Meta-analysis of clinical trials in the 2020s and beyond: a paradigm shift needed.

Background: A peer-reviewed meta-analysis methods article mathematically proved that mainstream random-effects methods, "weights inversely proportional to the estimated variance," are flawed and can lead to faulty public health recommendations. Because the arguments causing this off-label (unproven) use of mainstream practices were subtle, changing these practices will require much clearer explanations that can be grasped by clinical and translational scientists. There are five assumptions underlying the mainstream's derivation of its statistical properties.

Management of Cardiovascular Disease in Kidney Disease Study: Rationale and Design.

Introduction: Atherosclerosis, inflammation, and vascular stiffness are prominent interrelated risk factors contributing to the high incidence of cardiovascular disease (CVD) in patients with CKD. Conventional CVD management strategies in CKD largely target atherosclerotic CVD and have had a limited impact on the cardiovascular mortality in this population. Multiple in vivo and in vitro studies and epidemiological evidence from the rheumatologic cohorts have shown that low-dose hydroxychloroquine has beneficial effects on inflammation, endothelial function, insulin sensitivity, and metabolic syndrome.

Medication Use for ADHD and the Risk of Driving Citations and Crashes Among Teenage Drivers: A Population-Based Cohort Study.

To evaluate the real-world effectiveness of ADHD medications on adverse driving outcomes in teenage drivers with ADHD. We retrospectively followed 15- to 20-year-old ADHD patients with valid driver's license to compare the risk for crashes and citations between periods with and without ADHD medication use, using Florida Medicaid records linked to Department of Motor Vehicles data from 1999 to 2004. Patient-level demographic, clinical, and driver licensing characteristics as well as county-level crash and traffic statistics were adjusted in Cox models.

Randomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL: Children's Oncology Group Studies P9904 and P9905.

The delayed intensification (DI) enhanced outcome for patients with acute lymphoblastic leukemia (ALL) treated on BFM 76/79 and CCG 105 after a prednisone-based induction. Childrens Oncology Group protocols P9904/9905 evaluated DI via a post-induction randomization for eligible National Cancer Institute (NCI) standard (SR) and high-risk (HR) patients. A second randomization compared intravenous methotrexate (IV MTX) as a 24- (1 g/m) vs.

Elevated serum insulin-like growth factor 1 in recurrent aphthous stomatitis.

Over 100 million Americans experience recurrent aphthous stomatitis (RAS) at some point in life. To develop targeted drugs for RAS treatment, it is critical to identify its etiology. We determined if serum insulin-like growth factor 1 (IGF-1) and related factors are associated with RAS, because both RAS prevalence and IGF-1 are highest during puberty.

Withdrawn: How to investigate an accused serial sexual harasser.

Withdrawal: Shuster, JJ, Handler, M. How to investigate an accused serial sexual harasser. Statistics in Medicine.

Clinical and histologic features of adults with alpha-1 antitrypsin deficiency in a non-cirrhotic cohort.

Background & Aims: Alpha-1 antitrypsin deficiency (AATD) is an uncommonly recognized cause of liver disease in adults, with descriptions of its natural history limited to case series and patient-reported data from disease registries. Liver pathology is limited to selected patients or unavailable. Therefore, we aimed to determine the prevalence and severity of liver fibrosis in an adult AATD population who were not known to have cirrhosis, while defining risk factors for fibrosis and testing non-invasive markers of disease.

Adding electrical stimulation during standard rehabilitation after stroke to improve motor function. A systematic review and meta-analysis.

Background: Clinical studies have shown that sensory input improves motor function when added to active training after neurological injuries in the spinal cord.

Objective: We aimed to determine the effect on motor function of extremities of adding an electrical sensory modality without motor recruitment before or with routine rehabilitation for hemiparesis after stroke by a comprehensive systematic review and meta-analysis.

Methods: We searched databases including MEDLINE via PubMed and the Cochrane Central Register of Controlled Trials from 1978 to the end of November 2017 for reports of randomized controlled trials or controlled studies of patients with a clinical diagnosis of stroke who underwent 1) transcutaneous electrical nerve stimulation (TENS) or peripheral electromyography-triggered sensory stimulation over a peripheral nerve and associated muscles or 2) acupuncture to areas that produced sensory effects, without motor recruitment, along with routine rehabilitation.

Relationship Between Patient Satisfaction And Physician Characteristics.

Background: Physician care influences patient satisfaction. Inherent physician attributes may also affect scores.

Objective: To determine the relationship between physician characteristics and patient satisfaction regarding physician care and communication.

Development of a novel observer reported outcome tool as the primary efficacy outcome measure for a rare disease randomized controlled trial.

We developed an Observer-Reported Outcome (ObsRO) survey instrument to be applied in a multicenter, placebo-controlled, crossover randomized controlled trial of dichloroacetate in children with pyruvate dehydrogenase complex deficiency. The instrument quantifies a subject's at-home level of functionality, as reported by a parent/caregiver, who were instrumental in providing the clinical descriptors and domains that formed the instrument's content. Feasibility testing of the ObsRO tool showed it to be easy to use and comprehensive in capturing the major clinical functional limitations of affected children and requires less than 5min for a parent/caregiver to complete daily.

Carbon dioxide insufflation is associated with increased serrated polyp detection rate when compared to room air insufflation during screening colonoscopy.

Background And Study Aims: Sessile serrated adenomas (SSA) and traditional serrated adenomas (TSA) have been increasingly recognized as precursors of colorectal cancer. The aim of this study was to compare the effect of carbon dioxide insufflation (CO I) vs. room air insufflation (AI) on serrated polyp detection rate (SPDR) and to identify factors associated with SPDR.

Web-based Health Information Seeking and eHealth Literacy among Patients Living with Chronic Obstructive Pulmonary Disease (COPD).

Many people living with Chronic Obstructive Pulmonary Disease (COPD) have low general health literacy; however, there is little information available on these patients' eHealth literacy, or their ability to seek, find, understand, and appraise online health information and apply this knowledge to address or solve disease-related health concerns. A nationally representative sample of patients registered in the COPD Foundation's National Research Registry (N = 1,270) was invited to complete a web-based survey to assess socio-demographic (age, gender, marital status, education), health status (generic and lung-specific health-related quality of life), and socio-cognitive (social support, self-efficacy, COPD knowledge) predictors of eHealth literacy, measured using the 8-item eHealth literacy scale (eHEALS). Over 50% of the respondents (n = 176) were female (n = 89), with a mean age of 66.

Comparing glaucomatous disc change using stereo disc viewing and the MatchedFlicker programme in glaucoma experts and trainees.

Background/aims: The objective of this study is to evaluate the accuracy and speed of trainees and experienced glaucoma specialists using the MatchedFlicker software against the manual examination of stereoscopic disc photographs for detecting glaucomatous optic disc change.

Methods: Three experienced glaucoma specialists, two resident ophthalmologists and one glaucoma fellow from multiple institutions independently evaluated the same 140 image pairs from 100 glaucomatous/ocular hypertensive eyes using a handheld stereo viewer and the MatchedFlicker programme. Fifty had progression to glaucoma as determined by the Ocular Hypertension Treatment Study (OHTS) Optic Disc Reading Group and endpoint committee, and 50 more were negative controls for progression with photos taken a few minutes apart.

Linear combinations come alive in crossover designs.

Before learning anything about statistical inference in beginning service courses in biostatistics, students learn how to calculate the mean and variance of linear combinations of random variables. Practical precalculus examples of the importance of these exercises can be helpful for instructors, the target audience of this paper. We shall present applications to the "1-sample" and "2-sample" methods for randomized short-term 2-treatment crossover studies, where patients experience both treatments in random order with a "washout" between the active treatment periods.

A framework for the meta-analysis of Bland-Altman studies based on a limits of agreement approach.

Bland-Altman method comparison studies are common in the medical sciences and are used to compare a new measure to a gold-standard (often costlier or more invasive) measure. The distribution of these differences is summarized by two statistics, the 'bias' and standard deviation, and these measures are combined to provide estimates of the limits of agreement (LoA). When these LoA are within the bounds of clinically insignificant differences, the new non-invasive measure is preferred.

The Association of Health Literacy With Preventable Emergency Department Visits: A Cross-sectional Study.

Background: Policymakers argue that emergency department (ED) visits for conditions preventable with high-quality outpatient care contribute to waste in the healthcare system. However, access to ambulatory care is uneven, especially for vulnerable populations like minorities, the poor, and those with limited health literacy. The impact of limited health literacy on ED visits that are preventable with timely, high-quality ambulatory care is unknown.

Peripheral Blood Cytokine Levels After Acute Myocardial Infarction: IL-1β- and IL-6-Related Impairment of Bone Marrow Function.

Rationale: Intracoronary infusion of bone marrow (BM) mononuclear cells after acute myocardial infarction (AMI) has led to limited improvement in left ventricular function. Although experimental AMI models have implicated cytokine-related impairment of progenitor cell function, this response has not been investigated in humans.

Objective: To test the hypothesis that peripheral blood (PB) cytokines predict BM endothelial progenitor cell colony outgrowth and cardiac function after AMI.

A Patient-Centered Emergency Department Management Strategy for Sickle-Cell Disease Super-Utilizers.

Introduction: A subpopulation of sickle-cell disease patients, termed super-utilizers, presents frequently to emergency departments (EDs) for vaso-occlusive events and may consume disproportionate resources without broader health benefit. To address the healthcare needs of this vulnerable patient population, we piloted a multidisciplinary intervention seeking to create and use individualized patient care plans that alter utilization through coordinated care. Our goals were to assess feasibility primarily, and to assess resource use secondarily.

Efficacy and retention of Basic Life Support education including Automated External Defibrillator usage during a physical education period.

The American Heart Association (AHA) advocates for CPR education as a requirement of secondary school curriculum. Unfortunately, many states have not adopted CPR education. Our aim was to investigate a low-cost, time effective method to educate students on Basic Life Support (BLS), including reeducation.

Serum Trypsinogen Levels in Type 1 Diabetes.

Objective: The pancreas in type 1 diabetes exhibits decreased size (weight/volume) and abnormal exocrine morphology. Serum trypsinogen levels are an established marker of pancreatic exocrine function. As such, we hypothesized that trypsinogen levels may be reduced in patients with pre-type 1 diabetes and type 1 diabetes compared with healthy control subjects.

Does carbon dioxide insufflation impact adenoma detection rate? A single-center retrospective analysis.

Carbon dioxide (CO) has been associated with reduced post-procedural pain and improved patient satisfaction when compared to air insufflation (AI). The effect of CO insufflation (COI) on the adenoma detection rate (ADR) remains unclear. The aims of this study are to compare ADR in patients undergoing screening colonoscopy with AI vs.

Therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy is associated with short-term reduction of seizures after discharge from the neonatal intensive care unit.

Introduction: Therapeutic hypothermia for the treatment of moderate to severe neonatal hypoxic ischemic encephalopathy has been shown to reduce death and disability, but the effects on seizures after discharge from the Neonatal ICU are not known.

Methods: A retrospective cohort study was conducted involving 56 neonates admitted to the Neonatal ICU at Children's Hospital of Orange County, CA from January 1, 2007 to September 1, 2013 with hypoxic ischemic encephalopathy who met criteria for selective brain cooling. Fifteen patients received supportive care.

The effect of EHR-integrated patient-reported outcomes on satisfaction with chronic pain care.

Objectives: Given its complexity, chronic noncancer pain presents an opportunity to use health information technology (IT) to improve care experiences. The objective of this study was to assess whether integrating patient-reported outcomes (PROs) data in an electronic health record (EHR) affects provider and patient satisfaction with chronic noncancer pain care.

Study Design: We conducted a pragmatic cluster randomized trial involving 4 family medicine clinics.

Antithymocyte Globulin Plus G-CSF Combination Therapy Leads to Sustained Immunomodulatory and Metabolic Effects in a Subset of Responders With Established Type 1 Diabetes.

Low-dose antithymocyte globulin (ATG) plus pegylated granulocyte colony-stimulating factor (G-CSF) preserves β-cell function for at least 12 months in type 1 diabetes. Herein, we describe metabolic and immunological parameters 24 months following treatment. Patients with established type 1 diabetes (duration 4-24 months) were randomized to ATG and pegylated G-CSF (ATG+G-CSF) (N = 17) or placebo (N = 8).

Trauma Simulation Training Increases Confidence Levels in Prehospital Personnel Performing Life-Saving Interventions in Trauma Patients.

Introduction. Limited evidence is available on simulation training of prehospital care providers, specifically the use of tourniquets and needle decompression. This study focused on whether the confidence level of prehospital personnel performing these skills improved through simulation training.