2 Minute Medicine Rewind May 11, 2020

Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19)

1. No association was found between angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use and test-positivity for COVID-19.

Evidence Rating Level: 2 (Good)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), gains entry into host cells by binding to the extracellular domain of transmembrane angiotensin-converting enzyme 2 (ACE2) receptors. Given the limited human data on ACE2 expression in the lungs, knowing that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) upregulate ACE2 expression in animals does not provide sufficient information regarding their safety in COVID-19 patients. This retrospective cohort study as part of a prospective, observational study of all individuals tested for COVID-19 within the Cleveland Clinic Health System sought to determine the associations of ACEi and ARB use with the risk of incident SARS-CoV-2. to . Participants were tested for COVID-19 between March 8, 2020 and April 12, 2020 through nasopharyngeal and oropharyngeal swabs. A total of 18,472 patients (M [SD] age = 49 [21] years, 60% female, 69% Caucasian) were tested and subsequently included in analysis. Approximately 9.4% were COVID-19-positive. Among them, 9.3% were admitted to the ICU, 24.3% were admitted to the hospital, and 6.4% required mechanical ventilation. A high prevalence of comorbidities was noted in this COVID-19-positive group: hypertension (40%), diabetes (19%), coronary artery disease (12%), chronic obstructive pulmonary disease (12%), and heart failure (10%). A total of 116 (6.7%) of test-positive patients were taking ACEis and 98 (5.6%) were taking ARBs, which represented a group with a greater number of comorbidities than those who were not taking these medications. In those taking ACEIis, the test positivity rates were 8.6% and 9.5% in patients not taking ACEis (overlap propensity score-weighted OR 0.89, 95% CI 0.72 to 1.10). Those taking ARBs had a test positivity rate of 10.0% while this rate was 9.3% in those not taking ARBs (overlap propensity score-weighted OR 1.09, 95% CI 0.87 to 1.37). A total of 54% of patients taking ACEis were admitted to the hospital compared to 39% not taking these medications (OR 1.84, 95% CI 1.22 to 2.79), 24% of ACEi users were admitted to an ICU (OR 1.77, 95% CI 1.07 to 2.92), and 14% required mechanical ventilation (OR 1.35, 95% CI 0.74 to 2.47). In terms of ARB use in positive patients, 53% were admitted to the hospital (OR 1.61, 95% CI 1.04 to 2.50), 20% were admitted to an ICU (OR 1.16, 95% CI 0.67 to 2.02), and 14% required mechanical ventilation (OR 1.12, 95% CI 0.59 to 2.12). A total of 42 deaths occurred among 1,705 patients with available death data, with 3.8% taking either ACEis or ARBs and 2.1% not taking either medication type. This may be a representation of the effect of underlying comorbidities rather than medication effect. Overall, this study found no associations between ACEi or ARB use and risk of COVID-19, but the results cannot be used for conclusive evidence regarding outcomes.

Comparison Between Rituximab Treatment for New-Onset Generalized Myasthenia Gravis and Refractory Generalized Myasthenia Gravis

1. Rituximab was found to significantly reduce median time to remission in new-onset myasthenia gravis.

2. Rituximab appeared to outperform conventional immunosuppressant therapy in terms of need for rescue therapy and adverse effects resulting in discontinuation.

Evidence Rating Level: 2 (Good)

Myasthenia gravis (MG) is a serious neuromuscular disease, resulting from an autoreactive humoral response in the neuromuscular junction, which can be sudden in onset. Oral immunosuppressants are generally the chosen treatment to avoid negative outcomes with corticosteroids. Other treatment options are generally reserved for treatment-refractory cases of MG, as such little is known about the effects of biologic agents on new-onset MG. This retrospective cohort study with data prospectively collected from a Swedish community sample sought to investigate the effects of rituximab, a chimeric monoclonal antibody targeting CD20 on B cells, on both types of MG as well as how it compares to conventional immunotherapy. A total of 72 participants were identified for this study (M [SD] age = 60 [18] years, 43% female). Of these, 24 (33.3%) had received rituximab within one year of disease onset. Of the 48 (66.7%) who received rituximab at a later date, 34 had treatment-refractory MG. In the conventional immunosuppressant group, 26 participants were identified (M [SD] age = 68 [11] years, 12% women). Researchers found that the median time to remission was shorter for new-onset MG compared to refractory MG after adjusting for sex, age, and disease severity (difference 6 months, HR 2.53, 95% CI 1.26 to 5.07, p = 0.009). Remission time was also shorter for the rituximab group compared to conventional treatment (difference 5 months, HR 2.97, 95% CI 1.43 to 6.18, p = 0.004). Those taking rituximab required fewer rescue therapy episodes in the first two years (M [SD] = 0.28 [1.10] times vs 1.31 [1.59], p < 0.001). Further, a larger number of MG patients had significantly less need for additional immunotherapies (difference 35%, OR 5.47, 95% CI 1.40 to 21.43, p = 0.02). The rituximab group also had significantly lower discontinuation rates (difference 43%, p < 0.001). These findings suggest that rituximab is likely a viable treatment for both new-onset and refractory MG, with improved outcomes compared to conventional immunotherapies and reduced adverse events resulting in discontinuation.

Association of Racial Residential Segregation Throughout Young Adulthood and Cognitive Performance in Middle-Aged Participants In the CARDIA Study

1. High exposure to racial residential segregation among African Americans resulted in worse mid-life processing speed performance compared to those with medium and low exposure, though set-shifting and memory changes were not significantly different across groups.

Evidence Rating Level: 2 (Good)

Residential segregation is a social determinant of health, found to be associated with poor health outcomes among African American individuals. The degree to which this segregation impacts cognitive performance in mid-life has been largely unexplored. The Coronary Artery Risk Development in Young Adults (CARDIA) study is a prospective cohort study which recruited 5,115 African American and Caucasian adults between the ages of 18 and 30 years across four medical centers across the U.S. Data was acquired from February 1985 to May 2011. This study was limited to those who self-reported as African American and excluded those who did not undergo cognitive testing, resulting in a total of 1,568 participants for analysis (M [SD] age = 25 [4] years, 59.7% female). The Getis and Ord local Gi* statistic was used to measure neighborhood-level residential segregation, a method that is empirically-supported by measuring the relative racial composition of a given neighborhood compared to the larger metropolitan region. Proportions of African Americans in these neighborhood and metropolitan areas were obtained from the census, and spatial weight of individual racial tracts were compared to nearby tracts. The Gi* produces a z score representing the number of SDs that an individual’s neighborhood racial composition is from the surrounding area. Gi* was grouped into high (>1.96), medium (0-1.96), and low (<0). Individuals in high-segregation areas had lower education than medium- and low-segregation groups (difference 1 year). The high-segregation group was also more likely to be married and be current smokers. Lastly, this group exhibited decreased median total physical activity compared to medium- and low-segregation groups. Body mass index, number of depressive symptoms, alcohol consumption, and systolic blood pressure were similar across segregation groups. Cumulative racial residential segregation exposure was associated with decreased Digit Symbol Substitution Test (DSST; also known as Coding) performance (z scores) in a dose-dependent manner (high segregation β = -0.37 [95% CI -0.61 to -0.13]; medium segregation β = -0.25 [95% CI -0.51 to 0.0002]) compared to low segregation exposure. The baseline age coefficient (-0.07, 95% CI -0.08 to -0.06) suggested that a 0.07-point decrease in DSST z score would occur for every one year of aging. Tests of set-shifting and memory did not yield statistically significant differences across segregation groups; the DSST is a measure of processing speed that includes a motor component. Overall, this study suggests a negative, duration-dependent effect of racial residential segregation on processing speed in mid-life among African Americans. There are also notable differences between the groups in social determinants of health, such that this study highlights future areas of research.

Evaluating the Risk of Macrovascular Events and Mortality Among People With Multiple Sclerosis In England

1. Compared to healthy matched controls, individuals with multiple sclerosis demonstrated significantly increased risk of cerebrovascular disease, acute coronary syndrome, cardiovascular disease-related mortality, and all-cause mortality.

Evidence Rating Level: 2 (Good)

Multiple sclerosis (MS) is an autoimmune disease characterized by the demyelination of nerve fibers in the central nervous system, resulting in severe pain, decreased mobility, fatigue, and vision loss. MS is also associated with cardiovascular disease and mortality. However, population-based studies on this relationship are limited. This population-based, retrospective matched cohort study among participants in England investigated the risk of major cardiovascular events and mortality in MS and healthy matched controls. A total of 12,251 participants with MS (M [SD] age = 44.9 [13.3] years, 66.9% female) and without MS (mean [SD] age = 44.9 [13.3] years, 69.8% female) were included in analyses. MS participants demonstrated increased risk of cerebrovascular disease (HR 1.59, 95% CI 1.32 to 1.92), acute coronary syndrome (HR 1.28, 95% CI 1.09 to 1.51), any major vascular disease (HR 1.32, 95% CI 1.15 to 1.52), all-cause mortality (HR 3.46, 95% CI 3.28 to 3.65), and cardiovascular disease-related mortality (HR 1.47, 95% CI 1.27 to 1.71). Mortality risk and occurrence of major vascular events were higher among women. Regarding treatment, lipid-reducing medications such as statins were associated with lower rates of mortality among individuals with MS. Overall, this study illustrates the risk factor MS poses for affected individuals and points toward future directions of research on MS.

Patterns of Influenza Vaccination and Vaccine Effectiveness Among Youth US Children Who Receive Outpatient Care for Acute Respiratory Tract Illness

1. The full two-dose influenza vaccination series was significantly more effective in preventing future influenza compared to partial vaccination (1 dose).

Evidence Rating Level: 2 (Good)

Childhood influenza is a significant health burden, with vaccination being the primary strategy to prevent transmission. Guidelines suggest a primer dose followed by a booster for patients receiving the influenza vaccine for the first time. Few studies to-date have investigated the clinical importance of vaccination sequence and outcomes in children who receive one dose rather than the recommended full two-dose series for initial vaccination against influenza. . This case-control study of 7,533 children (46% female) from the US Influenza Vaccine Effectiveness Network sought to determine vaccine effectiveness (VE) based on this sequence. This study was performed during periods of local influenza transmission between November 4, 2014 and April 12, 2018. Children between the ages of six months and eight years presenting within seven days of onset of acute respiratory tract illness with cough were included. A total of 52% of the sample was unvaccinated, 9% were partially vaccinated, and 39% were fully vaccinated. Among fully vaccinated children, adjusted VE against influenza was 51% while VE was 41% among children partially vaccinated. The VE of a two-dose series among 1,519 vaccine-naïve children during recruitment season was 53% (95% CI 28% to 70%) while the VE of just one dose was 23% (95% CI -11% to 47%). The full two-dose series resulted in decreased likelihood of testing positive for influenza compared to partial vaccination (adjusted OR 0.57, 95% CI 0.35 to 0.93) in previously vaccine naïve children. This study highlights the importance of receiving the two-dose influenza series and ensuring that children have access to vaccination.

Image: PD

©2020 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.