Fluorouracil cream reduces actinic keratosis
A SINGLE course of fluorouracil cream, 5%, effectively reduces actinic keratosis (AK) counts and the need for spot treatments for more than 2 years, according to research published in JAMA Dermatology. The randomised, double-blinded, placebo-controlled trial included 932 elderly and mostly male US veterans (mean age 71 years) who had two or more keratinocyte carcinomas in the 5 years before enrolment. Mean follow-up was 2.6 years. Of the participants, 468 were randomised to topical fluorouracil cream, 5%, twice daily for up to 4 weeks, and 464 to vehicle control cream. The mean total AK count on the face and ears at enrolment was 11.1 in the fluorouracil group and 10.7 in the control group. Six months after randomisation, the number of AKs on the face or ears in the fluorouracil group was reduced to 3.0 per participant (73% reduction) compared with 8.1 per participant (24% reduction) in the control group. The total number of AKs requiring individual spot treatment for up to 42 months after randomisation was 6491 in the fluorouracil group and 12 204 in the control group. “Our results were notable for the larger decrease in total AKs and the larger increase in complete AK clearance rates in the fluorouracil group than in the control group at study visits, even when the fluorouracil group received fewer spot treatments”, the researchers wrote. “The consistently fewer AK counts and fewer spot AK treatments in the fluorouracil group indicate that field treatment with fluorouracil prevents occurrence and/or recurrence of AKs in the treated area.” They said the study highlighted the long-term efficacy of topical fluorouracil cream in treating and preventing AKs.

Heparin no benefit for recurrent pregnancy loss
A MULTICENTRE, randomised trial has found the use of low molecular weight heparin (LMWH) in women with unexplained recurrent pregnancy loss did not increase intact pregnancies up to 24 weeks’ gestation or improve live-birth rates. The research, published in the Annals of Internal Medicine, also found the use of LMWH did not show a different treatment effect for any of the subgroups of patients or in the treatment effect for other outcomes, such as pre-eclampsia. The research included 449 women presenting at 14 university hospitals and perinatal care centres in Germany and Austria. Each woman had a viable pregnancy, confirmed by ultrasound, of 5‒8 weeks’ gestation and had had at least two previous consecutive early miscarriages or one late miscarriage. Women in the control group received multivitamin pills, and the intervention group received vitamins and 5000 IU of dalteparin–sodium up to 24 weeks’ gestation. The dalteparin was well tolerated and not discontinued because of side effects by any women. The researchers found that at 24 weeks’ gestation, 191 of 200 pregnancies (86.8%) in the intervention group and 188 of 214 pregnancies (87.9%) in the control group were intact. The live-birth rates were 86.0% (185 of 215 women) in the intervention group and 86.7% (183 of 211 women) in the control group. During the study period there were three intrauterine fetal deaths (1 woman in the LMWH group); nine cases of pre-eclampsia or the haemolysis, elevated liver enzyme level and low platelet count (HELLP) syndrome (three in the LMWH group); and 11 cases of intrauterine growth restriction or placental insufficiency (five in the LMWH group). “Given the burden of daily injection, we do not recommend [LMWH] use in such women for the purpose of reducing miscarriage rates”, the authors concluded. An accompanying editorial said the research did not mean that LMWH had no future in the prevention of recurrent pregnancy loss. New therapeutic trials in the future that focused on homogeneous subcategories of patients who might have the most promising benefits could clearly define the role of LMWH and other treatments for some women with recurrent pregnancy loss, the editorial said.

Higher prevalence of AMD in patients with HIV
PEOPLE with AIDS have an increased prevalence of intermediate stage age-related macular degeneration (AMD) compared with those without HIV infection, research has found. The longitudinal, observational cohort study, published in the American Journal of Ophthalmology, included 1825 people diagnosed with AIDS, enrolled between 1998 and 2011, who had no intraocular infections. At enrolment, all participants provided a detailed HIV-related disease history and AMD was determined by grading retinal photographs. The authors found that 9.9% of the study group had intermediate stage AMD. One risk factor was age, where the prevalence of AMD ranged from 4.0% for participants aged 30–39 years to 24.3% in those aged 60 years and older. Smoking was also associated with intermediate stage AMD, where current smokers had a higher prevalence than former smokers or those who had never smoked. The authors found that people whose risk for HIV infection was either injection drug use or heterosexual contact had a higher prevalence of AMD than did men who had sex with men, or other risk groups. Diabetes, hypertension and cardiovascular disease were also associated with intermediate stage AMD. Overall, people with AIDS appeared to have an approximately fourfold increased prevalence of intermediate stage AMD when compared with a similarly aged population without HIV. The authors said the reasons for this increased prevalence were not fully explained, but it could relate “to the state of chronic immune activation and systemic inflammation seen in these patients”. The results of this study were consistent with the increased prevalence of other age-related diseases in antiretroviral-treated, immune restored, HIV-infected people compared to the uninfected population, the authors wrote.

Intervention improves food intake in cystic fibrosis
A BEHAVIOURAL and nutritional intervention improves energy intake and height score outcomes in children with cystic fibrosis (CF), a US study published in JAMA Pediatrics has found. The randomised trial included 78 children aged 2–6 years with CF and pancreatic insufficiency who received either an intervention or a control treatment. The intervention combined individualised nutritional counselling targeting increased energy and fat intake, and parent training in behavioural child management skills. The control group received education on general nutrition, enzyme therapy, respiratory infection control and typical child development guidance. Both treatments were delivered weekly for 8 weeks and then monthly for 4 months. Patients then returned to standard care for 1 year, followed by 12-month follow-up. The authors measured changes in energy intake, weight z scores (WAZ) and height z scores (HAZ). At baseline, mean energy intake was 329 kilocalories per day, WAZ sore was -0.44 and HAZ score was -0.55. From pretreatment to post-treatment, the daily energy intake in the intervention group increased by 485 calories, compared with 58 calories for the control group, the authors found. The intervention was associated with a 0.12 unit increase in the WAZ score, compared with 0.06 in the control group, a difference that was not statistically significant. The HAZ score increased significantly to 0.09 in the intervention group, compared with -0.02 in the control treatment. The authors said their results indicated that the intervention resulted in significantly improved energy intake and HAZ scores, but not WAZ scores. They recommended that this treatment be included in care plans to ensure optimal nutritional and growth status in preschool-aged children with CF and pancreatic insufficiency. An accompanying editorial said the challenge was now to determine how this behavioural intervention could be carried out in conjunction with usual clinical care, and what resources would be needed.

Hospital practices determine preterm infants’ survival
DIFFERENT hospital practices on initiating active treatment for infants born at 22, 23 or 24 weeks of gestation explain some of the variation between hospitals in the survival of extremely preterm infants, research has found. The study, published in the New England Journal of Medicine, used data from 4987 infants born before 27 weeks of gestation without congenital anomalies across 24 US hospitals. Active treatment was defined as any potentially lifesaving intervention administered after birth. Survival and neurodevelopmental impairment at 18‒22 months of corrected age were assessed in 94.3% of children. The authors found that rates of active treatment ranged from 22.1% among infants born at 22 weeks of gestation to 99.8% among those born at 26 weeks. Overall rates of survival and survival without severe impairment ranged from 5.1% and 3.4%, respectively, among children born at 22 weeks, to 81.4% and 75.6%, respectively, among those born at 26 weeks. Hospital rates of active treatment accounted for 78% and 75%, respectively, of the between-hospital variation in survival and survival without severe impairment among children born at 22 and 23 weeks. This also accounted for 22% and 16%, respectively, among those born at 24 weeks, but did not account for any of the variation in outcomes for those born at 25 or 26 weeks. “Hospitals at which active treatment was more often initiated had higher rates of risk-adjusted survival both with and without impairment than did hospitals at which active treatment was less frequently initiated”, the authors wrote. They said they did not have information regarding when or how decisions about the initiation of active treatment were made, and could not determine the cause of the variation in rates of active treatment. An accompanying editorial said the study highlighted the need for unbiased data to inform chances of overall survival and survival without major neurodevelopmental impairment. “Information on survival, morbidity, and policies regarding active intervention should be available to assist parents in making an informed choice about transfer to a specialist hospital, if feasible, and the level of intervention provided after birth”, the editorial authors wrote.

New biomarker investigates impact of psychosocial events
US researchers have used a new biomarker of cortisol in hair to assess long-term hypothalamic–pituitary–adrenal (HPA) axis activity, correlating early psychosocial exposures in children with higher cortisol levels and significantly increased risk of common childhood diseases. The cohort study, published in Pediatrics, included 1876 children in the general community, using a questionnaire covering 11 psychosocial items in the family during pregnancy to develop a “vulnerability score”. The cumulative incidence of diagnoses until age 10 years was obtained from a regional health care register. An association was found between the vulnerability score and cortisol logarithm concentrations in the hair, and children with higher levels were significantly more often affected by 12 of the 14 most common childhood diseases, with a general pattern of increasing odds ratios. The authors wrote that the actual pathways linking psychosocial exposures to altered HPA axis activity in children were not fully known. They said their finding supported “the model of physiologic dysregulation as a plausible mechanism by which the duration and number of early detrimental psychosocial exposures act as a trajectory to poor health outcomes. “It also indicates that the multiplicity of psychosocial disparities is of importance and should be targeted in future interventions, because it could help to identify vulnerable children who are at high risk of poor health.”

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