The studies used a variety of methods of end-point assessment, most commonly the LLS and AMS-C/AMS-R. While these scores do correlate, they have been observed to identify different populations of patients with AMS.[48, 49] Furthermore, all the assessment tools for AMS suffer from having to apply an arbitrary cut-off to a complex clinical syndrome. These factors introduce a source of bias into our analysis; however, the lack of heterogeneity found in the assessment of the

primary end point suggests that this effect is GSK126 not large. Our findings suggest that acetazolamide 250 mg/d is associated with a similar benefit compared to higher doses and that adverse effects are dose related. Therefore, a dose of acetazolamide 250 mg/d should be recommended in most instances based on current evidence. Future trials will clarify this understanding. Only one trial used a single daily dose of acetazolamide and this study, which was hampered by a low number of cases of AMS and a high dropout rate, failed to demonstrate a benefit of acetazolamide. Therefore,

until further evidence emerges, divided TGF beta inhibitor daily dosing of acetazolamide should be suggested. This study could not address the interaction between dose and rate of ascent; further trials examining a range of doses in rapid ascent would be particularly helpful. In expedition-based trials, acetazolamide was started at low altitude whereas the location-based trials commenced treatment at moderate altitude. Both groups of trials demonstrated benefit from acetazolamide. However, since some patients in location-based studies were already experiencing altitude sickness Liothyronine Sodium when screened at moderate

altitude, it would seem reasonable to commence acetazolamide at low elevations before ascending to a height where symptoms are likely. This analysis, however, provides limited evidence to assist prescribers in deciding which patients are likely to benefit most from acetazolamide treatment. Since studies with a high placebo risk and high ascent rate had a larger absolute risk benefit (Figure 5), this suggests that travelers judged to be at highest risk of AMS may benefit most from acetazolamide prophylaxis. The risk factors for AMS are well described and include not only altitude and rate of ascent but also personal factors such as history of AMS, young age, and a history of respiratory disease. Therefore, decisions on the prescribing of acetazolamide should be based on an individualized assessment of the risk of AMS weighed against the risk of adverse effects. This is the approach suggested by the Wilderness Medicine Society guidelines.[2] Many tourists visiting East Africa join expeditions ascending Mount Kilimanjaro. On typical tourist expeditions rates of ascent are much higher than those recommended by published guidelines[50] and the incidence of AMS is high.