Bias estimation in study design: a meta-epidemiological analysis of transcatheter versus surgical aortic valve replacement

Background: Paucity of RCTs of non-drug technologies lead to widespread dependence on non-randomized studies. Relationship between nonrandomized study design attributes and biased estimates of treatment effects are poorly understood. Our purpose was to estimate the bias associated with specific nonrandomized study attributes among studies comparing transcatheter aortic valve implantation with surgical aortic valve replacement for the treatment of severe aortic stenosis. Results: We included 6 RCTs and 87 nonrandomized studies. Surgical risk scores were similar for comparison groups in RCTs, but were higher for patients having transcatheter aortic valve implantation in nonrandomized studies. Nonrandomized studies underestimated the benefit of transcatheter aortic valve implantation compared with RCTs. For example, nonrandomized studies without adjustment estimated a higher risk of postoperative mortality for transcatheter aortic valve implantation compared with surgical aortic valve replacement (OR 1.43 [95% CI 1.26 to 1.62]) than high quality RCTs (OR 0.78 [95% CI 0.54 to 1.11). Nonrandomized studies using propensity score matching (OR 1.13 [95% CI 0.85 to 1.52]) and regression modelling (OR 0.68 [95% CI 0.57 to 0.81]) to adjust results estimated treatment effects closer to high quality RCTs. Nonrandomized studies describing losses to follow-up estimated treatment effects that were significantly closer to high quality RCT than nonrandomized studies that did not. Conclusion: Studies with different attributes produce different estimates of treatment effects. Study design attributes related to the completeness of follow-up may explain biased treatment estimates in nonrandomized studies, as in the case of aortic valve replacement where high-risk patients were preferentially selected for the newer (transcatheter) procedure

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events

Joint Observation of the Galactic Center with MAGIC and CTA-LST-1

MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes (IACTs), designed to detect very-high-energy gamma rays, and is operating in stereoscopic mode since 2009 at the Observatorio del Roque de Los Muchachos in La Palma, Spain. In 2018, the prototype IACT of the Large-Sized Telescope (LST-1) for the Cherenkov Telescope Array, a next-generation ground-based gamma-ray observatory, was inaugurated at the same site, at a distance of approximately 100 meters from the MAGIC telescopes. Using joint observations between MAGIC and LST-1, we developed a dedicated analysis pipeline and established the threefold telescope system via software, achieving the highest sensitivity in the northern hemisphere. Based on this enhanced performance, MAGIC and LST-1 have been jointly and regularly observing the Galactic Center, a region of paramount importance and complexity for IACTs. In particular, the gamma-ray emission from the dynamical center of the Milky Way is under debate. Although previous measurements suggested that a supermassive black hole Sagittarius A* plays a primary role, its radiation mechanism remains unclear, mainly due to limited angular resolution and sensitivity. The enhanced sensitivity in our novel approach is thus expected to provide new insights into the question. We here present the current status of the data analysis for the Galactic Center joint MAGIC and LST-1 observations

Meta-Review of the Quantity and Quality of Evidence for Knee Arthroplasty Devices

<div><p>Introduction</p><p>Some cardiovascular devices are licensed based on limited evidence, potentially exposing patients to devices that are not safe or effective. Research is needed to ascertain if the same is true of other types of medical devices. Knee arthroplasty is a widely-used surgical procedure yet implant failures are not uncommon. The purpose of this study was to characterize available evidence on the safety and effectiveness of knee implants.</p><p>Methods</p><p>A review of primary studies included in health technology assessments (HTA) on total (TKA) and unicompartmental knee arthroplasty (UKA) was conducted. MEDLINE, EMBASE, CINAHL, Cochrane Library and Biotechnology & BioEngineering Abstracts were searched from 2005 to 2014, plus journal tables of contents and 32 HTA web sites. Patients were aged 18 and older who underwent primary TKA or UKA assessed in cohort or randomized controlled studies. Summary statistics were used to report study characteristics.</p><p>Results</p><p>A total of 265 eligible primary studies published between 1986 and 2014 involving 59,217 patients were identified in 10 HTAs (2 low, 7 moderate, 1 high risk of bias). Most evaluated TKA (198, 74.5%). The quality of evidence in primary studies was limited. Most studies were industry-funded (23.8%) or offered no declaration of funding or conflict of interest (44.9%); based on uncontrolled single cohorts (58.5%), enrolled fewer than 100 patients (66.4%), and followed patients for 2 years or less (UKA: single cohort 29.8%, comparative cohort 16.7%, randomized trial 25.0%; TKA: single cohort 25.0%, comparative cohort 31.4%, randomized trial 48.6%). Furthermore, most devices were evaluated in only one study (55.3% TKA implants, 61.1% UKA implants).</p><p>Conclusions</p><p>Patients, physicians, hospitals and payers rely on poor-quality evidence to support decisions about knee implants. Further research is needed to explore how decisions about the use of devices are currently made, and how the evidence base for device safety and effectiveness can be strengthened.</p></div

Number of patients evaluated in eligible studies.

<p>Number of patients evaluated in eligible studies.</p