Systolic Pulmonary Artery Pressure Thresholds Predictive of Dyspnea on Stress Doppler Echocardiography in Mitral Stenosis.

Background: On Stress Doppler Echocardiography (SDE) in mitral stenosis, the systolic pulmonary artery pressure (SPAP) threshold at peak exercise recommended by the guidelines as an indication for percutaneous mitral commissurotomy (PMC) used to be 60 mmHg. However, because of the paucity of studies, that threshold has been controversial. The Europeans stopped using the value in 2007, followed by the Americans in 2014. Objective: Determine SPAP thresholds on SDE at peak exercise and post-exercise predictive of dyspnea as an indication for PMC in mitral stenosis. Method and results: Three hundred mitral stenosis patients with a mitral valve area (MVA) ≤ 2 cm2 and NYHA I-II-III were included. A treadmill stress test (Bruce protocol) was used in all cases to distinguish dyspneic patients (n = 182) from non dyspneic patients (n = 118). SDE was performed on a stress echocardiography bed, starting at 30 W and increasing by 30 W every 3 min. At peak exercise, the best SPAP threshold obtained was 75 mmHg: specificity (Sp) = 0.98 (0.94-1), positive likelihood ratio (LR+) = 47 (41-50), positive predictive value (PPV) = 0.99 (0.95-1), and positive predictive error (PPE) = 0.01 (0.002-0.05). This compared with, respectively, 0.34, 1, 0.69 and 0.31 at 60 mmHg. Post-exercise, the best SPAP threshold found was 60 mmHg: Sp = .94 (0.88-0.97), LR = 9 (4-10), PPV = 0.94 (0.87-0.97), and PPE = 0.06 (0.03-0.13). Conclusion: Regarding the prediction of dyspnea as an indication for PMC, our study shows that a SPAP value at peak exercise of 60 mmHg lacks predictive power (LR+=1). The optimal threshold observed was 75 mmHg at peak exercise (LR+ = 47 [41-50]) and 60 mmHg post-exercise (LR+ = 9 [4-10]).

Infant BCG vaccination and risk of pulmonary and extrapulmonary tuberculosis throughout the life course: a systematic review and individual participant data meta-analysis.

BACKGROUND: BCG vaccines are given to more than 100 million children every year, but there is considerable debate regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis (pulmonary and extrapulmonary) development and mortality. METHODS: In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts published between Jan 1, 1998, and April 7, 2018. Search terms included "mycobacterium tuberculosis", "TB", "tuberculosis", and "contact". We excluded cohort studies that did not provide information on BCG vaccination or were done in countries that did not recommend BCG vaccination at birth. Individual-level participant data for a prespecified list of variables, including the characteristics of the exposed participant (contact), the index case, and the environment, were requested from authors of all eligible studies. Our primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) tuberculosis in contacts exposed to tuberculosis. Secondary outcomes were pulmonary tuberculosis, extrapulmonary tuberculosis, and mortality. We derived adjusted odds ratios (aORs) using mixed-effects, binary, multivariable logistic regression analyses with study-level random effects, adjusting for the variable of interest, baseline age, sex, previous tuberculosis, and whether data were collected prospectively or retrospectively. We stratified our results by contact age and Mycobacterium tuberculosis infection status. This study is registered with PROSPERO, CRD42020180512. FINDINGS: We identified 14 927 original records from our database searches. We included participant-level data from 26 cohort studies done in 17 countries in our meta-analysis. Among 68 552 participants, 1782 (2·6%) developed tuberculosis (1309 [2·6%] of 49 686 BCG-vaccinated participants vs 473 [2·5%] of 18 866 unvaccinated participants). The overall effectiveness of BCG vaccination against all tuberculosis was 18% (aOR 0·82, 95% CI 0·74-0·91). When stratified by age, BCG vaccination only significantly protected against all tuberculosis in children younger than 5 years (aOR 0·63, 95% CI 0·49-0·81). Among contacts with a positive tuberculin skin test or IFNγ release assay, BCG vaccination significantly protected against tuberculosis among all participants (aOR 0·81, 95% CI 0·69-0·96), participants younger than 5 years (0·68, 0·47-0·97), and participants aged 5-9 years (0·62, 0·38-0·99). There was no protective effect among those with negative tests, unless they were younger than 5 years (0·54, 0·32-0·90). 14 cohorts reported on whether tuberculosis was pulmonary or extrapulmonary (n=57 421). BCG vaccination significantly protected against pulmonary tuberculosis among all participants (916 [2·2%] in 41 119 vaccinated participants vs 334 [2·1%] in 16 161 unvaccinated participants; aOR 0·81, 0·70-0·94) but not against extrapulmonary tuberculosis (106 [0·3%] in 40 318 vaccinated participants vs 38 [0·2%] in 15 865 unvaccinated participants; 0·96, 0·65-1·41). In the four studies with mortality data, BCG vaccination was significantly protective against death (0·25, 0·13-0·49). INTERPRETATION: Our results suggest that BCG vaccination at birth is effective at preventing tuberculosis in young children but is ineffective in adolescents and adults. Immunoprotection therefore needs to be boosted in older populations. FUNDING: National Institutes of Health.

Incidence of tuberculosis among children living in contact with smear-positive tuberculosis: Advantages and limits of the Quantiferon TB gold in tube test.

OBJECTIVE/BACKGROUND: Children living in contact with smear-positive pulmonary tuberculosis (TB) patients are highly exposed to TB infection. Our objective was to estimate the incidence of TB in children living in contact with a Smear Positive (M+) pulmonary tuberculosis (PTM+) index case during 2years following exposure. METHODS: This was a descriptive, cohort, prospective, multicenter study of children aged from 6months to 15years in contact with a PTM+ case. The recruitment of children has been based on the diagnosed PTM+ index case and taken in charge by the Services of Control of Tuberculosis and Respiratory Diseases located in Algiers during 2014. Seven centers were selected. All children were tested using the Quantiferon TB gold in tube (QTR) test and the tuberculin skin test (TST). For TST, an induration diameter ⩾10mm was considered positive. RESULTS: We included 456 children living in contact with a PTM+ patient. The results for TST and QFT were available for 319 children. The mean age of the children was 6.7years (standard deviation=3.9). The sex ratio (Male/Female) was 1.26, and 15.8% (50) did not have a Bacilli of Calmette & Guerin (BCG) vaccination scar. Among the children, 46.1% (147) and 43.4% (138) were positive for QFT and TST, respectively, and 6.1% (19) have received isoniazid preventive therapy. Fifty-one children progressed to TB and received antitubercular treatment. We analyzed and compared our results between children who progressed to TB and those who did not progress to TB. Finally, we discuss our methodology and results in relation to the literature.