Open Development and Clinical Validation of Multiple 3D-Printed Nasopharyngeal Collection Swabs: Rapid Resolution of a Critical COVID-19 Testing Bottleneck.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a severe international shortage of the nasopharyngeal swabs that are required for collection of optimal specimens, creating a critical bottleneck blocking clinical laboratories' ability to perform high-sensitivity virological testing for SARS-CoV-2. To address this crisis, we designed and executed an innovative, cooperative, rapid-response translational-research program that brought together health care workers, manufacturers, and scientists to emergently develop and clinically validate new swabs for immediate mass production by 3D printing. We performed a multistep preclinical evaluation of 160 swab designs and 48 materials from 24 companies, laboratories, and individuals, and we shared results and other feedback via a public data repository (http://github.com/rarnaout/Covidswab/). We validated four prototypes through an institutional review board (IRB)-approved clinical trial that involved 276 outpatient volunteers who presented to our hospital's drive-through testing center with symptoms suspicious for COVID-19. Each participant was swabbed with a reference swab (the control) and a prototype, and SARS-CoV-2 reverse transcriptase PCR (RT-PCR) results were compared. All prototypes displayed excellent concordance with the control (κ = 0.85 to 0.89). Cycle threshold (CT ) values were not significantly different between each prototype and the control, supporting the new swabs' noninferiority (Mann-Whitney U [MWU] test, P > 0.05). Study staff preferred one of the prototypes over the others and preferred the control swab overall. The total time elapsed between identification of the problem and validation of the first prototype was 22 days. Contact information for ordering can be found at http://printedswabs.org Our experience holds lessons for the rapid development, validation, and deployment of new technology for this pandemic and beyond.

Multidisciplinary Teams for the Management of Infective Endocarditis: A Systematic Review and Meta-analysis.

Background: The management of infective endocarditis (IE) is complex owing to a high burden of morbidity and mortality. Recent guidelines recommend dedicated multidisciplinary teams (MDTs) for the management of IE. The aim of this systematic review and meta-analysis was to evaluate and summarize the effect of MDT management on patient outcomes. Methods: A systematic review was performed and, where feasible, results were meta-analyzed; otherwise, results were summarized narratively. Data extraction and quality assessment were performed in duplicate. Restricted maximum likelihood random effects models were used to calculate unadjusted risk ratios and 95% CIs. Results: Screening of 2343 studies based on title and abstract yielded 60 full-text reviews; 18 studies were summarized narratively, of which 15 were included in a meta-analysis of short-term mortality. Meta-analysis resulted in a risk ratio of 0.61 (95% CI, .47-.78; I2 = 62%) for mortality in favor of a dedicated MDT as compared with usual care. Length of stay was variable, with 55% (10/18) of studies reporting an increased length of stay. Most studies (16/18, 88.9%) reported a decreased time to surgery and an increased rate of surgery (13/18, 73%). No studies reported on patient-reported outcomes. Conclusions: This is the first systematic review and meta-analysis to assess the impact of MDT management on IE. The sum of evidence demonstrated a significant association between MDTs and improved short-term mortality. Further research is needed to evaluate benefits of virtual MDT care, cost-effectiveness, and the impact on patient-reported outcomes and long-term mortality.

Unusual Mycobacterium marinum Infection in a Heart Transplant Recipient: A Case Report.

Mycobacterium marinum (M. marinum) is a species of nontuberculous mycobacteria that is a rare cause of disease in humans and is usually associated with aquatic exposures. Symptoms manifest, on average, three weeks after exposure, although cases with longer incubation periods have been reported in the literature. Herein, we describe an unusual case presentation of an M. marinum infection in the left upper extremity of a heart transplant recipient. The case is notable for its prolonged incubation period and for being the first documented case of M. marinum infection in a heart transplant recipient. We hypothesize that, given the patient's immunosuppressive medication regimen in the post-transplant period, this case could represent a reactivation phenomenon of a latent infection.

Safety and Effectiveness of High-Dose Cefazolin in Patients With High Body Weight: A Retrospective Cohort Study.

Background: Cefazolin is a commonly used antibiotic for the treatment of mild to severe infections. Despite the use of higher dose of cefazolin (3 g/dose) for surgical prophylaxis in patients with obesity, there is currently a paucity of data identifying the optimal dose to treat infections in this specific patient population. Methods: This was a multicenter, retrospective cohort study of patients who received cefazolin at weight-based (up to 9 g/day) or standard doses (up to 6 g/day) for the treatment of bacteremia or skin and soft tissue infection (SSTI). Study groups were stratified by body weight and cefazolin dose received. Primary outcome was the composite of treatment-emergent adverse events (TEAEs) and secondary outcome was treatment failure rate. Results: A total of 208 patients were included for study analysis. Fifty-nine patients had body weight >120 kg. Of these, 33 received high-dose cefazolin while 26 received standard doses. The remaining 149 patients had body weight of ≤120 kg and received standard doses. The occurrence of TEAEs did not differ across the 3 groups. The study also did not find any difference between the rate of treatment failure between groups. Conclusions: High-dose cefazolin (9 g/day) for the treatment of bacteremia or SSTIs in patients with high body weight was safe and well tolerated. Larger studies are needed to further explore the benefit of high-dose cefazolin in improving clinical outcomes.

The impact of smoking on patient outcomes in severe sepsis and septic shock.

BACKGROUND: To assess, in the setting of severe sepsis and septic shock, whether current smokers have worse outcomes compared to non-smokers. METHODS: This is a retrospective analysis of immunocompetent adult patients with severe sepsis and septic shock at a tertiary medical center. The primary outcome was the effect of active smoking on hospital mortality. Chi-square test and logistic regression were used to assess categorical outcomes. Wilcoxon rank-sum was utilized to test the differences in continuous outcomes among the varied smoking histories. Multivariable logistic regression was used to evaluate the association of smoking and mortality, need for vasopressors, mechanical ventilation, and ICU admission. RESULTS: Of the 1437 charts reviewed, 562 patients were included. Current smokers accounted for 19% (107/562) of patients, while 81% (455/562) were non-smokers. The median hospital length of stay in survivors was significantly longer in current smokers versus non-smokers (8 vs 7 days, p = 0.03). There was a trend towards a higher mortality among current smokers, but this failed to meet statistical significance (OR 1.81, 95% CI 0.92-3.54, p = 0.08). On multivariable analysis, current smoking was associated with the need for mechanical ventilation (OR 2.38, 95% CI 1.06-5.34, p = 0.04), but that association was not observed with the need for vasopressors (OR 2.10, 95% CI 1.01-4.36, p = 0.58) nor ICU admission (OR 0.93, 95% CI 0.41-2.13, p = 0.86). CONCLUSIONS: In patients with severe sepsis or septic shock, current smoking was associated with a longer hospital stay, the need for mechanical ventilation, and trended towards a higher mortality. Larger multicenter prospective case-control studies are needed to confirm these findings.