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Background. Lung volumes can be measured by body plethysmography (BP), by inert gas dilution during a single-breath or multiple breaths and by radiographic methods based on chest roentgenogram or CT scanning. Our objective was to analyze the concordance between several methods including a new pressure-derived method (PDM) in a variety of pulmonary conditions. Methods. We recruited four groups of adult volunteers at the chronic obstructive pulmonary disease and tobacco clinic of a respiratory referral hospital: patients with lung bullae, with obstructive lung diseases, with restrictive lung diseases and healthy controls; all subjects underwent lung volume measurements according to ATS/ERS standards in random order with each method and then CT scanning. Differences among groups were estimated by Kruskal–Wallis tests. Concordance correlation coefficients (CCC) and Bland–Altman plots were performed. Results. Sixty-two patients were studied including 15 with lung bullae, 14 with obstructive lung diseases, 12 with restrictive lung disease and 21 healthy subjects. Highest concordance was obtained between BP and CT scanning (CCC 0.95, mean difference −0.35 l) and the lowest, with TLC-DLCOsb (CCC 0.65, difference −1.05 l). TLC measured by BP had a moderate concordance with the PDM (CCC = 0.91, mean difference −0.19 l). The PDM on the other hand had the lowest intra-test repeatability (2.7%) of all tested methods. Conclusions. Lung volumes measured by BP and CT had high concordance in the scenario of varied pulmonary conditions including lung bullae, restrictive and obstructive diseases. The new PDM device, had low intra-test variability, and was easy to perform, with a reasonable concordance with BP.

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

BackgroundLung volumes can be measured by body plethysmography (BP), by inert gas dilution during a single-breath or multiple breaths and by radiographic methods based on chest roentgenogram or CT scanning. Our objective was to analyze the concordance between several methods including a new instrument in a variety of pulmonary conditions.MethodsWe recruited four groups of adult volunteers at the COPD and Tobacco Clinic of a respiratory referral hospital: patients with lung bullae, with obstructive lung diseases, with restrictive lung diseases and healthy controls; all subjects underwent lung volume measurements according to ATS/ERS standards in random order with each method and then CT scanning. Differences among groups were estimated by Kruskal-Wallis tests. Concordance correlation coefficients (CCC) and Bland-Altman plots were performed.ResultsSixty-two patients were studied including 15 with lung bullae, 14 with obstructive lung diseases, 12 with restrictive lung disease and 21 healthy subjects. Highest concordance was obtained between BP and CT scanning (CCC 0.95, mean difference −0.35 L) and the lowest, with TLC-DLCOsb (CCC 0.65, difference - 1.05 L). TLC measured by BP had a moderate concordance with Minibox (CCC=0.91, mean difference −0.19 L). Minibox, on the other hand had the lowest intratest repeatibility (2.7%) of all tested methods.ConclusionsLung volumes measured by BP and CT had a substantial concordance in the scenario of varied pulmonary conditions including lung bullae, restrictive and obstructive diseases. The new minibox device, had low intratest variability, and was easy to perform, with a reasonable concordance with BP.

BackgroundSubstantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aimed to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. Methods: Rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified published and unpublished RCTs by September 14, 2020 (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, PubMed, Cochrane COVID-19 registry). All-cause mortality was extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine/chloroquine. Prespecified subgroup analyses included patient setting, diagnostic confirmation, control type, and publication status.ResultsSixty-two trials were potentially eligible. We included 16 unpublished trials (1596 patients) and 10 publications/preprints (6317 patients). The combined summary OR on all-cause mortality for hydroxychloroquine was 1.08 (95%CI: 0.99, 1.18; I2=0%; 24 trials; 7659 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I2=0%; 4 trials; 307 patients). We identified no subgroup effects.ConclusionsWe found no benefit of hydroxychloroquine or chloroquine on the survival of COVID-19 patients. For hydroxychloroquine, the confidence interval is compatible with increased mortality (OR 1.18) or negligibly reduced mortality (OR 0.99). Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.