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An increasing growth of systematic reviews (SRs) presents notable challenges for decision-makers seeking to answer clinical questions. In 1997, an algorithm was created by Jadad to assess discordance in results across SRs on the same question. Our study aims to (1) replicate assessments done in a sample of studies using the Jadad algorithm to determine if the same SR would have been chosen, (2) evaluate the Jadad algorithm in terms of utility, efficiency and comprehensiveness, and (3) describe how authors address discordance in results across multiple SRs.
Guidelines are systematically developed recommendations to assist practitioner and patient decisions about treatments for clinical conditions. High quality and comprehensive systematic reviews and 'overviews of systematic reviews' (overviews) represent the best available evidence. Many guideline developers, such as the WHO and the Australian National Health and Medical Research Council, recommend the use of these research syntheses to underpin guideline recommendations. We aim to evaluate the impact and use of systematic reviews with and without pairwise meta-analysis or network meta-analyses (NMAs) and overviews in clinical practice guideline (CPG) recommendations.
The contribution of acute HIV infection (AHI) to transmission is widely recognized, and increasing AHI diagnosis capacity can enhance HIV prevention through subsequent behavior change or intervention. We examined the impact of targeted pooled nucleic acid amplification testing (NAAT) and social marketing to increase AHI diagnosis among men who have sex with men (MSM) in Vancouver.
When conducting an Overviews of Reviews on health-related topics, it is unclear which combination of bibliographic databases authors should use for searching for SRs. Our goal was to determine which databases included the most systematic reviews and identify an optimal database combination for searching systematic reviews.
One of the most conflicting methodological issues when conducting an overview is the overlap of primary studies across systematic reviews (SRs). Overlap in the pooled effect estimates across SRs may lead to overly precise effect estimates in the overview. SRs that focus on exercise-related interventions are often included in overviews aimed at grouping and determining the effectiveness of various interventions for managing specific health conditions. The aim of this systematic methodological review is to describe the strategies used by authors of overviews focusing on exercise-related interventions to manage the overlap of primary studies.
Digital sexually transmitted and bloodborne infection (STBBI) testing interventions have gained popularity. However, evidence of their health equity effects remains sparse. We conducted a review of the health equity effects of these interventions on uptake of STBBI testing and explored design and implementation factors contributing to reported effects.
Three meta-analyses and one systematic review have been conducted on the question of whether self-collected specimens are as accurate as clinician-collected specimens for STI screening. However, these reviews predate 2007 and did not analyze rectal or pharyngeal collection sites. Currently, there is no consensus on which sampling method is the most effective for the diagnosis of genital chlamydia (CT), gonorrhea (GC) or human papillomavirus (HPV) infection. Our meta-analysis aims to be comprehensive in that it will examine the evidence of whether self-collected vaginal, urine, pharyngeal and rectal specimens provide as accurate a clinical diagnosis as clinician-collected samples (reference standard).
Transient receptor potential vanilloid 2 is a calcium channel activated by probenecid. Probenecid is a Food and Drug Administration-approved uricosuric drug that has recently been shown to induce positive lusitropic and inotropic effects in animal models through cardiomyocyte transient receptor potential vanilloid 2 activation. The aim of this study was to test the hypothesis that oral probenecid can improve cardiac function and symptomatology in patients with heart failure with reduced ejection fraction and to further elucidate its calcium-dependent effects on myocyte contractility.
Overviews often identify and synthesise a large number of systematic reviews on the same topic, which is likely to lead to overlap (i.e. duplication) in primary studies across the reviews. Using a primary study result multiple times in the same analysis overstates its sample size and number of events, falsely leading to greater precision in the analysis. This paper aims to: (a) describe types of overlapping data that arise from the same primary studies reported across multiple reviews, (b) describe methods to identify and explain overlap of primary study data, and (c) present six case studies illustrating different approaches to manage overlap.
Multiple 'overviews of reviews' conducted on the same topic ("overlapping overviews") represent a waste of research resources and can confuse clinicians making decisions amongst competing treatments. We aimed to assess the frequency and characteristics of overlapping overviews. MEDLINE, Epistemonikos and Cochrane Database of Systematic Reviews were searched for overviews that: synthesized reviews of health interventions and conducted systematic searches. Overlap was defined as: duplication of PICO eligibility criteria, and not reported as an update nor a replication. We categorized overview topics according to 22 WHO ICD-10 medical classifications, overviews as broad or narrow in scope, and overlap as identical, nearly identical, partial, or subsumed. Subsummation was defined as when broad overviews subsumed the populations, interventions and at least one outcome of another overview. Of 541 overviews included, 169 (31%) overlapped across similar PICO, fell within 13 WHO ICD-10 medical classifications, and 62 topics. 148/169 (88%) overlapping overviews were broad in scope. Fifteen overviews were classified as having nearly identical overlap (9%); 123 partial overlap (73%), and 31 subsumed (18%) others. One third of overviews overlapped in content and a majority covered broad topic areas. A multiplicity of overviews on the same topic adds to the ongoing waste of research resources, time, and effort across medical disciplines. Authors of overviews can use this study and the sample of overviews to identify gaps in the evidence for future analysis, and topics that are already studied, which do not need to be duplicated.
Body image (BI) is an important issue for cancer patients, as patients with BI concerns are susceptible to depression, anxiety, difficulty coping, and poor quality of life (QoL). While this concern has been documented in patients with other malignancies, no data exists of this QoL issue in patients with primary brain tumors (PBT).
Mutations effects on p53 isoforms' activities remain largely unknown, although they are mutated in 92% of TP53 mutant cancers. Therefore, exploring the effect of mutations on p53 isoforms activities is a critical, albeit unexplored area in the p53 field. In this article, we report for the first time a mutant Δ133p53α-specific pathway which increases IL4I1 and IDO1 expression and activates AHR, a tumor-promoting mechanism. Accordingly, mutant Δ133p53α R273H increases glioblastoma cancer cells proliferation and invasion while the WT does not. Furthermore, while WT Δ133p53α reduces apoptosis to promote DNA repair, the mutant also reduces apoptosis but fails to maintain genomic stability.Furthermore, both WT and mutant Δ133p53α reduce cellular senescence in a senescence inducer-dependent manner (temozolomide or radiation) because they regulate different senescence-associated target genes. Hence, WT Δ133p53α rescues temozolomide-induced but not radiation-induced senescence, while mutant Δ133p53α R273H rescues radiation-induced but not temozolomide-induced senescence. Lastly, using TCGA data, we determined that IL4I1, IDO1 and AHR are significantly higher in GBMs compared to LGGs. IL4I1 expression is increased in mutant TP53 LGGs and GBMs, although only significantly in LGG. Importantly, high expression of all three genes in LGG and IL4I1 in GBM is significantly associated with poorer patients' survival. These data show that, compared to WT Δ133p53α, R273H mutation reorientates its activities toward carcinogenesis and activates the oncogenic IL4I1/IDO1/AHR pathway, a potential prognostic marker and therapeutic target in GBM by combining drugs specifically modulating Δ133p53α expression and IDO1/Il4I1/AHR inhibitors.
Canadian clinical guidelines recommend at least annual and up to quarterly bacterial sexually transmitted infection (STI) testing among sexually active gay, bisexual, and other men who have sex with men (GBM). However, testing rates are suboptimal. Innovative solutions are needed to close the gap because there is currently limited knowledge on how best to approach this issue.
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