Evaluation of the methodological quality of studies of the performance of diagnostic tests for bovine tuberculosis using QUADAS

There has been little assessment of the methodological quality of studies measuring the performance (sensitivity and/or specificity) of diagnostic tests for animal diseases. In a systematic review, 190 studies of tests for bovine tuberculosis (bTB) in cattle (published 1934-2009) were assessed by at least one of 18 reviewers using the QUADAS (Quality Assessment of Diagnostic Accuracy Studies) checklist adapted for animal disease tests. VETQUADAS (VQ) included items measuring clarity in reporting (n = 3), internal validity (n = 9) and external validity (n = 2). A similar pattern for compliance was observed in studies of different diagnostic test types. Compliance significantly improved with year of publication for all items measuring clarity in reporting and external validity but only improved in four of the nine items measuring internal validity (p < 0.05). 107 references, of which 83 had performance data eligible for inclusion in a meta-analysis were reviewed by two reviewers. In these references, agreement between reviewers' responses was 71% for compliance, 32% for unsure and 29% for non-compliance. Mean compliance with reporting items was 2, 5.2 for internal validity and 1.5 for external validity. The index test result was described in sufficient detail in 80.1% of studies and was interpreted without knowledge of the reference standard test result in only 33.1%. Loss to follow-up was adequately explained in only 31.1% of studies. The prevalence of deficiencies observed may be due to inadequate reporting but may also reflect lack of attention to methodological issues that could bias the results of diagnostic test performance estimates. QUADAS was a useful tool for assessing and comparing the quality of studies measuring the performance of diagnostic tests but might be improved further by including explicit assessment of population sampling strategy.The SE3238 project “Meta-analysis of diagnostic tests and modelling to identify appropriate testing strategies to reduce M. bovis infection in GB herds” was funded by the UK Department for Environment, Food and Rural Affairs (Defra).http://www.elsevier.com/locate/prevetmedam2018Veterinary Tropical Disease

Meta-analyses of the sensitivity and specificity of ante-mortem and post-mortem diagnostic tests for bovine tuberculosis in the UK and Ireland

Publication history: Accepted - 26 February 2017; Published online - 6th March 2017.Bovine Tuberculosis (bTB) in cattle is a global health problem and eradication of the disease requires accu-rate estimates of diagnostic test performance to optimize their efficiency. The objective of this study was,through statistical meta-analyses, to obtain estimates of sensitivity (Se) and specificity (Sp), for 14 differ-ent ante-mortem and post-mortem diagnostic tests for bTB in cattle. Using data from a systematic reviewof the scientific literature (published 1934–2009) diagnostic Se and Sp were estimated using Bayesianlogistic regression models adjusting for confounding factors. Random effect terms were used to accountfor unexplained heterogeneity. Parameters in the models were implemented using Markov Chain MonteCarlo (MCMC), and posterior distributions for the diagnostic parameters with adjustment for covariates(confounding factors) were obtained using the inverse logit function. Estimates for Se and/or Sp of thetuberculin skin tests and the IFN- blood test were compared with estimates published 2010–2015.Median Se for the single intradermal comparative cervical tuberculin skin (SICCT) test (standard inter-pretation) was 0.50 and Bayesian credible intervals (CrI) were wide (95% CrI 0.26, 0.78). Median Sp forthe SICCT test was 1.00 (95% CrI 0.99, 1.00). Estimates for the IFN- blood test Bovine Purified ProteinDerivative (PPD)-Avian PPD and Early Secreted Antigen target 6 and Culture Filtrate Protein 10 (ESAT-6/CFP10) ESAT6/CFP10 were 0.67 (95% CrI 0.49, 0.82) and 0.78 (95% CrI 0.60, 0.90) respectively for Se,and 0.98 (95% CrI 0.96, 0.99) and 0.99 (95% CrI 0.99, 1.00) for Sp. The study provides an overview of theaccuracy of a range of contemporary diagnostic tests for bTB in cattle. Better understanding of diagnostictest performance is essential for the design of effective control strategies and their evaluation.The SE3238 project “Meta-analysis of diagnostic tests and modelling to identify appropriate testing strategies to reduce M. bovis infection in GB herds” was funded by the UK Department for Envi-ronment, Food and Rural Affairs (Defra)

Drug burden index and its association with hip fracture among older adults:a national population-based study

Background: The Drug Burden Index (DBI) calculates the total sedative and anticholinergic load of prescribed medications and is associated with functional decline and hip fractures in older adults. However, it is unknown if confounding factors influence the relationship between the DBI and hip fractures. The objective of this study was to evaluate the association between the DBI and hip fractures, after correcting for mortality and multiple potential confounding factors. Methods: A competing-risks regression analysis conducted on a prospectively recruited New Zealand community-dwelling older population who had a standardized (International Resident Assessment Instrument) assessment between September 1, 2012, and October 31, 2015, the study's end date. Outcome measures were survival status and hip fracture, with time-varying DBI exposure derived from 90-day time intervals. The multivariable competing-risks regression model was adjusted for a large number of medical comorbidities and activities of daily living. Results: Among 70,553 adults assessed, 2,249 (3.2%) experienced at least one hip fracture, 20,194 (28.6%) died without experiencing a fracture, and 48,110 (68.2%) survived without a fracture. The mean follow-up time was 14.9 months (range: 1 day, 37.9 months). The overall DBI distribution was highly skewed, with median time-varying DBI exposure ranging from 0.93 (Q = 0.0, Q = 1.84) to 0.96 (Q = 0.0, Q = 1.90). DBI was significantly related to fracture incidence in unadjusted (

Role of Isoflurane on Hemodynamic Properties and Disposition of Nicardipine

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Bidirectional interactions between indomethacin and the murine intestinal microbiota

Abstract The vertebrate gut microbiota have been implicated in the metabolism of xenobiotic compounds, motivating studies of microbe-driven metabolism of clinically important drugs. Here, we studied interactions between the microbiota and indomethacin, a nonsteroidal antiinflammatory drug (NSAID) that inhibits cyclooxygenases (COX) -1 and -2. Indomethacin was tested in both acute and chronic exposure models in mice at clinically relevant doses, which suppressed production of COX-1-and COX-2-derived prostaglandins and caused small intestinal (SI) damage. Deep sequencing analysis showed that indomethacin exposure was associated with alterations in the structure of the intestinal microbiota in both dosing models. Perturbation of the intestinal microbiome by antibiotic treatment altered indomethacin pharmacokinetics and pharmacodynamics, which is probably the result of reduced bacterial b-glucuronidase activity. Humans show considerable inter-individual differences in their microbiota and their responses to indomethacin -thus, the drug-microbe interactions described here provide candidate mediators of individualized drug responses

BCG vaccination against tuberculosis in European badgers (Meles meles): a review

Tuberculosis (TB) is a significant animal health problem in many parts of the world, and reservoirs of infection in wild animals complicate disease control efforts in farmed livestock, particularly cattle. Badgers (Meles meles) are a significant wildlife reservoir of Mycobacterium bovis infection for cattle in the United Kingdom (UK) and Republic of Ireland (ROI). Vaccination of badgers using an M. bovis strain bacille Calmette–Guérin (BCG) vaccine could potentially be an option in the national TB eradication strategy. Wildlife vaccination has been used successfully for other diseases in wildlife species, and may have a role to play in reducing M. bovis transmission at the wildlife–livestock interface. Research to date has provided evidence that BCG is protective in badgers, and a parenteral badger BCG vaccine has been licensed in the UK. Further research is required to develop effective strategies for vaccine deployment and to determine the effect of badger vaccination on cattle TB incidence

Knowledge of Brucellosis, Health-Seeking Behaviour, and Risk Factors for Brucella Infection amongst Workers on Cattle Farms in Gauteng, South Africa

International audienceTBrucellosis in humans is under-detected and underreported in sub-Saharan Africa. Risk factors associated with Brucella infection and health seeking behaviour in response to brucellosis-like symptoms, amongst cattle farm workers and veterinary officials in South Africa, are unknown. Farm workers and veterinary officials (N = 230) were screened for brucellosis using commercial Rose Bengal Test (RBT®), IgM Enzyme-linked Immunoassay (ELISA)®, IgG ELISA® and the BrucellaCapt® test. Knowledge of brucellosis and risk factors for exposure to Brucella were also investigated. Seroprevalence varied according to test used: 10.1% (RBT®), 20.9% (IgG ELISA®) and 6.5% (BrucellaCapt®). Only 22.2% (6/27) of veterinary officials opt to visit a clinic, doctor, or hospital in response to self-experienced brucellosis-like symptoms, compared to 74.9% (152/203) of farm workers (p < 0.001). Of the BrucellaCapt® seropositive participants, 53% (7/15) did not visit a clinic in response to brucellosis-like symptoms. Weak evidence of an association between the handling of afterbirth or placenta and infection of a short evolution (RBT®, IgM ELISA® and IgG ELISA® seropositive) was found (OR = 8.9, 95% CI: 1.0–81.1, p = 0.052), and strong evidence of an association between this outcome and the slaughter of cattle (OR = 5.3, 95% CI: 1.4–19.6, p = 0.013). There was strong evidence of a positive association between inactive/resolved infection and veterinary officials vs. farm workers exposed to seropositive herds (OR = 7.0, 95% CI: 2.4–20.2, p < 0.001), with a simultaneous negative association with the handling of afterbirth or placenta (OR = 3.9, 95% CI: 1.3–11.3, p = 0.012). Findings suggest a proportion of undetected clinical cases of brucellosis amongst workers on cattle farms in Gauteng

Bovine Brucellosis in Gauteng, South Africa: Seroprevalence amongst Cattle Handlers and Variables Associated with Seropositive Cattle Herds, 2014–2016

International audienceIn South Africa, the prevalence of cattle handler exposure to Brucella on cattle farms is unknown and risk factors and cattle symptoms associated with infected cattle herds are unavailable. To address this gap, a case-control study of cattle herds was conducted in Gauteng province and farm workers and veterinary officials were tested for exposure to Brucella. Seroprevalence amongst farm workers exposed to case herds ranged from 4.0% (BrucellaCapt®) to 16.7% (IgG ELISA®), compared to those exposed to control herds, where seroprevalence ranged from 1.9% (BrucellaCapt®) to 5.7% (IgG ELISA®). Seroprevalence amongst veterinary officials was significantly greater compared to farm workers exposed to case herds for the outcome RBT+ IgM-IgG+ (OR = 11.1, 95% CI: 2.5–49.9, p = 0.002) and RBT-IgM-IgG+ (OR = 6.3, 95% CI: 2.3–17.3, p < 0.001). Risk factors associated with being an infected herd were: being a government-sponsored farm vs. private farm (OR 4.0; 95% CI: 1.4–11.3; p = 0.009), beef vs. dairy herd (OR 7.9; 95% CI: 1.4–44.9; p = 0.020), open vs. closed herd (OR 3.3; 95% CI: 1.1–10.4; p = 0.038) and the presence of antelope on the farm (OR 29.4; 95% CI: 4.0–218.2; p = 0.001). Abortions (OR = 5.1; 95% CI: 2.0–13.3; p < 0.001), weak calves in the herd (OR = 8.0; 95% CI: 2.6–24.4; p < 0.001), reduction in number of calves born (OR = 9.0; 95% CI: 2.1–43.6; p < 0.001), reduction in conception rate (OR = 3.9; 95% CI: 0.8–18.3; p = 0.046), hygromas in cattle (p = 0.011) and farmers reporting brucellosis-like symptoms in their farm workers or in him/herself (OR = 3.4; 95% CI: 1.3–8.7; p = 0.006) were more likely to be associated with Brucella infected herds than control herds. This evidence can be used in strategic planning to protect both human and herd health

OF PHARMACOLOGY Substrate-Selective Inhibition by Verapamil and Diltiazem: Differential Disposition of Antipyrine and Theophylline in Humans1

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