Physiological responses during ascent to high altitude and the incidence of acute mountain sickness.

Acute mountain sickness (AMS) occurs when there is failure of acclimatisation to high altitude. The aim of this study was to describe the relationship between physiological variables and the incidence of AMS during ascent to 5300 m. A total of 332 lowland-dwelling volunteers followed an identical ascent profile on staggered treks. Self-reported symptoms of AMS were recorded daily using the Lake Louise score (mild 3-4; moderate-severe ≥5), alongside measurements of physiological variables (heart rate, respiratory rate (RR), peripheral oxygen saturation (SpO2 ) and blood pressure) before and after a standardised Xtreme Everest Step-Test (XEST). The overall occurrence of AMS among participants was 73.5% (23.2% mild, 50.3% moderate-severe). There was no difference in gender, age, previous AMS, weight or body mass index between participants who developed AMS and those who did not. Participants who had not previously ascended >5000 m were more likely to get moderate-to-severe AMS. Participants who suffered moderate-to-severe AMS had a lower resting SpO2 at 3500 m (88.5 vs. 89.6%, p = 0.02), while participants who suffered mild or moderate-to-severe AMS had a lower end-exercise SpO2 at 3500 m (82.2 vs. 83.8%, p = 0.027; 81.5 vs. 83.8%, p 5000 m (OR 2.740, p-value 0.003) predicted the development of moderate-to-severe AMS. The Xtreme Everest Step-Test offers a simple, reproducible field test to help predict AMS, albeit with relatively limited predictive precision

Caudwell Xtreme Everest: A prospective study of the effects of environmental hypoxia on cognitive functioning.

BACKGROUND: The neuropsychological consequences of exposure to environmental hypobaric hypoxia (EHH) remain unclear. We thus investigated them in a large group of healthy volunteers who trekked to Mount Everest base camp (5,300 m). METHODS: A neuropsychological (NP) test battery assessing memory, language, attention, and executive function was administered to 198 participants (age 44.5±13.7 years; 60% male). These were studied at baseline (sea level), 3,500 m (Namche Bazaar), 5,300 m (Everest Base Camp) and on return to 1,300 m (Kathmandu) (attrition rate 23.7%). A comparable control group (n = 25; age 44.5±14.1 years; 60% male) for comparison with trekkers was tested at/or near sea level over an equivalent timeframe so as to account for learning effects associated with repeat testing. The Reliable Change Index (RCI) was used to calculate changes in cognition and neuropsychological function during and after exposure to EHH relative to controls. RESULTS: Overall, attention, verbal ability and executive function declined in those exposed to EHH when the performance of the control group was taken into account (RCI .05 to -.95) with decline persisting at descent. Memory and psychomotor function showed decline at highest ascent only (RCI -.08 to -.56). However, there was inter-individual variability in response: whilst NP performance declined in most, this improved in some trekkers. Cognitive decline was greater amongst older people (r = .42; p < .0001), but was otherwise not consistently associated with socio-demographic, mood, or physiological variables. CONCLUSIONS: After correcting for learning effects, attention, verbal abilities and executive functioning declined with exposure to EHH. There was considerable individual variability in the response of brain function to sustained hypoxia with some participants not showing any effects of hypoxia. This might have implications for those facing sustained hypoxia as a result of any disease

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A court of morals, a court of law, or a little bit of both?

The provision of healthcare was once relatively straightforward. Based upon the Hippocratic tradition, the doctor/patient relationship was not a partnership, rather there was an unequal relationship where an all knowing-and one would hope, all caring-doctor provided treatment in a manner consistent with their specific view of the world. There were few ethical or legal complexities and individual preferences were relevant only insofar as they impacted on the doctor’s clinical decision making. Medicine and the human condition have, however, moved on from this simpler time and there are deep complexities to be found at the intersection of law, religion and the provision of healthcare. This chapter explores this intersection and considers the ongoing struggle to respect the interests of all parties in the healthcare relationship, concluding that, despite the often competing priorities of healthcare providers, individual patients, regulatory regimes and religious organisations, there are a core set of principles that are appropriately supported in our current regulatory framework. These include: respect for individual dignity and autonomy, freedom of choice, and the inviolability of human life. This conclusion will be supported through a consideration of five ‘salient principles’ raised by the Archbishop of Westminster and considered by the court in the complex decision of Re A (Children) (Conjoined Twins: Surgical Separation) [2001] 2 WLR 480.Bernadette J. Richard

A woman who couldn't speak: report of methotrexate neurotoxicity

The association between methotrexate therapy and idiosyncratic neurological complications is well recognised in children. This case illustrates the importance of considering the diagnosis of methotrexate toxicity in an adult patient with behavioural and speech disturbances, who received it by intrathecal route only and in whom the only indicator was an abnormal electroencephalographic stud

Fulminant liver failure: an indicator of silent myocardial rupture

A 56 year old man presented with an atypical chest infection. Remote inferoposterior myocardial infarction was noted on electrocardiography and transthoracic echocardiography. Hepatic failure developed with sudden gross elevation of liver aminotransferases and coagulopathy. No primary hepatic cause could be identified. Subsequent right heart failure led to transoesophageal echocardiography that revealed a large inoperable ventricular septal defect. Histopathological data showed ischaemic hepatitis and reinfarction of the inferoposterior myocardial wall. Acute cardiac events may be silent and precipitate misleading severe hepatic dysfunction

Short communication: Antimicrobial activity of indoleacetic, gibberellic and coumaric acids against Paenibacillus larvae and its toxicity against Apis mellifera

Aim of study: To explore three isolated phytomolecules: indoleacetic acid (IAA), gibberellic acid (GA), and the secondary metabolite p-coumaric acid (CUM): (1) evaluating their toxicity against Apis mellifera larvae and adults under controlled conditions in the laboratory; (2) searching for antimicrobial activity against Paenibacillus larvae.Area of study: Honey bee larvae and adults were collected from the experimental apiary of the “Centro de Investigación en Abejas Sociales (CIAS)” (-37.9348798, -57.682817), Institute of the National University of Mar del Plata (UNMdP), Argentina.Material and methods: Paenibacillus larvae strains were isolated from beehives from different provinces of Argentina (Buenos Aires, Córdoba and Entre Ríos) showing clinical symptoms of the American foulbrood. All strains (S1, S2, S3, S4) were genotypically identified using PL5 and PL4 primers and characterized as genotype ERIC1. Then standard essays were performed to determined toxicity of phytomolecules in honey bees and antimicrobial activity through the broth microdilution method.Main results:  The diet with GA, IAA and CUM did not present toxic effects in larvae or adult bees, and only CUM showed antimicrobial activity against P. larvae. In this study, we obtained in vitro values of MNIC (minimum non-inhibitory concentration) of 500 μg mL-1 and a MIC (minimum inhibitory concentration) of 650 μg mL-1 for CUM.Research highlights: The obtained results remark its potential as a natural alternative for the control of P. larvae, avoiding the problems generated by the use of synthetic antibiotics such as the resistance phenomena and the contamination of hive’s products