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Background Several reviews have noted shortcomings regarding the quality and reporting of network meta-analyses (NMAs). We suspect that this issue may be partially attributable to limitations in current NMA software which do not readily produce all of the output needed to satisfy current guidelines. Results To better facilitate the conduct and reporting of NMAs, we have created an R package called “BUGSnet” ( B ayesian inference U sing G ibbs S ampling to conduct a Net work meta-analysis). This R package relies upon Just Another Gibbs Sampler (JAGS) to conduct Bayesian NMA using a generalized linear model. BUGSnet contains a suite of functions that can be used to describe the evidence network, estimate a model and assess the model fit and convergence, assess the presence of heterogeneity and inconsistency, and output the results in a variety of formats including league tables and surface under the cumulative rank curve (SUCRA) plots. We provide a demonstration of the functions contained within BUGSnet by recreating a Bayesian NMA found in the second technical support document composed by the National Institute for Health and Care Excellence Decision Support Unit (NICE-DSU). We have also mapped these functions to checklist items within current reporting and best practice guidelines. Conclusion BUGSnet is a new R package that can be used to conduct a Bayesian NMA and produce all of the necessary output needed to satisfy current scientific and regulatory standards. We hope that this software will help to improve the conduct and reporting of NMAs.

Chronic kidney disease is an important risk factor for death and cardiovascular-related morbidity, but estimates to date of its prevalence in Canada have generally been extrapolated from the prevalence of end-stage renal disease. We used direct measures of kidney function collected from a nationally representative survey population to estimate the prevalence of chronic kidney disease among Canadian adults. We examined data for 3689 adult participants of cycle 1 of the Canadian Health Measures Survey (2007–2009) for the presence of chronic kidney disease. We also calculated the age-standardized prevalence of cardiovascular risk factors by chronic kidney disease group. We cross-tabulated the estimated glomerular filtration rate (eGFR) with albuminuria status. The prevalence of chronic kidney disease during the period 2007–2009 was 12.5%, representing about 3 million Canadian adults. The estimated prevalence of stage 3–5 disease was 3.1% (0.73 million adults) and albuminuria 10.3% (2.4 million adults). The prevalence of diabetes, hypertension and hypertriglyceridemia were all significantly higher among adults with chronic kidney disease than among those without it. The prevalence of albuminuria was high, even among those whose eGFR was 90 mL/min per 1.73 m2 or greater (10.1%) and those without diabetes or hypertension (9.3%). Awareness of kidney dysfunction among adults with stage 3–5 chronic kidney disease was low (12.0%). The prevalence of kidney dysfunction was substantial in the survey population, including individuals without hypertension or diabetes, conditions most likely to prompt screening for kidney dysfunction. These findings highlight the potential for missed opportunities for early intervention and secondary prevention of chronic kidney disease.

The importance of body size versus weight distribution for cancer risk is unclear. We investigated associations between measures of body size and shape and the risk of developing cancer. The study population consisted of 26,607 participants from the Alberta’s Tomorrow Project cohort. Two main measures of body shape and size were examined: i) body mass index (BMI) and ii) waist circumference (WC). Incident cancers were identified via linkage to the Alberta Cancer Registry. Cox proportional hazards models were used. Males and females classified as obese (BMI ≥ 30 kg /m −2 ) have a 33% and 22% increased risk of all-cancer, respectively, than their normal weight counterparts. Similar all-cancer risk increases are observed for those above sex-specific WC guidelines. Mutual adjustment for WC attenuates the association between BMI and all-cancer risk, especially among females. Central adiposity appears to be a stronger predictor of all-cancer risk than body size. Obesity is linked to increased cancer risk but the impact of body size versus weight distribution in determining the increased risk is unclear. Here the authors examined body mass index, waist circumference, and waist to hip ratio in relation to all-cancer incidence and incidence of seven individual cancers in a population of approximately 26,000 individual and conclude that central adiposity appears to be a stronger predictor of all-cancer risk than body size.

The role of hepatitis C virus (HCV) infection in increasing the risk of cardiovascular disease (CVD) is controversial. The objective of the present study is to estimate the 10-year risk of CVD in HCV- positive subjects and describe their profile of cardiometabolic risk markers compared to HCV-negative subjects. We conducted a cross-sectional study to estimate 10-year CVD risk, calculated using the Framingham Risk Score (FRS), in participants from the Canadian Health Measures Survey (CHMS; 2007-2015, n = 10,115) and the US-National Health and Nutrition Examination Survey (NHANES; 2007-2016, n = 16,668). Subjects included in our analysis were aged 30 to 74 years with no prior history of CVD. FRS estimates, sociodemographic and cardiometabolic risk factors were compared between HCV- positive and -negative subjects in the two surveys. HCV-positive subjects had a distinct sociodemographic profile compared to their HCV-negative counterparts. Cardiometabolic risk factors, inflammatory markers and serum levels of micronutrients were comparable between the two survey populations, both in HCV-positive and -negative subjects. The average FRS in HCV-positive patients was in the range of \"intermediate\" 10-year CVD risk (i.e., 10-20%) and was significantly higher (P<0.01) than their HCV-negative counterparts who were within the \"low\" 10-year CVD risk range (i.e., ≤10%). Using a multivariable linear regression model adjusted for ethnicity, number of metabolic syndrome components and BMI, HCV infection was significantly associated with a 2.5-3.5% absolute risk increase of 10-year CVD (P<0.01). The results of the present study suggest a potential association between HCV infection and risk of subclinical and clinical CVD. The expansion of anti-HCV therapy may also contribute to reduced CVD risk and burden in patients with chronic HCV infection and should be explored further in other datasets and population modelling studies.

Flavivirus diseases such as dengue fever (DENV), West Nile virus (WNV), Zika and yellow fever represent a substantial global public health concern. Preexisting chronic conditions such as cardiovascular diseases, diabetes, obesity, and asthma were thought to predict risk of progression to severe infections. We aimed to quantify the frequency of chronic comorbidities in flavivirus diseases to provide an estimate for their prevalence in severe and non-severe infections and examine whether chronic diseases contribute to the increased risk of severe viral expression. We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic and grey literature databases to identify studies reporting prevalence estimates of comorbidities in flavivirus diseases. Study quality was assessed with the risk of bias tool. Age-adjusted odds ratios (ORs) were estimated for severe infection in the presence of chronic comorbidities. We identified 65 studies as eligible for inclusion for DENV (47 studies) and WNV (18 studies). Obesity and overweight (i.e., BMI> 25 kg/m2, prevalence: 24.5%, 95% CI: 18.6-31.6%), hypertension (17.1%, 13.3-21.8%) and diabetes (13.3%, 9.3-18.8%) were the most prevalent comorbidities in DENV. However, hypertension (45.0%, 39.1-51.0%), diabetes (24.7%, 20.2-29.8%) and heart diseases (25.6%, 19.5-32.7%) were the most prevalent in WNV. ORs of severe flavivirus diseases were about 2 to 4 in infected patients with comorbidities such as diabetes, hypertension and heart diseases. The small number of studies in JEV, YFV and Zika did not permit estimating the prevalence of comorbidities in these infections. Higher prevalence of chronic comorbidities was found in severe cases of flavivirus diseases compared to non-severe cases. Findings of the present study may guide public health practitioners and clinicians to evaluate infection severity based on the presence of comorbidity, a critical public health measure that may avert severe disease outcome given the current dearth of clear prevention practices for some flavivirus diseases.

Typhoid fevers are infections caused by the bacteria Salmonella enterica serovar Typhi (Salmonella Typhi) and Paratyphi A, B and C (Salmonella Paratyphi). Approximately 17.8 million incident cases of typhoid fever occur annually, and incidence is highest in children. The accuracy of current diagnostic tests of typhoid fever is poorly understood. We aimed to determine the comparative accuracy of available tests for the pediatric population. We first conducted a systematic literature review to identify studies that compared diagnostic tests for typhoid fever in children (aged ≤15 years) to blood culture results. We applied a Bayesian latent-class extension to a network meta-analysis model. We modelled known diagnostic properties of bone marrow culture and the relationship between bone marrow and blood culture as informative priors in a Bayesian framework. We tested sensitivities for the proportion of negative blood samples that were false as well as bone marrow sensitivity and specificity. We found 510 comparisons from 196 studies and 57 specific to the pediatric population. IgM-based tests outperformed their IgG-based counterparts for ELISA and Typhidot tests. The lateral flow IgG test performed comparatively well with 92% sensitivity (72% to 98% across scenario analyses) and 94% specificity. The most sensitive test of those investigated for the South Asian pediatric population was the Reverse Passive Hemagglutination Assay with 99% sensitivity (98% - 100% across scenario analyses). Adding a Widal slide test to other typhoid diagnostics did not substantially improve diagnostic performance beyond the single test alone, however, a lateral flow-based IgG rapid test combined with the typhoid/paratyphoid (TPT) assay yielded improvements in sensitivity without substantial declines in specificity and was the best performing combination test in this setting. In the pediatric population, lateral-flow IgG, TPT and Reverse Passive Hemagglutination tests had high diagnostic accuracy compared to other diagnostics. Combinations of tests may provide a feasible option to increase diagnostic sensitivity. South Asia has the most informed set of data on typhoid diagnostic testing accuracy, and the evidence base in other important regions needs to be expanded.

ObjectivesThe present study evaluates the extent of association between hepatitis C virus (HCV) infection and cardiovascular disease (CVD) risk and identifies factors mediating this relationship using Bayesian network (BN) analysis.Design and settingA population-based cross-sectional survey in Canada.ParticipantsAdults from the Canadian Health Measures Survey (n=10 115) aged 30 to 74 years.Primary and secondary outcome measuresThe 10-year risk of CVD was determined using the Framingham Risk Score in HCV-positive and HCV-negative subjects. Using BN analysis, variables were modelled to calculate the probability of CVD risk in HCV infection.ResultsWhen the BN is compiled, and no variable has been instantiated, 73%, 17% and 11% of the subjects had low, moderate and high 10-year CVD risk, respectively. The conditional probability of high CVD risk increased to 13.9%±1.6% (p<2.2×10-16) when the HCV variable is instantiated to ‘Present’ state and decreased to 8.6%±0.2% when HCV was instantiated to ‘Absent’ (p<2.2×10-16). HCV cases had 1.6-fold higher prevalence of high-CVD risk compared with non-infected individuals (p=0.038). Analysis of the effect modification of the HCV-CVD relationship (using median Kullback-Leibler divergence; DKL) showed diabetes as a major effect modifier on the joint probability distribution of HCV infection and CVD risk (DKL=0.27, IQR: 0.26 to 0.27), followed by hypertension (0.24, IQR: 0.23 to 0.25), age (0.21, IQR: 0.10 to 0.38) and injection drug use (0.19, IQR: 0.06 to 0.59).ConclusionsExploring the relationship between HCV infection and CVD risk using BN modelling analysis revealed that the infection is associated with elevated CVD risk. A number of risk modifiers were identified to play a role in this relationship. Targeting these factors during the course of infection to reduce CVD risk should be studied further.

This work sought to quantify pathologists’ diagnostic bias over time in their evaluation of colorectal polyps to assess how this may impact the utility of statistical process control (SPC). All colorectal polyp specimens(CRPS) for 2011–2017 in a region were categorized using a validated free text string matching algorithm. Pathologist diagnostic rates (PDRs) for high grade dysplasia (HGD), tubular adenoma (TA_ad), villous morphology (TVA + VA), sessile serrated adenoma (SSA) and hyperplastic polyp (HP), were assessed (1) for each pathologist in yearly intervals with control charts (CCs), and (2) with a generalized linear model (GLM). The study included 64,115 CRPS. Fifteen pathologists each interpreted > 150 CRPS/year in all years and together diagnosed 38,813. The number of pathologists (of 15) with zero or one ( p  < 0.05) outlier in seven years, compared to their overall PDR, was 13, 9, 9, 5 and 9 for HGD, TVA + VA, TA_ad, HP and SSA respectively. The GLM confirmed, for the subset where pathologists/endoscopists saw > 600 CRPS each(total 52,760 CRPS), that pathologist, endoscopist, anatomical location and year were all strongly correlated (all p  < 0.0001) with the diagnosis. The moderate PDR stability over time supports the hypothesis that diagnostic rates are amendable to calibration via SPC and outcome data.

Approximately 2.4 million people are living with HIV in India. This large disease burden, and potential for epidemic spread in some areas, demands a full understanding of transmission in that country. We wished to quantify the effects of key sexual risk factors for HIV infection for each gender and among high- and low-HIV risk populations in India. We conducted a systematic review of sexual risk factors for HIV infection from 35 published studies. Risk factors analyzed were: male circumcision/religion, Herpes Simplex Virus 2, syphilis, gonorrhoea, genital ulcer, multiple sexual partners and commercial sex. Studies were included if they met predetermined criteria. Data were extracted and checked by two researchers and random-effects meta analysis of effects was conducted. Heterogeneity in effect estimates was examined by I(2) statistic. Publication bias was tested by Begg's test and funnel plots. Meta regression was used to assess effect modification by various study attributes. All risk factors were significantly associated with HIV status. The factor most strongly associated with HIV for both sexes was HSV-2 infection (OR(men): 5.87; 95%CI: 2.46-14.03; OR(women): 6.44; 95%CI: 3.22-12.86). The effect of multiple sexual partners was similar among men (OR = 2.46; 95%CI: 1.91-3.17,) and women (OR = 2.02; 95%CI: 1.43-2.87) and when further stratified by HIV-risk group. The association between HSV-2 and HIV prevalence was consistently stronger than other STIs or self-reported genital ulcer. If the strong associations between HSV-2 and HIV were interpreted causally, these results implied that approximately half of the HIV infections observed in our study population were attributable to HSV-2 infection. The risk factors examined in our analysis should remain targets of HIV prevention programs. Our results confirm that sexual risk factors for HIV infection continue to be an important part of Indian HIV epidemic 26 years after it began.

IntroductionLyme disease—also known as Lyme borreliosis (LB)—is the most common vector-borne disease in North America and Europe. It may result in substantial morbidity, primarily from persistent Lyme arthritis (LA) that—although treatable—can develop into antibiotic-refractory LA (A-RLA). The aim of this study is to systematically review and evaluate a range of biomarkers for their potential predictive value in the development of A-RLA.MethodsWe conducted a systematic review of studies examining biomarkers among patients with A-RLA from MEDLINE via OVID, EMBASE and Web of Science databases and identified a total of 26 studies for qualitative analysis.ResultsAll studies were of patient populations from the USA, with the exception of one from Europe. We identified an array of biomarkers that are commonly modulated in the A-RLA compared with subjects with antibiotic-responsive LA. These included a range of inflammatory markers (IL-6, IL-8, IL-10, IL-1β, IL-23, IL-17F, TNFα, IFNγ, CXCL9, CXCL10, CCL2, CCL3 and CCL4, CRP), factors along the innate and adaptive immune response pathways (e.g., CD4+ T cells, GITR receptors, OX40 receptors, IL-4+CD4+Th2 cells, IL-17+CD4+ T cells) and an array of miRNA species (e.g., miR-142, miR-17, miR-20a, let-7c and miR-30fam).ConclusionThe evidence base of biologic markers for A-RLA is limited. However, a range of promising biomarkers have been identified. Cytokines and chemokines related to Th17 pathway together with a number of miRNAs species (miR-146a, miR-155 and let-7a) may be promising candidates in the prediction of A-RLA. A panel of multiple biomarkers may yield clinically relevant prediction of the possible resistance at the time of LA first diagnosis.FundingPublic Health Agency of Canada.