Objectives: Amid the increasing number of pandemic coronavirus disease 2019 (COVID-19) cases, there is a need for a quick and easy method to obtain a non-invasive sample for the detection of this novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2). We aimed to investigate the potential use of saliva samples as a non-invasive tool for the diagnosis of COVID-19. Methods: From 27 March to 4 April 2020, we prospectively collected saliva samples and a standard nasopharyngeal and throat swab in persons seeking care at an acute respiratory infection clinic in a university hospital during the outbreak of COVID-19. Real-time polymerase chain reaction (RT-PCR) was performed, and the results of the two specimens were compared. Results: Two-hundred pairs of samples were collected. Sixty-nine (34.5%) individuals were male, and the median (interquartile) age was 36 (28e48) years. Using nasopharyngeal and throat swab RT-PCR as the reference standard, the prevalence of COVID-19 diagnosed by nasopharyngeal and throat swab RT-PCR was 9.5%. The sensitivity and specificity of the saliva sample RT-PCR were 84.2% (95% CI 60.4%e96.6%), and 98.9% (95% CI 96.1%e99.9%), respectively. An analysis of the agreement between the two specimens demonstrated 97.5% observed agreement (k coefficient 0.851, 95% CI 0.723e0.979; p < 0.001). Conclusions: Saliva might be an alternative specimen for the diagnosis of COVID-19. The collection is non-invasive, and non-aerosol generating. This method could facilitate the diagnosis of the disease, given the simplicity of specimen collection and good diagnostic performance.

26Objectives. Amid the increasing number of global pandemic coronavirus disease 2019 27 cases, there is a need for a quick and easy method to obtain a non-invasive 28 sample for the detection of this novel coronavirus 2019 (SARS-CoV-2). We aimed to 29 investigate the potential use of saliva samples as a non-invasive tool for the diagnosis of 30 Methods. From 27 March to 4 April, 2020, we prospectively collected saliva samples and a 32 standard nasopharyngeal and throat swab in persons seeking care at an acute respiratory 33 infection clinic in a university hospital during the outbreak of COVID-19. Real-time 34 polymerase chain reaction (RT-PCR) was performed, and the results of the two specimens 35 were compared. 36Results. Two-hundred pairs of the samples were collected. Sixty-nine (34.5%) patients were 37 male, and the median (interquartile) age was 36 (28-48) years. Using nasopharyngeal and 38 throat swab RT-PCR as the reference standard, the prevalence of COVID-19 diagnosed by 39 nasopharyngeal and throat swab RT-PCR was 9.5%. The sensitivity and specificity of the 40 saliva sample RT-PCR were 84.2% [95% confidence interval (CI) 79.2%-89.3%], and 98.9% 41 (95% CI 97.5-100.3%), respectively. An analysis of the agreement between the two 42 specimens demonstrated 97.5% observed agreement (kappa coefficient 0.851, 95% CI 0.723-43 0.979; p <0.001). 44Conclusions. Saliva specimens can be used for the diagnosis of COVID-19. The collection 45 method is non-invasive, and non-aerosol generating. Using a saliva sample as a specimen for 46 the detection of SARS-CoV-2 could facilitate the diagnosis of the disease, which is one of the 47

Essentials The association of body weight and patient-important outcomes remains unknown. Phase III randomized controlled trials of direct oral anticoagulants (DOACs) were searched. Risk of outcomes varying among body weight subgroups is not attributable to anticoagulant type. Dose adjustment of DOACs, outside that recommended, is unlikely to improve the outcomes. Click to hear Dr Braunwald's perspective on antithrombotic therapy in cardiovascular disease SUMMARY: Background Concerns have arisen in direct oral anticoagulant (DOAC)-treated patients about safety and efficacy in extremes of body weight. The aims of this systematic review were to investigate the association of body weight and patient-important outcomes in patients treated with DOACs or warfarin, and to demonstrate the fixed-dose effect of DOACs. Methods MEDLINE and EMBASE were searched until November 2016. Phase III randomized controlled trials (RCTs) using DOACs in atrial fibrillation (AF) and acute venous thromboembolism (VTE) were included. Relative risk and 95% confidence interval were calculated. The pooled estimates were performed using a Mantel-Haenszel random effects model. Results A total of 11 phase III RCTs were included. Low body weight was associated with increased risk of thromboembolism compared with non-low body weight (relative risk [RR], 1.57; 95% confidence interval [CI], 1.34-1.85). High body weight was not associated with risk of thromboembolism compared with non-high body weight (RR, 0.88; 95% CI, 0.63-1.23). The subgroup of AF patients with high body weight had a lower risk of thromboembolism compared with non-high body weight (RR, 0.43; 95% CI, 0.28-0.67). Bleeding outcomes were comparable for all body weight comparisons. There were no clear interactions between types of anticoagulant in all outcomes. Conclusion The pooled effect of both the DOAC and comparison arms was likely to be attributable to differences in baseline thrombotic risk in each body weight category, rather than an effect of the type or dose of DOAC used for each indication. Dose adjustment of DOACs, outside that recommended in the package insert, is unlikely to improve safety or efficacy.

Background Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, the incidence of thromboembolism has been increasingly reported. The aim of this systematic review was to explore the incidence of venous and arterial thromboembolism among COVID-19 patients requiring hospitalization. Methods Medline, Embase, Scopus, and grey literature were searched until June 2020. Observational studies reported on the incidence of venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT) or arterial thromboembolism (ATE) were included. The pool incidences and their 95% confidence intervals (CI) were calculated using the random-effects model. Results A total of 36 studies were included. In the intensive care unit (ICU) setting, the pooled incidence of VTE was 28% (95% CI, 22–34%). Subgroups based on compression ultrasound (CUS) screening revealed a higher incidence of DVT in the CUS screening group than in the no CUS screening group (32% [95% CI, 18–45%] vs. 6% [95% CI, 4–9%]). The pooled incidence of ATE in ICU was 3% (95% CI, 2–5%). In the non-ICU setting, the pooled incidence of VTE was 10% (95% CI, 6–14%,). Conclusions The incidence of VTE in COVID-19 patients was higher in the ICU setting than in the non-ICU setting, and also significantly higher in studies that incorporated the CUS screening protocol. The incidence of ATE in the ICU setting was low. VTE prophylactic measures should be given to all hospitalized patients diagnosed with COVID-19.

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is recognized as a common complication in critically ill patients. Risk factors including critical illness, mechanical ventilation, sedative medications, and central venous catheter insertion are major contributing factors to the high risk of VTE. Because of their impaired cardiopulmonary reserve, PE arising from thrombosis in the deep veins of the calf that propagates proximally is poorly tolerated by critically ill patients. Pharmacologic prophylaxis with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) has been shown to decrease the incidence of VTE in medical, surgical, and critically ill patients. As a result, over the past decades, VTE prophylaxis had become a standard of preventive measure in the intensive care unit (ICU). In clinical practice, the rate of VTE prophylaxis varies and may be inadequate in some centers. A perception of a high bleeding risk in critically ill patients is a major concern for most physicians that may lead to inadequate prophylaxis.

Background Extended-duration anticoagulation is beneficial for preventing recurrent venous thromboembolism (VTE). Reduced-dose direct oral anticoagulants (DOACs) may be preferable if they preserve efficacy and cause less bleeding. We conducted a systematic review and meta-analysis of trials comparing reduced-dose DOACs with full-dose DOACs and aspirin or placebo in the extended phase of VTE treatment. Methods A literature search was conducted by use of the MEDLINE, EMBASE and CINAHL databases, supplemented by hand-searching. One thousand three hundred and ninety-nine titles were screened, with data from accepted studies being extracted by two independent reviewers. Major outcomes analyzed included recurrent VTE and major and clinically relevant non-major bleeding events, presented as risk ratios (RRs) and 95% confidence intervals (CI). Results Two trials met the prespecified inclusion criteria. Data from 5847 patients were analyzed for efficacy outcomes, and from 5842 patients for safety outcomes. Reduced-dose DOACs were as effective as full-dose treatment in preventing recurrent VTE at 1 year (RR 1.12 [95% CI 0.67-1.87]), and more effective than aspirin or placebo (RR 0.26 [95% CI 0.14-0.46]). Rates of major or clinically relevant non-major bleeding events were similar between patients receiving reduced-dose DOACs and and those receiving aspirin or placebo (RR 1.19 [95% CI 0.81-1.77]). There was a trend towards less bleeding when reduced-dose and full-dose DOACs were compared (RR 0.74 [95% CI 0.52-1.05]). Conclusions Extended-duration treatment of VTE with reduced-dose DOACs may be as efficacious as full-dose treatment, with rates of major bleeding being similar to those in patients receiving treatment with aspirin or placebo, but further long-term studies are needed.

Summary. Background: Dabigatran, a direct thrombin inhibitor, is effective for the treatment of venous thromboembolism and the prevention of stroke and systemic embolism resulting from atrial fibrillation. The most effective way of reversing the anticoagulant effect of dabigatran in patients who have bleeding complications is unknown. Objectives: To document the clinical outcomes of patients undergoing renal replacement therapy (RRT) for dabigatran-associated bleeding. Methods: We searched MED-LINE and EMBASE up to May 2015. Articles were selected if the patients presented with dabigatran-associated bleeding, underwent RRT for dabigatran removal, and reported an effect on bleeding. Results: The search yielded 22 studies representing 35 unique patient cases. The median patient age was 74.1 years (range, 56-94 years). Thirteen patients (37.1%) were female, and 32 (91.4%) patients received dabigatran for atrial fibrillation. Twentythree patients (65.7%) underwent intermittent hemodialysis, 10 patients (28.6%) underwent continuous RRT (CRRT), and two patients underwent both intermittent hemodialysis and CRRT. Following RRT, there were significant reductions in dabigatran concentrations (P = 0.001). Rebound of the dabigatran concentration was reported in 12 (57.1%) patients following cessation of RRT. Hemostasis was reportedly achieved in 24 patients (70.6%), and 10 patients (29.4%) died because of bleeding. Conclusions: In patients with dabigatran-associated bleeding, RRT appears to be effective in reducing dabigatran concentrations, and in case reports this has been associated with a reduction in the duration and/or severity of bleeding. However, a rebound in concentrations may be seen following withdrawal of RRT, suggesting that a prolonged course of RRT may be more effective.

BackgroundChronic kidney disease (CKD) with edema is a common clinical problem resulting from defects in water and solute excretion. Furosemide is the drug of choice for treatment. In theory, good perfusion and albumin are required for the furosemide to be secreted at the tubular lumen. Thus, in the situation of low glomerular filtration rate (GFR) and hypoalbuminemia, the efficacy of furosemide alone might be limited. There has been no study to validate the effectiveness of the combination of furosemide and albumin in this condition.MethodsWe conducted a randomized controlled crossover study to compare the efficacy of diuretics between furosemide alone and the combination of furosemide plus albumin in stable hypoalbuminemic CKD patients by measuring urine output and sodium. The baseline urine output/sodium at 6 and 24 hours were recorded. The increment of urine output/sodium after treatment at 6 and 24 hours were calculated by using post-treatment minus baseline urine output/sodium at the corresponding period.ResultsTwenty-four CKD patients (GFR = 31.0 ± 13.8 mL/min) with hypoalbuminemia (2.98 ± 0.30 g/dL) were enrolled. At 6 hours, there were significant differences in the increment of urine volume (0.47 ± 0.40 vs 0.67 ± 0.31 L, P < 0.02) and urine sodium (37.5 ± 29.3 vs 55.0 ± 26.7 mEq, P < 0.01) between treatment with furosemide alone and with furosemide plus albumin. However, at 24 hours, there were no significant differences in the increment of urine volume (0.49 ± 0.47 vs 0.59 ± 0.50 L, P = 0.46) and urine sodium (65.3 ± 47.5 vs 76.1 ± 50.1 mEq, P = 0.32) between the two groups.ConclusionThe combination of furosemide and albumin has a superior short-term efficacy over furosemide alone in enhancing water and sodium diuresis in hypoalbuminemic CKD patients.Trial registrationThe Australian New Zealand Clinical Trials Registration (ANZCTR12611000480987)