Ramirez-Sandoval, Juan C., Maria F. Castilla-Peón, José Gotés-Palazuelos, Juan C. Vázquez-García, Michael P. Wagner, Carlos A. Merelo-Arias, Olynka Vega-Vega, Rodolfo Rincón-Pedrero, and Ricardo Correa-Rotter. Bicarbonate values for healthy residents living in cities above 1500 m of altitude: a theoretical model and systematic review. High Alt Med Biol. 17:85-92, 2016.-Plasma bicarbonate (HCO3(-)) concentration is the main value used to assess the metabolic component of the acid-base status. There is limited information regarding plasma HCO3(-) values adjusted for altitude for people living in cities at high altitude defined as 1500 m (4921 ft) or more above sea level. Our aim was to estimate the plasma HCO3(-) concentration in residents of cities at these altitudes using a theoretical model and compare these values with HCO3(-) values found on a systematic review, and with those venous CO2 values obtained in a sample of 633 healthy individuals living at an altitude of 2240 m (7350 ft). We calculated the PCO2 using linear regression models and calculated plasma HCO3(-) according to the Henderson-Hasselbalch equation. Results show that HCO3(-) concentration falls as the altitude of the cities increase. For each 1000 m of altitude above sea level, HCO3(-) decreases to 0.55 and 1.5 mEq/L in subjects living at sea level with acute exposure to altitude and in subjects acclimatized to altitude, respectively. Estimated HCO3(-) values from the theoretical model were not different to HCO3(-) values found in publications of a systematic review or with venous total CO2 measurements in our sample. Altitude has to be taken into consideration in the calculation of HCO3(-) concentrations in cities above 1500 m to avoid an overdiagnosis of acid-base disorders in a given individual.

Background: Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19. Methods: We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described. Results: We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44–64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24–0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively). Conclusion: Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.

Background: The e-Learning with flipped classroom approach educational program is an alternative to online learning (e-Learning) and face-to-face learning for addressing the challenges related to long-distance skill training. Methods: Consisting of weekly live-time virtual sessions with expert physicians, available resources including updated guidelines, review articles, and blog interactions between colleagues for discussing the clinical cases to improve learning techniques. The availability of all the content (recorded lectures and bibliography) at any time for review is an important aspect for easy learning. This multimodal approach was directed to medical students working in rural communities to get the necessary skills for preventing, diagnosing, treating, and improving the quality of care in non-communicable chronic diseases (NCCD). In addition, this model includes a pre and post-course evaluation, a quality of care test, and a dropout and satisfaction survey. The students who obtain the approving grade at the end of the course get a certificate with medical endorsement.

Background: Hospitalized patients with severe COVID-19 have an increased risk of developing severe systemic inflammatory response, pulmonary damage, and acute respiratory distress syndrome (ARDS), resulting in end-organ damage and death. Acetylcholine modulates the acute inflammatory response through a neuro-immune mechanism known as the inflammatory reflex. Pyridostigmine, an acetylcholine-esterase inhibitor, increases the half-life of endogenous ACh, chemically stimulating the inflammatory reflex. This trial aimed to evaluate whether pyridostigmine could decrease invasive mechanical ventilation (IMV) and death in patients with severe COVID-19. Methods: We performed a parallel-group, multicenter, double-blinded, placebo-controlled, randomized clinical trial to evaluate if add-on pyridostigmine to standard treatment reduced the composite outcome of initiation of IMV and 28-day all-cause mortality among hospitalized patients with severe COVID-19. Results: 188 participants were randomly assigned to placebo (n=94) or pyridostigmine (n=94). The composite outcome occurred in 22 (23.4%) vs. 11 (11.7%) participants, respectively (hazard ratio 0.46, 95% confidence interval 0.22-0.96, p=0.03). Most of the adverse events were mild to moderate, with no serious adverse events related to pyridostigmine; discontinuation of the study drugs was similar in both groups. Conclusions: We provide evidence indicating that the addition of pyridostigmine to standard treatment resulted in a clinically significant reduction in the composite outcome (IMV/death) among patients hospitalized for severe COVID-19. (Funded by Consejo Nacional de Ciencia y Tecnología, México; ClinicalTrials.gov number: NCT04343963).