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Contemp Clin Trials 2021 Apr 7:106394. Epub 2021 Apr 7.

Yale School of Medicine, Department of Internal Medicine, Section of Infectious Disease, Yale AIDS Program, New Haven, CT, USA. Electronic address:

Background: Hospitalization with co-occurring opioid use disorder (OUD) and infections presents a critical time to intervene to improve outcomes for these intertwined epidemics that are typically managed separately. A surge in life-threatening infectious diseases associated with injection drug use, including bacterial and fungal infections, HIV, and HCV accounts for substantial healthcare utilization, morbidity, and mortality. Infectious Disease (ID) specialists manage severe infections that require hospitalization and are a logical resource to engage patients in medication treatment for OUD (MOUD). Read More

J Shoulder Elbow Surg 2021 Apr 1. Epub 2021 Apr 1.

Holy Cross Orthopedic Institute, Fort Lauderdale, FL, USA. Electronic address:

Introduction: Prosthetic Joint Infections (PJI) following shoulder arthroplasty are a major source of morbidity, and are most commonly caused by Cutibacterium acnes (C. acnes), a bacteria found concentrated in the dermis. Skin preparation using hydrogen peroxide has been shown to reduce positive cultures, however direct application to the dermis has not been investigated. Read More

Trials 2021 Apr 2;22(1):245. Epub 2021 Apr 2.

Kaleido Biosciences, Inc, Lexington, MA, USA.

Objectives: These 2 parallel studies (K031 and K032) aim to evaluate the safety of KB109 in addition to supportive self-care (SSC) compared with SSC alone in outpatients with mild to moderate coronavirus disease 2019 (COVID-19). KB109 is a novel synthetic glycan that was formulated to modulate the gut microbiome composition and metabolic output in order to increase beneficial short-chain fatty acid (SCFA) production in the gut. The K031 study is designed to evaluate the safety of KB109 and characterize its impact on the natural progression of COVID-19 in patients with mild to moderate disease. Read More

Am J Orthod Dentofacial Orthop 2021 Mar 29. Epub 2021 Mar 29.

Department of Orthodontics, Bauru Dental School, University of São Paulo, Bauru, Brazil.

Introduction: This single-center, 2-arm, parallel-group randomized clinical trial aimed to compare the dimensional dental arch changes after anterior open bite (AOB) treatment with bonded spurs associated with posterior build-ups vs bonded spurs alone.

Methods: Patients aged between 7 and 11 years with AOB were recruited at a university clinic and randomly allocated into 2 groups. The experimental group was treated with bonded spurs associated with posterior build-ups (SBU) and the comparison group with bonded spurs alone (S). Read More

Trials 2021 Apr 1;22(1):242. Epub 2021 Apr 1.

Division of Reproductive Biology, Maternal & Child Health (RBM&CH), Indian Council of Medical Research (ICMR) Headquarters, V Ramalingaswami Bhawan, Ansari Nagar, New Delhi, Delhi, 110029, India.

Background: Progress has been made in the reduction of under-five mortality in India; however, neonatal mortality is reducing at a slower rate. Efforts are required to bring down neonatal mortality in order to attain the Sustainable Development Goal-3. Prevention of sepsis among the high-risk, vulnerable low birth weight neonates by a newer intervention with probiotic supplementation is promising. Read More

N Engl J Med 2021 04;384(13):1216-1226

From the Department of Pediatric Nephrology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam (S.F.G., J.W.G.); the Division of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem (Y.F.); the Department of Nephrology, Birmingham Women's and Children's Hospital, Birmingham (S.A.H.), and the Department of Paediatric Nephrology, Great Ormond Street Hospital (W.G.H.), and UCL Department of Renal Medicine, Royal Free Hospital (S.H.M.), London - both in the United Kingdom; Jacksonville Center for Clinical Research, Jacksonville, FL (M.J.K.); eStudySite, San Diego, CA (W.D.O.); Center for Rare Renal Diseases and INSERM Pediatric Clinical Investigation Center-Hospices Civils de Lyon and Université de Lyon, Lyon (P.C.), and the Department of Pediatric Nephrology, Hôpital Robert-Debré, Paris (G.D.) - both in France; the Pediatric Nephrology Unit, Galilee Medical Center, Nahariya (H.S.-L.), and the Pediatric Nephrology Institute, Rambam Health Care Campus, Haifa (D.M.) - both in Israel; the Icahn School of Medicine at Mount Sinai, New York (J.M.S., K.A.M.); the Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (D.G.F.); the University of Bonn, Bonn, Germany (G.S.); Al Jalila Children's Hospital, Dubai, United Arab Emirates (E.S.); the Divisions of Pediatric Nephrology and Hypertension (D.J.S.) and Nephrology and Hypertension (J.C.L.), Mayo Clinic, Rochester, MN; and Alnylam Pharmaceuticals, Cambridge, MA (J.L., M.T.S., P.P.G., A.K.V., J.M.G., T.L.M.).

Background: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease caused by hepatic overproduction of oxalate that leads to kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. Lumasiran, an investigational RNA interference (RNAi) therapeutic agent, reduces hepatic oxalate production by targeting glycolate oxidase.

Methods: In this double-blind, phase 3 trial, we randomly assigned (in a 2:1 ratio) patients with PH1 who were 6 years of age or older to receive subcutaneous lumasiran or placebo for 6 months (with doses given at baseline and at months 1, 2, 3, and 6). Read More

JAMA Cardiol 2021 Mar 31. Epub 2021 Mar 31.

Department of Cardiology, Medizinische Klinik und Poliklinik I, Munich University Clinic, Ludwig-Maximilian University of Munich, Munich, Germany.

Importance: The assessment of new antithrombotic agents with a favorable safety profile is clinically relevant.

Objective: To test the efficacy and safety of revacept, a novel, lesion-directed antithrombotic drug, acting as a competitive antagonist to platelet glycoprotein VI.

Design, Setting, And Participants: A phase 2 randomized clinical trial; patients were enrolled from 9 centers in Germany from November 20, 2017, to February 27, 2020; follow-up ended on March 27, 2020. Read More

Clin Res Cardiol 2021 Mar 27. Epub 2021 Mar 27.

Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany.

Aims: Observational evidence suggests that physical activity (PA) is inversely and sedentarism positively related with cardiovascular disease risk. We performed a two-sample Mendelian randomization (MR) analysis to examine whether genetically predicted PA and sedentary behavior are related to coronary artery disease, myocardial infarction, and ischemic stroke.

Methods And Results: We used single nucleotide polymorphisms (SNPs) associated with self-reported moderate to vigorous PA (n = 17), accelerometer based PA (n = 7) and accelerometer fraction of accelerations > 425 milli-gravities (n = 7) as well as sedentary behavior (n = 6) in the UK Biobank as instrumental variables in a two sample MR approach to assess whether these exposures are related to coronary artery disease and myocardial infarction in the CARDIoGRAMplusC4D genome-wide association study (GWAS) or ischemic stroke in the MEGASTROKE GWAS. Read More

Lancet 2021 Mar;397(10280):1195-1203

Infectious Disease Department, Saint-Louis University Hospital, AP-HP, University of Paris, Paris, France.

Background: Shortening the duration of antibiotic therapy for patients admitted to hospital with community-acquired pneumonia should help reduce antibiotic consumption and thus bacterial resistance, adverse events, and related costs. We aimed to assess the need for an additional 5-day course of β-lactam therapy among patients with community-acquired pneumonia who were stable after 3 days of treatment.

Methods: We did this double-blind, randomised, placebo-controlled, non-inferiority trial (the Pneumonia Short Treatment [PTC]) in 16 centres in France. Read More

Front Genet 2021 9;12:608311. Epub 2021 Mar 9.

Department of Urology, Sir Run-Run Shaw Hospital College of Medicine, Zhejiang University, Hangzhou, China.

The relationship between serum uric acid (UA) levels and cancer risk remains controversial. Here, a two-sample Mendelian randomization analysis was performed to identify a causal effect of serum UA levels on cancer risk. Twenty-six single nucleotide polymorphisms strongly associated with serum UA levels were screened as genetic variants from large-scale meta-analysis data of a genome-wide association study of 110,347 European individuals. Read More

Alzheimers Res Ther 2021 03 25;13(1):64. Epub 2021 Mar 25.

Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.

Background: To explore the utility of the International Working Group (IWG)-1 criteria in recruitment for Alzheimer's disease (AD) clinical trials, we applied the more recently proposed research diagnostic criteria to individuals enrolled in a randomized controlled prevention trial (RCT) and assessed their disease progression.

Methods: The multinational LipiDiDiet RCT targeted 311 individuals with IWG-1 defined prodromal AD. Based on centrally analyzed baseline biomarkers, participants were classified according to the IWG-2 and National Institute on Aging-Alzheimer's Association (NIA-AA) 2011 and 2018 criteria. Read More

ESC Heart Fail 2021 Mar 23. Epub 2021 Mar 23.

Department of Clinical and Molecular Medicine, NTNU - Norwegian University of Science and Technology, Trondheim, Norway.

Aims: Whether an exercise training intervention is associated with reduction in long-term high-sensitivity cardiac troponin T (hs-cTnT) concentration (a biomarker of subclinical myocardial injury) in patients with heart failure with reduced ejection fraction (HFrEF) is unknown. The aims were to determine (i) the effect of a 12 week endurance exercise training intervention with different training intensities on hs-cTnT in stable patients with HFrEF (left ventricular ejection fraction ≤ 35%) and (ii) associations between hs-cTnT and peak oxygen uptake (VO ).

Methods And Results: In this sub-study of the SMARTEX-HF trial originally including 261 patients from nine European centres, 213 eligible patients were included after withdrawals and appropriate exclusions [19% women, mean age 61. Read More

Clin Epigenetics 2021 Mar 22;13(1):60. Epub 2021 Mar 22.

The Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA, 01702, USA.

Background: DNA methylation is a key epigenetic modification that can directly affect gene regulation. DNA methylation is highly influenced by environmental factors such as cigarette smoking, which is causally related to chronic obstructive pulmonary disease (COPD) and lung cancer. To date, there have been few large-scale, combined analyses of DNA methylation and gene expression and their interrelations with lung diseases. Read More

iScience 2021 Mar 27;24(3):102241. Epub 2021 Feb 27.

Laboratory of Cardiovascular Pathobiology, Quebec Heart and Lung Institute/Research Center, Department of Surgery, Laval University, 2725 Chemin Ste-Foy, G1V-4G5, Québec City, QC, Canada.

Genome-wide association studies for calcific aortic valve stenosis (CAVS) previously reported strong signal for noncoding variants at 1p21.2. Previous study using Mendelian randomization suggested that the locus controls the expression of encoding Palmdelphin (PALMD). Read More

J Med Internet Res 2021 Apr 9;23(4):e24639. Epub 2021 Apr 9.

Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, United States.

Background: Health information technology (IT) interventions to decrease readmissions for cirrhosis may be limited by patient-associated factors.

Objective: The aim of this study was to determine perspectives regarding adoption versus refusal of health IT interventions among patient-caregiver dyads.

Methods: Inpatients with cirrhosis and their caregivers were approached to participate in a randomized health IT intervention trial requiring daily contact with research teams via the Patient Buddy app. Read More

Breast Cancer Res Treat 2021 Mar 19. Epub 2021 Mar 19.

Department of Plastic and Reconstructive Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, 21205, USA.

Introduction: PlasmaBlade® is a thermal dissection device that may allow for improved perfusion of the mastectomy flap by limiting thermal injury. In this study we aim to compare the mastectomy flap perfusion using PlasmaBlade® versus traditional electrocautery.

Methods: Patients undergoing bilateral mastectomy with immediate breast reconstruction were recruited. Read More

J Am Coll Cardiol 2021 Mar;77(11):1397-1407

Baylor University Medical Center, Dallas, Texas, USA; Imperial College, London, United Kingdom.

Background: Mineralocorticoid receptor antagonists (MRAs) and sodium glucose co-transporter 2 inhibitors favorably influence the clinical course of patients with heart failure and reduced ejection fraction.

Objectives: This study sought to study the mutual influence of empagliflozin and MRAs in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction).

Methods: Secondary analysis that compared the effects of empagliflozin versus placebo in 3,730 patients with heart failure and a reduced ejection fraction, of whom 71% used MRAs at randomization. Read More

J Am Coll Cardiol 2021 Mar;77(11):1381-1392

Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists, University Hospital, University of Lorraine, Nancy, France.

Background: Investigators have hypothesized that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert diuretic effects that contribute to their ability to reduce serious heart failure events, and this action is particularly important in patients with fluid retention.

Objectives: This study sought to evaluate the effects of the SGLT2 inhibitor empagliflozin on symptoms, health status, and major heart failure outcomes in patients with and without recent volume overload.

Methods: This double-blind randomized trial compared the effects of empagliflozin and placebo in 3,730 patients with heart failure and a reduced ejection fraction, with or without diabetes. Read More

Contemp Clin Trials Commun 2021 Jun 16;22:100754. Epub 2021 Feb 16.

Department of Preventive Medicine, Division of Biostatistics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Covariate constrained randomization (CCR) is a method of controlling imbalance in important baseline covariates in cluster-randomized trials (CRT). We use simulated CRTs to investigate the performance (control of imbalance) of CCR relative to simple randomization (SR) under conditions of misspecification of the cluster-level variable used in the CCR algorithm. We use data from a Patient-Centered Outcomes Research Institute (PCORI)-funded CRT evaluating the Mothers and Babies (MB) intervention (AD-1507-31,473). Read More

JAMA Pediatr 2021 Mar 15. Epub 2021 Mar 15.

Division of Psychiatry, Imperial College London, London, United Kingdom.

Importance: Behavior problems are one of the most common mental health disorders in childhood and can undermine children's health, education, and employment outcomes into adulthood. There are few effective interventions for early childhood.

Objective: To test the clinical effectiveness of a brief parenting intervention, the Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD), in reducing behavior problems in children aged 12 to 36 months. Read More

Trials 2021 Mar 10;22(1):202. Epub 2021 Mar 10.

St. Michael's Hospital, Applied Health Research Centre, Li Ka Shing Knowledge Institute, University of Toronto, Toronto, Canada.

Objectives: To determine the effect of therapeutic anticoagulation, with low molecular weight heparin (LMWH) or unfractionated heparin (UFH, high dose nomogram), compared to standard care in hospitalized patients admitted for COVID-19 with an elevated D-dimer on the composite outcome of intensive care unit (ICU) admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death up to 28 days.

Trial Design: Open-label, parallel, 1:1, phase 3, 2-arm randomized controlled trial PARTICIPANTS: The study population includes hospitalized adults admitted for COVID-19 prior to the development of critical illness. Excluded individuals are those where the bleeding risk or risk of transfusion would generally be considered unacceptable, those already therapeutically anticoagulated and those who have already have any component of the primary composite outcome. Read More

Trials 2021 Mar 6;22(1):190. Epub 2021 Mar 6.

Center on Aging and Health, Division of Geriatric Medicine and Gerontology, Johns Hopkins University, 2024 East Monument Street, Baltimore, MD, 21205, USA.

Background: Pragmatic trials often consist of cluster-randomized controlled trials (C-RCTs), where staff of existing clinics or sites deliver interventions and randomization occurs at the site level. Covariate-constrained randomization (CCR) methods are often recommended to minimize imbalance on important site characteristics across intervention and control arms because sizable imbalances can occur by chance in simple randomizations when the number of units to be randomized is relatively small. CCR methods involve multiple random assignments initially, an assessment of balance achieved on site-level covariates from each randomization, and the final selection of an allocation that produces acceptable balance. Read More

Trials 2021 Mar 5;22(1):186. Epub 2021 Mar 5.

Department of Obstetrics & Gynecology, School of Medicine, University of North Carolina, Chapel Hill, USA.

Background: Depression and anxiety impact up to 1 in 5 pregnant and postpartum women worldwide. Yet, as few as 20% of these women are treated with frontline interventions such as evidence-based psychological treatments. Major barriers to uptake are the limited number of specialized mental health treatment providers in most settings, and problems with accessing in-person care, such as childcare or transportation. Read More

J Am Coll Cardiol 2021 Mar;77(9):1182-1193

Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

Background: Inclisiran is a double-stranded small interfering RNA that suppresses proprotein convertase subtilisin-kexin type 9 (PCSK9) translation in the liver, leading to sustained reductions in low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipoproteins with twice-yearly dosing.

Objectives: The purpose of this study was to conduct a patient-level pooled analysis from 3 phase 3 studies of inclisiran.

Methods: Participants with heterozygous familial hypercholesterolemia (ORION-9 [Trial to Evaluate the Effect of Inclisiran Treatment on Low Density Lipoprotein Cholesterol (LDL-C) in Subjects With Heterozygous Familial Hypercholesterolemia (HeFH)]), atherosclerotic cardiovascular disease (ASCVD) (ORION-10 [Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol]), or ASCVD and ASCVD risk equivalents (ORION-11 [Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol]) taking maximally tolerated statin therapy, with or without other LDL-C-lowering agents, were randomly assigned in a 1:1 ratio to receive either inclisiran or placebo, administered by subcutaneous injection on day 1, day 90, and every 6 months thereafter for 540 days. Read More

Pilot Feasibility Stud 2021 Mar 1;7(1):61. Epub 2021 Mar 1.

R Adams Cowley Shock Trauma Center, Department of Orthopedics, University of Maryland School of Medicine, Baltimore, MD, USA.

Background: Preoperative antiseptic skin solutions are used prior to most surgical procedures; however, there is no definitive research comparing infection-related outcomes following use of the various solutions available to orthopedic trauma surgeons. The objective of this pilot study was to test the feasibility of a cluster randomized crossover trial that assesses the comparative effectiveness of a 10% povidone-iodine solution versus a 4% chlorhexidine gluconate solution for the management of open fractures.

Methods: Two orthopedic trauma centers participated in this pilot study. Read More

Br J Surg 2021 Jan;108(1):40-48

Breast Clinic, Royal Perth Hospital, Perth, Western Australia, Australia.

Background: Previous studies have suggested improved efficiency and patient outcomes with 125I seed compared with hookwire localization (HWL) in breast-conserving surgery, but high-level evidence of superior surgical outcomes is lacking. The aim of this multicentre pragmatic RCT was to compare re-excision and positive margin rates after localization using 125I seed or hookwire in women with non-palpable breast cancer.

Methods: Between September 2013 and March 2018, women with non-palpable breast cancer eligible for breast-conserving surgery were assigned randomly to preoperative localization using 125I seeds or hookwires. Read More

N Engl J Med 2021 Feb 25. Epub 2021 Feb 25.

From Baylor College of Medicine, Houston (I.O.R.); James J. Peters Veterans Affairs Medical Center, Bronx, and Icahn School of Medicine at Mount Sinai, New York - both in New York (N.B.); eStudy Site, Chula Vista (M.W.), Genentech, South San Francisco (M.B., L.T.), and the University of California, San Diego, La Jolla (A.M.) - all in California; Hackensack Meridian School of Medicine and Hacksensack University Medical Center, Hackensack, NJ (R.C.G.); Intermountain Healthcare, Salt Lake City (B.D.H.); Royal Free Hospital (S.B.) and Imperial College London (N.C., T.Y.), London, Leeds Teaching Hospitals NHS Trust and National Institute for Health Research-Leeds Biomedical Research Centre, Leeds (S.S.), North Manchester General Hospital, Manchester (A.U.), and Roche Products, Welwyn Garden City (S.D., E.G., B.M., H.S.) - all in the United Kingdom; the University of Massachusetts Medical School-Baystate, Springfield (D.S.); Rush University Medical Center, Chicago (M.S.A.); Denver Health Medical Center, Denver (I.S.D.), and the University of Colorado, Anschutz School of Medicine, Aurora (I.S.D.); University Health Network, Toronto (L.D.S.); Hospital Universitario HM Sanchinarro, Centro Integral, Oncológico Clara Campal and Departamento de Ciencias Médicas Clínicas, Facultad de Medicina, Universidad CEU San Pablo, Madrid (A.C.G.); and the University of Miami Miller School of Medicine, Miami (D.J.D.L.Z.).

Background: Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials. Read More

Bone Jt Open 2021 Feb;2(2):72-78

Trauma and Orthopaedics, Northumbria Healthcare NHS Foundation Trust, Ashington, UK.

Aims: Patients receiving cemented hemiarthroplasties after hip fracture have a significant risk of deep surgical site infection (SSI). Standard UK practice to minimize the risk of SSI includes the use of antibiotic-loaded bone cement with no consensus regarding type, dose, or antibiotic content of the cement. This is the protocol for a randomized clinical trial to investigate the clinical and cost-effectiveness of high dose dual antibiotic-loaded cement in comparison to low dose single antibiotic-loaded cement in patients 60 years and over receiving a cemented hemiarthroplasty for an intracapsular hip fracture. Read More

Nat Commun 2021 02 24;12(1):1279. Epub 2021 Feb 24.

Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Doha, Qatar.

Blood circulating proteins are confounded readouts of the biological processes that occur in different tissues and organs. Many proteins have been linked to complex disorders and are also under substantial genetic control. Here, we investigate the associations between over 1000 blood circulating proteins and body mass index (BMI) in three studies including over 4600 participants. Read More

Mol Divers 2021 Feb 24. Epub 2021 Feb 24.

Department of Medicinal Chemistry, School of Pharmaceutical Science, NanChang University, Nanchang, 330006, China.

Histone deacetylases (HDACs) were highlighted as a novel category of anticancer targets. Several HDACs inhibitors were approved for therapeutic use in cancer treatment. Comparatively, receptor-dependent 4D-QSAR, LQTA-QSAR, is a new approach which generates conformational ensemble profiles of compounds by molecular dynamics simulations at binding site of enzyme. Read More