IMPORTANCEThe role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in the setting of the coronavirus disease 2019 (COVID-19) pandemic is hotly debated. There have been recommendations to discontinue these medications, which are essential in the treatment of several chronic disease conditions, while, in the absence of clinical evidence, professional societies have advocated their continued use. OBJECTIVE To study the association between use of ACEIs/ARBs with the likelihood of testing positive for COVID-19 and to study outcome data in subsets of patients taking ACEIs/ARBs who tested positive with severity of clinical outcomes of COVID-19 (eg, hospitalization, intensive care unit admission, and requirement for mechanical ventilation). DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study with overlap propensity score weighting was conducted at the Cleveland Clinic Health System in Ohio and Florida. All patients tested for COVID-19 between March 8 and April 12, 2020, were included. EXPOSURES History of taking ACEIs or ARBs at the time of COVID-19 testing. MAIN OUTCOMES AND MEASURES Results of COVID-19 testing in the entire cohort, number of patients requiring hospitalizations, intensive care unit admissions, and mechanical ventilation among those who tested positive.RESULTS A total of 18 472 patients tested for COVID-19. The mean (SD) age was 49 (21) years, 7384 (40%) were male, and 12 725 (69%) were white. Of 18 472 patients who underwent COVID-19 testing, 2285 (12.4%) were taking either ACEIs or ARBs. A positive COVID-19 test result was observed in 1735 of 18 472 patients (9.4%). Among patients who tested positive, 421 (24.3%) were admitted to the hospital, 161 (9.3%) were admitted to an intensive care unit, and 111 (6.4%) required mechanical ventilation. Overlap propensity score weighting showed no significant association of ACEI and/or ARB use with COVID-19 test positivity (overlap propensity score-weighted odds ratio, 0.97; 95% CI, 0.81-1.15). CONCLUSIONS AND RELEVANCEThis study found no association between ACEI or ARB use and COVID-19 test positivity. These clinical data support current professional society guidelines to not discontinue ACEIs or ARBs in the setting of the COVID-19 pandemic. However, further study in larger numbers of hospitalized patients receiving ACEI and ARB therapy is needed to determine the association with clinical measures of COVID-19 severity.

Tools for genetically-determined visualization of synaptic circuits and interactions are necessary to build connectomics of the vertebrate brain and to screen synaptic properties in neurological disease models. Here we develop a transgenic FingR (fibronectin intrabodies generated by mRNA display) technology for monitoring synapses in live zebrafish. We demonstrate FingR labeling of defined excitatory and inhibitory synapses, and show FingR applicability for dissecting synapse dynamics in normal and disease states. Using our system we show that chronic hypoxia, associated with neurological defects in preterm birth, affects dopaminergic neuron synapse number depending on the developmental timing of hypoxia.

Objective:To summarize risk factors for Clostridioides (formerly Clostridium) difficile infection (CDI) in hospitalized pediatric patients as determined by previous observational studies.Design:Meta-analysis and systematic review.Patients:Studies evaluating risk factors for CDI in pediatric inpatients were eligible for inclusion.Method:We systematically searched MEDLINE, Web of Science, Scopus, and EMBASE for subject headings and text words related to CDI and pediatrics from 1975 to 2017. Two of the investigators independently screened studies, extracted and compiled data, assessed study quality, and performed the meta-analysis.Results:Of the 2,033 articles screened, 14 studies reporting 10,531,669 children met the inclusion criteria. Prior antibiotic exposure (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.31–3.52) and proton pump inhibitor (PPI) use (OR, 1.33; 95% CI, 1.07–1.64) were associated with an increased risk of CDI in children. Subgroup analyses using studies reporting only adjusted results suggested that prior antibiotic exposure is not a significant risk factor for CDI. H2 receptor antagonist (H2RA) use (OR, 1.36; 95% CI, 0.31–5.98) and that female gender (OR, 0.87; 95% CI, 0.74–1.03) did not play a significant role as a risk factor for developing CDI.Conclusion:Prior antibiotic exposure appears to be an important risk factor for CDI based on the combined analysis but not significant using adjusted studies. PPI use was associated with an increased risk of CDI. Judicious and appropriate use of antibiotics and PPIs may help reduce the risk of CDI in this vulnerable population.

Objective: To identify risk factors for asymptomatic Clostridioides difficile colonization among hospitalized adults utilizing a meta-analysis, which may enable early identification of colonized patients at risk of spreading C. difficile. Design: Meta-analysis and systematic review. Methods: We systematically searched MEDLINE, Scopus, Web of Science, and EMBASE from January 1, 1975, to February 15, 2020, for articles related to C. difficile colonization among hospitalized adults. Studies with multivariable analyses evaluating risk factors for asymptomatic colonization were eligible. Results: Among 5,506 studies identified in the search, 19 studies met the inclusion criteria. Included studies reported 20,334 adult patients of whom 1,588 were asymptomatically colonized with C. difficile. Factors associated with an increased risk of colonization were hospitalization in the previous 6 months (OR, 2.18; 95% CI, 1.86–2.56; P < .001), use of gastric acid suppression therapy within the previous 8 weeks (OR, 1.42; 95% CI, 1.17–1.73; P < .001), tube feeding (OR, 2.02; 95% CI, 1.06–3.85; P = .03), and corticosteroid use in the previous 8 weeks (OR, 1.58; 95% CI, 1.14–2.17; P = .006). Receipt of antibiotics in the previous 3 months (OR, 1.37; 95% CI, 0.94–2.01; P = .10) was not associated with statistically significant effects on risk of colonization. Conclusions: C. difficile colonization was significantly associated with previous hospitalization, gastric acid suppression, tube feeding, and corticosteroid use. Recognition of these risk factors may assist in identifying asymptomatic carriers of C. difficile and taking appropriate measures to reduce transmission.

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CRT is a valuable tool in the treatment of heart failure in the setting of CHD. Current evidence points toward the ability of this therapy to increase hemodynamic parameters and reduce heart failure-related symptoms. Within the CHD population, patients with systemic left ventricles appear to benefit the most from CRT. Utilization of CRT in CHD has been technically difficult due to the complexity and variety of anatomic substrates. However, lateral thoracotomies and other advances have made implantation more feasible. The most up-to-date evidence continues to support the use of CRT in the heterogeneous population of CHD with careful and individualized patient selection. Further studies are needed to evaluate the utility of CRT for specific anatomic substrates within this population.

Radiofrequency ablation (RFA) is a common treatment of atrial fibrillation. However, current treatment is associated with a greater than 20% recurrence rate, in part due to inadequate monitoring of tissue viability during ablation. Spectral parameters, in particular cyclic variation of integrated backscatter (CVIB), have shown promise as early indicators of myocardial recovery from ischemia. Our aim was to demonstrate the use of spectral parameters to differentiate atrial myocardium before and after radiofrequency ablation. An AcuNav 10 F catheter was used to collect radiofrequency signals from the posterior wall of the left atrium of patients before and immediately after RFA for AF. The normalized power spectrum was obtained and three spectral parameters (integrated backscatter [IB], slope, and intercept) were extracted across two continuous heart cycles. Parameters were gated for ventricular end-diastole and compared before and after ablation. Additionally, the cyclic variation of each of these three parameters was generated as an average of the variation across the two recorded heart cycles. Data from 14 patients before and after ablation demonstrated a significant difference in the magnitude of the cyclic variation of integrated backscatter (9.0 vs. 6.0 dB, p < .001) and cyclic variation of the intercept (14.0 vs. 11.5 dB, p = .04). No significant difference was noted in the magnitude of the cyclic variation of the slope. Among spectral parameters gated for end-diastole, significant differences were noted in the slope (−4.39 vs. −3.73 dB/MHz, p = .002) and intercept (16.8 vs. 11.9 dB, p = .002). No significant difference was noted in the integrated backscatter. Spectral parameters are able to differentiate atrial myocardium before and immediately following ablation and may be useful in monitoring atrial ablations.

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