No abstract

A previous pharmacokinetic study on dosing of colistin methanesulfonate (CMS) at 240 mg (3 million units [MU]) every 8 h indicated that colistin has a long half-life, resulting in insufficient concentrations for the first 12 to 48 h after initiation of treatment. A loading dose would therefore be beneficial. The aim of this study was to evaluate CMS and colistin pharmacokinetics following a 480-mg (6-MU) loading dose in critically ill patients and to explore the bacterial kill following the use of different dosing regimens obtained by predictions from a pharmacokinetic-pharmacodynamic model developed from an in vitro study on Pseudomonas aeruginosa. The unbound fractions of colistin A and colistin B were determined using equilibrium dialysis and considered in the predictions. Ten critically ill patients (6 males; mean age, 54 years; mean creatinine clearance, 82 ml/min) with infections caused by multidrug-resistant Gram-negative bacteria were enrolled in the study. The pharmacokinetic data collected after the first and eighth doses were analyzed simultaneously with the data from the previous study (total, 28 patients) in the NONMEM program. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.026 and 2.2 h, respectively. For colistin, a one-compartment model was sufficient and the estimated half-life was 18.5 h. The unbound fractions of colistin in the patients were 26 to 41% at clinical concentrations. Colistin A, but not colistin B, had a concentration-dependent binding. The predictions suggested that the time to 3-log-unit bacterial kill for a 480-mg loading dose was reduced to half of that for the dose of 240 mg.

Very little is known about the association between sleep and (fatal) occupational accidents. This study investigated this relationship using register data of self‐rated sleep difficulties, together with occupational and demographic characteristics. The variables were related to subsequent occupational fatal accidents. A national sample of 47 860 individuals was selected at regular intervals over a period of 20 years, and interviewed over the phone on issues related to work and health. The responses were linked to the cause of death register (suicides excluded) and the data set was subjected to a (multivariate) Cox regression survival analysis. One hundred and sixty six fatal occupational accidents occurred, and the significant predictors were: male vs. female: relative risk (RR)=2.30 with a 95% confidence interval (CI) of 1.56–3.38; difficulties in sleeping (past 2 weeks): RR=1.89 with CI=1.22–2.94; and non‐day work: RR=1.63 with CI=1.09–2.45. No significant effect was seen for age, socio‐economic group, hectic work, overtime (>50 h per week), or physically strenuous work. It was concluded that self‐reported disturbed sleep is a predictor of accidental death at work, in addition to non‐day work and male gender.

Intimate partner violence (IPV) is a global public health and gender problem, especially in low-income countries. The study focused on verbal abuse, physical abuse and abuse by restricting food provision to wives by their husbands by victim and perpetrator characteristics, emphasizing the socioeconomic context of rural Bangladesh. Using a cross-sectional household survey of 4411 randomly selected married women of reproductive age, the study found that a majority of the respondents are exposed to verbal abuse (79%), while 41% are exposed to physical abuse. A small proportion (5%) of the women had suffered food-related abuse. Risk factors observed were age of the wife, illiteracy (of both victims and perpetrators), alcohol misuse, dowry management, husband's monetary greed involving parents-in-law, and wife's suspicions concerning husband's extramarital affairs. Well-established risk factors for wife abuse, along with dowry and husband's monetary greed, have a relatively high prevalence in rural Bangladesh.

No abstract