To provide guidance to the general public, clinicians, and avalanche professionals about best practices, the Wilderness Medical Society convened an expert panel to revise the evidence-based guidelines for the prevention, rescue, and resuscitation of avalanche and nonavalanche snow burial victims. The original panel authored the Wilderness Medical Society Practice Guidelines for Prevention and Management of Avalanche and Nonavalanche Snow Burial Accidents in 2017. A second panel was convened to update these guidelines and make recommendations based on quality of supporting evidence.

Introduction-North American guidelines propose 125 mg acetazolamide twice daily as the recommended prophylactic dose to prevent acute mountain sickness (AMS). To our knowledge, a dose lower than 125 mg twice daily has not been studied. Methods-We conducted a prospective, double-blind, randomized, noninferiority trial of trekkers to Everest Base Camp in Nepal. Participants received the reduced dose of 62.5 mg twice daily or the standard dose of 125 mg twice daily. Primary outcome was incidence of AMS, and secondary outcomes were severity of AMS and side effects in each group. Results-Seventy-three participants had sufficient data to be included in the analysis. Overall incidence of AMS was 21 of 38 (55.3%) in reduced-dose and 21 of 35 (60.0%) in standard-dose recipients. The daily incidence rate of AMS was 6.7% (95% CI 2.5-10.9) for each individual in the reduced-dose group and 8.9% (95% CI 4.5-13.3) in the standard-dose group. Overall severity of participants' Lake Louise Score was 1.014 in the reduced-dose group and 0.966 in the standard-dose group (95% CI 0.885-1.144). Side effects were similar between the groups. Conclusions-The reduced dose of acetazolamide at 62.5 mg twice daily was noninferior to the currently recommended dose of 125 mg twice daily for the prevention of AMS. Low incidence of AMS in the study population may have limited the ability to differentiate the treatment effects. Further research with more participants with greater rates of AMS would further elucidate this reduced dosage for preventing altitude illness.

Acetazolamide is the standard agent of choice for medical prophylaxis against acute mountain sickness (AMS). The current North American guidelines propose 125 mg twice daily (BID) as the recommended prophylactic dose. To our knowledge, a dose lower than 125 mg twice daily has not been studied. We sought to determine whether 62.5 mg twice daily was as effective as 125 mg twice daily for the prevention of AMS. In addition, we sought to measure the number and severity of side effects experienced by users of each dose. We conducted a prospective double-blind randomized noninferiority trial of healthy trekkers and climbers traveling to Everest Basecamp in Nepal or those ascending Denali in Alaska. Participants received either the reduced dose of acetazolamide at 62.5 mg twice daily or the standard dose of 125 mg twice daily before and during ascent. Outcome measures included the incidence and severity of AMS in each group as well as the prevalence of common side effects of the medication. Ninety participants had data sufficient to be included in the analysis. The incidence of AMS did not vary significantly between the 2 groups; the mean Lake Louise Score was 0.966 for the 125 mg BID dose group and 1.014 for the 62.5 mg BID dose group (CI, 0.885–1.144). Side effects experienced by the 62.5 mg BID group were, curiously, slightly higher than those of 125 mg BID dose group, but these differences diminished when controlling for participant weight. A reduced dose of acetazolamide 62.5 mg BID is as effective as the currently recommended dose of 125 mg BID for the prevention of AMS. These results could influence future recommendations for climbers and trekkers with ascent profiles similar to those seen in our study.

To provide guidance to clinicians and avalanche professionals about best practices, the Wilderness Medical Society convened an expert panel to develop evidence-based guidelines for the prevention, rescue, and medical management of avalanche and nonavalanche snow burial victims. Recommendations are graded on the basis of quality of supporting evidence according to the classification scheme of the American College of Chest Physicians.

We would like to thank Dr Cooper and Mr Frost for their comments1Cooper DC, Frost JR. In Response to Wilderness Search Strategy and Tactics, by Phillips et al. Wilderness Environ Med. In press.Google Scholar regarding our recent article “Wilderness Search Strategy and Tactics.”2Phillips K. Longden M.J. Vandergraff B. et al.Wilderness search strategy and tactics.Wilderness Environ Med. 2014; 25: 166-176Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Their experience and points provide an excellent complementary perspective. We would like to point out that the intent of our article was to summarize current search strategies in a manner that would illustrate the basics of search strategy to medical providers and readers with no background in search management. It was not intended to be a treatise on land search techniques. Thus, we purposefully limited content and focused on the topics that would be most valuable to the Wilderness & Environmental Medicine readership. Although the 2011 Land Search and Rescue Addendum to the National Search and Rescue Supplement to the International Aeronautical and Maritime Search and Rescue Manual (LSA)3US National Search and Rescue Committee (NSARC). Land Search and Rescue Addendum to the National Search and Rescue Supplement to the International Aeronautical and Maritime Search and Rescue Manual, Version1.0. Washington,DC: US National Search and Rescue Committee; 2011. Available at: http://www.uscg.mil/hq/cg5/cg534/nsarc/land_sar_addendum/published_land%20sar%20addendum%20(1118111)%20-%20bookmark.pdf Accessed September 7, 2014.Google Scholar is a wonderful reference for search strategy and tactics, to suggest that it is the “standard of care” or the accepted “best practice” is misleading as there is still considerable incongruity by experts regarding some of the strategies suggested. The LSA attempts to reconcile maritime and military search tactics to land search and rescue (SAR) operations. There are several problems with this approach. The most prominent issue is that maritime search is considered a closed system (a vessel will remain in a body of water), whereas land search is an open system (the subject may not be within the search area or could travel outside the original search area, or criminal intent could be involved). These variables introduce uncertainty and complexity into the management of land search. The authors of the WEM article referenced are all considered subject matter experts in their field, each with countless hours of practical application of the techniques described in the article. Despite some differences in opinion, we would suggest that WEM readers interested in this topic and engaged in its application pursue further education in search management topics. Finally, we would like to end this discussion with an excerpt from the Introduction to the LSA:The guidance within this Addendum is intended to assist SAR personnel without preempting their experience and sound judgment. SAR planning in particular is both an art and a science, relying greatly on the creativity and experience of the personnel involved. Because of the many variables encountered during SAR operations and the uniqueness of each individual SAR case, any guidance must be tempered with sound judgment, having regard for the individual situation. Nothing in this Addendum should be construed as relieving SAR personnel of the need for initiative and sound judgment. Therefore, few actions or procedures discussed in this Addendum are mandatory. In Response to Wilderness Search Strategy and Tactics, by Phillips et alWilderness & Environmental MedicineVol. 26Issue 2PreviewWe are writing regarding a recently published Concepts article, titled “Wilderness Search Strategy and Tactics.”1 Although we have great respect for the authors and their work, we would like to highlight where some of the content of the article deviates from the scientific literature, and US-accepted practices, regarding search theory and its application to land search. Even though the article includes the disclaimer, “The views expressed in this paper…do not necessarily reflect the views of the National Park Service,” the current and former positions of some of the authors, and the fact that the example search used throughout the article is set in a National Park (Yosemite), strongly suggest that the methodology described reflects current National Park Service (NPS) policies and procedures for conducting searches. Full-Text PDF

The Wilderness Medical Society convened an expert panel to develop evidence-based guidelines for the management of pain in austere environments. Recommendations are graded based on the quality of supporting evidence as defined by criteria put forth by the American College of Chest Physicians.

Reports of overdue persons are common for search and rescue personnel. Search incidents for missing persons are conducted following established industry standard practices, which are continuously refined through experience and the analysis of previous search operations. Throughout this process, elements of uncertainty exist, and the knoWledge and experience of the searchers and search managers may influence the outcome significantly. A sound knowledge of current search tactics will help search and rescue medical providers function more effectively during search operations. Initial actions during a search incident include 3 primary tasks that must be accomplished on any search: investigation, containment, and then hasty search efforts. Concurrent with these initial actions are the establishment of the search area and a formal US National Incident Management System incident command system. That is essential for an efficient operation and will lay the groundwork for expanding the operation past the initial operational period. The goal of applying these standard search management practices is to allow searchers to maximize their efforts, reduce some of the inherent uncertainty, and most importantly, place searchers in a position to detect the missing person.

Background.-Minimal data exist regarding the activity, membership, training, and medical oversight of search and rescue (SAR) teams.Objective.-Our objective was to describe these characteristics in the Intermountain West SAR organizations.Methods.-A contact list was generated and electronic surveys were sent to SAR officials in each Intermountain West county. Results were descriptively analyzed.Results.-Of the contacted jurisdictions, 56% (156) responded to the survey. The annual average call volume was 29 missions (range, 5 to 152). Multiple levels of medical training were represented on SAR teams, ranging from first aid/cardiopulmonary resuscitation providers to the physician level, and 79% of teams provided some medical training to their membership. Of the SAR medical professionals, 23% had formal wilderness medical training. Local emergency medical services provided 60% of the medical care on SAR missions rather than SAR personnel. Formal physician medical oversight was present in 41% of the SAR teams These physicians participated in a range of SAR activities including medical protocol drafting (including expanded scope of practice), medical trainings, mission participation, medical consultation, and prescribing medications for field use. The majority (69%) of those physicians were trained in emergency medicine, and 45% of the active medical directors had protocols allowing for an expanded scope of practice due to the remote nature of SAR medical care.Conclusions.-Intermountain West SAR teams vary in their activity, composition, training, and level of medical oversight. This study confirms that opportunities exist for physician integration with SAR teams in the studied states and likely throughout the United States.

As I pack for a return to Alaska in a week's time, I am forced to reflect on the eventful climbing season prior. It was not the number of climbers (1,232) or the summit success rate (56%) that made 2011 of note. It was the number of serious accidents (15) and resulting fatalities (9, second highest in a season, only behind 11 in 1992) that made last year stand out from all others in recent memory. Causes of these deaths included climbing falls (5), unknown (2), icefall (1), and sudden cardiac death (1). Three of these falls occurred on the steep traversing terrain known as the Autobahn at approximately 18 200 feet, and the 2 unknown causes were either an avalanche resulting in a fall or a fall while climbing in technical terrain. Consistent with historical data, 5 of the fatalities (61.5% between 1932 and 2006) occurred while the climber was descending, travel direction for 2 (13.5% between 1932 and 2006) was unknown, and 2 occurred while the climber was in camp.1McIntosh S.E. Campbell A.D. Dow J. Grissom C.K. Mountaineering fatalities on Denali.High Alt Med Biol. 2008; 9: 89-95Crossref PubMed Scopus (44) Google Scholar Each of these tragic accidents serves as sobering and valuable reminders of the risks inherent in mountaineering. (Details of these incidents can be found online in the 2011 Denali Annual Mountaineering Summary.) “Good judgment comes from bad judgment” was a statement I heard recently from Dr Thomas Russell, former executive director of the American College of Surgeons. I was struck by the truth of this quotation, but even more so by the frightening reality and consequence of its implication. In spite of the plethora of antagonistic examples, decisions will continue to be made in the mountains that have high potential for disaster. Studies have repeatedly shown that it typically is not a single choice but a cascade of poor decisions that lead to an ultimately bad outcome. Regardless, I write this editorial with purposeful and ignorant optimism that these principles needn't be relearned firsthand by anyone in the future. In the months that have passed since the conclusion of last season, I have fielded countless inquiries pertaining to the specific factors that led to the events of 2011. This line of questioning has prompted thorough contemplation on my behalf. Even still, I am left at times shrugging my shoulders and telling the curious party that I just don't know. Sure, I do have some ideas, but concrete and factual causes, as with many disasters, may never be fully realized. Two of the common themes that I find myself reiterating have been the hostile weather of last season and the lack of preparedness for these adverse conditions. Of course, these are broad generalizations, and undoubtedly individual human factors played a role in each of the accidents. Some say that Mount McKinley is the coldest peak on earth, and she certainly lived up to that reputation this past summer. Cold temperatures and bare glacial ice dominated the Alaska Range landscape for much of April and May. Early season climbers reported temperatures consistently below zero Fahrenheit, 24 hours a day, through mid May. Perhaps this unrelenting deep freeze ultimately affected the judgment and challenged the technical abilities of the climbers. Whenever traveling in technical terrain, any diminishment in mental capacities and resulting missteps creates the potential for a much higher set of consequences. Owing to the intense winds and limited snowfall during the winter of 2010/2011, the majority of the upper mountain was completely devoid of snow when the early expeditions began climbing. These conditions led to extremely difficult footing on the standard climbing route and made self-arrest nearly impossible in the event of a fall. Cramponing and self-arrest skills are typically learned on lower angle slopes with sufficient snow underfoot. This is a terrific venue in which to learn but should not represent the culmination of one's tutelage. On these mellow slopes and in deeper snow conditions, much of the arrest is accomplished merely by gravity and friction. When the angle steepens and the terrain becomes icy, I often hear the term “no fall zone” used when commands are passed between teammates. I think this notion represents naïve risk management. Climbers need to maintain a constant awareness of their surroundings and mitigate potential risks should an error occur. If a fall cannot be arrested in the traditional manner, it is incumbent on the climbers to either unrope to prevent pulling additional teammates down the slope or, preferably, place protection (snow pickets, ice screws, and so forth) along the path of travel. I agree wholeheartedly with Alaska Mountaineering School owner Colby Coombs when he says, “Denali is a final exam.” A lengthy apprenticeship is a mandatory component toward gaining expertise in most pursuits, be it climbing, medicine, or any other discipline. Amazing educators and guides can teach the progression from basic to advanced skills and help the student begin to manage risk on his or her own. It would be absurd to expect a surgical resident to move directly from cyst removal to a Whipple procedure. The same is true in skipping necessary benchmarks along one's development as a self-sufficient wilderness traveler. My intent here is the furthest from assigning blame or dwelling on the exact circumstances surrounding each accident. Instead, I am invested in promoting safe climbing practices “ … that others may live,” as the USAF Pararescue motto implies. The Denali Mountaineering Operation is likely the most extensive registration and climber-briefing program in the world. Initially, every climber is screened by resume and, later, upon arrival in Alaska, briefed on the route, current conditions, anticipated technical and medical complications, and park policy specifics. To continue to improve on this exemplary service, we utilize the most current wilderness medical and mountain rescue literature. That allows us to be better able to advise expedition members on problems likely to be encountered and their solution algorithms. In light of these accidents, the following adages seem poignant as the upcoming climbing season rapidly approaches. These are the lessons I desperately hope will make a difference in the decisions of future expeditions, by furthering Dr Russell's wisdom and allowing the previous judgments of others to assist in the cultivation of their own good judgment. As you venture into the backcountry, events outside of our control will occur. We can attempt to mitigate as much risk as possible but must remain cognizant that completely objective events will unfold regardless. We can be prepared for worst-case scenarios, however. That is best accomplished by pondering potentials during travel and, more importantly, by considering how you and your team will remedy those situations should they occur. Human factors can have very direct and drastic repercussions on our safety, with both our decisions and our indecisions climaxing in disastrous consequence. A key to risk mitigation is familiarity with the decision-making traps to which you are most prone and keenly recognizing when those factors begin to derail your process. Listening to one's intuition and speaking up accordingly are so often reported as missed opportunities by the individual members of parties involved in mishaps. Remaining silent and hoping that events go in your favor is a horrible risk management tool. And above all, if you find yourself doing what others are not, you should have a very good reason.

Scott E. McIntosh, Aaron Campbell, David Weber, Jennifer Dow, Elizabeth Joy, and Colin K. Grissom. Mountaineering Medical Events and Trauma on Denali, 1992-2011. High Alt Med Biol 13:275-280, 2012.-Denali (Mt. McKinley) is the tallest mountain in North America and a popular climbing destination for high altitude mountaineering expeditions. National Park Service (NPS) personnel care for and manage medical incidences and traumatic injuries for mountaineers each year. We retrospectively examined NPS medical reports from the climbing seasons of 1992-2011. Medical complaints, diagnoses, treatment, provider training, and overall numbers of injuries and illness were analyzed. Fatalities were included only if they were cared for by NPS medical personnel prior to death. Of the 24,079 climbers on Denali during this period, 831 (3.5%) required medical assistance from the NPS. There were 819 diagnoses; 502 were due to medical illness and 317 were traumatic injuries. Patient encounters occurred most frequently (71%) at the 4328m camp. Frostbite was the most common individual diagnosis (18.1%), while altitude-related syndromes were the most common illness category (29%). Most patients (84%) were treated and released to descend without additional intervention, whereas 11% needed air evacuation, and 4% needed another type of NPS assistance to descend. The only fatality in this series was caused by traumatic brain injury due to a climbing fall. A broad variety of medical complaints were evaluated and treated by NPS personnel, most commonly altitude related problems and frostbite. The results of the study will enhance the awareness of potential illness and injuries encountered by medical providers participating in high altitude mountaineering expeditions. Additionally, providers responsible for evaluating mountaineers prior to their expeditions can educate them on the spectrum of physical and environmental conditions that increase the chances of illness or injury. This ideally will decrease the incidence of morbidity on both Denali and other high altitude mountaineering destinations.

We report crystal structures of the human enzyme phosphoenolpyruvate carboxykinase (PEPCK) with and without bound substrates. These structures are the first to be determined for a GTP-dependent PEPCK, and provide the first view of a novel GTP-binding site unique to the GTP-dependent PEPCK family. Three phenylalanine residues form the walls of the guanine-binding pocket on the enzyme's surface and, most surprisingly, one of the phenylalanine side-chains contributes to the enzyme's specificity for GTP. PEPCK catalyzes the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle. Because the gluconeogenic pathway contributes to the fasting hyperglycemia of type II diabetes, inhibitors of PEPCK may be useful in the treatment of diabetes.

Molecular features of ligand binding to MHC class II HLA-DR molecules have been elucidated through a combination of peptide structure-activity studies and structure-based drug design, resulting in analogues with nanomolar affinity in binding assays. Stabilization of lead compounds against cathepsin B cleavage by N-methylation of noncritical backbone NH groups or by dipeptide mimetic substitutions has generated analogues that compete effectively against protein antigens in cellular assays, resulting in inhibition of T-cell proliferation. Crystal structures of four ternary complexes of different peptide mimetics with the rheumatoid arthritis-linked MHC DRB10401 and the bacterial superantigen SEB have been obtained. Peptide-sugar hybrids have also been identified using a structure-based design approach in which the sugar residue replaces a dipeptide. These studies illustrate the complementary roles played by phage display library methods, peptide analogue SAR, peptide mimetics substitutions, and structure-based drug design in the discovery of inhibitors of antigen presentation by MHC class II HLA-DR molecules.