Systematic review and meta-analysis of refractometry for diagnosis of inadequate transfer of passive immunity in dairy calves: Quantifying how accuracy varies with threshold using a Bayesian approach.

Inadequate transfer of passive immunity (TPI) is associated with increased risk for calfhood disease and increased risk of mortality and morbidity. Accurately diagnosing calves and herds with inadequate TPI is of primary importance and brix (BRIX) or classical refractometer (REF) devices are more practical for this purpose than measuring the serum immunoglobulin G concentration in neonatal calves. We previously reported a systematic review and meta-analysis for quantifying the pooled accuracy of BRIX and REF for detecting calves with serum IgG < 10 g/L noting that sparse data were available especially because studies did not report the same thresholds. We updated the previous systematic review using different methods that accounted for the test results distribution in calves with or without inadequate TPI. With this approach, all reported cut-offs for a specific study are used in that Bayesian approach that quantifies how accuracy varied among all reported thresholds. Five new manuscripts were included, which represented 4 new studies since the initial study was performed. A total of 11 REF and 9 BRIX studies were available. The meta-analytic methods allowed reporting variation of the true and false positive rate across and among all reported cut-offs. Pooled points estimates (95 % Bayesian credible intervals) for sensitivity (Se) and specificity (Sp) of REF < 5.5 g/L were 86.1 % (68.5-97.9%) and 76.2 % (65.9-88.4%) whereas BRIX < 8.4 % was associated with Se of 91.6 % (77.2-99.5%) and Sp of 88.2 % (65.4-99.8%). Interestingly, the accuracy (Se + Sp-1) was generally higher for BRIX than for REF at the reported cut-offs. Besides the benefit of providing pooled estimates for all reported and unreported BRIX and REF thresholds, the general framework used in this study could potentially be used in many veterinary diagnostic tests studies that reported multiple thresholds accounting for potentially different tests distributions in population with and without the target condition.

Accuracy of paratuberculosis diagnostic tests in small ruminants: protocol for a systematic review and meta-analysis.

Paratuberculosis is a worldwide infectious disease caused by Mycobacterium avium ssp. paratuberculosis (MAP). Various ruminant species can be affected by the disease, and the diagnosis of the disease is challenging in the absence of a gold standard test. The aim of this systematic review protocol is to determine the accuracy of the direct and indirect diagnostic tests for MAP infection with a special focus on sheep and goats.

Diagnostic accuracy of clinical illness for bovine respiratory disease (BRD) diagnosis in beef cattle placed in feedlots: A systematic literature review and hierarchical Bayesian latent-class meta-analysis.

Diagnosis of bovine respiratory disease (BRD) in beef cattle placed in feedlots is typically based on clinical illness (CI) detected by pen-checkers. Unfortunately, the accuracy of this diagnostic approach (namely, sensitivity [Se] and specificity [Sp]) remains poorly understood, in part due to the absence of a reference test for ante-mortem diagnosis of BRD. Our objective was to pool available estimates of CI's diagnostic accuracy for BRD diagnosis in feedlot beef cattle while adjusting for the inaccuracy in the reference test. The presence of lung lesions (LU) at slaughter was used as the reference test. A systematic review of the literature was conducted to identify research articles comparing CI detected by pen-checkers during the feeding period to LU at slaughter. A hierarchical Bayesian latent-class meta-analysis was used to model test accuracy. This approach accounted for imperfections of both tests as well as the within and between study variability in the accuracy of CI. Furthermore, it also predicted the SeCI and SpCI for future studies. Conditional independence between CI and LU was assumed, as these two tests are not based on similar biological principles. Seven studies were included in the meta-analysis. Estimated pooled SeCI and SpCI were 0.27 (95% Bayesian credible interval: 0.12-0.65) and 0.92 (0.72-0.98), respectively, whereas estimated pooled SeLU and SpLU were 0.91 (0.82-0.99) and 0.67 (0.64-0.79). Predicted SeCI and SpCI for future studies were 0.27 (0.01-0.96) and 0.92 (0.14-1.00), respectively. The wide credible intervals around predicted SeCI and SpCI estimates indicated considerable heterogeneity among studies, which suggests that pooled SeCI and SpCI are not generalizable to individual studies. In conclusion, CI appeared to have poor Se but high Sp for BRD diagnosis in feedlots. Furthermore, considerable heterogeneity among studies highlighted an urgent need to standardize BRD diagnosis in feedlots.

Systematic review and meta-analysis of antigen detection tests for the diagnosis of tuberculosis.

Tests that detect Mycobacterium tuberculosis antigens in clinical specimens could provide rapid direct evidence of active disease. We performed a systematic review to assess the diagnostic accuracy of antigen detection tests for active tuberculosis (TB) according to standard methods and summarized test performance using bivariate random effects meta-analysis. Overall, study quality was a concern. For pulmonary TB (47 studies, 5,036 participants), sensitivity estimates ranged from 2% to 100% and specificity from 33% to 100%. Lipoarabinomannan (LAM) was the antigen most frequently targeted (23 studies, 49%). The pooled sensitivity of urine LAM was higher in HIV-infected than HIV-uninfected individuals (47%; 95% confidence interval [CI], 26 to 68% versus 14%; 95% CI, 4 to 38%); pooled specificity estimates were similar: 96%; 95% CI, 81 to 100% and 97%; 95% CI, 86 to 100%, respectively. For extrapulmonary TB (21 studies, 1,616 participants), sensitivity estimates ranged from 0% to 100% and specificity estimates from 62% to 100%. Five studies targeting LAM, ESAT-6, Ag85 complex, and the 65-kDa antigen in cerebrospinal fluid, when pooled, yielded the highest sensitivity (87%; 95% CI, 61 to 98%), but low specificity (84%; 95% CI, 60 to 95%). Because of the limited number of studies targeting any specific antigen other than LAM, we could not draw firm conclusions about the overall clinical usefulness of these tests. Further studies are warranted to determine the value of LAM detection for TB meningitis in high-HIV-prevalence settings. Considering that antigen detection tests could be translated into rapid point-of-care tests, research to improve their performance is urgently needed.

The clinical effectiveness of negative pressure wound therapy: a systematic review.

OBJECTIVE: To estimate the efficacy of negative pressure wound therapy (NPWT), on the basis of a systematic review of reported randomised controlled trials (RCTs). METHOD: A systematic literature search for relevant RCTs was carried out. The credibility of the outcome of each study was evaluated using a specially constructed instrument. RESULTS: We identified 17 RCTs, of which five had not been included in previous reviews or health technology assessments. For diabetic foot ulcers (seven RCTs), there was consistent evidence of the benefit of NPWT compared with control treatments. For pressure ulcers (three RCTs), results were conflicting. In trials involving mixed wounds (five RCTs), evidence was encouraging but of inadequate quality. Significant complications were not increased. CONCLUSION: There is now sufficient evidence to show that NPWT is safe, and will accelerate healing, to justify its use in the treatment of diabetes-associated chronic leg wounds. There is also evidence, though of poor quality, to suggest that healing of other wounds may also be accelerated.

Improving the estimation of tuberculosis infection prevalence using T-cell-based assay and mixture models.

BACKGROUND: The prevalence of latent tuberculosis infection (LTBI) is traditionally estimated using the tuberculin skin test (TST). Highly specific blood-based interferon-gamma release assays (IGRAs) are now available and could enhance the estimation of LTBI prevalence in combination with model-based methods. DESIGN: We compared conventional and model-based methods for estimating LTBI prevalence among 719 Indian health care workers who underwent both TST and QuantiFERON-TB Gold In-Tube (QFT-G). In addition to using standard cut-off points on TST and QFT-G, Bayesian mixture model analyses were performed with: 1) continuous TST data and 2) categorical data using both TST and QFT-G results in a latent class analysis (LCA), accounting for prior information on sensitivity and specificity. RESULTS: Estimates of LTBI prevalence varied from 33.8% to 60.7%, depending on the method used. The mixture model based on TST alone estimated the prevalence at 36.5% (95%CI 28.5-47.0). When results from both tests were combined using LCA, the prevalence was 45.4% (95%CI 39.5-51.1). The LCA provided additional results on the sensitivity, specificity and predictive values of joint results. CONCLUSION: The availability of novel, specific IGRAs and development of methods such as mixture analyses allow a more realistic and informative approach to prevalence estimation.

The role of gowns in preventing nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA): gown use in MRSA control.

During a 2-year period, a standard isolation protocol for control of methicillin-resistant Staphylococcus aureus was compared with a similar protocol in which gowns were not used but the availability of alcohol-based hand disinfectant was increased. Intervention wards had 0.10 fewer new MRSA transmissions per ward per month, compared with control wards (P was not significant).

Delirium in older medical inpatients and subsequent cognitive and functional status: a prospective study.

BACKGROUND: Delirium in older hospital inpatients appears to be associated with various adverse outcomes. The limitations of previous research on this association have included small sample sizes, short follow-up periods and lack of consideration of important confounders or modifiers, such as severity of illness, comorbidity and dementia. The objective of this study was to determine the prognostic significance of delirium, with or without dementia, for cognitive and functional status during the 12 months after hospital admission, independent of premorbid function, comorbidity, severity of illness and other potentially confounding variables. METHODS: Patients 65 years of age and older who were admitted from the emergency department to the medical services were screened for delirium during their first week in hospital. Two cohorts were enrolled: patients with prevalent or incident delirium and patients without delirium, but similar in age and cognitive impairment. The patients were followed up at 2, 6 and 12 months after hospital admission. Analyses were conducted for 4 patient groups: 56 with delirium, 53 with dementia, 164 with both conditions and 42 with neither. Baseline measures included delirium (Confusion Assessment Method), dementia (Informant Questionnaire on Cognitive Decline in the Elderly), physical function (Barthel Index [BI] and premorbid instrumental activities of daily living, IADL), the Mini-Mental State Examination (MMSE), comorbidity, and physiologic and clinical severity of illness. Outcome variables measured at follow-up were the MMSe, Barthel Index, IADL and admission to a long-term care facility. RESULTS: After adjustment for covariates, the mean differences in MMSE scores at follow-up between patients with and without delirium were -4.99 (95% confidence interval [CI] -7.17 to -2.81) for patients with dementia and -3.36 (95% CI -6.15 to -0.58) for those without dementia. At 12 months, the adjusted mean differences in the BI were -16.45 (95% CI -27.42 to -5.50) and -13.89 (95% CI -28.39 to 0.61) for patients with and without dementia respectively. Patients with both delirium and dementia were more likely to be admitted to long-term care than those with neither condition (adjusted odds ratio 3.18, 95% CI 1.19 to 8.49). Dementia but not delirium predicted worse IADL scores at follow-up. Unadjusted analyses yielded similar results. INTERPRETATION: For older patients with and without dementia, delirium is an independent predictor of sustained poor cognitive and functional status during the year after a medical admission to hospital.

Bayesian approaches to modeling the conditional dependence between multiple diagnostic tests.

Many analyses of results from multiple diagnostic tests assume the tests are statistically independent conditional on the true disease status of the subject. This assumption may be violated in practice, especially in situations where none of the tests is a perfectly accurate gold standard. Classical inference for models accounting for the conditional dependence between tests requires that results from at least four different tests be used in order to obtain an identifiable solution, but it is not always feasible to have results from this many tests. We use a Bayesian approach to draw inferences about the disease prevalence and test properties while adjusting for the possibility of conditional dependence between tests, particularly when we have only two tests. We propose both fixed and random effects models. Since with fewer than four tests the problem is nonidentifiable, the posterior distributions are strongly dependent on the prior information about the test properties and the disease prevalence, even with large sample sizes. If the degree of correlation between the tests is known a priori with high precision, then our methods adjust for the dependence between the tests. Otherwise, our methods provide adjusted inferences that incorporate all of the uncertainty inherent in the problem, typically resulting in wider interval estimates. We illustrate our methods using data from a study on the prevalence of Strongyloides infection among Cambodian refugees to Canada.

Rapid emergency department intervention for older people reduces risk of functional decline: results of a multicenter randomized trial.

OBJECTIVES: To determine the effectiveness of a two-stage (screening and nursing assessment) intervention for older patients in the emergency department (ED) who are at increased risk of functional decline and other adverse outcomes. DESIGN: Controlled trial, randomized by day of ED visit, with follow-up at 1 and 4 months. SETTING: Four university-affiliated hospitals in Montreal. PARTICIPANTS: Patients age 65 and older expected to be released from the ED to the community with a score of 2 or more on the Identification of Seniors At Risk (ISAR) screening tool and their primary family caregivers. One hundred seventy-eight were randomized to the intervention, 210 to usual care. INTERVENTION: The intervention consisted of disclosure of results of the ISAR screen, a brief standardized nursing assessment in the ED, notification of the primary care physician and home care providers, and other referrals as needed. The control group received usual care, without disclosure of the screening result. MEASUREMENTS: Patient outcomes assessed at 4 months after enrollment included functional decline (increased dependence on the Older American Resources and Services activities of daily living scale or death) and depressive symptoms (as assessed by the short Geriatric Depression Scale). Caregiver outcomes, also assessed at baseline and 4 months, included the physical and mental summary scales of the Medical Outcomes Study Short Form-36. Patient and caregiver satisfaction with care were assessed 1 month after enrollment. RESULTS: The intervention increased the rate of referral to the primary care physician and to home care services. The intervention was associated with a significantly reduced rate of functional decline at 4 months, in both unadjusted (odds ratio (OR) = 0.60, 95% confidence interval (CI) = 0.36-0.99) and adjusted (OR = 0.53, 95% CI = 0.31-0.91) analyses. There was no intervention effect on patient depressive symptoms, caregiver outcomes, or satisfaction with care. CONCLUSION: A two-stage ED intervention, consisting of screening with the ISAR tool followed by a brief, standardized nursing assessment and referral to primary and home care services, significantly reduced the rate of subsequent functional decline.