BackgroundMany studies have examined the association between ambient temperature and mortality. However, less evidence is available on the temperature effects on gender- and age-specific emergency department visits, especially in developing countries. In this study, we examined the short-term effects of daily ambient temperature on emergency department visits (ED visits) in Shanghai.MethodsDaily ED visits and daily ambient temperatures between January 2006 and December 2011 were analyzed. After controlling for secular and seasonal trends, weather, air pollution and other confounding factors, a Poisson generalized additive model (GAM) was used to examine the associations between ambient temperature and gender- and age-specific ED visits. A moving average lag model was used to evaluate the lag effects of temperature on ED visits.ResultsLow temperature was associated with an overall 2.76% (95% confidence interval (CI): 1.73 to 3.80) increase in ED visits per 1°C decrease in temperature at Lag1 day, 2.03% (95% CI: 1.04 to 3.03) and 2.45% (95% CI: 1.40 to 3.52) for males and females. High temperature resulted in an overall 1.78% (95% CI: 1.05 to 2.51) increase in ED visits per 1°C increase in temperature on the same day, 1.81% (95% CI: 1.08 to 2.54) among males and 1.75% (95% CI: 1.03 to 2.49) among females. The cold effect appeared to be more acute among younger people aged <45 years, whereas the effects were consistent on individuals aged ≥65 years. In contrast, the effects of high temperature were relatively consistent over all age groups.ConclusionsThese findings suggest a significant association between ambient temperature and ED visits in Shanghai. Both cold and hot temperatures increased the relative risk of ED visits. This knowledge has the potential to advance prevention efforts targeting weather-sensitive conditions.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-069X-13-100) contains supplementary material, which is available to authorized users.

Cyclophosphamide (CP) is widely used in anticancer therapy regimens and 2-dechloroethylcyclophosphamide (DECP) is its side-chain dechloroethylated metabolite. N-dechloroethylation of CP mediated by the enzyme CYP3A4 yields nephrotoxic and neurotoxic chloroacetaldehyde (CAA) in equimolar amount to DECP. This study aimed to evaluate the inhibitory effect of ketoconazole (KTZ) on CP metabolism through in vitro and in vivo drug-drug interaction (DDI) research. Long-term treatment of KTZ induces hepatic injury; thus single doses of KTZ at low, middle, and high levels (10, 20, and 40 mg/kg) were investigated for pharmacokinetic DDI with CP. Our in vitro human liver microsome modeling approach suggested that KTZ inhibited CYP3A4 activity and then decreased DECP exposure. In addition, an UHPLC-MS/MS method for quantifying CP, DECP, and KTZ in rat plasma was developed and fully validated with a 4 min analysis coupled with a simple and reproducible one-step protein precipitation. A further in vivo pharmacokinetic study demonstrated that combination use of CP (10 mg/kg) and KTZ (10, 20, and 40 mg/kg) in rats caused a KTZ dose-dependent decrease in main parameters of DECP (Cmax, Tmax, and AUC0–∞) and provided magnitude exposure of DECP (more than a 50% AUC decrease) as a consequence of CYP3A inhibition but had only a small effect on the CP plasma concentration. Our results suggested that combination usage of a CYP3A4 inhibitor like KTZ may decrease CAA exposure and thus intervene against CAA-induced adverse effects in CP clinical treatment.