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of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished.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 We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed,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 We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients).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.

This nationwide prospective cohort study demonstrates that DVT and PE risks significantly increased in patients with RA compared with those of the general population.

Objective In this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study. Methods Subjects admitted to 11 designated public hospitals in Taiwan between April 1 and May 31, 2020, with COVID-19 diagnosis confirmed by pharyngeal real-time RT-PCR for SARS-CoV-2, were randomized at a 2:1 ratio and stratified by mild or moderate illness. HCQ (400 mg twice for 1 d or HCQ 200 mg twice daily for 6 days) was administered. Both the study and control group received standard of care (SOC). Pharyngeal swabs and sputum were collected every other day. The proportion and time to negative viral PCR were assessed on day 14. In the retrospective study, medical records were reviewed for patients admitted before March 31, 2020. Results There were 33 and 37 cases in the RCT and retrospective study, respectively. In the RCT, the median times to negative rRT-PCR from randomization to hospital day 14 were 5 days (95% CI; 1, 9 days) and 10 days (95% CI; 2, 12 days) for the HCQ and SOC groups, respectively (p = 0.40). On day 14, 81.0% (17/21) and 75.0% (9/12) of the subjects in the HCQ and SOC groups, respectively, had undetected virus (p = 0.36). In the retrospective study, 12 (42.9%) in the HCQ group and 5 (55.6%) in the control group had negative rRT-PCR results on hospital day 14 (p = 0.70). Conclusions Neither study demonstrated that HCQ shortened viral shedding in mild to moderate COVID-19 subjects.

Studies on the association between asthma and pulmonary thromboembolism are considerably limited. We investigated whether pulmonary embolism is associated with asthma using a nationwide cohort study.We identified 31 356 patients with newly diagnosed asthma in 2002-2008 and 125 157 individuals without asthma randomly selected from the general population, frequency matched by age, sex and index year using the National Health Insurance Research Database. Both cohorts were followed-up until the end of 2010 to measure the incidence of pulmonary embolism. Cox proportional hazards regression analysis was used to measure the hazard ratio of pulmonary embolism for the asthmatic cohort, compared with the nonasthmatic cohort.We followed 186 182 person-years for asthmatic patients and 743 374 person-years for nonasthmatic subjects. The hazard ratio of pulmonary embolism was 3.24 for the asthmatic cohort, compared with the nonasthmatic cohort after adjusting for sex, age, comorbidities and oestrogen supplementation. The risk of developing pulmonary embolism significantly increased with the increased frequency of asthma exacerbation and hospitalisation.This nationwide cohort study suggests that the risk of developing pulmonary embolism is significantly increased in asthmatic patients compared to the general population. Frequent asthma exacerbation and hospitalisation are significantly associated with pulmonary embolism risk. @ERSpublications Risk of pulmonary embolism in an asthmatic cohort was 3.24-fold compared with a nonasthmatic cohort

Epidemiologic studies investigating the differences in respiratory outcomes between asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS) and chronic obstructive pulmonary disease (COPD) in an Asian population are lacking.We conducted a population-based cohort study to compare the incidence of acute respiratory events between ACOS and COPD cohorts in Taiwan. This study investigated the incidence of acute respiratory events, namely, pneumonia, acute exacerbation, acute respiratory failure, and cardiopulmonary arrest, in 8571 patients with physician-diagnosed ACOS between 2000 and 2007 from the Longitudinal Health Insurance Database. The comparison cohort comprised 17,088 COPD patients, frequency-matched according to age, sex, and the index-year. The duration of follow-up was measured for each patient from the index date to 5 years thereafter. We used univariable and multivariable Poisson regression models to analyze the risk of acute respiratory events by including the variables of sex, age, and comorbidity.The overall prevalence of ACOS was approximately 17.4% in patients with COPD. The prevalence of ACOS increased with age. During the 5-year follow-up, a greater incidence of acute respiratory events was observed in the ACOS cohort than in the COPD cohort (11.5 and 4.62, per 100 person-years, respectively) with an adjusted incidence rate ratio (IRR) of 1.72 (95% confidence interval [CI] = 1.63–1.81). Compared with the COPD cohort, the ACOS patients had a 1.13-fold adjusted IRR of pneumonia (95% CI = 1.07–1.20) and a 2.58-fold adjusted IRR of acute exacerbation (95% CI = 2.43–2.74). Clinicians should be aware of frequent exacerbation of ACOS and prescribe appropriate treatment.

BackgroundPolysomnography (PSG) is treated as the gold standard for diagnosing obstructive sleep apnea (OSA). However, it is labor-intensive, time-consuming, and expensive. This study evaluates validity of overnight pulse oximetry as a diagnostic tool for moderate to severe OSA patients.MethodsA total of 699 patients with possible OSA were recruited for overnight oximetry and PSG examination at the Sleep Center of a University Hospital from Jan. 2004 to Dec. 2005. By excluding 23 patients with poor oximetry recording, poor EEG signals, or respiratory artifacts resulting in a total recording time less than 3 hours; 12 patients with total sleeping time (TST) less than 1 hour, possibly because of insomnia; and 48 patients whose ages less than 20 or more than 85 years old, data of 616 patients were used for further study. By further considering 76 patients with TST < 4 h, a group of 540 patients with TST ≥ 4 h was used to study the effect of insufficient sleeping time. Alice 4 PSG recorder (Respironics Inc., USA) was used to monitor patients with suspected OSA and to record their PSG data. After statistical analysis and feature selection, models built based on support vector machine (SVM) were then used to diagnose moderate and moderate to severe OSA patients with a threshold of AHI = 30 and AHI = 15, respectively.ResultsThe SVM models designed based on the oxyhemoglobin desaturation index (ODI) derived from oximetry measurements provided an accuracy of 90.42-90.55%, a sensitivity of 89.36-89.87%, a specificity of 91.08-93.05%, and an area under ROC curve (AUC) of 0.953-0.957 for the diagnosis of severe OSA patients; as well as achieved an accuracy of 87.33-87.77%, a sensitivity of 87.71-88.53%, a specificity of 86.38-86.56%, and an AUC of 0.921-0.924 for the diagnosis of moderate to severe OSA patients. The predictive outcome of ODI to diagnose severe OSA patients is better than to diagnose moderate to severe OSA patients.ConclusionsOvernight pulse oximetry provides satisfactory diagnostic performance in detecting severe OSA patients. Home-styled oximetry may be a tool for severe OSA diagnosis.

Background: 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 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. Results: Sixty-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; I-square=0%; 24 trials; 7659 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-square=0%; 4 trials; 307 patients). We identified no subgroup effects. Conclusions: We 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.

To cite this article: Chung WS, Lin CL, Chang SN, Lu CC, Kao CH. Systemic lupus erythematosus increases the risks of deep vein thrombosis and pulmonary embolism: a nationwide cohort study. J Thromb Haemost 2014; 12: 452-8.Summary. Background: Studies on the risks of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with systemic lupus erythematosus (SLE) are limited. We evaluated the effects of SLE on the risks of developing DVT and PE in a nationwide, populationbased cohort study in Taiwan. Methods: We randomly selected patients without SLE from the National Health Insurance database (N = 23.74 million), and frequencymatched four of them, on the basis of age, sex, and index year, to each SLE patient in the catastrophic illness registry of the NHI who was diagnosed with SLE between 1998 and 2008. Using a follow-up period ending in 2010, we analyzed the risks of DVT and PE with a Cox proportional-hazards regression analysis. Results: The 13 084 SLE patients (87.9% women; mean age of 35.6 years) and 52 336 controls were followed for 90 237 and 379 185 person-years, respectively. After adjustment for age, sex, and comorbidities, the SLE patients' risks of developing DVT and PE were 12.8-fold and 19.7-fold higher, respectively, than those of the comparison cohort. The risks of DVT and PE increased in both study groups when the data were stratified on the basis of sex, age, and comorbidities. The SLE patients aged ≤ 35 years had the highest risks of developing DVT and PE. The multiplicative increased risks of DVT and PE were also significant in SLE patients with any comorbidity. Conclusion: The risks of DVT and PE are significantly higher in SLE patients than in the general population.