Psoralidin acts as a dual protease inhibitor against PL and M of SARS-CoV-2.

The emergence of new coronavirus variants and concerns about vaccine effectiveness against these novel variants emphasize the need for broad-spectrum therapeutics targeting conserved coronaviral non-structural proteins. Accordingly, a virtual library of 178 putative inhibitors targeting SARS-CoV-2 Papain-like protease (PL) was compiled through a systematic review of published literature and subsequently screened using molecular docking. Selected hits were analyzed for protease inhibitory activities, binding strength, and antiviral activities against HCoV229E-based surrogate system and subsequently against SARS-CoV-2 for validation.

Chlorthalidone vs Hydrochlorothiazide and Kidney Outcomes in Patients With Hypertension: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Hypertension is a risk factor for the development and progression of chronic kidney disease (CKD). It is unclear whether different thiazide diuretics have a differential impact on kidney outcomes.

Objective: To compare kidney outcomes in patients with hypertension taking chlorthalidone and hydrochlorothiazide.

As-Needed Blood Pressure Medication and Adverse Outcomes in VA Hospitals.

Importance: Asymptomatic blood pressure (BP) elevations in the hospital are commonly treated with as-needed BP medications, including recurring as-needed and 1-time administration. Veterans represent a population at risk of ischemic events from rapid lowering of BP, but the impact of as-needed BP medication use in this population is unknown.

Objective: To assess the risks of acute kidney injury (AKI) and other outcomes from as-needed BP medication administration in a hospitalized veteran cohort.

Fusion of spectral and topographic features for land use mapping using a machine learning framework for a regional scale application.

This study investigated the dynamics of land use and land cover (LULC) modelling, mapping, and assessment in the Kegalle District of Sri Lanka, where policy decision-making is crucial in agricultural development where LULC temporal datasets are not readily available. Employing remotely sensed datasets and machine learning algorithms, the work presented here aims to compare the accuracy of three classification approaches in mapping LULC categories across the time in the study area primarily using the Google Earth Engine (GEE). Three classifiers namely random forest (RF), support vector machines (SVM), and classification and regression trees (CART) were used in LULC modelling, mapping, and change analysis.

Brief Report: Nasal colonization with Staphylococcus aureus and methicillin resistant Staphylococcus aureus among community-dwelling older adults with comorbidities seeking follow-up medical care in Central Sri Lanka.

Older adults are more severely affected by infections caused by drug-resistant bacteria including Methicillin-Resistant (MRSA). We aimed to identify the MRSA colonization rates and associated factors among older adults aged more than 65-years-old. Among the 309 recruited, 152 (49.

Chronic Kidney Disease and Military Service in US Adults, 1999-2018.

Background: Although the management of chronic kidney disease (CKD) has changed considerably in US adults, it is uncertain whether the burden, risk factors, and temporal trends of CKD are similar regarding prior military service.

Methods: This observational study used National Health and Nutrition Examination Survey data to quantify the association between CKD and military service in a generalizable sample of US adults between 1999 and 2018.

Results: The respective frequencies (standard error [SE]) of CKD and military service were 15.

Chlorthalidone vs Hydrochlorothiazide for Hypertension Treatment After Myocardial Infarction or Stroke: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Patients with prior myocardial infarction (MI) or stroke have a greater risk of recurrent cardiovascular (CV) events.

Objective: To evaluate the association of chlorthalidone (CTD) vs hydrochlorothiazide (HCTZ) with CV outcomes and noncancer deaths in participants with and without prior MI or stroke.

Design, Setting, And Participants: This was a prespecified secondary analysis of the Diuretic Comparison Project (DCP), a pragmatic randomized clinical trial conducted within 72 participating Veterans Affairs health care systems from June 2016 to June 2021, in which patients aged 65 years or older with hypertension taking HCTZ at baseline were randomized to continue HCTZ or switch to CTD at pharmacologically comparable doses.

A cohort study of sodium-glucose cotransporter-2 inhibitors after acute kidney injury among Veterans with diabetic kidney disease.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk for several adverse outcomes among patients with diabetic kidney disease. Yet, optimal timing for SGLT2i after acute kidney injury (AKI) is uncertain, as are the providers responsible for post-AKI SGLT2i initiation. Using a retrospective cohort of United States Veterans with diabetes mellitus type 2 and proteinuria, we examined encounters by provider specialty before SGLT2i initiation and subsequent all-cause mortality after hospitalization with AKI, defined by a 50% or more rise in serum creatinine.

Kidney Outcomes with Sodium-Glucose Cotransporter-2 Inhibitor Initiation after AKI among Veterans with Diabetic Kidney Disease.

Key Points: Post-AKI sodium–glucose cotransporter-2 inhibitor use was associated with a reduced risk for progression of CKD and for recurrent AKI among veterans with diabetic kidney disease even after accounting for recovery from the index AKI. A minority of Veterans with diabetic kidney disease received a sodium–glucose cotransporter-2 inhibitor after having had AKI during the study period.

Background: The effect of sodium–glucose cotransporter-2 inhibitor (SGLT2i) on kidney function after AKI is unknown.

Strategies for secondary use of real-world clinical and administrative data for outcome ascertainment in pragmatic clinical trials.

Background: Pragmatic trials are gaining popularity as a cost-effective way to examine treatment effectiveness and generate timely comparative evidence. Incorporating supplementary real-world data is recommended for robust outcome monitoring. However, detailed operational guidelines are needed to inform effective use and integration of heterogeneous databases.

Pharmacist-driven outreach initiative to increase prescribing of sodium-glucose cotransporter-2 inhibitors in eligible VHA patients with chronic kidney disease: a study protocol.

Background: Patients with chronic kidney disease (CKD) are at increased risk for multiple adverse events, several of which have been proven to be less likely with the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i). As a result, guidelines now recommend SGLT2i be given to those with mild to moderate CKD and type 2 diabetes. The objective of this study is to evaluate if a pharmacist-driven SGLT2i prescribing initiative among eligible patients with CKD and diabetes within the VA could more rapidly improve the adoption of SGLT2i via a pragmatic approach aligned with learning health systems.

Effect of Intensive Blood Pressure Control on Kidney Outcomes: Long-Term Electronic Health Record-Based Post-Trial Follow-Up of SPRINT.

Background: Intensive BP lowering in the Systolic Blood Pressure Intervention Trial (SPRINT) produced acute decreases in kidney function and higher risk for AKI. We evaluated the effect of intensive BP lowering on long-term changes in kidney function using trial and outpatient electronic health record (EHR) creatinine values.

Methods: SPRINT data were linked with EHR data from 49 (of 102) study sites.

Renin-Angiotensin-Aldosterone System Blockade after AKI with or without Recovery among US Veterans with Diabetic Kidney Disease.

Significance Statement: Among patients with CKD, optimal use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers after AKI is uncertain. Despite these medications' ability to reduce risk of mortality and other adverse outcomes, there is concern that ACEi/ARB use may delay recovery of kidney function or precipitate recurrent AKI. Prior studies have provided conflicting data regarding the optimal timing of these medications after AKI and have not addressed the role of kidney recovery in determining appropriate timing.

Telephone informed consent in a pragmatic point-of-care clinical trial embedded in primary care.

Background: One benefit of pragmatic clinical trials is reduction of the burden on patients and clinical staff while facilitating a learning healthcare system. One way to decrease the work of clinical staff is through decentralized telephone consent.

Methods: The Diuretic Comparison Project (DCP) was a nationwide Point of Care pragmatic clinical trial conducted by the VA Cooperative Studies Program.

Ascertainment of stroke from administrative data to support a pragmatic embedded clinical trial.

The goal of this observational study was to identify stroke hospitalizations using International Classification of Disease (ICD)-10 codes and use these codes to develop an ascertainment algorithm for use in pragmatic clinical trials, reducing or eliminating the need for manual chart adjudication in future. Using VA (Veterans Affairs) electronic medical records, 9959 patient charts with ICD-10 codes indicating stroke were screened and a sample of 304 were adjudicated by three clinical reviewers. Hospitalizations were categorized as stroke or non-stroke and positive predictive value (PPV) was calculated for each ICD-10 code that was sampled.

The impact of COVID-19 on a large pragmatic clinical trial embedded in primary care.

Introduction: The COVID-19 pandemic had significant impact on clinical care and clinical trial operations, but the impact on decentralized pragmatic trials is unclear. The Diuretic Comparison Project (DCP) is a Point-of Care (POC) pragmatic trial testing whether chlorthalidone is superior to hydrochlorothiazide in preventing major cardiovascular (CV) events and non-cancer death. DCP utilized telephone consent, data collection from the electronic health record and Medicare, forwent study visits, and limited provider commitment beyond usual care.

Concordance between clinical outcomes in the Systolic Blood Pressure Intervention Trial and in the electronic health record.

Background: Randomized trials are the gold standard for generating clinical practice evidence, but follow-up and outcome ascertainment are resource-intensive. Electronic health record (EHR) data from routine care can be a cost-effective means of follow-up, but concordance with trial-ascertained outcomes is less well-studied.

Methods: We linked EHR and trial data for participants of the Systolic Blood Pressure Intervention Trial (SPRINT), a randomized trial comparing intensive and standard blood pressure targets.

Chlorthalidone vs. Hydrochlorothiazide for Hypertension-Cardiovascular Events.

Background: Whether chlorthalidone is superior to hydrochlorothiazide for preventing major adverse cardiovascular events in patients with hypertension is unclear.

Methods: In a pragmatic trial, we randomly assigned adults 65 years of age or older who were patients in the Department of Veterans Affairs health system and had been receiving hydrochlorothiazide at a daily dose of 25 or 50 mg to continue therapy with hydrochlorothiazide or to switch to chlorthalidone at a daily dose of 12.5 or 25 mg.

Effect of Intensive versus Standard BP Control on AKI and Subsequent Cardiovascular Outcomes and Mortality: Findings from the SPRINT EHR Study.

Background: Adjudication of inpatient AKI in the Systolic Blood Pressure Intervention Trial (SPRINT) was based on billing codes and admission and discharge notes. The purpose of this study was to evaluate the effect of intensive versus standard BP control on creatinine-based inpatient and outpatient AKI, and whether AKI was associated with cardiovascular disease (CVD) and mortality.

Methods: We linked electronic health record (EHR) data from 47 clinic sites with trial data to enable creatinine-based adjudication of AKI.