Visualization tool of variable selection in bias-variance tradeoff for inverse probability weights.

Purpose: Inversed probability weighted (IPW) estimators are commonly used to adjust for time-fixed or time-varying confounders. However, in high-dimensional settings, including all identified confounders may result in unstable weights leading to higher variance. We aimed to develop a visualization tool demonstrating the impact of each confounder on the bias and variance of IPW estimates, as well as the propensity score overlap.

Considerations for using distributed research networks to conduct aspects of randomized trials.

Stakeholders in the clinical research enterprise are aligned around the need to make clinical research in general, and randomized controlled trials in particular, more meaningful and efficient. To that end, we have built distributed research networks (DRNs) for the Sentinel System, the National Institutes of Health (NIH) Collaboratory, and the National Patient-Centered Clinical Research Network (PCORnet). DRNs reuse electronic health record (EHR) and claims data for research.

Recording transcriptional histories using Record-seq.

It is difficult to elucidate the transcriptional history of a cell using current experimental approaches, as they are destructive in nature and therefore describe only a moment in time. To overcome these limitations, we recently established Record-seq, a technology that enables transcriptional recording by CRISPR spacer acquisition from RNA. The recorded transcriptomes are recovered by SENECA, a method that selectively amplifies expanded CRISPR arrays, followed by deep sequencing.

The Limited Utility of Ranking Hospitals Based on Their Colon Surgery Infection Rates.

Background: The Centers for Medicare and Medicaid Services (CMS) use colon surgical site infection (SSI) rates to rank hospitals and apply financial penalties. The CMS' risk-adjustment model omits potentially impactful variables that might disadvantage hospitals with complex surgical populations.

Methods: We analyzed adult patients who underwent colon surgery within facilities associated with HCA Healthcare from 2014 to 2016.

Acetaminophen use during pregnancy and the risk of attention deficit hyperactivity disorder: A causal association or bias?

Background: The association between acetaminophen use during pregnancy and the development of attention deficit hyperactivity disorder (ADHD) in the offspring may be due to bias.

Objectives: The primary objective was to assess the role of potential unmeasured confounding in the estimation of the association between acetaminophen use during pregnancy and the risk of ADHD, through bias analysis. The secondary objective was to assess the roles of selection bias and exposure misclassification.

Differential Expression in Testis and Liver Transcriptomes from Four Species of Peromyscus (Rodentia: Cricetidae).

The genus Peromyscus represents a rapidly diverged clade of Cricetid rodents that contains multiple cryptic species and has a propensity for morphologic conservation across its members. The unresolved relationships in previously proposed phylogenies reflect a suspected rapid adaptive radiation. To identify functional groups of genes that may be important in reproductive isolation in a reoccurring fashion across the Peromyscus phylogeny, liver and testis transcriptomes from four species (P.

Adaptive Treatment Strategies With Survival Outcomes: An Application to the Treatment of Type 2 Diabetes Using a Large Observational Database.

Sequences of treatments that adapt to a patient's changing condition over time are often needed for the management of chronic diseases. An adaptive treatment strategy (ATS) consists of personalized treatment rules to be applied through the course of a disease that input the patient's characteristics at the time of decision-making and output a recommended treatment. An optimal ATS is the sequence of tailored treatments that yields the best clinical outcome for patients sharing similar characteristics.

Group sample sizes in nonregulated health care intervention trials described as randomized controlled trials were overly similar.

Objectives: We evaluated whether sample sizes in different arms of two-arm parallel group randomized controlled trials of nonregulated interventions were systematically closer in size than would plausibly occur by chance if simple randomization had been applied.

Study Design And Setting: We searched PubMed for trials of nonregulated health care interventions that did not report using restricted randomization from journals in behavioral sciences and psychology, nursing, nutrition and dietetics, rehabilitation, and surgery. We emailed trial authors to clarify randomization procedures.

Ondansetron use in the first trimester of pregnancy and the risk of neonatal ventricular septal defect.

Background: Literature is divided regarding the risk of neonatal ventricular septal defect (VSD) associated with first trimester ondansetron use in pregnancy.

Methods: We evaluated the risk of VSD associated with first trimester exposure to intravenous or oral ondansetron in 33 677 deliveries at Magee-Womens Hospital in Pittsburgh, PA (2006-2014). Using log-binomial regression, we evaluated the risk: (1) in the full cohort, (2) using propensity score designs with both matching and inverse probability weighting and (3) utilizing clustered trajectory analysis evaluating the role of dose.

Primary Care Prescriptions of Potentially Nephrotoxic Medications in Children with CKD.

Background And Objectives: Pediatric CKD management focuses on limiting kidney injury, including avoiding nephrotoxic medications. Nephrotoxic medication prescription practices for children with CKD are unknown. Our objective was to determine the prevalence and rates of primary care prescriptions for potentially nephrotoxic medications in children with CKD versus without CKD.

Protocol for a partially nested randomized controlled trial to evaluate the effectiveness of the Scleroderma Patient-centered Intervention Network Support Group Leader EDucation (SPIN-SSLED) Program.

Background: Some people with rare diseases rely on peer-led support groups for disease-specific education and emotional and practical support. Systemic sclerosis (SSc), or scleroderma, is a rare autoimmune connective tissue disease. Many people with SSc cannot access support groups, and, when support groups exist, they may not be sustained due to challenges that could be addressed via leader training.

Incidence of statin use in older adults with and without cardiovascular disease and diabetes mellitus, January 2008- March 2018.

Background: Data from randomized controlled trials and observational studies on older adults who take statins for primary prevention of atherosclerotic cardiovascular disease are limited. To determine the incidence of statin use in older adults with and without cardiovascular disease (CVD) and/or diabetes (DM), we conducted a descriptive observational study.

Methods: The cohort consisted of health plan members in the NIH Collaboratory Distributed Research Network aged >75 years who had continuous drug and medical benefits for ≥183 days during the study period, January 1, 2008- March 31, 2018.

Scleroderma Patient-centered Intervention Network-Scleroderma Support group Leader EDucation (SPIN-SSLED) program: non-randomised feasibility trial.

Objectives: The Scleroderma Patient-centered Intervention Network-Scleroderma Support group Leader EDucation (SPIN-SSLED) Programme was designed to improve confidence and self-efficacy and to reduce burden for support group leaders. Objectives were to (1) evaluate feasibility of programme delivery, including required resources, management issues and scientific aspects (eg, performance of outcome measures) and (2) assess user satisfaction and identify any modifications needed to improve programme content or delivery based on participant feedback.

Design: Non-randomised feasibility trial.

Training people with dementia/cognitive impairment and their carers in the use of web-based supportive technologies (Innovative practice).

Little is known about the training and support people with dementia and their carers need to use digital solutions. This paper shares learning from a bespoke programme that successfully trained people with dementia or mild cognitive impairment and their informal carers to use a social networking website. This work was undertaken as part of the European Horizon 2020 Caregiverspro-mmd trial (ISRCTN15654731).

Implementation of Off-Site Integrated Care for Children: A Scoping Review.

Background: As an alternative to co-located integrated care, off-site integration (partnerships between primary care and non-embedded specialty mental health providers) can address the growing need for pediatric mental health services. Our goal is to review the existing literature on implementing off-site pediatric integrated care.

Methods: We systematically searched the literature for peer-reviewed publications on off-site pediatric integrated care interventions.

The CAREGIVERSPRO-MMD Platform as an Online Informational and Social Support Tool for People Living With Memory Problems and Their Carers: An Evaluation of User Engagement, Usability and Usefulness.

People living with dementia or cognitive impairment (PwD) and their carers often have unmet needs for informational and social support postdiagnosis. Web-based platforms have the potential to address these needs, although few have been developed for use by both PwD and carers. The CAREGIVERSPRO-MMD platform was developed to provide both user groups with informational and peer-to-peer social support.

Reproducing Protocol-Based Studies Using Parameterizable Tools-Comparison of Analytic Approaches Used by Two Medical Product Surveillance Networks.

The US Sentinel System and the Canadian Network for Observational Drug Effect Studies (CNODES) are two medical product safety surveillance networks. Using Sentinel's preprogrammed, parameterizable analytic tools, we reproduced two protocol-based studies conducted by CNODES to assess the risks of acute pancreatitis and heart failure (HF) associated with the use of incretin-based drugs, compared with use of ≥ 2 oral hypoglycemic agents. Results from the replication new-user cohort analyses aligned with those from the CNODES nested case-control studies.

Symptoms of Secondary Hyperparathyroidism in Patients Receiving Maintenance Hemodialysis: A Prospective Cohort Study.

Rationale & Objective: Although multiple lines of evidence suggest a negative impact of secondary hyperparathyroidism on patients with kidney failure treated by hemodialysis, it is uncertain whether patients can detect associated symptoms. The objective was to determine whether changes in parathyroid hormone (PTH) levels are associated with changes in symptoms within this patient population.

Study Design: Prospective cohort.

Association of Open Approach vs Laparoscopic Approach With Risk of Surgical Site Infection After Colon Surgery.

Importance: Colon surgery is associated with a high rate of surgical site infection (SSI), and there is an urgent need for strategies to reduce infection rates.

Objective: To assess whether laparoscopic colon surgery is associated with a lower surgical site infection rate than open-approach laparoscopy, especially in patients with medically complex conditions.

Design, Setting, And Participants: This cohort study used previously validated diagnosis and procedure codes from Medicare beneficiaries who underwent colon surgery from January 1, 2009, to November 30, 2013.

Mapping human cell phenotypes to genotypes with single-cell genomics.

The cumulative activity of all of the body's cells, with their myriad interactions, life histories, and environmental experiences, gives rise to a condition that is distinctly human and specific to each individual. It is an enduring goal to catalog our human cell types, to understand how they develop, how they vary between individuals, and how they fail in disease. Single-cell genomics has revolutionized this endeavor because sequencing-based methods provide a means to quantitatively annotate cell states on the basis of high-information content and high-throughput measurements.

The Critical Importance of Asking Good Questions: The Role of Epidemiology Doctoral Training Programs.

Epidemiologic methods have advanced tremendously in the last several decades. As important as they are, even the most sophisticated approaches are unable to provide meaningful answers when the user lacks a clear study question. Yet, instructors have more and more resources on how to conduct studies and analyze data but few resources on how to ask clearly defined study questions that will guide those methods.

Estimation of high-dimensional propensity scores with multiple exposure levels.

Purpose: Little information is available on the performance of high-dimensional propensity scores (HDPS) in settings with more than two exposure levels. Our objective was to adapt the HDPS algorithm to allow for the inclusion of multilevel treatments and compare estimates obtained via this approach with those obtained via pairwise comparisons in a case study using real-world data.

Methods: We conducted a retrospective cohort study of cardiovascular events associated with three smoking cessation drugs (varenicline, bupropion, nicotine replacement therapy [NRT]) using the Clinical Practice Research Datalink.