trial of weight loss intervention. Sex-related differences in means and rates of decline of cognitive scores were assessed.

Association of glycemia with insulin sensitivity and β-cell function in adults with early type 2 diabetes on metformin alone.

Aims: Evaluate the relationship between measures of glycemia with β-cell function and insulin sensitivity in adults with early type 2 diabetes mellitus (T2DM).

Methods: This cross-sectional analysis evaluated baseline data from 3108 adults with T2DM <10 years treated with metformin alone enrolled in the Glycemia Reduction Approaches in Diabetes. A Comparative Effectiveness (GRADE) Study.

Type 2 Diabetes Subgroups, Risk for Complications, and Differential Effects Due to an Intensive Lifestyle Intervention.

Objective: We reevaluated the Action for Health in Diabetes (Look AHEAD) intervention, incorporating diabetes subgroups, to identify whether intensive lifestyle intervention (ILI) is associated with differential risk for cardiovascular disease (CVD) by diabetes subgroup.

Research Design And Methods: In the Look AHEAD trial, 5,145 participants, aged 45-76 years, with type 2 diabetes (T2D) and overweight or obesity were randomly assigned to 10 years of ILI or a control condition of diabetes support and education. The ILI focused on weight loss through decreased caloric intake and increased physical activity.

Precision and accuracy of hyperglycemic clamps in a multicenter study.

Application of glucose clamp methodologies in multicenter studies brings challenges for standardization. The Restoring Insulin Secretion (RISE) Consortium implemented a hyperglycemic clamp protocol across seven centers using a combination of technical and management approaches to achieve standardization. Two-stage hyperglycemic clamps with glucose targets of 200 mg/dL and >450 mg/dL were performed utilizing a centralized spreadsheet-based algorithm that guided dextrose infusion rates using bedside plasma glucose measurements.

Effect of linagliptin versus placebo on cardiovascular and kidney outcomes in nephrotic-range proteinuria and type 2 diabetes: the CARMELINA randomized controlled trial.

Background: Nephrotic-range proteinuria (NRP) is associated with rapid kidney function loss and increased cardiovascular (CV) disease risk. We assessed the effects of linagliptin (LINA) on CV and kidney outcomes in people with Type 2 diabetes (T2D) with or without NRP.

Methods: Cardiovascular and renal microvascular outcome study with LINA randomized participants with T2D and CV disease and/or kidney disease to LINA 5 mg or placebo (PBO).