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.

Optic Nerve Sheath Diameter Increase on Ascent to High Altitude: Correlation With Acute Mountain Sickness.

OBJECTIVES: Elevated optic nerve sheath diameter on sonography is known to correlate with increased intracranial pressure and is observed in acute mountain sickness. This study aimed to determine whether optic nerve sheath diameter changes on ascent to high altitude are associated with acute mountain sickness incidence. METHODS: Eighty-six healthy adults enrolled at 1240 m (4100 ft), drove to 3545 m (11,700 ft) and then hiked to and slept at 3810 m (12,500 ft). Lake Louise Questionnaire scores and optic nerve sheath diameter measurements were taken before, the evening of, and the morning after ascent. RESULTS: The incidence of acute mountain sickness was 55.8%, with a mean Lake Louise Questionnaire score ± SD of 3.81 ± 2.5. The mean maximum optic nerve sheath diameter increased on ascent from 5.58 ± 0.79 to 6.13 ± 0.73 mm, a difference of 0.91 ± 0.55 mm (P = .09). Optic nerve sheath diameter increased at high altitude regardless of acute mountain sickness diagnosis; however, compared to baseline values, we observed a significant increase in diameter only in those with a diagnosis of acute mountain sickness (0.57 ± 0.77 versus 0.21 ± 0.76 mm; P = .04). This change from baseline, or Δ optic nerve sheath diameter, was associated with twice the odds of developing acute mountain sickness (95% confidence interval, 1.08-3.93). CONCLUSIONS: The mean optic nerve sheath diameter increased on ascent to high altitude compared to baseline values, but not to a statistically significant degree. The magnitude of the observed Δ optic nerve sheath diameter was positively associated with acute mountain sickness diagnosis. No such significant association was found between acute mountain sickness and diameter elevation above standard cutoff values, limiting the utility of sonography as a diagnostic tool.

Ibuprofen prevents altitude illness: a randomized controlled trial for prevention of altitude illness with nonsteroidal anti-inflammatories.

STUDY OBJECTIVE: Acute mountain sickness occurs in more than 25% of the tens of millions of people who travel to high altitude each year. Previous studies on chemoprophylaxis with nonsteroidal anti-inflammatory drugs are limited in their ability to determine efficacy. We compare ibuprofen versus placebo in the prevention of acute mountain sickness incidence and severity on ascent from low to high altitude. METHODS: Healthy adult volunteers living at low altitude were randomized to ibuprofen 600 mg or placebo 3 times daily, starting 6 hours before ascent from 1,240 m (4,100 ft) to 3,810 m (12,570 ft) during July and August 2010 in the White Mountains of California. The main outcome measures were acute mountain sickness incidence and severity, measured by the Lake Louise Questionnaire acute mountain sickness score with a diagnosis of ≥ 3 with headache and 1 other symptom. RESULTS: Eighty-six participants completed the study; 44 (51%) received ibuprofen and 42 (49%) placebo. There were no differences in demographic characteristics between the 2 groups. Fewer participants in the ibuprofen group (43%) developed acute mountain sickness compared with those receiving placebo (69%) (odds ratio 0.3, 95% confidence interval 0.1 to 0.8; number needed to treat 3.9, 95% confidence interval 2 to 33). The acute mountain sickness severity was higher in the placebo group (4.4 [SD 2.6]) than individuals receiving ibuprofen (3.2 [SD 2.4]) (mean difference 0.9%; 95% confidence interval 0.3% to 3.0%). CONCLUSION: Compared with placebo, ibuprofen was effective in reducing the incidence of acute mountain sickness.

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.

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.

Prospective, double-blind, randomized, placebo-controlled comparison of acetazolamide versus ibuprofen for prophylaxis against high altitude headache: the Headache Evaluation at Altitude Trial (HEAT).

OBJECTIVE: High altitude headache (HAH) is the most common neurological complaint at altitude and the defining component of acute mountain sickness (AMS). However, there is a paucity of literature concerning its prevention. Toward this end, we initiated a prospective, double-blind, randomized, placebo-controlled trial in the Nepal Himalaya designed to compare the effectiveness of ibuprofen and acetazolamide for the prevention of HAH. METHODS: Three hundred forty-three healthy western trekkers were recruited at altitudes of 4280 m and 4358 m and assigned to receive ibuprofen 600 mg, acetazolamide 85 mg, or placebo 3 times daily before continued ascent to 4928 m. Outcome measures included headache incidence and severity, AMS incidence and severity on the Lake Louise AMS Questionnaire (LLQ), and visual analog scale (VAS). RESULTS: Two hundred sixty-five of 343 subjects completed the trial. HAH incidence was similar when treated with acetazolamide (27.1%) or ibuprofen (27.5%; P = .95), and both agents were significantly more effective than placebo (45.3%; P = .01). AMS incidence was similar when treated with acetazolamide (18.8%) or ibuprofen (13.7%; P = .34), and both agents were significantly more effective than placebo (28.6%; P = .03). In fully compliant participants, moderate or severe headache incidence was similar when treated with acetazolamide (3.8%) or ibuprofen (4.7%; P = .79), and both agents were significantly more effective than placebo (13.5%; P = .03). CONCLUSIONS: Ibuprofen and acetazolamide were similarly effective in preventing HAH. Ibuprofen was similar to acetazolamide in preventing symptoms of AMS, an interesting finding that implies a potentially new approach to prevention of cerebral forms of acute altitude illness.

Major dietary patterns, ethnicity, and prevalence of type 2 diabetes in rural Hawaii.

OBJECTIVE: The association of type 2 diabetes (T2DM) with the overall dietary pattern and its relation with ethnicity was examined. METHODS: A cross-sectional study with 1257 participants with four ethnicities (Caucasian, Filipino, Native Hawaiian, and Japanese) in the North Kohala region of Hawaii was conducted. Participants 18-95 y of age were surveyed for their ethnic and demographic backgrounds, dietary intakes, and biochemical indexes of glucose intolerance between 1997 and 2000. RESULTS: Three dietary patterns from the food-frequency questionnaire were identified by factor analysis. Factor 1 was characterized by a healthy diet with a frequent intake of vegetables and fruits, and factor 2 was dominated by animal foods and local ethnic dishes. Factor 3 was characterized by a Western diet, which was dominated by French fries, fast-food hamburgers, pizza, and chips. Multivariate logistic regression model for T2DM prevalence included ethnicity and three dietary factors after adjustment for age, sex, income, physical activity, smoking status, and energy intake. Ethnicity was significantly associated with T2DM, with an odds ratio of 1.83 (95% confidence interval [CI] 1.12-3.00) for Native Hawaiians and 1.92 (95% CI 1.12-3.29) for Filipinos compared with Caucasians 1.92 (95% CI 1.12-3.29). Among the three dietary factors, factor 2 was positively associated with T2DM (odds ratio 1.30, 95% CI 1.03-1.68), but the significance disappeared after adjustment for energy intake. CONCLUSION: The findings show that ethnicity is a stronger risk factor for T2DM than dietary patterns when energy intake is adjusted for. Reducing energy intake to prevent T2DM deserves more attention during health promotion for the multiethnic population of Hawaii.

Acetazolamide fails to decrease pulmonary artery pressure at high altitude in partially acclimatized humans.

In this randomized, double-blind placebo controlled trial our objectives were to determine if acetazolamide is capable of preventing high altitude pulmonary edema (HAPE) in trekkers traveling between 4250 m (Pheriche)\4350 m (Dingboche) and 5000 m (Lobuje) in Nepal; to determine if acetazolamide decreases pulmonary artery systolic pressures (PASP) at high altitude; and to determine if there is an association with PASP and signs and symptoms of HAPE. Participants received either acetazolamide 250 mg PO BID or placebo at Pheriche\Dingboche and were reassessed in Lobuje. The Lake Louise Consensus Criteria were used for the diagnosis of HAPE, and cardiac ultrasonography was used to measure the velocity of tricuspid regurgitation and estimate PASP. Complete measurements were performed on 339 of the 364 subjects (164 in the placebo group, 175 in the acetazolamide group). No cases of HAPE were observed in either study group nor were differences in the signs and symptoms of HAPE found between the two groups. Mean PASP values did not differ significantly between the acetazolamide and placebo groups (31.3 and 32.6 mmHg, respectively). An increasing number of signs and symptoms of HAPE was associated with elevated PASP (p < 0.01). The efficacy of acetazolamide against acute mountain sickness, however, was significant with a 21.9% incidence in the placebo group compared to 10.2 % in the acetazolamide group (p < 0.01). Given the lack of cases of HAPE in either group, we can draw no conclusions about the efficacy of acetazolamide in preventing HAPE, but the absence of effect on PASP suggests that any effect may be minor possibly owing to partial acclimatization during the trek up to 4200 m.

Acetazolamide 125 mg BD is not significantly different from 375 mg BD in the prevention of acute mountain sickness: the prophylactic acetazolamide dosage comparison for efficacy (PACE) trial.

750 mg per day of acetazolamide in the prevention of acute mountain sickness (AMS), as recommended in the meta-analysis published in 2000 in the British Medical Journal, may be excessive and is controversial. To determine if the efficacy of low-dose acetazolamide 125 mg bd (250 mg), as currently used in the Himalayas, is significantly different from 375 mg bd (750 mg) of acetazolamide in the prevention of AMS, we designed a prospective, double-blind, randomized, placebo-controlled trial. The participants were sampled from a diverse population of (non-Nepali) trekkers at Namche Bazaar (3440 m) in Nepal on the Everest trekking route as they ascended to study midpoints (4280 m/4358 m) and the endpoint, Lobuje (4928 m), where data were collected. Participants were randomly assigned to receive 375 mg bd of acetazolamide (82 participants), 125 mg bd of acetazolamide (74 participants), or a placebo (66 participants), beginning at 3440 m for up to 6 days as they ascended to 4928 m. The results revealed that composite AMS incidence for 125 mg bd was similar to the incidence for 375 mg bd (24% vs. 21%, 95% confidence interval, -12.6%, 19.8%), in contrast to significantly greater AMS (51%) observed in the placebo group (95% confidence interval for differences: 8%, 46%; 12%, 49% for low and high comparisons, respectively). Both doses of acetazolamide improved oxygenation equally (82.9% for 250 mg daily and 82.8% for 750 mg daily), while placebo endpoint oxygen saturation was significantly less at 80.7% (95% confidence interval for differences: 0.5%, 3.9% and 0.4%, 3.7% for low and high comparisons, respectively). There was also more paresthesia in the 375-mg bd group (p < 0.02). We conclude that 125 mg bd of acetazolamide is not significantly different from 375 mg bd in the prevention of AMS; 125 mg bd should be considered the preferred dosage when indicated for persons ascending to altitudes above 2500 m.

Dentists' preparedness for responding to bioterrorism: A survey of Hawaii dentists.

BACKGROUND: The authors conducted a survey of dentists in Hawaii to assess their knowledge of, perceived readiness for and willingness to respond to bioterrorist (BT) events. METHODS: Using a cross-sectional study design to access a random sample (n = 240) of all licensed dentists residing in the state of Hawaii (N = 1,016), the authors mailed study participants an anonymous survey up to three times during June and July 2004. Knowledge-based questions were taken from accredited Internet-based free continuing medical education offerings. RESULTS: Of 234 deliverable surveys, 133 were returned (response rate of 56.8 percent). Only 2.3 percent of respondents reported having received prior BT preparedness training. A total of 14.5 percent felt able to identify and recognize a BT event, and 9.2 percent indicated they were able to respond effectively to a BT attack. A total of 73.8 percent expressed willingness to provide assistance to the state in the event of a BT attack. Dentists scored a mean of 62 percent correct (5.6 of nine questions) on the objective knowledge-based questions. CONCLUSIONS: A low prevalence of prior training coupled with a high degree of willingness to provide assistance indicates the need for additional BT preparedness training. This should be provided as continuing education offerings to practicing dentists and incorporated into the dental school curriculum. CLINICAL IMPLICATIONS: Dentists have the basic knowledge and experience to perform a number of key roles in a BT event; however, additional training must be provided to develop BT preparedness competencies.

Hawaii physician and nurse bioterrorism preparedness survey.

INTRODUCTION: Physicians and nurses are integral components of the public health bioterrorism surveillance system. However, most published bioterrorism preparedness surveys focus on gathering information related to self-assessed knowledge or perceived needs and abilities. OBJECTIVE: A survey of physicians and nurses in Hawaii was conducted to assess objective knowledge regarding bioterrorism agents and diseases and perceived response readiness for a bioterrorism event. METHODS: During June and July 2004, an anonymous survey was mailed up to three times to a random sample of all licensed physicians and nurses residing in Hawaii. RESULTS: The response rate was 45% (115 of 255) for physicians and 53% (146 of 278) for nurses. Previous bioterrorism preparedness training associated significantly with knowledge-based test performance in both groups. Only 20% of physicians or nurses had had previous training in bioterrorism preparedness, and < 15% felt able to respond effectively to a bioterrorism event. But, > 70% expressed willingness to assist the state in the event of a bioterrorist attack. CONCLUSIONS: Additional bioterrorism preparedness training should be made available through continuing education and also should become a component of both medical and nursing school curricula. It is important to provide the knowledge necessary for physicians and nurses to improve their ability to perform in the event of a bioterrorist attack.

Hawaii veterinarians' bioterrorism preparedness needs assessment survey.

The purpose of this study was to assess the objective bioterrorism-related knowledge base and the perceived response readiness of veterinarians in Hawaii to a bioterrorism event, and also to identify variables associated with knowledge-based test performance. An anonymous survey instrument was mailed to all licensed veterinarians residing in Hawaii (N = 229) up to three times during June and July 2004, using numeric identifiers to track non-respondents. The response rate for deliverable surveys was 59% (125 of 212). Only 12% (15 of 123) of respondents reported having had prior training on bioterrorism. Forty-four percent (55 of 125) reported being able to identify a bioterrorism event in animal populations; however, only 17% (21 of 125) felt able to recognize a bioterrorism event in human populations. Only 16% (20 of 123) felt they were able to respond effectively to a bioterrorist attack. Over 90% (106 of 116) expressed their willingness to provide assistance to the state in its response to a bioterrorist event. Veterinarians scored a mean of 70% correct (5.6 out of 8 questions) on the objective knowledge-based questions. Additional bioterrorism preparedness training should be made available, both in the form of continuing educational offerings for practicing veterinarians and as a component of the curriculum in veterinary schools.

Using social norms theory to explain perceptions and sexual health behaviors of undergraduate college students: an exploratory study.

The authors and associates conducted a social norms-based intervention targeting high-risk sexual behaviors among undergraduate students at 4 college campuses. Social norms theory predicts that widely held misperceptions may encourage risky behavior in a misguided attempt to conform to perceived norms and that information correcting these misperceptions will lead to a decrease in such behaviors. Students overestimated their peers' levels of sexual activity, numbers of partners, incidence of sexually transmitted infections, and rates of unintended pregnancies, but underestimated rates of condom use. Rates of HIV test taking, however, were accurately estimated. Although some components of sexual risk behaviors lend themselves well to social norms-based interventions, others, specifically inconsistent condom use and avoiding HIV tests, do not. Although no changes in reported beliefs or practices were apparent at the end of a 9-month intervention period, longer or modified interventions may be needed to make a fair assessment of the efficacy of this approach.

The role of tumor ablation in bridging patients to liver transplantation.

HYPOTHESIS: Treatment of hepatocellular carcinoma before liver transplantation can curb local tumor progression and thereby prolong patients' transplantation eligibility. DESIGN: Retrospective case-control pilot study. Twelve of 39 patients receiving liver transplantation for hepatocellular carcinoma had treatment before transplantation. Pretreatment included radiofrequency ablation (n = 8), percutaneous ethanol injection (n = 2), both modalities (n = 1), and tumor resection (n = 1). Twelve control subjects without pretreatment who were age-, sex-, and score-matched on the Model for End-stage Liver Disease and Child-Turcotte-Pugh classification were selected. The primary outcome measure was the waiting period for transplantation. RESULTS: Patients with pretreatment waited on the transplant list significantly longer than their counterparts without pretreatment (median, 484 vs 253 days; P =.03). CONCLUSIONS: Treatment before transplantation with tumor ablation or resection is associated with a longer waiting period on the transplant list. This enables patients who might otherwise be removed from the list because of tumor progression to receive transplantation.

Heart disease prevention for Alaska Native women: a review of pilot study findings.

BACKGROUND: Although historically Alaska Native women have had a relatively low incidence of cardiovascular disease (CVD), this pattern has changed dramatically in recent years. Alaska Native leaders have identified decreasing cardiovascular risk as an intervention priority. METHODS: From October 2000 to April 2001, Southcentral Foundation, an Alaska Native-owned and managed health corporation in Anchorage, conducted a pilot randomized controlled trial of a heart disease prevention program tailored for Alaska Native women. The aim was to assess feasibility and cultural acceptability and to develop enrollment procedures. Of 76 women who enrolled, 44 were randomized to the intervention group. Thirty-seven of 44 attended at least two intervention sessions, 23 completed prequestionnaires and postquestionnaires, and 27 returned for 12-month follow-up screening. Thirty of 32 control group participants returned for 12-month follow-up screening. The intervention included 12 weekly sessions on lifestyle change and goal setting. At baseline and 12 months, participants' height, weight, resting blood pressure, fasting lipid levels, and blood glucose were measured. At sessions 1 and 12, participants completed assessments regarding diet, physical activity, tobacco use, and psychosocial status. RESULTS: At 12 weeks, significant improvements were noted in moderate walking and physical activity self-efficacy. Also observed was substantial movement from the contemplation and preparation stages to the action stage regarding physical activity and heart-healthy eating. CONCLUSIONS: Although the small sample size precludes drawing conclusions about the intervention's effect, participants reported lifestyle and psychosocial changes. The pilot study resulted in protocol changes that improved the design and implementation of a subsequent large-scale study.

Seroepidemiology of hepatitis B virus infection: analysis of mass screening in Hawaii.

BACKGROUND: Although hepatitis B seroprevalence has been studied extensively in California and New York, detailed information for other high-risk areas in the United States is lacking. To study current prevalence and risk for hepatitis B virus (HBV) infection in Hawaii, we analyzed cross-sectional data from Hawaii residents screened between July 2003 and April 2006. METHODS: We retrospectively reviewed the screening records of 3,989 participants recruited at health fairs and clinics. Prevalence and risk factors for HBV infection were estimated using univariate and multivariate logistic regression models. RESULTS: Total prevalence of hepatitis B surface antigen (HBsAg) was 3.6%. Gender, age, and ethnicity were independently associated with HBsAg seropositivity. In a multivariate logistic regression model, males were at increased risk for HBsAg compared with females (odds ratio [OR] = 1.53, 95% confidence interval [CI]: 1.09-2.16) and persons aged 70 years or older were less likely to test positive than those younger than 30 (OR = 0.25, 95% CI: 0.11-0.61). In addition, multivariate ORs of HBsAg seropositivity were 3.24 (95% CI: 1.04-10.09), 4.13 (95% CI: 1.66-10.29), and 7.47 (95% CI: 2.52-22.11) for Vietnamese, Chinese, and Pacific Islanders, respectively, compared with Whites. CONCLUSIONS: This study furthers current knowledge of HBV epidemiology in areas with large populations of high-risk immigrants and demonstrates the relevance of screening programs for hepatitis B.