This study identified CYP2C variants, including CYP2C9*3, known to reduce drug clearance, as important genetic factors associated with phenytoin-related severe cutaneous adverse reactions.

-A common model for security price dynamics is the continuoustime stochastic volatility model. For this model, Hull and White (1987) show that the price of a derivative claim is the conditional expectation of the Black-Scholes price with the forward integrated variance replacing the Black-Scholes variance. Implementing the Hull and White characterization requires both estimates of the price dynamics and the conditional distribution of the forward integrated variance given observed variables. Using daily data on close-to-close price movement and the daily range, we find that standard models do not fit the data very well and that a more general three-factor model does better, as it mimics the long-memory feature of financial volatility. We develop techniques for estimating the conditional distribution of the forward integrated variance given observed variables.

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Background The antihypertensive agent hydrochlorothiazide has been associated with increased risks of non-melanoma skin cancer (NMSC) and possibly some melanoma subtypes. Previous studies were, however, conducted in predominantly Caucasian populations. We therefore examined the association between hydrochlorothiazide and skin cancer risk in an Asian population. Methods By using Taiwan’s National Health Insurance Research Database (NHIRD), we conducted three separate case–control studies of lip cancer, non-lip non-melanoma skin cancer and melanoma. Cases (n = 29,082) with a first-ever skin cancer diagnoses (2008–2015) were matched 1:10 to population controls. We estimated odds ratios (ORs) associating hydrochlorothiazide use with skin cancer risk by using conditional logistic regression. Results Hydrochlorothiazide use showed no overall association with any of the three outcomes: ORs for high cumulative use of HCTZ (≥50,000 mg) were 0.86 (95% CI 0.09–7.81) for lip cancer, 1.16 (95% CI 0.98–1.37) for non-lip NMSC and 1.07 (95% CI 0.65–1.76) for melanoma. There was some evidence of a dose–response pattern for non-lip NMSC, with an OR of 1.66 (95% CI 0.82–3.33) for 100,000–149,999 mg of HCTZ. The null findings were robust across subgroup and sensitivity analyses. Conclusion Use of HCTZ appears safe in terms of skin cancer risk in an Asian population.