2 Minute Medicine Rewind March 15, 2021

Association of intensive vs standard blood pressure control with magnetic resonance imaging biomarkers of Alzheimer’s Disease

1. Intensive treatment of blood pressure resulted in small but statistically significant greater decline in hippocampal volume compared to standard treatment.

2. No significant differences between treatment groups in other Alzheimer’s disease biomarkers.

Evidence Rating Level: 2 (Good)

Several randomized clinical trials have suggested that control of hypertension reduces future risk of cognitive impairment and dementia. However, meta-analyses of these trials have not demonstrated how Alzheimer’s disease (AD) pathology is affected by the treatment of hypertension. This secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT MIND) randomized trial aimed to investigate the association of intensive blood pressure control on AD biomarkers, such as hippocampal volume, regional atrophy, posterior cerebral blood flow, and mean fractional anisotropy in the cingulum bundle. Participants were 50 years of age or older with documented hypertension and without a history of stroke or diabetes. A total of 673 participants had baseline MRI (M [SD] age = 67.3 [8.2] years, 40.3% female) and 454 completed the follow-up MRI (median (IQR) time = 3.98 [3.7 to 4.1] years) after randomization to either a systolic blood pressure goal of ≥120 mm Hg (intensive treatment, n = 356) or ≤140 mm Hg (standard treatment, n = 317). The intensive treatment group demonstrated small but statistically significant greater decrease in hippocampal volume (difference -0.06cm3, 95% CI -0.08 to -0.04) compared to the standard treatment group (difference, -0.02cm3, 95% CI -0.05 to -0.003, p = 0.03). Interestingly, no significant differences were found between treatment groups in measures of cerebral blood flow, AD regional atrophy, or mean fractional anisotropy. Overall, this study suggests that intensive control of blood pressure results in greater reductions of hippocampal volume and, thus, total brain volume, compared to standard treatment. However, these differences were small and not found in the context of other AD biomarkers.


Short-course antimicrobial therapy for pediatric community-acquired pneumonia

1. Five-day treatment of community-acquired pneumonia in children was comparable to standard, 10-day treatment.

Evidence Rating Level: 2 (Good)

Community-acquired pneumonia (CAP) is a common presenting illness among children. Due to the high occurrence, it is important to understand the most appropriate treatment for CAP among this age group. This study aimed to compare the effectiveness of brief, high-dose amoxicillin (5 days) and standard high-dose amoxicillin treatment (10 days). The Short-Course Antimicrobial Therapy and Pediatric Respiratory Infections (SAFER) study was a two-center, parallel-group, noninferiority randomized clinical trial. This included a single-center pilot study from December 2012 to March 31, 2014 and a follow-up main study from August 2016 to December 31, 2019 at two Canadian hospital emergency departments. Children were required to be between the ages of 6 months and 10 years and had a fever within 48 hours, respiratory symptoms, chest radiography-confirming pneumonia, and a primary diagnosis of pneumonia. Exclusions included the need for hospitalization, previous β-lactam antibiotic therapy, and comorbidities that predispose children to severe disease/pneumonia. A total of 281 participants (median [IQR] age = 2.6 [1.6 to 4.9], 42.3% female) were randomly assigned to either 5 days high-dose amoxicillin plus 5 days of placebo (intervention) or 5 days high-dose amoxicillin plus 5 days of high-dose amoxicillin or another formulation (control). In per-protocol analyses, pneumonia was cured in 88.6% of intervention participants compared to 90.8% of the control group (risk difference -0.016, 97.5% confidence limit -0.087). Clinical cure at 2-3 weeks occurred in 85.7% of the intervention group compared to 84.1% of the control group in the intention-to-treat analysis (risk difference 0.023, 97.5% confidence limit -0.061). Overall, this study found that short-course (5-day) antibiotic treatment is comparable to standard care for children with CAP who did not require hospitalization. This sample was composed of children who were otherwise healthy, such that results may vary among more complex cases. However, clinical recommendations should take these results into consideration when treating CAP.


Sex differences in ischemic stroke outcomes in patients with pulmonary hypertension

1. Pulmonary hypertension (PH) was associated with a 15% increase in odds of prolonged hospitalization.

2. PH was associated with a 31% decrease in odds of routine home discharge.

3. There was no association between PH and in-hospital mortality, though males had 31% higher odds of dying in the hospital compared to females.

Evidence Rating Level: 3 (Average)

Systemic and pulmonary hypertension (PH) are known to be associated with cerebrovascular disease and risk factors for stroke. However, little is known about the impact of PH on acute ischemic stroke outcomes. This study aimed to investigate the association between PH and adverse in-hospital outcomes following acute ischemic stroke, as well as potential sex differences among this sample. Admissions data for acute ischemic stroke were retrieved from the US National Inpatient Sample between October 2015 and December 2017. A total of 1,106,045 (median [IQR] age = 72 [61 to 82] years, 50.41% female) participants were included in analyses. The median length of stay was 3 days (IQR 2 to 6). The 31,830 (2.88%) participants with PH, compared to those without PH, were significantly older (median age = 80, difference 9 years) and were more likely to be female (difference 14.67%). Participants with PH were more likely to have co-occurring atrial fibrillation (difference 32.25%). Participants with PH were also more likely to receive revascularization therapies such as intravenous thrombolysis and endovascular thrombectomy. PH was not found to be associated with in-hospital mortality (OR 0.96, 95% CI 0.86 to 1.09) but it was associated with increased odds of prolonged hospitalization of greater than four days (OR 1.15, 95% CI 1.09 to 1.22). PH was also associated with decreased odds of routine discharge for both males and females (OR 0.87, 95% CI 0.81 to 0.94). Compared to younger participants, older persons with PH were less likely to be discharged routinely (p = 0.028) and men with PH were 31% more likely to die while in the hospital than their female counterparts (p = 0.024). Overall, this study found that PH was not associated with in-hospital mortality, though factors such as gender impact these outcomes. Further, PH is associated with prolonged hospitalization (>4 days) and adverse discharge status.


Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child

1. Children of mothers who supplemented with folic acid (FA) during the second and third trimesters demonstrated greater processing speed at 11 years of age.

2. FA supplementation in later pregnancy resulted in stronger verbal comprehension skills among females.

Evidence Rating Level: 2 (Good)

Folic acid (FA) has been shown to prevent neural tube defects (NTD) when supplementation occurs before and during early pregnancy. This study investigated the benefits of continued FA supplementation through the second and third trimesters and its impact on neurocognitive performance in children. Included participants were followed up at 11 years of age from the randomized trial of Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) in pregnancy. They were randomly assigned to be given 400 μg/day FA or placebo beginning in the 14th gestational week. Cognitive performance was measured with the Wechsler Intelligence Scale for Children in the following domains: Full Scale IQ, Verbal Comprehension, Perceptual Reasoning, Working Memory, and Processing Speed. Magnetoencephalographic (MEG) brain imaging was used to assess neuronal function. Of 119 mother-child pairs in the FASSTT trial, the cognitive performance of 68 children was assessed at the 11-year follow-up. A total of 31 were in the placebo group (M age = 28.1 years, 95% CI 26.6 to 29.6, 52% female) and 37 were in the FA group (M age = 29.7 years, 95% CI 28.5 to 30.8, 59.8% female). Children of mothers in the FA group scored significantly higher on two Processing Speed tests: Symbol Search (mean difference 2.9, 95% CI 0.3 to 5.5, p = 0.03) and Cancellation (mean difference 11.3, 95% CI 2.5 to 20.1, p = 0.04). Verbal Comprehension was higher in the FA group as well, but only for females (mean difference 6.5, 95% CI 1.2 to 11.8, p = 0.03). MEG assessment with a language tasks demonstrated more efficient semantic processing based on increased power at the High Gamma (49-70 Hz, p = 0.04) and Beta (13-30 Hz, p = 0.01) bands in children from the FA group. Overall, this study found that FA supplementation continues to benefit children when undergone in the second and third trimesters, with cognitive abilities proving stronger in multiple domains into the eleventh year of life.


Attributes and predictors of long COVID

1. Those testing positive for COVID-19 and experiencing five or more symptoms during the first week had greater odds of having a symptom duration longer than 28 days (long COVID).

2. The most predictive symptoms of long COVID were fatigue, headache, dyspnea, hoarse voice, and myalgia.

3. Among individuals ≥70 years of age, anosmia was the strongest predictor of long COVID.

Evidence Rating Level: 3 (Average)

The effects of COVID-19 are being studied in great detail to determine the risk factors of serious illness and death. One heterogeneous factor in COVID-19 is symptom duration, which is underrepresented in research among the general population. The term ‘long COVID’ (LC28) has been defined as symptoms persisting for over 28 days while ‘short COVID’ refers to less than 10 days. This prospective observational cohort study of COVID-19 symptoms used data from users of the COVID Symptom Study. These individuals reported testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and used the app to report when their symptoms subsided. These participants were then compared to symptomatic, SARS-CoV-2-negative controls matched for age, sex, and body mass index (BMI). Between March 24, 2020 and September 2020, 4,223,955 adults registered with the app (M [SD] age = 45.97 [15.8] years, 57% female, 88.2% United Kingdom). A total of 4,182 participants testing positive met eligibility criteria and were included in subsequent analyses with their matched controls. A total of 13.3% reported LC28, 4.5% reported symptoms for ≥8 weeks, and 2.3% reported symptoms for >12 weeks. LC28 was commonly associated with headache (OR = 2.62, 95% CI 2.04 to 3.37), fatigue (OR = 2.83, 95% CI 2.09 to 3.83), myalgia (OR = 2.22, 95% CI 1.80 to 2.73), hoarse voice (OR = 2.33, 95% CI 1.88 to 2.90), and dyspnea (OR = 2.36, 95% CI 1.91 to 2.91), exacerbated by older age, female sex, and elevated BMI. LC28 was associated with experiencing more than five symptoms in the first week of illness (OR = 3.53, 95% CI 2.76 to 4.50). In older adults (≥70 years), anosmia was the most predictive symptom of LC28 (OR 7.35, 95% CI 1.58 to 34.22). Those with LC28 were also more likely to report symptom relapses than those with a duration of <28 days (p < 0.0005). Investigators then used a simple model to determine the differences between short and long COVID at 7 days (n = 2,149). This model showed an area under the curve of the receiver operating characteristic curve of 76%, such that it could be utilized to identify symptomatic patients at risk for long COVID. Overall, this study suggests specific symptoms associated with long COVID and has demonstrated risk factors as well as the ability to predict who may be at greatest risk based on symptom duration. This information could guide clinical decisions for prevention and treatment of adults at risk for COVID-19.

Image: PD

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