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.
Background: Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has now been confirmed worldwide. Yet, COVID-19 is strangely and tragically selective. Morbidity and mortality due to COVID19 rise dramatically with age and co-existing health conditions, including cancer and cardiovascular diseases. Human genetic factors may contribute to the extremely high transmissibility of SARS-CoV-2 and to the relentlessly progressive disease observed in a small but significant proportion of infected individuals, but these factors are largely unknown. Main body: In this study, we investigated genetic susceptibility to COVID-19 by examining DNA polymorphisms in ACE2 and TMPRSS2 (two key host factors of SARS-CoV-2) from~81,000 human genomes. We found unique genetic susceptibility across different populations in ACE2 and TMPRSS2. Specifically, ACE2 polymorphisms were found to be associated with cardiovascular and pulmonary conditions by altering the angiotensinogen-ACE2 interactions, such as p.Arg514Gly in the African/African-American population. Unique but prevalent polymorphisms (including p.Val160Met (rs12329760), an expression quantitative trait locus (eQTL)) in TMPRSS2, offer potential explanations for differential genetic susceptibility to COVID-19 as well as for risk factors, including those with cancer and the highrisk group of male patients. We further discussed that polymorphisms in ACE2 or TMPRSS2 could guide effective treatments (i.e., hydroxychloroquine and camostat) for COVID-19. Conclusion: This study suggested that ACE2 or TMPRSS2 DNA polymorphisms were likely associated with genetic susceptibility of COVID-19, which calls for a human genetics initiative for fighting the COVID-19 pandemic.
BACKGROUND: Coronavirus disease 2019 (COVID-19) is sweeping the globe. Despite multiple case-series, actionable knowledge to tailor decision-making proactively is missing. RESEARCH QUESTION: Can a statistical model accurately predict infection with COVID-19? STUDY DESIGN AND METHODS: We developed a prospective registry of all patients tested for COVID-19 in Cleveland Clinic to create individualized risk prediction models. We focus here on the likelihood of a positive nasal or oropharyngeal COVID-19 test. A least absolute shrinkage and selection operator logistic regression algorithm was constructed that removed variables that were not contributing to the model's cross-validated concordance index. After external validation in a temporally and geographically distinct cohort, the statistical prediction model was illustrated as a nomogram and deployed in an online risk calculator. RESULTS: In the development cohort, 11,672 patients fulfilled study criteria, including 818 patients (7.0%) who tested positive for COVID-19; in the validation cohort, 2295 patients fulfilled criteria, including 290 patients who tested positive for COVID-19. Male, African American, older patients, and those with known COVID-19 exposure were at higher risk of being positive for COVID-19. Risk was reduced in those who had pneumococcal polysaccharide or influenza vaccine or who were on melatonin, paroxetine, or carvedilol. Our model had favorable discrimination (c-statistic ¼ 0.863 in the development cohort and 0.840 in the validation cohort) and calibration. We present sensitivity, specificity, negative predictive value, and positive predictive value at different prediction cutoff points. The calculator is freely available at https://riskcalc.org/COVID19. INTERPRETATION: Prediction of a COVID-19 positive test is possible and could help direct health-care resources. We demonstrate relevance of age, race, sex, and socioeconomic characteristics in COVID-19 susceptibility and suggest a potential modifying role of certain common vaccinations and drugs that have been identified in drug-repurposing studies.
The long-term seizure-free rates after hemispherectomy remained stable at 63% at 5 years and beyond. This study will assist in better candidate selection for hemispherectomy, presurgical counseling, and early identification of surgical failures.
Summary Purpose: Stereo‐electroencephalography (SEEG) enables precise recordings from deep cortical structures, multiple noncontiguous lobes, as well as bilateral explorations while avoiding large craniotomies. Despite a long reported successful record, its application in the United States has not been widely adopted. We report on our initial experience with the SEEG methodology in the extraoperative mapping of refractory focal epilepsy in patients who were not considered optimal surgical candidates for other methods of invasive monitoring. We focused on the applied surgical technique and its utility and efficacy in this subgroup of patients. Methods: Between March 2009 and May 2011, 100 patients with the diagnosis of medically refractory focal epilepsy who were not considered optimal candidates for subdural grids and strips placement underwent SEEG implantation at Cleveland Clinic Epilepsy Center. Demographics, noninvasive clinical data, number and location of implanted electrodes, electrophysiologic localization of the epileptic zone, complications, and short‐term seizure outcome after resection were prospectively collected and analyzed. Key Findings: Mean age was 32 years (range 5–68 years); 54 were male and 46 female. The mean follow‐up after resection was 15 months. In total, 1,310 electrodes were implanted. Analyses of the SEEG recordings resulted in the electrographic localization of the epileptogenic focus in 96 patients. In the group of 75 patients who underwent resection, only 53 had at least 12 months follow‐up. From this group, 33 patients (62.3%) were seizure‐free at the end of the follow‐up period. The presence of abnormal pathologic finding was strongly associated with postoperative seizure control (p = 0.005). The risk of hemorrhagic complications per electrode was 0.2%. Significance: In patients who are not considered to be ideal candidates for subdural grids and strips implantation, the SEEG methodology is a safe, useful and reliable alternative option for invasive monitoring in patients with refractory focal epilepsy, providing an additional mean for seizure localization and control in a “difficult to localize” subgroup of patients.
ObjectivesTo provide information on the effect of the coronavirus disease of 2019 (COVID-19) pandemic on people with epilepsy and provide consensus recommendations on how to provide the best possible care for people with epilepsy while avoiding visits to urgent care facilities and hospitalizations during the novel coronavirus pandemic. MethodsThe authors developed consensus statements in 2 sections. The first was "How should we/ clinicians modify our clinical care pathway for people with epilepsy during the COVID-19 pandemic?" The second was "What general advice should we give to people with epilepsy during this crisis? The authors individually scored statements on a scale of −10 (strongly disagree) to +10 (strongly agree). Five of 11 recommendations for physicians and 3/5 recommendations for individuals/families were rated by all the authors as 7 or above (strongly agree) on the first round of rating. Subsequently, a teleconference was held where statements for which there was a lack of strong consensus were revised. ResultsAfter revision, all consensus recommendations received a score of 7 or above. The recommendations focus on administration of as much care as possible at home to keep people with epilepsy out of health care facilities, where they are likely to encounter COVID-19 (including strategies for rescue therapy), as well as minimization of risk of seizure exacerbation through adherence, and through ensuring a regular supply of medication. We also provide helpful links to additional helpful information for people with epilepsy and health providers. ConclusionThese recommendations may help health care professionals provide optimal care to people with epilepsy during the coronavirus pandemic.
Background Recently, van Walraven developed a weighted summary score (VW) based on the 30 comorbidities from the Elixhauser comorbidity system. One of the 30 comorbidities, cardiac arrhythmia, is currently excluded as a comorbidity indicator in administrative datasets such as the Nationwide Inpatient Sample (NIS), prompting us to examine the validity of the VW score and its use in the NIS. Methods Using data from the 2009 Maryland State Inpatient Database, we derived weighted summary scores to predict in-hospital mortality based on the full (30) and reduced (29) set of comorbidities and compared model performance of these and other comorbidity summaries in 2009 NIS data. Results Weights of our derived scores were not sensitive to the exclusion of cardiac arrhythmia. When applied to NIS data, models containing derived summary scores performed nearly identically (c statistics for 30 and 29 variable-derived summary scores: 0.804 and 0.802, respectively) to the model using all 29 comorbidity indicators (c = 0.809), and slightly better than the VW score (c = 0.793). Each of these models performed substantially better than those based on a simple count of Elixhauser comorbidities (c = 0.745) or a categorized count (0, 1, 2, or ≥3 comorbidities; c = 0.737). Conclusions The VW score and our derived scores are valid in the NIS and are statistically superior to summaries using simple co-morbidity counts. Researchers wishing to summarize the Elixhauser comorbidities with a single value should use the VW score or those derived in this study.
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