Verification bias

This article is part of the Catalogue of Bias series. We present a description of verification bias, and outline its potential impact on research studies and the preventive steps to minimise its risk. We also present teaching slides in the online supplementary file. Verification bias (sometimes referred to as 'work-up bias') concerns the test(s) used to confirm a diagnosis within a diagnostic accuracy study. Verification bias occurs when only a proportion of the study participants receive confirmation of the diagnosis by the reference standard test, or if some participants receive a different reference standard test

Long-term effects of functional appliances in treated versus untreated patients with Class II malocclusion: A systematic review and meta-analysis

Objective To assess the cephalometric skeletal and soft-tissue of functional appliances in treated versus untreated Class II subjects in the long-term (primarily at the end of growth, secondarily at least 3 years after retention). Search methods Unrestricted electronic search of 24 databases and additional manual searches up to March 2018. Selection criteria Randomised and non-randomised controlled trials reporting on cephalometric skeletal and soft-tissue measurements of Class II patients (aged 16 years or under) treated with functional appliances, worn alone or in combination with multi-bracket therapy, compared to untreated Class II subjects. Data collection and analysis Mean differences (MDs) and 95% confidence intervals (95% CIs) were calculated with the random-effects model. Data were analysed at 2 primary time points (above 18 years of age, at the end of growth according to the Cervical Vertebral Maturation method) and a secondary time point (at least 3 years after retention). The risk of bias and quality of evidence were assessed according to the ROBINS tool and GRADE system, respectively. Results Eight non-randomised studies published in 12 papers were included. Functional appliances produced a significant improvement of the maxillo-mandibular relationship, at almost all time points (Wits appraisal at the end of growth, MD -3.52 mm, 95% CI -5.11 to -1.93, P < 0.0001). The greatest increase in mandibular length was recorded in patients aged 18 years and above (Co-Gn, MD 3.20 mm, 95% CI 1.32 to 5.08, P = 0.0009), although the improvement of the mandibular projection was negligible or not significant. The quality of evidence was ‘very low’ for most of the outcomes at both primary time points. Conclusions Functional appliances may be effective in correcting skeletal Class II malocclusion in the long-term, however the quality of the evidence was very low and the clinical significance was limited

Macrophage Heterogeneity in the Immunopathogenesis of Tuberculosis

Macrophages play a central role in tuberculosis, as the site of primary infection, inducers and effectors of inflammation, innate and adaptive immunity, as well as mediators of tissue destruction and repair. Early descriptions by pathologists have emphasized their morphological heterogeneity in granulomas, followed by delineation of T lymphocyte-dependent activation of anti-mycobacterial resistance. More recently, powerful genetic and molecular tools have become available to describe macrophage cellular properties and their role in host-pathogen interactions. In this review we discuss aspects of macrophage heterogeneity relevant to the pathogenesis of tuberculosis and, conversely, lessons that can be learnt from mycobacterial infection, with regard to the immunobiological functions of macrophages in homeostasis and disease

Defining Value-based Healthcare in the NHS

‘Value’ is gaining prominence in healthcare systems facing increased demand for services with limited resources. However, value-based healthcare has not yet been embraced as part of the everyday language and business of the NHS in the way that evidence-based healthcare has. The absence of an agreed definition of ‘value-based healthcare’ in the NHS, the lack of skills required to deliver value-based healthcare and a clear understanding of the barriers to effective development and implementation inhibits the health system in addressing problems such as overdiagnosis, too much medicine, poor allocation of resources and the introduction of inadequately evidenced technologies This report sets out a route to defining value-based healthcare in the NHS, an assessment of the barriers to its development, and an understanding of what skills and training would support implementation. A stakeholder workshop informs the report with patients and leaders across the NHS and value sector

Transmission of SARS-CoV-2 associated with cruise ship travel: a systematic review

Background: Maritime and river travel may be associated with respiratory viral spread via infected passengers and/or crew and potentially through other transmission routes. The transmission models of SARS-CoV-2 associated with cruise ship travel are based on transmission dynamics of other respiratory viruses. We aimed to provide a summary and evaluation of relevant data on SARS-CoV-2 transmission aboard cruise ships, report policy implications, and highlight research gaps. Methods: We searched four electronic databases (up to 26 May 2022) and included studies on SARS-CoV-2 transmission aboard cruise ships. The quality of the studies was assessed based on five criteria, and relevant findings were reported. Results: We included 23 papers on onboard SARS-CoV-2 transmission (with 15 reports on different aspects of the outbreak on Diamond Princess and nine reports on other international cruises), 2 environmental studies, and 1 systematic review. Three articles presented data on both international cruises and the Diamond Princess. The quality of evidence from most studies was low to very low. Index case definitions were heterogeneous. The proportion of traced contacts ranged from 0.19 to 100%. Studies that followed up >80% of passengers and crew reported attack rates (AR) up to 59%. The presence of a distinct dose−response relationship was demonstrated by findings of increased ARs in multi-person cabins. Two studies performed viral cultures with eight positive results. Genomic sequencing and phylogenetic analyses were performed in individuals from three cruises. Two environmental studies reported PCR-positive samples (cycle threshold range 26.21−39.00). In one study, no infectious virus was isolated from any of the 76 environmental samples. Conclusion: Our review suggests that crowding and multiple persons per cabin were associated with an increased risk of transmission on cruise ships. Variations in design, methodology, and case ascertainment limit comparisons across studies and quantification of transmission risk. Standardized guidelines for conducting and reporting studies on cruise ships of acute respiratory infection transmission should be developed

Genetic Variants in MARCO Are Associated with the Susceptibility to Pulmonary Tuberculosis in Chinese Han Population

BACKGROUND: Susceptibility to tuberculosis is not only determined by Mycobacterium tuberculosis infection, but also by the genetic component of the host. Macrophage receptor with a collagenous structure (MARCO) is essential components required for toll like receptor-signaling in macrophage response to Mycobacterium tuberculosis, which may contribute to tuberculosis risk. PRINCIPAL FINDINGS: To specifically investigated whether single nucleotide polymorphisms (SNPs) in MARCO gene are associated with pulmonary tuberculosis in Chinese Han population. By selecting tagging SNPs in MARCO gene, 17 tag SNPs were identified and genotyped in 923 pulmonary tuberculosis patients and 1033 healthy control subjects using a hospital based case-control association study. Single-point and haplotype analysis revealed an association in intron and exon region of MARCO gene. One SNP (rs17009726) was associated with susceptibility to pulmonary tuberculosis, where the carriers of the G allele had a 1.65 fold (95% CI = 1.32-2.05, p(corrected) = 9.27E-5) increased risk of pulmonary tuberculosis. Haplotype analysis revealed that haplotype GC containing G allele of 17009726 and haplotype TGCC (rs17795618T/A, rs1371562G/T, rs6761637T/C, rs2011839C/T) were also associated with susceptibility to pulmonary tuberculosis (p(corrected) = 0.0001 and 0.029, respectively). CONCLUSIONS: Our study suggested that genetic variants in MARCO gene were associated with pulmonary tuberculosis susceptibility in Chinese Han population, and the findings emphasize the importance of MARCO mediated immune responses in the pathogenesis of tuberculosis

Relative Roles of the Cellular and Humoral Responses in the Drosophila Host Defense against Three Gram-Positive Bacterial Infections

BACKGROUND: Two NF-kappaB signaling pathways, Toll and immune deficiency (imd), are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial peptides, which are important components of a humoral defense response. However, it is less clear to what extent macrophage-like hemocytes contribute to host defense. METHODOLOGY/PRINCIPAL FINDINGS: In order to dissect the relative importance of humoral and cellular defenses after septic injury with three different gram-positive bacteria (Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus), we used latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival--independently of concomitant Toll or imd pathway activation. Our data failed to confirm a role of the PGRP-SA and GNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosis by hemocytes or S2 cells of E. faecalis and S. aureus, but not of M. luteus. In the case of M. luteus and E. faecalis, but not S. aureus, decreased survival due to defective phagocytosis could be compensated for by genetically enhancing the humoral immune response. CONCLUSIONS/SIGNIFICANCE: Our results underscore the fundamental importance of both cellular and humoral mechanisms in Drosophila immunity and shed light on the balance between these two arms of host defense depending on the invading pathogen

Innate Killing of Leishmania donovani by Macrophages of the Splenic Marginal Zone Requires IRF-7

Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ after pathogen uptake. Here, we have combined gene expression profiling and RNAi using a stromal macrophage cell line with in situ analysis of the leishmanicidal activity of marginal zone macrophages (MZM) and marginal metallophilic macrophages (MMM) in wild type and gene targeted mice. Our data demonstrate a critical role for interferon regulatory factor-7 (IRF-7) in regulating the killing of intracellular Leishmania donovani by these specialised splenic macrophage sub-populations. This study, therefore, identifies a new role for IRF-7 as a regulator of innate microbicidal activity against this, and perhaps other, non-viral intracellular pathogens. This study also highlights the importance of selecting appropriate macrophage populations when studying pathogen interactions with this functionally diverse lineage of cells

Use of ecstasy and other psychoactive substances among school-attending adolescents in Taiwan: national surveys 2004–2006

<p>Abstract</p> <p>Background</p> <p>With the backdrop of a global ecstasy epidemic, this study sought to examine the trend, correlates, and onset sequence of ecstasy use among adolescents in Taiwan, where a well-established gateway drug such as marijuana is much less popular.</p> <p>Methods</p> <p>A multistage probability survey of school-attending adolescents in grades 7, 9, 10, and 12, aged 11–19 years, was conducted in 2004, 2005, and 2006. A self-administered anonymous questionnaire elicited response rates ranging from 94.3% to 96.6%. The sample sizes were 18232 respondents in 2004, 17986 in 2005, and 17864 in 2006.</p> <p>Results</p> <p>In terms of lifetime prevalence and incidence, ecstasy and ketamine by and large appeared as the first and second commonly used illegal drugs, respectively, among middle (grades 7 and 9) and high school students (grades 10 and 12) during the 3-year survey period; however, this order was reversed in the middle school-aged students starting in 2006. Having sexual experience, tobacco use, and betel nut use were factors consistently associated with the onset of ecstasy use across years. The majority of ecstasy users had been involved in polydrug use, such as the use of ketamine (41.4%–53.5%), marijuana (12.7%–18.7%), and methamphetamine (4.2%–9.5%).</p> <p>Conclusion</p> <p>From 2004 to 2006, a decline was noted in the prevalence and incidence rate of ecstasy, a leading illegal drug used by school-attending adolescents in Taiwan since the early 2000s. The emerging ketamine use trend may warrant more attention in the future.</p