Effect of probiotics on multi-resistant organism colonisation in persons with spinal cord injury: secondary outcome of ProSCIUTTU, a randomised placebo-controlled trial.

Study Design: Randomised double-blind placebo-controlled trial.

Objectives: Multi-resistant organism (MRO) colonisation is common in people with SCI. We aimed to determine whether Lactobacillus reuteri RC-14 + Lactobacillus GR-1 (RC14-GR1) and/or Lactobacillus rhamnosus GG + Bifidobacterium BB-12 (LGG-BB12) are effective in preventing or clearing MRO colonisation.

Interventions and Operations 5 Years After Bariatric Surgery in a Cohort From the US National Patient-Centered Clinical Research Network Bariatric Study.

Importance: Additional data comparing longer-term problems associated with various bariatric surgical procedures are needed for shared decision-making.

Objective: To compare the risks of intervention, operation, endoscopy, hospitalization, and mortality up to 5 years after 2 bariatric surgical procedures.

Design, Setting, And Participants: Adults who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between January 1, 2005, and September 30, 2015, within the National Patient-Centered Clinical Research Network.

Evaluation of the US Food and Drug Administration Sentinel Analysis Tools Using a Comparator with a Different Indication: Comparing the Rates of Gastrointestinal Bleeding in Warfarin and Statin Users.

Background: The US Food and Drug Administration's Sentinel System was established to monitor safety of regulated medical products. Sentinel investigators identified known associations between drugs and adverse events to test reusable analytic tools developed for Sentinel. This test case used a comparator with a different indication.

Characterising and predicting persistent high-cost utilisers in healthcare: a retrospective cohort study in Singapore.

Objective: We aim to characterise persistent high utilisers (PHUs) of healthcare services, and correspondingly, transient high utilisers (THUs) and non-high utilisers (non-HUs) for comparison, to facilitate stratifying HUs for targeted intervention. Subsequently we apply machine learning algorithms to predict which HUs will persist as PHUs, to inform future trials testing the effectiveness of interventions in reducing healthcare utilisation in PHUs.

Design And Setting: This is a retrospective cohort study using administrative data from an Academic Medical Centre (AMC) in Singapore.

Right-Site Care Programme with a community-based family medicine clinic in Singapore: secondary data analysis of its impact on mortality and healthcare utilisation.

Objective: Stable patients with chronic conditions could be appropriately cared for at family medicine clinics (FMC) and discharged from hospital specialist outpatient clinics (SOCs). The Right-Site Care Programme with Frontier FMC emphasised care organised around patients in community rather than hospital-based providers, with one identifiable primary provider. This study evaluated impact of this programme on mortality and healthcare utilisation.

Analytic and Data Sharing Options in Real-World Multidatabase Studies of Comparative Effectiveness and Safety of Medical Products.

A wide range of analytic and data sharing options are available in nonexperimental multidatabase studies designed to assess the real-world benefits and risks of medical products. Researchers often consider six scientific domains when choosing among these options-study design, exposure type, outcome type, covariate summarization technique, covariate adjustment method, and data sharing approach. This article reviews available analytic and data sharing options and discusses key scientific and practical considerations when choosing among these options in multidatabase studies of comparative effectiveness and safety of medical products.

Larynx-preserving reconstruction after extended base of the tongue resection.

Background: As the base of the tongue (BOT) plays essential roles in speech and swallowing, surgical resection of BOT cancer is typically avoided. Moreover, standard reconstructive procedures for larynx-preserving BOT defects have not yet been established. We performed immediate flap reconstruction after wide resection of BOT cancer with laryngeal preservation.

Relationship between immune-related adverse events and the long-term outcomes in recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab.

Objectives: Immune-related adverse events (irAEs) have been shown to be associated with higher antitumor responses and a clinical benefit in non-small cell lung carcinoma, renal cell carcinoma, and melanoma patients. However, little is known regarding the association between irAEs and the clinical effect of nivolumab for recurrent/metastatic head and neck squamous cell carcinoma (R/MHNSCC).

Materials And Methods: We evaluated 108 patients treated with nivolumab for R/MHNSCC at 2 participating institutions.

Understanding utilization patterns of biologics and biosimilars in the United States to support postmarketing studies of safety and effectiveness.

Purpose: To describe utilization of filgrastim and infliximab, the first two products with biosimilars approved in the United States.

Methods: We identified use of filgrastim (reference, tbo-filgrastim, and filgrastim-sndz) and infliximab (reference, infliximab-dyyb, and infliximab-abda) in the Sentinel Distributed Database using Healthcare Common Procedure Coding System (HCPCS) codes and National Drug Codes (NDCs) from January 2015 to August 2018. We calculated the proportion of use by code type and assessed uptake over time.

Privacy-protecting estimation of adjusted risk ratios using modified Poisson regression in multi-center studies.

Background: Multi-center studies can generate robust and generalizable evidence, but privacy considerations and legal restrictions often make it challenging or impossible to pool individual-level data across data-contributing sites. With binary outcomes, privacy-protecting distributed algorithms to conduct logistic regression analyses have been developed. However, the risk ratio often provides a more transparent interpretation of the exposure-outcome association than the odds ratio.

Use of Antidiabetic drugs during pregnancy among U.S. women with Livebirth deliveries in the Mini-Sentinel system.

Background: As the prevalence of diabetes mellitus increases in the population, the exposure to antidiabetic drugs (ADDs) during pregnancies is expected to grow, as has been seen over the last decade. The objective of this study was to estimate the prevalence of ADD use during pregnancy among women in the Mini-Sentinel Distributed Database (MSDD) who delivered a liveborn infant.

Methods: We identified qualifying livebirth pregnancies among women aged 10 to 54 years in the MSDD from 2001 to 2013.

Clinical features and treatment outcomes of Hodgkin lymphoma: A retrospective review in a Malaysian tertiary hospital.

Background: Classical Hodgkin lymphoma (cHL) is a clinicopathologically unique, aggressive lymphoma arising from germinal center B-cells and is one of the most curable hematological malignancies. This study aimed to determine the clinical course, treatment regimens, response rates, and survival data of patients diagnosed with cHL in a tertiary center.

Methods: A retrospective review was conducted to include patients with a diagnosis of cHL from 2013 to 2017.

Sylvatic dengue virus type 4 in Aedes aegypti and Aedes albopictus mosquitoes in an urban setting in Peninsular Malaysia.

Dengue fever is endemic in Malaysia, contributing to significant economic and health burden in the country. Aedes aegypti and Ae. albopictus are the main vectors of the dengue virus (DENV), which circulates in sylvatic and human transmission cycles and has been present in Malaysia for decades.

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.

Privacy-protecting multivariable-adjusted distributed regression analysis for multi-center pediatric study.

Background: Privacy-protecting analytic approaches without centralized pooling of individual-level data, such as distributed regression, are particularly important for vulnerable populations, such as children, but these methods have not yet been tested in multi-center pediatric studies.

Methods: Using the electronic health data from 34 healthcare institutions in the National Patient-Centered Clinical Research Network (PCORnet), we fit 12 multivariable-adjusted linear regression models to assess the associations of antibiotic use <24 months of age with body mass index z-score at 48 to <72 months of age. We ran these models using pooled individual-level data and conventional multivariable-adjusted regression (reference method), as well as using the more privacy-protecting pooled summary-level intermediate statistics and distributed regression technique.

Use of Time-Dependent Propensity Scores to Adjust Hazard Ratio Estimates in Cohort Studies with Differential Depletion of Susceptibles.

Estimating hazard ratios (HR) presents challenges for propensity score (PS)-based analyses of cohorts with differential depletion of susceptibles. When the treatment effect is not null, cohorts that were balanced at baseline tend to become unbalanced on baseline characteristics over time as "susceptible" individuals drop out of the population at risk differentially across treatment groups due to having outcome events. This imbalance in baseline covariates causes marginal (population-averaged) HRs to diverge from conditional (covariate-adjusted) HRs over time and systematically move toward the null.

Safe Expectations: Current State and Future Directions for Medication Safety in Pregnancy Research.

Medication use in pregnancy is common, but information about the safety of most medications in pregnant women or their infants is limited. In the absence of data from randomized clinical trials to guide decisions made by regulators, clinicians, and patients, we often have to rely on well-designed observational studies to generate valid evidence about the benefits and risks of medications in pregnancy. Spontaneous reporting, primary case-control and cohort studies, pregnancy exposure registries, and electronic health data have been used extensively for studying medication safety in pregnancy.

Ambient and supplemental magnetic fields promote myogenesis a TRPC1-mitochondrial axis: evidence of a magnetic mitohormetic mechanism.

We show that both supplemental and ambient magnetic fields modulate myogenesis. A lone 10 min exposure of myoblasts to 1.5 mT amplitude supplemental pulsed magnetic fields (PEMFs) accentuated myogenesis by stimulating transient receptor potential (TRP)-C1-mediated calcium entry and downstream nuclear factor of activated T cells (NFAT)-transcriptional and P300/CBP-associated factor (PCAF)-epigenetic cascades, whereas depriving myoblasts of ambient magnetic fields slowed myogenesis, reduced TRPC1 expression, and silenced NFAT-transcriptional and PCAF-epigenetic cascades.

A dual-action chitosan-based nanogel system of triclosan and flurbiprofen for localised treatment of periodontitis.

This study aimed to develop a dual action, namely anti-inflammatory and antimicrobial, nanogels (NG) for the treatment of periodontitis using triclosan (TCS) and flurbiprofen (FLB). Triclosan, an antimicrobial drug, was prepared as nanoparticles (NPs) using poly-ε-caprolactone (PCL), while flurbiprofen, an anti-inflammatory drug, was directly loaded in a chitosan (CS) based hydrogel. The entwinement of both NPs and hydrogel loaded systems resulted in the NG.

Stress-triggered YAP1/SOX2 activation transcriptionally reprograms head and neck squamous cell carcinoma for the acquisition of stemness.

Purpose: The clinical importance of cancer stem cells (CSCs) in head and neck squamous cell carcinoma (HNSCC) is well recognized. However, a reliable method for the detection of functioning CSC has not yet been established. We hypothesized that YAP1, a transcriptional coactivator, and SOX2, a master transcription factor of SCC, may cooperatively induce stemness through transcriptional reprogramming.

Identification of potential drug name confusion errors in the Sentinel System.

Purpose: In July 2015, the US Food and Drug Administration (FDA) published a drug safety communication regarding errors in prescribing and dispensing of the antidepressant Brintellix (vortioxetine) and the antiplatelet Brilinta (ticagrelor) that arose due to proprietary drug name confusion. Brintellix is indicated for major depressive disorder; Brilinta is indicated to reduce cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome or history of myocardial infarction. Brintellix was renamed to Trintellix in May 2016.

Inverse probability weighted Cox model in multi-site studies without sharing individual-level data.

The inverse probability weighted Cox proportional hazards model can be used to estimate the marginal hazard ratio. In multi-site studies, it may be infeasible to pool individual-level datasets due to privacy and other considerations. We propose three methods for making inference on hazard ratios without the need for pooling individual-level datasets across sites.

Comprehensive analysis of transcriptome profiles in hepatocellular carcinoma.

Background: Hepatocellular carcinoma is the second most deadly cancer with late presentation and limited treatment options, highlighting an urgent need to better understand HCC to facilitate the identification of early-stage biomarkers and uncover therapeutic targets for the development of novel therapies for HCC.

Methods: Deep transcriptome sequencing of tumor and paired non-tumor liver tissues was performed to comprehensively evaluate the profiles of both the host and HBV transcripts in HCC patients. Differential gene expression patterns and the dys-regulated genes associated with clinical outcomes were analyzed.

IL6R-STAT3-ADAR1 (P150) interplay promotes oncogenicity in multiple myeloma with 1q21 amplification.

1q21 amplification is an important prognostic marker in multiple myeloma. In this study we identified that (the interleukin-6 membrane receptor) and (an RNA editing enzyme) are critical genes located within the minimally amplified 1q21 region. Loss of individual genes caused suppression to the oncogenic phenotypes, the magnitude of which was enhanced when both genes were concomitantly lost.

Use of Intrauterine Devices and Risk of Human Immunodeficiency Virus Acquisition Among Insured Women in the United States.

Concerns have been raised about progestin-containing contraceptives and the risk of human immunodeficiency virus (HIV) acquisition. Based on health insurance data from women in the United States with intrauterine device (IUD) insertions during 2011-2018, there was no increased risk of incident HIV diagnosis for levonorgestrel-releasing IUDs versus copper IUDs.