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Background : Older populations are increasing and comprise a substantial portion of high-altitude travelers. Aging physiology may influence susceptibility to acute mountain sickness, though prior research remains inconclusive. The goal of this study was to investigate the relationship between increasing age and acute mountain sickness. Materials & Methods : This study was a pooled analysis of five prospective randomized controlled trials conducted at White Mountain, California from 2010, 2016-2019 with identical 4-hour rapid ascent from 1242 m to overnight sojourn at 3810 m. Acute mountain sickness was defined by the 2018 Lake Louise Questionnaire criteria. Results : 491 participants were analyzed, 234 (48%) diagnosed with acute mountain sickness and 71 (14%) with moderate acute mountain sickness. Mean age was 37(±13). There was no significant correlation between Lake Louise Questionnaire severity and age (r = -0.02, 95% CI -0.11 to 0.07, p = 0.7), 40 year-old dichotomy (t = -0.6, 95% CI -0.53 to 0.28, p = 0.6), or decade of life (p = 0.4). Logistic regression found no increased odds of acute mountain sickness for increasing age by decade of life (OR =1.0, 95% CI 0.97 to 1.0) or 40 year-old dichotomy (OR = 1.4, 95% 0.97 to 2.1. A history of acute mountain sickness increased odds of acute mountain sickness (OR = 3.2, 95% CI 1.5 to 7.7). Conclusions : Older age was not associated with incidence nor severity of acute mountain sickness. A history of altitude illness increased odds of acute mountain sickness and should be used for pre-ascent risk stratification.

INTRODUCTION: Acetaminophen toxicity has been associated with elevation of microRNAs. The present study was to evaluate overall microRNA profiles and previously identified microRNAs to differentiate acetaminophen (APAP) toxicity from other causes of transaminase elevation. METHODS: This was an observational study of adults with presumed acetaminophen toxicity at presentation. Serum samples were collected every 12 hours during hospitalization. Total miRNAs were extracted from plasma and levels of 327 microRNAs were quantified using real-time polymerase chain reaction. A standard measure of miRNA expression (delta-delta cycle threshold) was calculated for each microRNAs. A two-level cluster analysis was performed using a random k-means algorithm. Demographic and clinical characteristics of each cluster were compared using ANOVA, Wilcoxon rank sum, Kruskal-Wallis, and chi-square tests. Performance of specific miRNAs of interest was also evaluated. RESULTS: Twenty-seven subjects were enrolled (21 with a final diagnosis of acetaminophen toxicity), and a total of 61 samples were analyzed. Five clusters were identified, two of which demonstrated clear clinical patterns and included specific elevated miRNAs previously reported to be elevated in APAP toxicity patients. Features associated with clusters 1 and 5 included confirmed acetaminophen toxicity, high peak alanine aminotransferase, and late presentation. Clusters 2–4 contained lower peak microRNAs, lower peak alanine aminotransferase, and heterogeneous clinical characteristics. CONCLUSIONS: Severe cases of acetaminophen toxicity showed two distinct patterns of microRNA elevation which were similar to previous work, while less severe cases were difficult to distinguish from non-acetaminophen-associated cases. Further work is needed to incorporate microRNA profiles into the diagnostic algorithm of acetaminophen toxicity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13181-019-00739-6) contains supplementary material, which is available to authorized users.

Author(s): Warner, Keiran J; Rider, Ashley C; Marvel, James; Gisondi, Michael A; Schertzer, Kimberly; Roszczynialski, Kelly N

Background Acetazolamide is the most common medication used for acute mountain sickness prevention, with speculation that a reduced dose may be as efficacious as standard dosing with fewer side effects. Methods This double-blind, randomized, controlled noninferiority trial compared acetazolamide 62.5 mg twice daily to the standard dose acetazolamide 125 mg twice daily starting the evening prior to ascent from 1240 m (4100 ft) to 3810 m (12,570 ft) over 4 hours. The primary outcome was acute mountain sickness incidence (ie, headache, Lake Louise Questionnaire ≥3, and another symptom). Results A total of 106 participants were analyzed, with 51 (48%) randomized to 125 mg and 55 (52%) to 62.5 mg, with a combined acute mountain sickness incidence of 53 (50%) and mean severity of 3 (± 2.1). The 62.5-mg group failed to fall within the prespecified 26% noninferiority margin for acute mountain sickness incidence (62.5 mg = 30 [55%] vs 125 mg = 23 [45%], 95% confidence interval [CI] -11% to 30%). Participants in the 62.5-mg group had a higher risk of acute mountain sickness (odds ratio = 1.5, 95% CI 0.7-3.2) and moderate acute mountain sickness (odds ratio = 1.8, 95% CI 0.6-5.9), with a number needed to harm (NNH) of 9, with a number needed to treat (NNT) in the 125-mg group of 4.8. Increased acute mountain sickness incidence and symptom severity corresponded to lower weight-based and body mass index dosing, with similar side effects between groups. Conclusion Acetazolamide 62.5 mg twice daily failed to demonstrate equal effectiveness to 125 mg twice daily for prevention of acute mountain sickness. With increased risk and no demonstrable symptomatic or physiologic benefits, acetazolamide 62.5 mg twice daily should not be recommended for acute mountain sickness prevention.