Sex differences in the association of sleep spindle density and cognitive performance among community-dwelling middle-aged and older adults with obstructive sleep apnea.

Recent studies have found associations between obstructive sleep apnea and cognitive decline. The underlying mechanisms are still unclear. Here, we investigate the associations between changes in micro-architecture, specifically sleep spindles, and cognitive function in community-dwelling middle-aged and older adults, some with obstructive sleep apnea, with a focus on sex differences. A total of 125 voluntary participants (mean age 66.0 ± 6.4 years, 64 females) from a larger cohort (participants of the Brain in Motion Studies I and II) underwent 1 night of in-home polysomnography and a neuropsychological battery (sleep and cognitive testing were conducted within 2 weeks of each other). A semi-automatic computerized algorithm was used to score polysomnography data and detect spindle characteristics in non-rapid eye movement Stages 2 and 3 in both frontal and central electrodes. Based on their apnea-hypopnea index, participants were divided into those with no obstructive sleep apnea (apnea-hypopnea index < 5 per hr, n = 21), mild obstructive sleep apnea (5 ≥ apnea-hypopnea index < 15, n = 47), moderate obstructive sleep apnea (15 ≥ apnea-hypopnea index < 30, n = 34) and severe obstructive sleep apnea (apnea-hypopnea index ≥ 30, n = 23). There were no significant differences in spindle characteristics between the four obstructive sleep apnea severity groups. Spindle density and percentage of fast spindles were positively associated with some verbal fluency measures on the cognitive testing. Sex might be linked with these associations. Biological sex could play a role in the associations between spindle characteristics and some verbal fluency measures. Obstructive sleep apnea severity was not found to be a contributing factor in this non-clinical community-dwelling cohort.

Differential effects of high-altitude exposure on markers of oxidative stress, antioxidant capacity, and iron profiles.

High-altitude (HA) exposure may stimulate significant physiological and molecular changes, resulting in HA-related illnesses. HA may impact oxidative stress, antioxidant capacity, and iron homeostasis, yet it is unclear how both repeated exposure and HA acclimatization may modulate such effects. Therefore, we assessed the effects of weeklong repeated daily HA exposure (2,900-5,050 m) in altitude-naïve individuals (n = 21 individuals, 13 females, mean ± SD, 25.3 ± 3.7 yr) to mirror the working schedule of HA workers (n = 19 individuals, all males, 41.1 ± 9.4 yr) at the Atacama Large Millimeter Array (ALMA) Observatory (San Pedro de Atacama, Chile). Markers of oxidative stress, antioxidant capacity, and iron homeostasis were measured in blood plasma. Levels of protein oxidation (P < 0.001) and catalase activity (P = 0.023) increased and serum iron (P < 0.001), serum ferritin (P < 0.001), and transferrin saturation (P < 0.001) levels decreased with HA exposure in both groups. HA workers had lower levels of oxidative stress, and higher levels of antioxidant capacity, iron supply, and hemoglobin concentration as compared with altitude-naïve individuals. On a second week of daily HA exposure, changes in levels of protein oxidation, glutathione peroxidase, and nitric oxide metabolites were lower as compared with the first week in altitude-naïve individuals. These results indicate that repeated exposure to HA may significantly alter oxidative stress and iron homeostasis, and the degree of such changes may be dependent on if HA is visited naïvely or routinely. Further studies are required to fully elucidate differences in HA-induced changes in oxidative stress and iron homeostasis profiles among visitors of HA.

Wilderness Mass Casualty Incident (MCI): Rescue Chain After Avalanche at Everest Base Camp (EBC) In 2015.

The Nepal Earthquake of 2015 killed over 8000 people and injured over 20,000 in Nepal. Moments after the earthquake, an avalanche of falling ice came down from above Everest Base Camp (EBC). The air blast created by the avalanche flattened the middle part of EBC, killing 15 people and injuring at least 70. The casualties were initially triaged and treated at EBC and then evacuated by air to Kathmandu for definitive care. There were intermediate stops at the villages of Pheriche and Lukla during which the casualties were offloaded, retriaged, treated, and loaded again for further transport. Most of the authors of this article helped to provide primary disaster relief at EBC, Pheriche, or Lukla immediately after the earthquake. We describe the process by which an ad hoc rescue chain evacuated the casualties. We discuss challenges, both medical and nonmedical, what went well, and lessons learned. We make recommendations for disaster planning in the Khumbu (Everest) region, an isolated high altitude roadless area of Nepal.

Prophylactic Acetaminophen or Ibuprofen Results in Equivalent Acute Mountain Sickness Incidence at High Altitude: A Prospective Randomized Trial.

OBJECTIVE: Recent trials have demonstrated the usefulness of ibuprofen in the prevention of acute mountain sickness (AMS), yet the proposed anti-inflammatory mechanism remains unconfirmed. Acetaminophen and ibuprofen were tested for AMS prevention. We hypothesized that a greater clinical effect would be seen from ibuprofen due to its anti-inflammatory effects compared with acetaminophen's mechanism of possible symptom reduction by predominantly mediating nociception in the brain. METHODS: A double-blind, randomized trial was conducted testing acetaminophen vs ibuprofen for the prevention of AMS. A total of 332 non-Nepali participants were recruited at Pheriche (4371 m) and Dingboche (4410 m) on the Everest Base Camp trek. The participants were randomized to either acetaminophen 1000 mg or ibuprofen 600 mg 3 times a day until they reached Lobuche (4940 m), where they were reassessed. The primary outcome was AMS incidence measured by the Lake Louise Questionnaire score. RESULTS: Data from 225 participants who met inclusion criteria were analyzed. Twenty-five participants (22.1%) in the acetaminophen group and 18 (16.1%) in the ibuprofen group developed AMS (P = .235). The combined AMS incidence was 19.1% (43 participants), 14 percentage points lower than the expected AMS incidence of untreated trekkers in prior studies at this location, suggesting that both interventions reduced the incidence of AMS. CONCLUSIONS: We found little evidence of any difference between acetaminophen and ibuprofen groups in AMS incidence. This suggests that AMS prevention may be multifactorial, affected by anti-inflammatory inhibition of the arachidonic-acid pathway as well as other analgesic mechanisms that mediate nociception. Additional study is needed.

Human intermittent hypoxia-induced respiratory plasticity is not caused by inflammation.

Ventilatory instability, reflected by enhanced acute hypoxic (AHVR) and hypercapnic (AHCVR) ventilatory responses is a fundamental component of obstructive sleep apnoea (OSA) pathogenesis. Intermittent hypoxia-induced inflammation is postulated to promote AHVR enhancement in OSA, although the role of inflammation in intermittent hypoxia-induced respiratory changes in humans has not been examined. Thus, this study assessed the role of inflammation in intermittent hypoxia-induced respiratory plasticity in healthy humans.In a double-blind, placebo-controlled, randomised crossover study design, 12 males were exposed to 6 h of intermittent hypoxia on three occasions. Prior to intermittent hypoxia exposures, participants ingested (for 4  days) either placebo or the nonsteroidal anti-inflammatory drugs indomethacin (nonselective cyclooxygenase (COX) inhibitor) and celecoxib (selective COX-2 inhibitor). Pre- and post-intermittent hypoxia resting ventilation, AHVR, AHCVR and serum concentration of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α were assessed.Pre-intermittent hypoxia resting ventilation, AHVR, AHCVR and TNF-α concentrations were similar across all three conditions (p≥0.093). Intermittent hypoxia increased resting ventilation and the AHVR similarly across all conditions (p=0.827), while the AHCVR was increased (p=0.003) and TNF-α was decreased (p=0.006) with only selective COX-2 inhibition.These findings indicate that inflammation does not contribute to human intermittent hypoxia-induced respiratory plasticity. Moreover, selective COX-2 inhibition augmented the AHCVR following intermittent hypoxia exposure, suggesting that selective COX-2 inhibition could exacerbate OSA severity by increasing ventilatory instability.

Altitude Sickness in Climbers and Efficacy of NSAIDs Trial (ASCENT): randomized, controlled trial of ibuprofen versus placebo for prevention of altitude illness.

OBJECTIVE: To study the effectiveness of ibuprofen versus placebo in preventing acute mountain sickness (AMS) and high altitude headache (HAH). METHODS: Double-blind, randomized, placebo-controlled trial. RESULTS: Two hundred ninety-four healthy Western trekkers were recruited on the Everest approach at 4280 m or 4358 m and randomly assigned to receive either 600 mg of ibuprofen or placebo 3 times daily before and during ascent to 4928 m. One hundred eighty-three of 294 participants completed the trial. Of the participants who did not complete the trial, 62 were lost to follow-up and another 49 broke trial protocol. In an intent-to-treat analysis (232 participants), ibuprofen was found to be more effective than placebo in reducing the incidence of AMS (24.4% vs 40.4%; P = .01) and the incidence of HAH (42.3% vs 60.5%; P < .01). Ibuprofen was also superior to placebo in reducing the severity of HAH (4.9% vs 14.7%; P = .01). The end point of oxygen saturation was also higher in the ibuprofen group (80.8 % vs 82.4%; P = .035). For the 183 participants who completed the trial and conformed to the protocol, the incidence of AMS between placebo and treatment groups was not significant (32.9% vs 22.7%; P = .129 for AMS incidence, 9.6% vs 8.2%; P = .74 for AMS severity, 54.8% vs 42.7%; P = .11 for HAH incidence, and 8.2% vs 3.6%; P = .18 for HAH severity). CONCLUSIONS: Ibuprofen was found to be effective in preventing AMS in the intent-to-treat analysis group but not in those who completed the trial. This loss of significance in the subjects who completed the trial may be explained by persons in the placebo group having a higher burden of illness and associated decreased compliance with the protocol. An important limitation of this study may be the possibility that ibuprofen can mask headache, which is a compulsory criterion for the diagnosis of AMS.

Impact of intermittent hypoxia on human vascular responses during sleep.

Exposure to intermittent hypoxia (IH) ≥15 times per hour is believed to be the primary mechanism for the increased risk of cerebrovascular and cardiovascular disease in patients with moderate to severe sleep apnea. Human experimental models of IH used to investigate this link have been predominantly employed during wakefulness, which limits extrapolation of findings to sleep apnea where IH occurs during sleep. Moreover, how IH impacts vascular regulation during sleep has not been measured quantitatively. Therefore, the objective of this study was to assess the impact sleep accompanied by IH on vascular responses to hypoxia and hypercapnia during sleep. Ten males performed two randomly scheduled 6-h overnight sleep studies. One sleep study was performed in room air (normoxia) and the other sleep study was performed during isocapnic IH (60 s hypoxia-60 s normoxia). On each night, cerebrovascular (peak blood velocity through the middle cerebral artery (V¯P); transcranial Doppler ultrasound) and cardiovascular (blood pressure, heart rate) responses to hypoxia and hypercapnia were measured before sleep onset (PM-Awake), within the first 2 h of sleep (PM-Asleep), in the 5th (out of 6) hours of sleep (AM-Asleep) and after being awoken in the morning (AM-Awake). Sleep accompanied by IH had no impact on the V¯P and blood pressure responses to hypoxia and hypercapnic at any timepoint (p ≥ 0.103 for all responses). However, the AM-Awake heart rate response to hypoxia was greater following sleep in IH compared to sleep in normoxia. Independent of the sleep environment, the V¯P response to hypoxia and hypercapnia were reduced during sleep. In conclusion, cerebral blood flow responses are reduced during sleep compared to wakefulness, but 6 h of sleep accompanied by IH does not alter cerebrovascular and cardiovascular response to hypoxia and hypercapnia during wakefulness or sleep in healthy young humans. However, it is likely that longer exposure to IH during sleep (i.e., days-to-weeks) is required to better elucidate IH's impact on vascular regulation in humans.

Spironolactone does not prevent acute mountain sickness: a prospective, double-blind, randomized, placebo-controlled trial by SPACE Trial Group (spironolactone and acetazolamide trial in the prevention of acute mountain sickness group).

OBJECTIVES: Over the last 20 years a number of small trials have reported that spironolactone effectively prevents acute mountain sickness (AMS), but to date there have been no large randomized trials investigating the efficacy of spironolactone in prevention of AMS. Hence, a prospective, double-blind, randomized, placebo-controlled trial was conducted to evaluate the efficacy of spironolactone in the prevention of AMS. METHODS: Participants were sampled from a diverse population of western trekkers recruited at 4300 m on the Mount Everest base camp approach (Nepal side) en route to the study endpoint at 5000 m. Three hundred and eleven healthy trekkers were enrolled, and 251 completed the trial from October to November 2007. Participants were randomly assigned to receive at least 3 doses of spironolactone 50 mg BID, acetazolamide 250 mg BID, or visually matched placebo. A Lake Louise AMS Score of 3 or more, together with the presence of headache and 1 other symptom, was used to evaluate the incidence and severity of AMS. Secondary outcome measures were blood oxygen content and the incidence and severity of high altitude headache (HAH). RESULTS: Acetazolamide was more effective than spironolactone in preventing AMS (OR = 0.28, 95% CI 0.12-0.60, p < 0.01). Spironolactone was not significantly different from placebo in the prevention of AMS. AMS incidence for placebo was 20.3%, acetazolamide 10.5%, and spironolactone 29.4%. Oxygen saturation was also significantly increased in the acetazolamide group (83% ± 0.04) vs spironolactone group (80% ± 0.05, p < 0.01). CONCLUSIONS: Spironolactone (50 mg BID) was ineffective in comparison to acetazolamide (250 mg BID) in the prevention of AMS in partially acclimatized western trekkers ascending to 5000 m in the Nepali Himalaya.

Impact of nocturnal oxygen and CPAP on the ventilatory response to hypoxia in OSA patients free of overt cardiovascular disease.

A primary characteristic of obstructive sleep apnea (OSA) is chronic exposure to intermittent hypoxia (IH) due to repeated upper airway obstruction. Chronic IH exposure is believed to increase OSA severity over time by enhancing the acute ventilatory response to hypoxia (AHVR), thus promoting ventilatory overshoot when apnea ends and perpetuation of apnea during sleep. Continuous positive airway pressure (CPAP), the gold-standard treatment of OSA, reduces the AHVR, believed to result from correction of IH. However, CPAP also corrects ancillary features of OSA such as intermittent hypercapnia, negative intrathoracic pressure and surges in sympathetic activity, which may also contribute to the reduction in AHVR. Therefore, the objective of this study was to investigate the impact of nocturnal oxygen therapy (to remove IH only) and CPAP (to correct IH and ancillary features of OSA) on AHVR in newly diagnosed OSA patients. Fifty-two OSA patients and twenty-two controls were recruited. The AHVR was assessed using a 5 min iscopanic-hypoxic challenge before, and after, treatment of OSA by nocturnal oxygen therapy and CPAP. Following baseline measurements, OSA patients were randomly assigned to nocturnal oxygen therapy (Oxygen, n = 26) or no treatment (Air; n = 26). The AHVR was re-assessed following two weeks of oxygen therapy or no treatment, after which all patients were treated with CPAP. The AHVR was quantified following ~4 weeks of adherent CPAP therapy (n = 40). Both nocturnal oxygen and CPAP treatments improved hypoxemia (p < 0.05), and, as expected, nocturnal oxygen therapy did not completely abolish respiratory events (i.e., apneas/hypopneas). Averaged across all OSA patients, nocturnal oxygen therapy did not change AHVR from baseline to post-oxygen therapy. Similarly, the AHVR was not altered pre- and post-CPAP (p > 0.05). However, there was a significant decrease in AHVR with both nocturnal oxygen therapy and CPAP in patients in the highest OSA severity quartile (p < 0.05). Nocturnal oxygen therapy and CPAP both reduce the AHVR in patients with the most severe OSA. Therefore, IH appears to be the primary mechanism producing ventilatory instability in patients with severe OSA via enhancement of the AHVR.

Effects of exposure to intermittent hypoxia on oxidative stress and acute hypoxic ventilatory response in humans.

RATIONALE: Periodic occlusion of the upper airway in patients with obstructive sleep apnea leads to chronic intermittent hypoxia, which increases the acute hypoxic ventilatory response (AHVR). Animal studies suggest that oxidative stress may modulate AHVR by increasing carotid body sensitivity to hypoxia. This has not been shown in humans. OBJECTIVES: To determine whether 4 days of exposure to chronic intermittent hypoxia increases AHVR and oxidative stress and to determine the strength of the association between oxidative stress and AHVR. METHODS: After two normoxic control days (Day -4 and Day 0), 10 young healthy men were exposed awake to 4 days (Days 1-4) of intermittent hypoxia for 6 hours per day. MEASUREMENTS AND MAIN RESULTS: AHVR, assessed using an isocapnic hypoxia protocol, was determined as the slope of the linear regression between ventilation and oxygen desaturation. Oxidative stress was evaluated by measuring plasma DNA, lipid and protein oxidation, uric acid and antioxidant status by measuring alpha-tocopherol, total vitamin C, and antioxidant enzymatic activities. Between baseline and Day 4, there were significant increases in AHVR, DNA oxidation, uric acid, and vitamin C, whereas antioxidant enzymatic activities and alpha-tocopherol were unchanged. There were strong correlations between the changes in AHVR and DNA oxidation (r = 0.88; P = 0.002). CONCLUSIONS: Chronic intermittent hypoxia increases oxidative stress by increasing production of reactive oxygen species without a compensatory increase in antioxidant activity. This human study shows that reactive oxygen species overproduction modulates increased AHVR. These mechanisms may be responsible for increased AHVR in patients with obstructive sleep apnea.

Lower Incidence of COVID-19 at High Altitude: Facts and Confounders.

Pun, Matiram, Rachel Turner, Giacomo Strapazzon, Hermann Brugger, and Erik R. Swenson. Lower incidence of COVID-19 at high altitude: Facts and confounders. High Alt Med Biol. 21:217-222, 2020.-The rapid transmission, increased morbidity, and mortality of coronavirus disease 2019 (COVID-19) has exhausted many health care systems and the global economy. Large variations in COVID-19 prevalence and incidence have been reported across and within many countries worldwide; however, this remains poorly understood. The variability and susceptibility across the world have been mainly attributed to differing socioeconomic status, burden of chronic diseases, access to health care, strength of health care systems, and early or late adoption of control measures. Environmental factors such as pollution, ambient temperature, humidity, and seasonal weather patterns at different latitudes may influence how severe the pandemic is and the incidence of infection in any part of the world. In addition, recent epidemiological data have been used to propose that altitude of residence may not only influence those environmental features considered key to lesser viral transmission, but also susceptibility to more severe forms of COVID-19 through hypoxic-hypobaria driven genomic or nongenomic adaptations specific to high-altitude populations. In this review, we critically examine these factors and attempt to determine based upon available scientific and epidemiological data whether living in high-altitude regions might be protective against COVID-19 as recent publications have claimed.

Intercultural Competence of Western Teachers for Nepalese Rescuers.

INTRODUCTION: Educational projects in mountain rescue in Nepal have a long tradition. They are usually led by Western experts who train their Nepalese colleagues using teams of people with diverse cultural background. To better understand the challenges of these encounters, we conducted a prospective cohort study during the first mountain rescue instructor course in Nepal. METHODS: Western instructors (WIs) and Nepalese instructor candidates (NICs) were asked to self-assess their intercultural competence with the help of questionnaires. The responses were compared and analyzed for differences between WIs and NICs and differences in a pre-post assessment of the WIs. In addition, semistructured interviews were conducted with randomly selected NICs. RESULTS: We found significant differences in communication styles between NICs and WIs: NICs showed a preference to establish relationships before discussing business and not to speak openly in conflict situations. WIs were much more direct and preferred dispassionate exchanges. In an assessment after the course, WIs had changed their attitude toward the host culture. CONCLUSIONS: We found differences in communication styles between WIs and NICs that are relevant to globalized medical education. Faculty members should be prepared before implementing medical training abroad and should have time to experience the host culture.

Cognitive Effects of Repeated Acute Exposure to Very High Altitude Among Altitude-Experienced Workers at 5050 m.

Background: We investigated altitude effects on different cognitive domains among perennial shift-workers at the Atacama Large Millimeter/submillimeter Array Observatory (5050 m), Chile. Materials and Methods: Twenty healthy male workers were recruited and assigned to either a moderate-altitude first (MAF group, Test 1: 2900 m and Test 2: 5050 m) or to a high-altitude first (HAF group, Test 1: 5050 m and Test 2: 2900 m). Test 1 was conducted at the beginning and Test 2 at the end of the shift-work week. Processing speed (RTI, reaction time), attention (AST, attention-switching task, and RVP, rapid visual processing), and executive function (OTS, One Touch Stockings of Cambridge) were assessed. Results: Of the three cognitive domains assessed, only processing speed showed altitude-at-test group interaction (RTI median five choice reaction time: F1, 17 = 6.980, [Formula: see text] = 0.291, p = 0.017). With acclimatization, there was a decrease in AST reaction latency mean (t17 = -2.155, dz = 1.086, p = 0.046), an increase in RVP accuracy (t17 = 2.733, dz = 1.398, p = 0.014), and a decrease in OTS mean latency first choice (t17 = -2.375, dz = 1.211, p = 0.03). Decreased variability in cognitive function was observed in AST reaction latency standard deviation (t17 = -2.524, dz = 1.282, p = 0.022) and in RVP response latency standard deviation (t17 = -2.35, dz = 1.177, p = 0.03) with acclimatization. At 5050 m of elevation, SpO2 was positively correlated with executive function in the MAF group (OTS problems solved on first choice: r(5) = 0.839, p = 0.018) and negatively correlated with executive function latency standard deviations in the HAF group (OTS latency to first choice standard deviation: r(10) = -0.618, p = 0.032). Conclusions: Our findings highlight the importance of acclimatization and improvement of blood oxygen level, even among high altitude-experienced workers, to optimize performance of cognitively demanding work and reduce high altitude-associated health risks.

Effect of Acute, Subacute, and Repeated Exposure to High Altitude (5050 m) on Psychomotor Vigilance.

Aim: High altitude (HA) hypoxia may affect cognitive performance and sleep quality. Further, vigilance is reduced following sleep deprivation. We investigated the effect on vigilance, actigraphic sleep indices, and their relationships with acute mountain sickness (AMS) during very HA exposure, acclimatization, and re-exposure. Methods: A total of 21 healthy altitude-naive individuals (25 ± 4 years; 13 females) completed 2 cycles of altitude exposure separated by 7 days at low altitude (LA, 520 m). Participants slept at 2900 m and spent the day at HA, (5050 m). We report acute altitude exposure on Day 1 (LA vs. HA1) and after 6 days of acclimatization (HA1 vs. HA6). Vigilance was quantified by reaction speed in the 10-min psychomotor vigilance test reaction speed (PVT-RS). AMS was evaluated using the Environmental Symptoms Questionnaire Cerebral Score (AMS-C score). Nocturnal rest/activity was recorded to estimate sleep duration using actigraphy. Results: In Cycle 1, PVT-RS was slower at HA1 compared to LA (4.1 ± 0.8 vs. 4.5 ± 0.6 s-1, respectively, p = 0.029), but not at HA6 (4.6 ± 0.7; p > 0.05). In Cycle 2, PVT-RS at HA1 (4.6 ± 0.7) and HA6 (4.8 ± 0.6) were not different from LA (4.8 ± 0.6, p > 0.05) and significantly greater than corresponding values in Cycle 1. In both cycles, AMS scores were higher at HA1 than at LA and HA6 (p < 0.05). Estimated sleep durations (TST) at LA, 1st and 5th nights were 431.3 ± 28.7, 418.1 ± 48.6, and 379.7 ± 51.4 min, respectively, in Cycle 1 and they were significantly reduced during acclimatization exposures (LA vs. 1st night, p > 0.05; LA vs. 5th night, p = 0.012; and 1st vs. 5th night, p = 0.054). LA, 1st and 5th nights TST in Cycle 2 were 477.5 ± 96.9, 430.9 ± 34, and 341.4 ± 32.2, respectively, and we observed similar deteriorations in TST as in Cycle 1 (LA vs. 1st night, p > 0.05; LA vs. 5th night, p = 0.001; and 1st vs. 5th night, p < 0.0001). At HA1, subjects who reported higher AMS-C scores exhibited slower PVT-RS (r = -0.56; p < 0.01). Subjects with higher AMS-C scores took longer time to react to the stimuli during acute exposure (r = 0.62, p < 0.01) during HA1 of Cycle 1. Conclusion: Acute exposure to HA reduces the PVT-RS. Altitude acclimatization over 6 days recovers the reaction speed and prevents impairments during subsequent altitude re-exposure after 1 week spent near sea level. However, acclimatization does not lead to improvement in total sleep time during acute and subacute exposures.

The STAR Data Reporting Guidelines for Clinical High Altitude Research.

Brodmann Maeder, Monika, Hermann Brugger, Matiram Pun, Giacomo Strapazzon, Tomas Dal Cappello, Marco Maggiorini, Peter Hackett, Peter Baärtsch, Erik R. Swenson, Ken Zafren (STAR Core Group), and the STAR Delphi Expert Group. The STARdata reporting guidelines for clinical high altitude research. High AltMedBiol. 19:7-14, 2018. AIMS: The goal of the STAR (STrengthening Altitude Research) initiative was to produce a uniform set of key elements for research and reporting in clinical high-altitude (HA) medicine. The STAR initiative was inspired by research on treatment of cardiac arrest, in which the establishment of the Utstein Style, a uniform data reporting protocol, substantially contributed to improving data reporting and subsequently the quality of scientific evidence. MATERIALS AND METHODS: The STAR core group used the Delphi method, in which a group of experts reaches a consensus over multiple rounds using a formal method. We selected experts in the field of clinical HA medicine based on their scientific credentials and identified an initial set of parameters for evaluation by the experts. RESULTS: Of 51 experts in HA research who were identified initially, 21 experts completed both rounds. The experts identified 42 key parameters in 5 categories (setting, individual factors, acute mountain sickness and HA cerebral edema, HA pulmonary edema, and treatment) that were considered essential for research and reporting in clinical HA research. An additional 47 supplemental parameters were identified that should be reported depending on the nature of the research. CONCLUSIONS: The STAR initiative, using the Delphi method, identified a set of key parameters essential for research and reporting in clinical HA medicine.

Effects on Cognitive Functioning of Acute, Subacute and Repeated Exposures to High Altitude.

Objective: Neurocognitive functions are affected by high altitude, however the altitude effects of acclimatization and repeated exposures are unclear. We investigated the effects of acute, subacute and repeated exposure to 5,050 m on cognition among altitude-naïve participants compared to control subjects tested at low altitude. Methods: Twenty-one altitude-naïve individuals (25.3 ± 3.8 years, 13 females) were exposed to 5,050 m for 1 week (Cycle 1) and re-exposed after a week of rest at sea-level (Cycle 2). Baseline (BL, 520 m), acute (Day 1, HA1) and acclimatization (Day 6, HA6, 5,050 m) measurements were taken in both cycles. Seventeen control subjects (24.9 ± 2.6 years, 12 females) were tested over a similar period in Calgary, Canada (1,103 m). The Reaction Time (RTI), Attention Switching Task (AST), Rapid Visual Processing (RVP) and One Touch Stockings of Cambridge (OTS) tasks were administered and outcomes were expressed in milliseconds/frequencies. Lake Louise Score (LLS) and blood oxygen saturation (SpO2) were recorded. Results: In both cycles, no significant changes were found with acute exposure on the AST total score, mean latency and SD. Significant changes were found upon acclimatization solely in the altitude group, with improved AST Mean Latency [HA1 (588 ± 92) vs. HA6 (526 ± 91), p < 0.001] and Latency SD [HA1 (189 ± 86) vs. HA6 (135 ± 65), p < 0.001] compared to acute exposure, in Cycle 1. No significant differences were present in the control group. When entering Acute SpO2 (HA1-BL), Acclimatization SpO2 (HA6-BL) and LLS score as covariates for both cycles, the effects of acclimatization on AST outcomes disappeared indicating that the changes were partially explained by SpO2 and LLS. The changes in AST Mean Latency [ΔBL (-61.2 ± 70.2) vs. ΔHA6 (-28.0 ± 58), p = 0.005] and the changes in Latency SD [ΔBL (-28.4 ± 41.2) vs. ΔHA6 (-0.2235 ± 34.8), p = 0.007] across the two cycles were smaller with acclimatization. However, the percent changes did not differ between cycles. These results indicate independent effects of altitude across repeated exposures. Conclusions: Selective and sustained attention are impaired at altitude and improves with acclimatization.The observed changes are associated, in part, with AMS score and SpO2. The gains in cognition with acclimatization during a first exposure are not carried over to repeated exposures.