Hypertension and Acute Mountain Sickness in Himalayan Trekkers in Nepal: An Observational Cohort Study.

INTRODUCTION: A history of preexisting hypertension is common in people participating in mountain activities; however, the relationship between blood pressure (BP), preexisting hypertension, and acute mountain sickness (AMS) is not well studied. We sought to determine these relationships among trekkers in the Everest region of Nepal. METHODS: This was a prospective observational cohort study of a convenience sample of adult, nonpregnant volunteers trekking in the Everest Base Camp region in Nepal. We recorded Lake Louise Scores for AMS and measured BP at 2860 m, 3400 m, and 4300 m. The primary outcome was AMS. RESULTS: A total of 672 trekkers (including 60 with history of preexisting hypertension) were enrolled at 2860 m. We retained 529 at 3400 m and 363 at 4300 m. At 3400 m, 11% of participants had AMS, and 13% had AMS at 4300 m. We found no relationship between AMS and measured BP values (P>0.05), nor was there any relation of BP to AMS severity as measured by higher Lake Louise Scores (P>0.05). Preexisting hypertension (odds ratio [OR] 0.16; 95% CI 0.025-0.57), male sex (OR 0.59; 95% CI 0.37-0.96), and increased SpO2 (OR 0.93; 95% CI 0.87-0.98) were associated with reduced rates of AMS in multivariate analyses adjusting for known risk factors for AMS. CONCLUSIONS: AMS is common in trekkers in Nepal, even at 3400 m. There is no relationship between measured BP and AMS. However, a medical history of hypertension may be associated with a lower risk of AMS. More work is needed to confirm this novel finding.

Surface melt driven summer diurnal and winter multi-day stick-slip motion and till sedimentology.

Fluctuations in glacier motion are very common and are thought to be controlled by subglacial hydrology and till deformation. There are few instrumented studies that have monitored seasonal changes. We use the innovative Glacsweb subglacial in situ wireless probes, combined with dGPS and custom geophone data from an Icelandic soft-bedded temperate glacier, to show that there are two distinct seasonal styles of speed-up events. Relatively small diurnal events occur during the melt season, whilst during winter there are larger multi-day events related to positive degree days. These events are accompanied by a distinct pattern of till deformation and basal icequakes. We argue these reflect stick-slip motion which occurs when the glacier hydrological system is unable to accommodate the melt water flux generated by surface melt episodes. We show a rare fully instrumented coupled glacier/till record of contrasting summer and winter stick-slip motion and discuss its implication for till sedimentology.

Accuracy of Estimated Creatinine in Multistage Ultramarathon Runners.

INTRODUCTION: Ultramarathon running is increasing in popularity worldwide, as is the growing body of research on these athletes. Multiple studies have examined acute kidney injury through estimated baseline creatinine (Cr) and glomerular filtration rate (GFR). Values are estimated through an age-based formula of GFR and the modification of diet in renal disease (MDRD) equation. However, the accuracy of this practice in a cohort of healthy athletes is unknown. METHODS: A prospective analysis of the first 40-km (25-mi) stage of 6-stage 250-km (155-mi) multistage ultramarathons in the Sahara, Namibia, Atacama, and Gobi Deserts. Runners had prerace measured baseline Cr compared to estimated values through age-based estimated GFR and back calculation of Cr through the MDRD equation. RESULTS: Forty-eight participants (27% female, age 39±10 y) had Cr values analyzed. The mean measured Cr was 0.99±0.17, which was 11% higher than an estimated Cr of 0.88±0.14 (P<0.01). Estimated age-based GFR was 95.9±5.8 mL⋅min-1 compared to GFR based on measured Cr and MDRD of 86.1±14.6 (P<0.001). CONCLUSIONS: Estimated values of GFR and Cr by standard age-based values and MDRD equation were significantly inaccurate, which would overinflate the incidence of acute kidney injury. Future studies should devise a new model for estimation of baseline Cr that is validated in this population.

Apostle Islands National Lakeshore: A Review of Search and Rescue and Emergency Medical Services Operations, 2006-2015.

INTRODUCTION: Apostle Islands National Lakeshore (APIS) lies at the northern tip of Wisconsin and is home to a network of 21 islands along Lake Superior. The goal of this report is to investigate search and rescue (SAR) and emergency medical services (EMS) trends at APIS in an effort to improve visitor safety and resource allocation. METHODS: This study is a retrospective analysis reviewing APIS SAR reports and annual EMS summary reports from January 1, 2006, to December 31, 2015. Information related to incident type, incident date, individual demographic characteristics and activities, injury/illness type, cost, and contributing factors were recorded and analyzed in frequency tables. RESULTS: From 2006 to 2015, APIS SAR conducted 133 total missions assisting 261 individuals-200 not injured/ill, 57 injured/ill, and 4 fatalities. Median cost per SAR incident involving aircraft totaled $21,695 (range: $2,993-141,849), whereas incidents not involving aircraft had a median cost of $363 (range: $35-8,830). Nonmotorized boating was the most common activity resulting in SAR incidents. All 4 fatalities were attributed to drowning while kayaking or swimming. Cold-related injury/illness accounted for nearly half of all injuries/illnesses (45%) with the most commonly reported contributing factor being high winds. EMS responded to a total of 134 incidents. Trauma and first aid accounted for 43% and 34% of EMS workload, respectively. CONCLUSIONS: Overall, this study highlights the hazards associated with the frigid and rough conditions of Lake Superior. The reported results aim to help APIS personnel more saliently convey risks to visitors and plan appropriately in an effort to decrease the need for future rescues.

Extreme event medicine: considerations for the organisation of out-of-hospital care during obstacle, adventure and endurance competitions.

Obstacle, adventure and endurance competitions in challenging or remote settings are increasing in popularity. A literature search indicates a dearth of evidence-based research on the organisation of medical care for wilderness competitions. The organisation of medical care for each event is best tailored to specific race components, participant characteristics, geography, risk assessments, legal requirements, and the availability of both local and outside resources. Considering the health risks and logistical complexities inherent in these events, there is a compelling need for guiding principles that bridge the fields of wilderness medicine and sports medicine in providing a framework for the organisation of medical care delivery during wilderness and remote obstacle, adventure and endurance competitions. This narrative review, authored by experts in wilderness and operational medicine, provides such a framework. The primary goal is to assist organisers and medical providers in planning for sporting events in which participants are in situations or locations that exceed the capacity of local emergency medical services resources.

Blood Pressure and Altitude: An Observational Cohort Study of Hypertensive and Nonhypertensive Himalayan Trekkers in Nepal.

Keyes, Linda E., Thomas Douglas Sallade, Charles Duke, Jennifer Starling, Alison Sheets, Sushil Pant, David S. Young, David Twillman, Nirajan Regmi, Benoit Phelan, Purshotam Paudel, Matthew McElwee, Luke Mather, Devlin Cole, Theodore McConnell, and Buddha Basnyat. Blood pressure and altitude: an observational cohort study of hypertensive and nonhypertensive Himalayan trekkers in Nepal. High Alt Med Biol. 18:267-277, 2017. OBJECTIVES: To determine how blood pressure (BP) changes with altitude in normotensive versus hypertensive trekkers. Secondary aims were to evaluate the prevalence of severe hypertension (BP ≥180/100 mmHg) and efficacy of different antihypertensive agents at high altitude. METHODS: This was an observational cohort study of resting and 24-hour ambulatory BP in normotensive and hypertensive trekkers at 2860, 3400, and 4300 m in Nepal. RESULTS: We enrolled 672 trekkers age 18 years and older, 60 with a prior diagnosis of hypertension. Mean systolic and diastolic BP did not change between altitudes in normotensive or hypertensive trekkers, but was higher in those with hypertension. However, there was large interindividual variability. At 3400 m, the majority (60%, n = 284) of normotensive participants had a BP within 10 mmHg of their BP at 2860 m, while 21% (n = 102) increased and 19% (n = 91) decreased. The pattern was similar between 3400 and 4300 m (64% [n = 202] no change, 21% [n = 65] increased, 15% [n = 46] decreased). BP decreased in a greater proportion of hypertensive trekkers versus normotensives (36% [n = 15] vs. 21% at 3400 m, p = 0.01 and 30% [n = 7] vs. 15% at 4300 m, p = 0.05). Severe hypertension occurred in both groups, but was asymptomatic. In a small subset of participants, 24-hour ambulatory BP monitoring showed that nocturnal BP decreased in normotensive (n = 4) and increased in hypertensive trekkers (n = 4). CONCLUSIONS: Most travelers, including those with well-controlled hypertension, can be reassured that their BP will remain relatively stable at high altitude. Although extremely elevated BP may be observed at high altitude in normotensive and hypertensive people, it is unlikely to be symptomatic. The ideal antihypertensive regimen at high altitude remains unclear.

Older age, chronic medical conditions and polypharmacy in Himalayan trekkers in Nepal: an epidemiologic survey and case series.

BACKGROUND: The number of tourists in Nepal doubled between 2003 and 2013 is nearly 800 000. With the increased popularity of trekking, the number of those with pre-existing medical conditions requiring access to healthcare is likely to increase. We therefore sought to characterize the demographics and health status of trekkers on the Everest Base Camp route in the Solukhumbu Valley. In addition, we report cases that illustrate the potential complications of an ageing and medicated population of trekkers with underlying diseases. METHODS: Trekkers over 18 years were enrolled in a larger observational cohort study on blood pressure at high altitude at 2860 m. They answered a questionnaire regarding demographics, medical history and current medications. Acute medical problems relating to medication use that were brought to the attention of investigators were documented and are presented as case reports. RESULTS: We enrolled 670 trekkers, 394 (59%) male, with a mean age of 48 years (range 18-76). Pre-existing medical conditions were reported by 223 participants (33%). The most frequent conditions included hypertension, hypercholesterolemia, migraines and thyroid dysfunction. A total of 276 participants (41%) reported taking one or more medications. The most common medications were acetazolamide (79, 12%), antihypertensives (50, 8%) and NSAIDs (47, 7%), with 30 classes of drugs represented. Excluding acetazolamide, older trekkers (age >50 years) were more likely than younger ones to take medications (OR = 2.17; 95% CI 1.57-3.00; P <0.05). Acetazolamide use was not related to age. CONCLUSIONS: Our findings illustrate a wide variety of medical conditions present in trekkers in Nepal with wide-ranging potential complications that could pose difficulties in areas where medical care is scarce and evacuation difficult. Our cases illustrate the potential problems polypharmacy poses in trekkers, and the need for local and expedition healthcare workers to be aware of, and prepared for the common medical conditions present.

Ethical, Legal, and Administrative Considerations for Preparticipation Evaluation for Wilderness Sports and Adventures.

Preparticipation evaluations (PPEs) are common in team, organized, or traditional sports but not common in wilderness sports or adventures. Regarding ethical, legal, and administrative considerations, the same principles can be used as in traditional sports. Clinicians should be trained to perform such a PPE to avoid missing essential components and to maximize the quality of the PPE. In general, participants' privacy should be observed; office-based settings may be best for professional and billing purposes, and adequate documentation of a complete evaluation, including clearance issues, should be essential components. Additional environmental and personal health issues relative to the wilderness activity should be documented, and referral for further screening should be made as deemed necessary, if unable to be performed by the primary clinician. Travel medicine principles should be incorporated, and recommendations for travel or adventure insurance should be made.

Ethical, Legal, and Administrative Considerations for Preparticipation Evaluation for Wilderness Sports and Adventures.

Preparticipation evaluations (PPEs) are common in team, organized, or traditional sports but not common in wilderness sports or adventures. Regarding ethical, legal, and administrative considerations, the same principles can be used as in traditional sports. Clinicians should be trained to perform such a PPE to avoid missing essential components and to maximize the quality of the PPE. In general, participants' privacy should be observed; office-based settings may be best for professional and billing purposes, and adequate documentation of a complete evaluation, including clearance issues, should be essential components. Additional environmental and personal health issues relative to the wilderness activity should be documented, and referral for further screening should be made as deemed necessary, if unable to be performed by the primary clinician. Travel medicine principles should be incorporated, and recommendations for travel or adventure insurance should be made.

Experimental passage of St. Louis encephalitis virus in vivo in mosquitoes and chickens reveals evolutionarily significant virus characteristics.

St. Louis encephalitis virus (SLEV; Flaviviridae, flavivirus) was the major cause of epidemic flaviviral encephalitis in the U.S. prior to the introduction of West Nile virus (WNV) in 1999. However, outbreaks of SLEV have been significantly more limited then WNV in terms of levels of activity and geographic dispersal. One possible explanation for these variable levels of activity is that differences in the potential for each virus to adapt to its host cycle exist. The need for arboviruses to replicate in disparate hosts is thought to result in constraints on both evolution and host-specific adaptation. If cycling is the cause of genetic stability observed in nature and arboviruses lack host specialization, then sequential passage should result in both the accumulation of mutations and specialized viruses better suited for replication in that host. Previous studies suggest that WNV and SLEV differ in capacity for both genetic change and host specialization, and in the costs each accrues from specializing. In an attempt to clarify how selective pressures contribute to epidemiological patterns of WNV and SLEV, we evaluated mutant spectra size, consensus genetic change, and phenotypic changes for SLEV in vivo following 20 sequential passages via inoculation in either Culex pipiens mosquitoes or chickens. Results demonstrate that the capacity for genetic change is large for SLEV and that the size of the mutant spectrum is host-dependent using our passage methodology. Despite this, a general lack of consensus change resulted from passage in either host, a result that contrasts with the idea that constraints on evolution in nature result from host cycling alone. Results also suggest that a high level of adaptation to both hosts already exists, despite host cycling. A strain significantly more infectious in chickens did emerge from one lineage of chicken passage, yet other lineages and all mosquito passage strains did not display measurable host-specific fitness gains. In addition, increased infectivity in chickens did not decrease infectivity in mosquitoes, which further contrasts the concept of fitness trade-offs for arboviruses.

Characterization of mosquito-adapted West Nile virus.

West Nile virus (WNV), a mosquito-borne flavivirus, has significantly expanded its geographical and host range since its 1999 introduction into North America. The underlying mechanisms of evolution of WNV and other arboviruses are still poorly understood. Studies evaluating virus adaptation and fitness in relevant in vivo systems are largely lacking. In order to evaluate the capacity for host-specific adaptation and the genetic correlates of adaptation in vivo, this study measured phenotypic and genotypic changes in WNV resulting from passage in Culex pipiens mosquitoes. An increase in replicative ability of WNV in C. pipiens was attained for the two lineages of WNV tested. This adaptation for replication in mosquitoes did not result in a replicative cost in chickens, but did decrease cell-to-cell spread of virus in vertebrate cell culture. Genetic analyses of one mosquito-adapted lineage revealed a total of nine consensus nucleotide substitutions with no accumulation of a significant mutant spectrum. These results differed significantly from previous in vitro studies. When St Louis encephalitis virus (SLEV), a closely related flavivirus, was passaged in C. pipiens, moderately attenuated growth in C. pipiens was observed for two lineages tested. These results suggest that significant differences in the capacity for mosquito adaptation may exist between WNV and SLEV, and demonstrate that further comparative studies in relevant in vivo systems will help elucidate the still largely unknown mechanisms of arboviral adaptation in ecologically relevant hosts.

Molecular epidemiology of eastern equine encephalitis virus, New York.

Perpetuation, overwintering, and extinction of eastern equine encephalitis virus (EEEV) in northern foci are poorly understood. We therefore sought to describe the molecular epidemiology of EEEV in New York State during current and past epizootics. To determine whether EEEV overwinters, is periodically reintroduced, or both, we sequenced the E2 and partial NSP3 coding regions of 42 EEEV isolates from New York State and the Eastern Seaboard of the United States. Our phylogenetic analyses indicated that derived subclades tended to contain southern strains that had been isolated before genetically similar northern strains, suggesting southern to northern migration of EEEV along the Eastern Seaboard. Strong clustering among strains isolated during epizootics in New York from 2003-2005, as well as from 1974-1975, demonstrates that EEEV has overwintered in this focus. This study provides molecular evidence for the introduction of southern EEEV strains to New York, followed by local amplification, perpetuation, and overwintering.

Declining growth rate of West Nile virus in North America.

To determine the demographic history of West Nile virus (WNV) in North America, we employed a coalescent method to envelope coding region data sets for the NY99 and WN02 genotypes. Although the observed genetic diversities in both genotypes were of approximately the same age, the mean rate of epidemiological growth of the WN02 population was approximately three times that of the NY99 population, a finding compatible with the recent dominance of the former genotype. However, there has also been a marked decrease in the recent growth rate of WN02, suggesting that WNV has reached its peak prevalence in North America.

Crow deaths caused by West Nile virus during winter.

In New York, an epizootic of American crow (Corvus brachyrhynchos) deaths from West Nile virus (WNV) infection occurred during winter 2004-2005, a cold season when mosquitoes are not active. Detection of WNV in feces collected at the roost suggests lateral transmission through contact or fecal contamination.

Phylogenetic analysis of North American West Nile virus isolates, 2001-2004: evidence for the emergence of a dominant genotype.

The distribution of West Nile virus has expanded in the past 6 years to include the 48 contiguous United States and seven Canadian provinces, as well as Mexico, the Caribbean islands, and Colombia. The suggestion of the emergence of a dominant genetic variant has led to an intensive analysis of isolates made across North America. We have sequenced the pre-membrane and envelope genes of 74 isolates and the complete genomes of 25 isolates in order to determine if a dominant genotype has arisen and to better understand how the virus has evolved as its distribution has expanded. Phylogenetic analyses revealed the continued presence of genetic variants that group in a temporally and geographically dependent manner and provide evidence that a dominant variant has emerged across much of North America. The implications of these findings are discussed as they relate to transmission and spread of the virus in the Western Hemisphere.