2 Minute Medicine Rewind October 26, 2020

Microbleeds and the Effect of Anticoagulation in Patients With Embolic Stroke of Undetermined Source

1. Microbleeds increase risk of intracerebral hemorrhage, ischemic stroke, recurrent stroke, and mortality.

2. Microbleeds do not appear to influence the effects of rivaroxaban treatment.

Evidence Rating Level: 2 (Good)

Cerebral microbleeds are known to be associated with intracerebral hemorrhage and recurrent. Questions have been raised related to antithrombitic treatment for those with a history of microbleeds and stroke. This international, double-blind, randomized, event-driven phase 3 clinical trial sought to investigate microbleeds in embolic strokes of undetermined source (ESUS) and how these relationships are impacted in the context of daily treatment with anticoagulant rivaroxaban 15mg compared to aspirin 100mg. This study included 459 stroke centers across 31 countries, including patients over the age of 50 years with imaging-confirmed ESUS between seven days and six months prior to screening. A total of 395 of the 3,699 participants had microbleeds on MRI (11%) and were included in subsequent analyses (M [SD] age = 69.5 [9.4] years, 39% female, 51% White). Several variables were independently associated with microbleeds, including occult intracerebral hemorrhage (OR = 5.23, 95% CI 2.76 to 9.90), hypertension (OR = 2.20, 95% CI 1.54 to 3.15), multiterritorial infarcts (OR = 1.95, 95% CI 1.42 to 2.67), chronic infarcts (OR = 1.78, 95% CI 1.42 to 2.23), East Asian race (OR = 1.57, 95% CI 1.04 to 2.37), and advancing age (OR = 1.03, 95% CI 1.01 to 1.04). Microbleed presence was associated with a four-fold risk of intracerebral hemorrhage (HR = 4.2, 95% CI 1.3 to 13.9) and 1.5-fold risk of recurrent stroke (HR = 1.5, 95% CI 1.0 to 2.3). Lobar-specific microbleeds were associated with a 2.5-fold risk of ischemic stroke (HR = 2.3, 95% CI 1.3 to 4.3) and all-cause mortality was increased by 200% (HR = 2.1, 95% CI 1.1 to 4.3). No evidence was found for interactions between microbleeds and treatment type for ischemic stroke, recurrent stroke, or all-cause mortality. Further, HRs of intracerebral hemorrhage on rivaroxaban were not significantly different between those with microbleeds (HR = 3.1, 95% CI 0.3 to 30.0) and those without (HR = 3.0, 95% CI 0.6 to 14.7, p>.99). This study demonstrates that microbleeds increase the risk of intracerebral hemorrhage, ischemic stroke, recurrent stroke, and mortality. However, microbleeds do not influence the effects of rivaroxaban treatment in the context of ESUS.


Association Between Parent Comfort With English and Adverse Events Among Hospitalized Children

1. Children of parents expressing limited comfort with English demonstrated 2.1 higher odds of adverse events compared to children of parents expressing comfort with English.

Evidence Rating Level: 2 (Good)

Many individuals in the US express limited comfort with English (LCE), which can negatively impact healthcare. Further, children of parents expressing LCE may be at an elevated risk of adverse events due to communication difficulties. This multicenter, prospective cohort study, conducted from December 2014 to January 2017, aimed to investigate the association between parent LCE and adverse events among their hospitalized children. A total of 1,666 parents across seven hospitals provided data on language comfort and were included in subsequent analyses (M [SD] age = 35.4 [10.0] years, 80.5% female). Parents spoke English, Spanish, Chinese, and Arabic. Approximately 8.8% of these individuals expressed LCE, with 71.4% of this group preferring Spanish. Children of parents expressing LCE had 2.1 higher odds of having at least one adverse event when compared with children whose parents were comfortable with English (difference 8.1%, adjusted OR = 2.1, 95% CI 1.2 to 3.7), after adjusting for parent education, race, length of stay, site, chronic conditions, and intervention period. With the same adjustments, children of parents with LCE were also more likely to experience at least one preventable adverse event (adjusted OR 2.3, 95% CI 1.2 to 4.2). Overall, this study demonstrates the need to improve communication between healthcare professionals and those who are less comfortable with English. Improvements in this area may contribute to reduced adverse events among this vulnerable pediatric population.


Pregnant Women with COVID-19 and Risk of Adverse Birth Outcomes and Maternal-Fetal Vertical Transmission: A Population-Based Cohort Study in Wuhan, China

1. COVID-19 infection in late pregnancy was associated with adverse birth outcomes, such as cesarean section delivery and iatrogenic preterm birth.

2. Limited evidence was found for maternal-fetal vertical transmission of SARS-CoV-2.

Evidence Rating Level: 3 (Average)

Coronavirus disease 2019 (COVID-19) is an ongoing concern in the healthcare sector. However, little is currently known about the transmission of COVID-19 during pregnancy. This retrospective cohort study used the Maternal and Child Health Information System of Wuhan, China, aiming to investigate the association between maternal COVID-19 and adverse birth outcomes. Included in analyses were all pregnant women with singleton, live births occurring between January 13, 2020 and March 18, 2020. A total of 11,078 pregnant women were included in analyses, with 65 (0.587%) confirmed cases of COVID-19. Roughly 78% of COVID-19 and 83% of COVID-19+ women were between the ages of 25 and 34 years. Of the positive cases, 65% had a bachelor’s degree or higher. Compared to COVID-19- mothers, those with COVID-19 had 3.34 greater odds of preterm birth (adjusted OR = 3.34, 95% CI 1.60 to 7.00) and 3.63 higher odds of cesarean section birth (adjusted OR = 3.63, 95% CI 1.95 to 6.76). Mothers with COVID-19 also demonstrated greater odds for preterm birth with cesarean section delivery (adjusted OR = 3.71, 95% CI 1.70 to 8.03). No statistical differences between groups were found in low birth weight, premature rupture of membrane, or neonatal asphyxia. Further, none of the newborns born to mothers with COVID-19 were positive for SARS-CoV-2, nor did they have abnormal CT findings. Symptoms occurred in four children, one experiencing diarrhea and three experiencing fever. Overall, COVID-19 among pregnant women appears to increase the odds of adverse birth outcomes. However, maternal-fetal transmission of the virus does not seem to be a concern based on this study.


Altered Acylcarnitine Metabolism is Associated With an Increased Risk of Atrial Fibrillation

1. A total of 7 medium- and long-chain acylcarnitines were associated with higher risk of atrial fibrillation (AF).

2. Caffeine and acisoga were associated with increased risk of incident AF while beta carotene was associated with a lower risk.

Evidence Rating Level: 2 (Good)

Atrial fibrillation (AF) is the most common cardiac arrhythmia, being noted on 175,326 death certificates in 2018 according to the CDC. However, its pathogenesis is not fully understood and the answers may lie in metabolomics. A total of 3,770 participants of the Malmö Diet and Cancer Study had 112 baseline fasting metabolites measured to investigate metabolic pathways in the development of AF (M [SD] = 58.0 [6.0] years, 59% female). Profiling was performed using liquid chromatography-mass spectrometry. Follow-ups occurred for a median of 23.2 years and 650 (17%) AF cases were identified (incidence rate = 8.6 per 1,000 person-years) with a mean age of 60.0 years (SD = 5.4 years). Adjusting for known AF risk factors, a total of 7 medium- and long-chain acylcarnitines were found to be associated with higher risk of AF (smallest HR = 1.09, 95% CI 1.00 to 1.18, largest HR = 1.14, 95% CI 1.05 to 1.24, per 1 SD increment of acylcarnitines). Beta carotene was associated with a lower risk of incident AF (HR = 0.90, 95% CI 0.82 to 0.99) while acisoga (HR = 1.08, 95% CI 1.00 to 1.18) and caffeine (HR = 1.17, 95% CI 1.06 to 1.28) were associated with an increased risk of incident AF. Overall, this study suggests alterations in acylcarnitine metabolism among those with incident AF, independent of known AF risk factors. With these metabolic changes occurring prior to AF diagnosis, there is potential to treat and prevent this condition before AF onset.


Variation in Racial/Ethnic Disparities in COVID-19 Mortality by Age in the United States

1. Age-specific mortality rates varied significantly by race in the context of COVID-19 infection.

Evidence Rating Level: 3 (Average)

The United States has faced the omnipresent reality of racial health disparities, with COVID-19 opening the door to bring these issues to the forefront. Non-Hispanic White individuals are being impacted at a significantly reduced rate compared to underrepresented minorities. This cross-sectional study drew data from the US Census between February 1, 2020 and July 22, 2020 to investigate age-specific variations in COVID-19 mortality rates stratified by racial group. The number of deaths related to COVID-19 by race were 68,377 for Whites, 29,476 for Blacks, 23,256 for Hispanics, 1,143 for American Indians/Alaskan Natives, and 6,468 for Asians/Pacific Islanders. Relative to White individuals, the age-standardized rate ratios were calculated for Blacks (RR = 3.6, 95% CI 3.5 to 3.8, p<.001), Hispanics (RR = 2.8, 95% CI 2.7 to 3.0, p<.001), American Indians/Alaskan Natives (RR = 2.2, 95% CI 1.8 to 2.6, p<.001), and Asians/Pacific Islanders (RR = 1.6, 95% CI 1.4 to 1.7, p<.001). For persons between the ages of 35 and 44 years, rate ratios relative to Whites were quite high, with Blacks being 9.0 (95% CI 7.9 to 10.0, p<.001) and Hispanics being 7.0 (95% CI 5.8 to 8.7, p<.001). American Indians/Alaskan Natives demonstrated similarly high rate ratios through 74 years of age. Age-standardized rates alone would not result in these findings. However, this study suggests that there is substantial variation by race in age-specific mortality rates amidst COVID-19. Further research should exercise caution in the use of age standardization when working within age strata.

Image: PD

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