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Patients with systemic morphological right ventricles (RVs), including congenitally corrected transposition of the great arteries and dextro-transposition of the great arteries with a Mustard or Senning atrial baffle repair, have a high likelihood of developing systemic ventricular dysfunction. Unfortunately, there are a limited number of clinical studies on the efficacy of medical therapy for systemic RV dysfunction. We performed a systematic review and meta-analysis to assess the effect of angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), beta blockers, and aldosterone antagonists in adults with systemic RVs. The inclusion criteria included age ≥18 years, systemic RVs, and at least 3 months of treatment with ACE inhibitor, ARB, beta blocker, or aldosterone antagonist. The outcomes included RV end-diastolic and end-systolic dimensions, RV ejection fraction, functional class, and exercise capacity. EMBASE, PubMed, and Cochrane databases were searched. The selected data were pooled and analyzed with the DerSimonian-Laird random-effects meta-analysis model. Between-study heterogeneity was assessed with Cochran's Q test. A Bayesian meta-analysis model was also used in the event that heterogeneity was low. Bias assessment was performed with the Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool, and statistical risk of bias was assessed with Begg and Mazumdar's test and Egger's test. Six studies met the inclusion criteria, contributing a total of 187 patients; treatment with beta blocker was the intervention that could not be analyzed because of the small number of patients and diversity of outcomes reported. After at least 3 months of treatment with ACE inhibitors, ARBs, or aldosterone antagonists, there was no statistically significant change in mean ejection fraction, ventricular dimensions, or peak ventilatory equivalent of oxygen. The methodological quality of the majority of included studies was low, mainly because of a lack of a randomized and controlled design, small sample size, and incomplete follow-up. In conclusion, pooled results across the limited available studies did not provide conclusive evidence with regard to a beneficial effect of medical therapy in adults with systemic RV dysfunction. Randomized controlled trials or comparative-effectiveness studies that are sufficiently powered to demonstrate effect are needed to elucidate the efficacy of ACE inhibitors, ARBs, beta blockers, and aldosterone antagonists in patients with systemic RVs.

Secundum atrial septal defect (ASD) is the most common adult congenital heart defect and can present with wide variation in clinical findings. With the intention of preventing morbidity and mortality associated with late presentation of ASD, consensus guidelines have recommended surgical or percutaneous ASD closure in adults with right heart enlargement, with or without symptoms. The aim of the present analysis was to determine if the protective effect of secundum ASD closure in adults could be qualified by pooling data from published studies. A systematic review and meta-analysis were performed by using EMBASE, MEDLINE (through PubMed), and the Cochrane Library databases to assess the effect of secundum ASD percutaneous or surgical closure in unoperated adults ≥18 years of age. Data were pooled across studies with the DerSimonian-Laird random-effects model or a Bayesian meta-analysis model. Between-study heterogeneity was assessed with Cochran's Q test. Bias assessment was performed with the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool, and statistical risk of bias was assessed with Begg and Mazumdar's test and Egger's test. A total of 11 nonrandomized studies met the inclusion criteria, contributing 603 patients. Pooled analysis showed a protective effect of ASD closure on New York Heart Association functional class and on right ventricular systolic pressure, volumes, and dimensions. Two additional studies comprising 652 patients were reviewed separately for mortality outcome and primary outcome of interest because they did not meet the inclusion criteria. Those studies showed that ASD closure was associated with a weak protective effect on adjusted mortality rate but no significant impact on atrial arrhythmias in patients >50 years of age. Across all studies, there was significant heterogeneity between studies for nearly all clinical outcomes. The overall body of evidence was limited to observational cohort studies, the limitations of which make for low-strength evidence. Even within the parameters of the included studies, quality of evidence was further diminished by the lack of well-defined clinical outcomes. In conclusion, pooled data analysis on the impact of secundum ASD closure in adults was notably limited because of the lack of randomized controlled trials in patients with only secundum ASD. The few cohort studies in this population demonstrated improvement in functional status and right ventricular size and function as shown by echocardiogram. However, our findings suggest that at the time of this publication, insufficient data are available to determine the impact of ASD repair on mortality rate in adults.

Background: Much attention is paid to the negative aspects of aging with HIV. Less is known about those doing well, yet much could be learned from those aging successfully. Objective: The purpose of this study is to estimate the extent to which people aging with HIV met criteria for successful aging and maintained this status over time. A second objective was to identify factors that placed people at promise for successful aging. Methods: Participants were members of the Positive Brain Health Now (BHN) cohort which recruited from five Canadian sites (2014-2016) with prospective follow-up over 27 months. People ≥50 were classified as aging successfully if they were at or above norms on 7 or 8 of 8 health-related quality of life domains from the RAND-36. Promise factors covered socio-demographic, HIV, co-morbidity, lifestyle, resilience, and environmental domains. Group-based Trajectory Analysis, logistic regression and regression tree analysis, a form of machine learning, were applied. Results: Of the 513 people age ≥50 at study entry, 73 (14·2%) met criteria for successful aging at entry and over time. The most influential factor was loneliness: splitting the sample into two groups with the prevalence of successful aging 28·4% in the not-lonely compared to 4·6% in the lonely. Other influential factors were feeling safe, social network, motivation, stigma, and socioeconomic status. These factors identified 17 sub-groups with at least 30 members with the proportions classified as aging successfully ranging from 0% to 79·4%. Conclusion: The results indicate the important role of social determinants of health in successful aging in people with HIV. Funding Statement: This project was supported by grants from the Canadian Institutes of Health Research (LKF,MJB, NM, TCO-125272), the CIHR Canadian HIV Trials Network (CTN 273), and salary support from the Fonds de Recherche Sante du Quebec (LKF) and the Research Institute of the McGill University Health Centre (MJB). Declaration of Interests: Authors declare that they have no conflicts of interest. Ethics Approval Statement: All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The project was approved by the Research Ethics Board of each of the participating institutions. All participants provided informed consent.

Background: Confirmation of sepsis by Standard blood cultures(STD) is often inconclusive due to slow growth and low positivity. Molecular diagnostics (MOL) are faster and may have higher positivity, but test performance can be inaccurately estimated if STD methods are used as comparators.Bayesian Latent class models(LCMs) can evaluate diagnostic methods when there is no “gold standard”. Intensive Care Unit studies which have used LCMs to combine and compare STD and MOL method performance, and estimate prevalence of sepsis have not been described. Methods: Results from an ICU sepsis study which used both tests were analyzed. Bayesian LCMs combined prior prevalences of sepsis, diagnostic characteristics of the two methods ,and the study results to estimate posterior prevalence and diagnostic characteristics.Sensitivity analyses were performed by using varying objective and subjective prior parameters. Positive predictive values(PPVs) of the prevalence of sepsis were estimated for all combinations of test results. Finding: Posterior estimates were: sepsis prevalence(0·38–0·88), sensitivities(STD:0·2–0·35,MOL: 0·56–0·86) and specificities(STD:0·87–0·99,MOL:0·72–0·95) . The PPV (sepsis) of both tests being positive was (0·72–0·99). Interpretation: LCMs combined two imperfect methods to estimate prevalence,PPV, and diagnostic characteristics. The posterior estimates (STD sensitivity and STD specificity) seem to reflect clinical experience appropriately. The high PPV when both methods show positive results can be useful for ruling in disease. Funding Statement: This study has not received any funding from any source. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: This study had recruited patients from the ICU of St John’s Medical College, Bangalore from April 2010 to September 2010 after Institutional Ethical Committee approval (IEC: Ref-188/2008). Further consent for performance of this study was also obtained (IEC: Ref-002/2020).

Background: Stents immediately implanted in thrombus-laden arteries cause embolization, which paradoxically impairs myocardial reperfusion and function. Methods: We conducted a Bayesian open-label randomized trial across 15 centres in France and Canada. Patients with acute ST-elevation myocardial infarction (STEMI) and reperfused by thrombectomy or small-size balloon angioplasty were randomly assigned to immediate stenting or to a bridging anti-thrombin therapy and delayed stenting between 18h to 48h after reperfusion. Using a hierarchical Bayesian analysis, we borrowed data from exchangeable twin trials to form a posterior probability of the risk ratio (RR) for the combined occurrence of cardiovascular death, heart failure, non-fatal myocardial infarction (MI), or target-vessel revascularisation (TVR) over 9 months in the intent-to-treat populations. Findings: Between April 2014 and September 2017, 305 participants were randomly assigned to delayed (n = 152) or immediate stenting (n = 153). In parallel, four similar RCTs were reported that satisfied exchangeability requirements, leading to 1,873 participants, including 930 assigned to delayed and 943 assigned to immediate stenting. The primary endpoint occurred in 167 participants (18.1%) assigned to delayed stenting compared to 194 participants (20.6%) assigned to immediate stenting (RR, 0.91; 95% credible interval [95%CrI], 0.76 to 1.09; probability of superiority, 89%). Delayed stenting led to a meaningful increase in unplanned target revascularization acutely (RR, 1.54; 95% CrI, 0.98 to 2.41, probability of inferiority, 99%). At long term, delayed stenting reduced the combined occurrence of CV death or heart failure (RR, 0.83; 95% CrI, 0.67 to 1.02, probability of superiority, 99%). Interpretation: In patients with STEMI, delayed stenting did not reduce the occurrence of cardiovascular death, non-fatal MI, heart failure and unplanned TVR compared to the immediate stenting. There is a high probability that delayed stenting substantially reduces cardiovascular death and heart failure in the longer-term. Trial Registration: ClinicalTrials.gov identifier: NCT01542385. Funding Statement: The trial was supported by an operating grant from the peer-reviewed, publically funded Canadian Institute of Health Research (CIHR), through the Industry-Partnered Collaborative Research program (grant #298937), in collaboration with Boston Scientific and AstraZeneca (unrestricted grants support). The industry partners played no role in the conduct and oversight of the study. Declaration of Interests: The investigators disclose the following relationships: E. Marc Jolicoeur: Advisory Board: Institut National d’Excellence en Sante et Services Sociaux du Quebec, Servier, Imbria Pharmaceutical, Carre technology; Board of Directors, Societe de Sciences Vasculaires du Quebec; Data Safety Monitoring Board: XyloCor; Research grants; Boston Scientific, AstraZeneca; The University of Glasgow (employer, C Berry) holds research and/or consultancy agreements with AstraZeneca, Abbott Vascular, Boehringer Ingelheim, GSK, HeartFlow, Novartis and Siemens Healthcare; Francois Roubille: Advisory Board: Abbott, Air liquide, Research grants; Boston Scientific, AstraZeneca. Consultancy agreements with AstraZeneca, Abbott Vascular, Air liquide, Amgen, Boehringer Ingelheim, GSK, MSD, Novartis, Sanofi, Novartis, Novonordisk, Vifor; Geraud Souteyrand: Consultancy agreements; Medtronic, Abbott, and Terumo; Guillaume Cayla: Consultancy agreements; Astra Zeneca, Amgen, Abbot Vascular, BMS, Boston, Biotronik, Medtronic, Pfizer, and Sanofi; Nicolas Delarche: Advisory board: Novartis; Samer Mansour: Consultant/Advisory board/Speaker’s Bureau: Abbott vascular, Soundbite, Boehringer Ingelheim, AstraZeneca, Bayer, BMS-Pfizer Alliance, Medtronic, Amgen, Sanofi, Servier, Gilead and Novartis; Erick Schampaert: Consultant/Advisory board/Speaker’s Bureau: Abbott, AstraZeneca, Bayer, BMS-Pfizer Alliance, Medtronic, Philips-Volcano, Servier; Loic Belle: Research Grant: AstraZeneca, Medtronic, Biotronic, Boston Scientific, Abbott Vascular, Terumo Ethics Approval Statement: The protocol complied with the Declaration of Helsinki and was approved by IRB at each participating centers. The trial was coordinated by the Montreal Health Innovation Coordinating Centre under the direction of the executive committee, which was responsible for trial conduct, the integrity of the data analysis, and the reporting of results.

Using a milk sample for pregnancy diagnosis in dairy cattle is extremely convenient due to the low technical inputs required for collection of biological materials. Determining accuracy of a novel pregnancy diagnostic test that relies on a milk sample is, however, difficult since no gold standard test is available for comparison. The objective of the current study was to estimate diagnostic accuracy of the milk PAG-based ELISA and of transrectal ultrasonographic (TUS) exam for determining pregnancy status of individual dairy cows using a methodology suited for test validation in the absence of gold standard. Secondary objectives were to evaluate whether test accuracy varies with cow's characteristics and to identify the optimal ELISA optical density threshold for PAG test interpretation. Cows (n=519) from 18 commercial dairies tested with both TUS and PAG between 28 and 45days following breeding were included in the study. Other covariates (number of days since breeding, parity, and daily milk production) hypothesized to affect TUS or PAG test accuracy were measured. A Bayesian hierarchical latent class model (LCM) methodology assuming conditional independence between tests was used to obtain estimates of tests' sensitivities (Se) and specificities (Sp), to evaluate impact of covariates on these, and to compute misclassification costs across a range of ELISA thresholds. Very little disagreement was observed between tests with only 23 cows yielding discordant results. Using the LCM model with non-informative priors for tests accuracy parameters, median (95% credibility intervals [CI]) TUS Se and Sp estimates of 0.96 (0.91, 1.00) and 0.99 (0.97, 1.0) were obtained. For the PAG test, median (95% CI) Se of 0.99 (0.98, 1.00) and Sp of 0.95 (0.89, 1.0) were observed. The impact of adjusting for conditional dependence between tests was negligible. Test accuracy of the PAG test varied slightly by parity number. When assuming false negative to false positive costs ratio≥3:1, the optimal ELISA optical density threshold allowing minimization of misclassification costs was 0.25. In conclusion, both TUS and PAG showed excellent accuracy for pregnancy diagnosis in dairy cows. When using the PAG test, a threshold of 0.25 could be used for test interpretation.

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.

The ARRIVE trial showed that adverse perinatal outcomes among low-risk nulliparous women at 39 weeks’ gestation were lower following labor induction (4.3%) compared with expectant management (5.4%; P value 0.049). Although this difference was deemed to be not statistically significant (since the significance threshold had been set at 0.046), there is a need to interpret trial results using a Bayesian approach and to review the conceptual significance of trial findings. The ARRIVE trial hypothesis represents a challenge to the central paradigm of modern obstetrics because it abandons maternal or fetal compromise as a pre-requisite for early delivery. The P value function based on the ARRIVE trial shows that study findings are not consistent with even a modest increase in adverse perinatal outcomes following labor induction for 39 weeks’ gestation, and instead, consistent with a substantial reduction in adverse perinatal outcomes. Physiologic evidence, epidemiologic evidence (on gestational age-specific rates of pregnancy complications, fetal growth-restriction and perinatal morbidity and mortality), and meta-analyses of related randomized trials show that pregnancies accrue small and progressively increasing risks of adverse outcomes at later gestation. Bayesian analysis, based on previous randomized trials updated with ARRIVE trial results, also shows that labor induction for 39 weeks’ gestation has a protective effect with regard to adverse perinatal outcomes. Obstetricians need to be cognizant of this balance of risks and benefits with regard to labor induction and expectant management at 39 weeks’ gestation and beyond, though as always, the ultimate valuation in decision-making has to be guided by principles of patient autonomy.

Summary Background Microbiological confirmation of childhood tuberculosis is rare because of the difficulty of collection of specimens, low sensitivity of smear microscopy, and poor access to culture. We aimed to establish summary estimates for sensitivity and specificity of of the Xpert MTB/RIF assay compared with microscopy in the diagnosis of pulmonary tuberculosis in children. Methods We searched for studies published up to Jan 6, 2015, that used Xpert in any setting in children with and without HIV infection. We systematically reviewed studies that compared the diagnostic accuracy of Xpert MTB/RIF (Xpert) with microscopy for detection of pulmonary tuberculosis and rifampicin resistance in children younger than 16 years against two reference standards—culture results and culture-negative children who were started on anti-tuberculosis therapy. We did meta-analyses using a bivariate random-effects model. Findings We identified 15 studies including 4768 respiratory specimens in 3640 children investigated for pulmonary tuberculosis. Culture tests were positive for tuberculosis in 12% (420 of 3640) of all children assessed and Xpert was positive in 11% (406 of 3640). Compared with culture, the pooled sensitivities and specificities of Xpert for tuberculosis detection were 62% (95% credible interval 51–73) and 98% (97–99), respectively, with use of expectorated or induced sputum samples and 66% (51–81) and 98% (96–99), respectively, with use of samples from gastric lavage. Xpert sensitivity was 36–44% higher than was sensitivity for microscopy. Xpert sensitivity in culture-negative children started on antituberculosis therapy was 2% (1–3) for expectorated or induced sputum. Xpert's pooled sensitivity and specificity to detect rifampicin resistance was 86% (95% credible interval 53–98) and 98% (94–100), respectively. Interpretation Compared with microscopy, Xpert offers better sensitivity for the diagnosis of pulmonary tuberculosis in children and its scale-up will improve access to tuberculosis diagnostics for children. Although Xpert helps to provide rapid confirmation of disease, its sensitivity remains suboptimum compared with culture tests. A negative Xpert result does not rule out tuberculosis. Good clinical acumen is still needed to decide when to start antituberculosis therapy and continued research for better diagnostics is crucial. Funding WHO, Global TB Program of Texas Children's Hospital.

There is currently no gold standard method for the diagnosis of bovine respiratory disease (BRD) complex in Holstein pre-weaned dairy calves. Systematic thoracic ultrasonography (TUS) has been used as a proxy for BRD, but cannot be directly used by producers. The Wisconsin calf respiratory scoring chart (CRSC) is a simpler alternative, but with unknown accuracy. Our objective was to estimate the accuracy of CRSC, while adjusting for the lack of a gold standard. Two cross sectional study populations with a high BRD prevalence (n=106 pre-weaned Holstein calves) and an average BRD prevalence (n=85 pre-weaned Holstein calves) from North America were studied. All calves were simultaneously assessed using CRSC (cutoff used ≥ 5) and TUS (cutoff used ≥ 1cm of lung consolidation). Bayesian latent class models allowing for conditional dependence were used with informative priors for BRD prevalence and TUS accuracy (sensitivity (Se) and specificity (Sp)) and non-informative priors for CRSC accuracies. Robustness of the model was tested by relaxing priors for prevalence or TUS accuracy. The SeCRSC (95% credible interval (CI)) and SpCRSC were 62.4% (47.9-75.8) and 74.1% (64.9-82.8) respectively. The SeTUS was 79.4% (66.4-90.9) and SpTUS was 93.9% (88.0-97.6). The imperfect accuracy of CRSC and TUS should be taken into account when using those tools to assess BRD status.

Background Clostridium difficile (CD) is the leading cause of health care–associated diarrhea and can result in asymptomatic carriage. Rates of asymptomatic CD colonization on hospital admission range from 1.4%-21%. The objective of this study was to evaluate host and bacterial factors associated with colonization on admission. Methods The Consortium de recherche quebecois sur le Clostridium difficile study provided data for analysis, including demographic information, known risk factors, and potential confounding factors, prospectively collected for 5,232 patients from 6 hospitals in Quebec and Ontario over 15 months from 2006-2007. Stool or rectal swabs were obtained for culture on admission. Pulsed-field gel electrophoresis was performed on the isolates. The presence of antibody against CD toxins A and B was measured. Results There were 212 (4.05%) patients colonized with CD on admission, and 5,020 patients were not colonized with CD. Multivariate logistic regression analysis showed that hospitalization within the last 12 months, use of corticosteroids, prior CD infection, and presence of antibody against toxin B were associated with colonization on admission. Of patients colonized on admission, 79.4% had non-NAP1, non-NAP2 strains. Conclusion There are identifiable risk factors among asymptomatic CD carriers that could serve in their detection and provide a basis for targeted screening.

Objectives The purpose of this study was to test the value of gait speed, a clinical marker for frailty, to improve the prediction of mortality and major morbidity in elderly patients undergoing cardiac surgery. Background It is increasingly difficult to predict the elderly patient's risk posed by cardiac surgery because existing risk assessment tools are incomplete. Methods A multicenter prospective cohort of elderly patients undergoing cardiac surgery was assembled at 4 tertiary care hospitals between 2008 and 2009. Patients were eligible if they were 70 years of age or older and were scheduled for coronary artery bypass and/or valve replacement or repair. The primary predictor was slow gait speed, defined as a time taken to walk 5 m of ≥6 s. The primary end point was a composite of in-hospital post-operative mortality or major morbidity. Results The cohort consisted of 131 patients with a mean age of 75.8 ± 4.4 years; 34% were female patients. Sixty patients (46%) were classified as slow walkers before cardiac surgery. Slow walkers were more likely to be female (43% vs. 25%, p = 0.03) and diabetic (50% vs. 28%, p = 0.01). Thirty patients (23%) experienced the primary composite end point of mortality or major morbidity after cardiac surgery. Slow gait speed was an independent predictor of the composite end point after adjusting for the Society of Thoracic Surgeons risk score (odds ratio: 3.05; 95% confidence interval: 1.23 to 7.54). Conclusions Gait speed is a simple and effective test that may identify a subset of vulnerable elderly patients at incrementally higher risk of mortality and major morbidity after cardiac surgery.

We compared the performance of 8 Clostridium difficile enzyme immunoassays to cell cytotoxicity neutralization assay and toxigenic culture. The effect of strain type on assay performance was also examined. There were a total of 71 (14.4%) samples in which C. difficile was recovered; 58 (81.7%) of 71 were toxigenic. Compared to a composite reference standard of either C. difficile cytotoxin assay positive or toxigenic C. difficile culture positive, the sensitivities of these assays varied from 31.7% to 55.2%, while the specificities were excellent, ranging from 98.1% to 100%. Among the 57 C. difficile isolates, 30 (51.7%) were of the NAP1 genotype. Stool samples positive for the C. difficile NAP1 strain had a higher positivity rate for the toxin assays.