High-end arteriolar resistance limits uterine artery blood flow and restricts fetal growth in preeclampsia and gestational hypertension at high altitude.

The reduction in infant birth weight and increased frequency of preeclampsia (PE) in high-altitude residents have been attributed to greater placental hypoxia, smaller uterine artery (UA) diameter, and lower UA blood flow (Q(UA)). This cross-sectional case-control study determined UA, common iliac (CI), and external iliac (EI) arterial blood flow in Andeans residing at 3,600-4,100 m, who were either nonpregnant (NP, n = 23), or experiencing normotensive pregnancies (NORM; n = 155), preeclampsia (PE, n = 20), or gestational hypertension (GH, n = 12). Pregnancy enlarged UA diameter to ~0.62 cm in all groups, but indices of end-arteriolar vascular resistance were higher in PE or GH than in NORM. Q(UA) was lower in early-onset (≤34 wk) PE or GH than in NORM, but was normal in late-onset (>34 wk) illness. Left Q(UA) was consistently greater than right in NORM, but the pattern reversed in PE. Although Q(CI) and Q(EI) were higher in PE and GH than NORM, the fraction of Q(CI) distributed to the UA was reduced 2- to 3-fold. Women with early-onset PE delivered preterm, and 43% had stillborn small for gestational age (SGA) babies. Those with GH and late-onset PE delivered at term but had higher frequencies of SGA babies (GH=50%, PE=46% vs. NORM=15%, both P < 0.01). Birth weight was strongly associated with reduced Q(UA) (R(2) = 0.80, P < 0.01), as were disease severity and adverse fetal outcomes. We concluded that high end-arteriolar resistance, not smaller UA diameter, limited Q(UA) and restricted fetal growth in PE and GH. These are, to our knowledge, the first quantitative measurements of Q(UA) and pelvic blood flow in early- vs. late-onset PE in high-altitude residents.

The 3-minute emergency medicine medical student presentation: a variation on a theme.

Oral presentations are a critical element in the communication of medical knowledge between students and faculty, but in most locations, the amount of time spent on teaching the oral presentation is minimal. Furthermore, the standard oral presentation does not work well within the emergency medicine (EM) setting, due to time constraints and the different principles that make EM a unique specialty. This article provides a suggested approach on how to educate students on optimal oral presentations in EM, as well as providing a link to an online guide instructing medical students how to give oral presentations.

Suicide and High Altitude: An Integrative Review.

Reno, Elaine, Talia L. Brown, Marian E. Betz, Michael H. Allen, Lilian Hoffecker, Jeremy Reitinger, Robert Roach, and Benjamin Honigman. Suicide and high altitude: an integrative review. High Alt Med Biol 19:99-108, 2018. INTRODUCTION: Suicide rates are greater at high altitudes, and multiple mechanisms have been suggested for this relationship, including hypoxia, differences in population density, characteristics of suicide victims, and firearms ownership and access. To better understand these potential mechanisms, studies evaluating the associations between high altitude and suicide were examined. METHODS: A literature review of published studies on high altitude and suicide was conducted in Medline, Embase, Web of Science, the Cochrane Database of Systematic Reviews, and the Cochrane CENTRAL database. We extracted and analyzed all studies that met the inclusion criteria, excluding foreign language studies and letters. Most of the measurements and results were synthesized using modified Letts' criteria. RESULTS: Searches using an extensive list of keywords returned 470 articles, but only 6 met the inclusion criteria. The studies' samples ranged in size from 8871 to 596,704, while studies which did not document sample size reported suicide rates. In five of the studies selected, individuals living at high altitudes were at greater risk of suicide. Four studies used aggregated data at a county or state level to analyze variables, such as age, gender, race, socioeconomic factors, and firearms access. All the studies found that high altitude was independently associated with suicide. One study found that many individual characteristics of those who committed suicide were different at high altitudes than low altitude, including a lack of access or barriers to mental healthcare. Depression exacerbated by hypoxia was hypothesized as a possible biologic mechanism in three studies. CONCLUSION: These research studies published since 2009 support an association between high altitude and suicide rates at the state or county level, but do not provide sufficient data to estimate the effect of high altitude on an individuals' suicide risk. Although the impact of hypoxia on mood and depression has been hypothesized to be a contributing cause, many other individual factors likely play more important roles.

Long-Term Health Outcomes in High-Altitude Pulmonary Hypertension.

Robinson, Jeffrey C., Cheryl Abbott, Christina A. Meadows, Robert C. Roach, Benjamin Honigman, and Todd M. Bull. Long-term health outcomes in high-altitude pulmonary hypertension. High Alt Med Biol. 18:61-66, 2017. BACKGROUND: High-altitude pulmonary hypertension (HAPH) is one of several known comorbidities that effect populations living at high altitude, but there have been no studies looking at long-term health consequences of HAPH. We aimed to determine whether HAPH during adolescence predisposes to significant pulmonary hypertension (PH) later in life, as well as identify how altitude exposure and HAPH correlate with functional class and medical comorbidities. METHODS: We utilized a previously published cohort of 28 adolescents from Leadville, Colorado, that underwent right heart catheterization at 10,150 ft (3094 m) in 1962, with many demonstrating PH as defined by resting mean pulmonary arterial pressure ≥25 mmHg. We located participants of the original study and had living subjects complete demographic and health surveys to assess for the presence of PH and other medical comorbidities, along with current functional status. RESULTS: Seventy-five percent of the individuals who participated in the original study were located. Those with HAPH in the past were more prone to have exertional limitation corresponding to WHO functional class >1. Fifty-five years following the original study, we found no significant differences in prevalence of medical comorbidities, including PH, among those with and without HAPH in their youth. CONCLUSIONS: Surveyed individuals did not report significant PH, but those with HAPH in their youth were more likely to report functional limitation. With a significant worldwide population living at moderate and high altitudes, further study of long-term health consequences is warranted.

Coordination Program Reduced Acute Care Use And Increased Primary Care Visits Among Frequent Emergency Care Users.

Many high utilizers of the emergency department (ED) have public insurance, especially through Medicaid. We evaluated how participation in Bridges to Care (B2C)-an ED-initiated, multidisciplinary, community-based program-affected subsequent ED use, hospital admissions, and primary care use among publicly insured or Medicaid-eligible high ED utilizers. During the six months after the B2C intervention was completed, participants had significantly fewer ED visits (a reduction of 27.9 percent) and significantly more primary care visits (an increase of 114.0 percent), compared to patients in the control group. In a subanalysis of patients with mental health comorbidities, we found that recipients of B2C services had significantly fewer ED visits (a reduction of 29.7 percent) and hospitalizations (30.0 percent), and significantly more primary care visits (an increase of 123.2 percent), again compared to patients in the control group. The B2C program reduced acute care use and increased the number of primary care visits among high ED utilizers, including those with mental health comorbidities.

Hospital to Post-Acute Care Facility Transfers: Identifying Targets for Information Exchange Quality Improvement.

INTRODUCTION: Information exchange is critical to high-quality care transitions from hospitals to post-acute care (PAC) facilities. We conducted a survey to evaluate the completeness and timeliness of information transfer and communication between a tertiary-care academic hospital and its related PAC facilities. METHODS: This was a cross-sectional Web-based 36-question survey of 110 PAC clinicians and staff representing 31 PAC facilities conducted between October and December 2013. RESULTS: We received responses from 71 of 110 individuals representing 29 of 31 facilities (65% and 94% response rates). We collapsed 4-point Likert responses into dichotomous variables to reflect completeness (sufficient vs insufficient) and timeliness (timely vs not timely) for information transfer and communication. Among respondents, 32% reported insufficient information about discharge medical conditions and management plan, and 83% reported at least occasionally encountering problems directly related to inadequate information from the hospital. Hospital clinician contact information was the most common insufficient domain. With respect to timeliness, 86% of respondents desired receipt of a discharge summary on or before the day of discharge, but only 58% reported receiving the summary within this time frame. Through free-text responses, several participants expressed the need for paper prescriptions for controlled pain medications to be sent with patients at the time of transfer. DISCUSSION: Staff and clinicians at PAC facilities perceive substantial deficits in content and timeliness of information exchange between the hospital and facilities. Such deficits are particularly relevant in the context of the increasing prevalence of bundled payments for care across settings as well as forthcoming readmissions penalties for PAC facilities. Targets identified for quality improvement include structuring discharge summary information to include information identified as deficient by respondents, completion of discharge summaries before discharge to PAC facilities, and provision of hard-copy opioid prescriptions at discharge.

Risk of impaired coagulation in warfarin patients ascending to altitude (>2400 m).

Approximately 476,000 people on warfarin therapy visit a resort at altitude (>2400 m) annually in Colorado. Clinicians practicing at altitude have expressed concern that ascent to altitude adversely affects coagulation in patients taking warfarin in both high altitude residents and visitors. We sought to determine the effect of ascent to and descent from altitude on coagulation in warfarin patients, as assessed by the international normalized ratio (INR). A retrospective medical chart review was conducted on all warfarin patients treated between August 1998 and October 2003 at a cardiology clinic in which travel to and from altitude was documented in association with each INR measurement in high altitude residents. Of the 1139 INR measurements in 49 patients, 143 were associated with changes in altitude (in 32 of 49 patients). The odds of an INR measurement being below the prescribed range were 2.7 times (95% CI: 1.2-5.8) higher among warfarin patients with recent ascent to altitude, 2.1 times (95% CI: 1.4-3.2) higher among warfarin patients with atrial fibrillation, and 5.6 (95% CI: 2.3-13.7) times higher among warfarin patients with both atrial fibrillation and recent ascent to altitude. Increasing altitude is a risk factor for subtherapeutic INR in warfarin patients and this risk is doubled in atrial fibrillation patients.

Physiologic response to moderate altitude exposure among infants and young children.

Substantial numbers of children are exposed to moderate altitude while traveling to mountain resorts with their families. Although there has been extensive study of the adult physiologic response to altitude exposure, few studies of infants and young children exist. This investigation examines the acute physiologic responses to moderate altitude exposure among young children and the relationship of these responses to the development of acute mountain sickness (AMS). Children 3 to 36 months old participated in the prospective observational study, which included baseline measurements at 1610 m and measurements after a 24-h exposure to 3109 m. Measurements included pulse and respiratory rate, end-tidal CO(2), arterial oxygen saturation (pulse oximetry), cerebral tissue oxygenation (St(O2)) by near-infrared spectroscopy, middle cerebral artery resistive index by transcranial Doppler, lateral ventricle volumes (ultrasound), and clinical evaluation for the presence of acute mountain sickness (Children's Lake Louise Score). Twenty-four children (13 girls and 11 boys, age 14.5 +/- 10.2 months) participated. After acute exposure to 3109 m, these children showed an increase in respiratory rate from 45 +/- 13 to 51.9 +/- 15 breaths/min (p < 0.008), accompanied by a decrease of end-tidal CO(2) from 31 +/- 3 to 28 +/- 2 mm Hg (p < 0.001) and a reduction of arterial oxygen saturation from 95 +/- 2 to 91 +/- 2% (p < 0.001). St(O2) also decreased from 78 +/- 8 to 67 +/- 13% (p < 0.001), and this reduction appeared to be related to age (r = 0.58, p < 0.05), with lower saturations found in younger children. No evidence of increased intracranial pressure, as assessed by middle cerebral artery resistive index, was seen during ascent. Seven subjects developed symptoms of AMS; however, no relationship was found between the physiologic changes observed and the presence of symptoms. Ascent from 1610 to 3109 m resulted in tachypnea, relative hypoxia, hypocapnia, and a reduction in cerebral tissue oxygenation (St(O2)). The reduction in St(O2) appeared to be related to age, with infants appearing to be the most susceptible to cerebral tissue oxygen desaturation at high altitude. No relationship appears to exist between the presence of AMS and the physiologic measurements.

Acute, transient urinary retention from combined ecstasy and methamphetamine use.

Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") are synthetic amphetamine analogs that have become increasingly popular, particularly among adolescents and young adults. Many deleterious physiologic effects arising from the use of these agents have been well documented in the medical literature. Urinary retention, however, has rarely been reported as an effect of MDMA or methamphetamine use and is thought to occur as a result of alpha-adrenoceptor stimulation of the bladder neck. We report a case of acute, transient urinary retention due to combined MDMA and methamphetamine use with laboratory confirmation.

The relationship between hepatopulmonary syndrome and altitude.

BACKGROUND: In a previous small retrospective study, the authors reported that hepatopulmonary syndrome was less common among liver transplant candidates at high-altitude centres compared with low-altitude centres. OBJECTIVE: To further explore the relationship between hepatopulmonary syndrome and altitude of residence in a larger patient cohort. METHODS: A cohort of 65,264 liver transplant candidates in the Organ Procurement and Transplantation Network liver database between 1988 and 2006 was analyzed. Hepatopulmonary syndrome diagnosis was determined during a comprehensive evaluation at a liver transplant centre by physicians who were experienced in the diagnosis and treatment of hepatopulmonary syndrome. The altitude of residence was determined for each patient by assigning the mean altitude of the zip code of residence at the time of entry on the wait list. Mean zip code elevation was calculated using the National Elevation Dataset of the United States Geological Survey, which provides exact elevation measurements across the entire country. RESULTS: Hepatopulmonary syndrome was significantly less common at higher resident altitudes (P=0.015). After adjusting for age, sex and Model for End-Stage Liver Disease score, there was a 46% decrease in the odds of hepatopulmonary syndrome with every increase of 1000 m of resident elevation (OR 0.54 [95% CI 0.33 to 0.89]). CONCLUSION: There was a negative association between altitude and hepatopulmonary syndrome. One plausible explanation is that the lower ambient oxygen found at higher elevation leads to pulmonary vasoconstriction, which mitigates the primary physiological lesion of hepatopulmonary syndrome, namely, pulmonary vasodilation.

Altitude, life expectancy and mortality from ischaemic heart disease, stroke, COPD and cancers: national population-based analysis of US counties.

BACKGROUND: There is a substantial variation in life expectancy across US counties, primarily owing to differentials in chronic diseases. The authors' aim was to examine the association of life expectancy and mortality from selected diseases with altitude. METHODS: The authors used data from the National Elevation Dataset, National Center for Heath Statistics and US Census. The authors analysed the crude association of mean county altitude with life expectancy and mortality from ischaemic heart disease (IHD), stroke, chronic obstructive pulmonary disease (COPD) and cancers, and adjusted the associations for socio-demographic factors, migration, average annual solar radiation and cumulative exposure to smoking in multivariable regressions. RESULTS: Counties above 1500 m had longer life expectancies than those within 100 m of sea level by 1.2-3.6 years for men and 0.5-2.5 years for women. The association between altitude and life expectancy became non-significant for women and non-significant or negative for men in multivariate analysis. After adjustment, altitude had a beneficial association with IHD mortality and harmful association with COPD, with a dose-response relationship. IHD mortality above 1000 m was 4-14 per 10,000 people lower than within 100 m of sea level; COPD mortality was higher by 3-4 per 10,000. The adjusted associations for stroke and cancers were not statistically significant. CONCLUSIONS: Living at higher altitude may have a protective effect on IHD and a harmful effect on COPD. At least in part due to these two opposing effects, living at higher altitude appears to have no net effect on life expectancy.

The effect of altitude-induced hypoxia on heart disease: do acute, intermittent, and chronic exposures provide cardioprotection?

With the global prevalence of heart disease continuing to increase and large populations living at altitude around the world, we review the concept of altitude and cardioprotection. Current epidemiologic data, as well as the basic science and molecular mechanisms involved in acute, intermittent, and chronic exposure to altitude, are discussed. Intermittent and chronic exposures have been demonstrated to increase coronary vasculature, decrease infarction size, and provide more efficient metabolism and better cardiac functional recovery postischemia. Mechanisms demonstrated in these situations include those mediated by the hypoxia inducible factor, as well as reactive oxygen species, certain ion channels, and protein kinases. Although current epidemiologic studies are difficult to interpret owing to many confounders, many studies point to the possibility that living at altitude provides cardiovascular protection. Further research is needed to determine if the bench studies showing mechanisms consistent with cardioprotection translate to the population living at altitude.

Elevated suicide rates at high altitude: sociodemographic and health issues may be to blame.

Suicide rates are higher at high altitudes; some hypothesize that hypoxia is the cause. We examined 8,871 suicides recorded in 2006 in 15 states by the National Violent Death Reporting System, with the victim's home county altitude determined from the National Elevation Dataset through FIPS code matching. We grouped cases by altitude (low<1000m; middle=1000-1999m; high≥2000m). Of reported suicides, 5% were at high and 83% at low altitude, but unadjusted suicide rates per 100,000 population were higher at high (17.7) than at low (5.7) altitude. High and low altitude victims differed with respect to race, ethnicity, rural residence, intoxication, depressed mood preceding the suicide, firearm use and recent financial, job, legal, or interpersonal problems. Even after multivariate adjustment, there were significant differences in personal, mental health, and suicide characteristics among altitude groups. Compared to low altitude victims, high altitude victims had higher odds of having family or friends report of a depressed mood preceding the suicide (OR 1.78; 95%CI:1.46-2.17) and having a crisis within 2weeks before death (OR 2.00; 95%CI:1.63-1.46). Suicide victims at high and low altitudes differ significantly by multiple demographic, psychiatric, and suicide characteristics; these factors, rather than hypoxia or altitude itself, may explain increased suicide rates at high altitude.

Enhanced leukocyte HIF-1alpha and HIF-1 DNA binding in humans after rapid ascent to 4300 m.

Hypoxia plays a crucial role in the pathogenesis of a multitude of diseases and clinical conditions such as cancer, diabetes, cardiovascular disease, stroke, pulmonary disease, inflammation, organ transplant, and wound healing. Investigations into the role of hypoxia-inducible transcription factor (HIF) in disease development have been conducted with the basic premise that HIF is activated in vivo during hypoxia in humans, yet this basic physiologic premise has never verified. Thus, we hypothesized that HIF-1 DNA binding would be enhanced in vivo in humans in response to acute global hypoxia. Fourteen human subjects were exposed to normoxia (1600 m) and hypoxia (4300 m, approximately 12% O(2)) in a hypobaric hypoxic chamber (8 h). HIF-1 DNA binding and HIF-1alpha protein were evaluated in circulating leukocytes. Oxidative markers were evaluated by plasma metabolomics using nuclear magnetic resonance and by urinary 15-F(2t)-isoprostane concentrations. Leukocyte HIF-1 DNA binding was increased (p=0.007) and HIF-1alpha was greater during hypoxia compared to normoxia. Circulating total glutathione was reduced by 35% (p=0.001), and lactate and succinate were increased by 29 and 158%, respectively (p=0.007 and 0.001), as were urinary 15-F(2t)-isoprostanes (p=0.037). HIF-1 DNA binding and HIF-1alpha were elevated in vivo in leukocytes of healthy human subjects exposed to 12% oxygen, in association with plasma and urinary markers of hypoxic stress.