The safety and efficacy of botulinum toxin-A in the management of bladder oversensitivity: a randomised double-blind placebo-controlled trial

Objective: To assess the safety and efficacy of botulinum toxin‐A (botn‐A) in the management of patients with bladder oversensitivity (BO). Patients and methods: Twenty‐three consecutive patients with a diagnosis of BO refractory to anticholinergics were enrolled in this randomised, double blind, placebo‐controlled trial. Patients were randomly allocated to receive intradetrusor injections of either botn‐A (100 U Botox^®) or saline (placebo) via a flexible cystoscopic approach. The study was designed to have 90% power to detect a change in the maximum cystometric capacity (MCC) of 30%. It was calculated that a total cohort of 58 patients would be required. Urodynamic assessment (UDS), voiding diaries (VD) and quality of life (QoL) were assessed at baseline and at 4 and 12 weeks following intervention. Results: An interim analysis was performed and the trial halted after recruitment of 23 patients as a result of poorly perceived patient benefit. Data were analysed for 21 patients (10 botn‐A; 11 placebo). In the treatment arm, there was a significant increase in MCC (mean rise 105 ml; p = 0.009). However, storage symptoms remained statistically unchanged following botn‐A. Three patients in the treatment arm were required to perform clean intermittent self‐catheterisation with no clinical improvement. The limitations of this trial include the small sample size and the unplanned interim analysis. Conclusions: This is the first randomised, double blind, placebo‐controlled trial examining the effects of botn‐A exclusively in patients with BO. A significant increase in MCC was observed but this did not translate to clinical benefit with no change observed in the symptoms and quality of life for the majority of patients.     

Neuropsychiatric complications of aging with HIV

Persons over age 50 are not only aging with human immunodeficiency virus (HIV) infection but also represent a high proportion of new HIV infections. Neuropsychiatric symptoms, including depression, cognitive impairment, and substance abuse, are very common in individuals infected with HIV. However, there is little understanding of the relationship between these HIV-related comorbid conditions in newly infected elderly patients compared to uninfected elderly and those who have survived after 20 years of HIV/AIDS. We summarize the current theories and research that link aging and HIV with psychiatric illnesses and identify emerging areas for improved research, treatment, and patient care.     

Serum biomarkers of drug‐induced liver injury: Current status and future directions

Drug‐induced liver injury (DILI), which is caused by drugs and herbal or dietary supplements, remains a serious concern for drug developers, regulators, and clinicians; however, serum biomarkers utilized to detect and monitor DILI have not changed in decades and have limitations. Data‐driven mathematical modeling that incorporates the release and clearance kinetics of traditional biomarkers has improved their use in the prediction of liver safety liabilities for new drug candidates. Several newer biomarkers have shown promise in terms of liver specificity, predicting the outcome of DILI events, and providing insight into its underlying mechanisms. For these new biomarkers to be qualified for regulatory acceptance, it will require their assessment in large numbers of patients who are receiving a wide range of compounds and who develop a broad spectrum of liver injuries. The ongoing and evolving international biomarker consortia should play a major role in this effort, which is likely to transform the assessment of liver safety in clinical trials and in the clinic.     

Adaptive responses of the embryo to maternal diet and consequences for post-implantation development

Maternal periconceptional (PC) nutrition, coupled with maternal physiological condition, can impact on reproductive performance and potential across mammalian species. Oocyte quality and embryo development are affected adversely by either nutrient restriction or excess. Moreover, the quality of maternal PC nutrition can have lasting effects through fetal development and postnatally into adulthood. Chronic disease, notably cardiovascular and metabolic disease, and abnormal behaviour have been identified in adult offspring in small and large animal models of PC nutrient restriction. These long-term effects associate with compensatory responses that begin from the time of early embryo development. This review assesses the field of PC nutrition in vivo on short- and long-term developmental consequences in rodent and ruminant models and considers the implications for human health.     

The Air Force health study: an epidemiologic retrospective

In 1979, the U.S. Air Force announced that an epidemiologic study would be undertaken to determine whether the Air Force personnel involved in Operation Ranch Hand-the program responsible for herbicide spraying in Vietnam-had experienced adverse health effects as a result of that service. In January 1982 the Air Force Health Study (AFHS) protocol was approved and the 20 year matched cohort study consisting of independent mortality, morbidity and reproductive health components was initiated. This controversial study has been criticized regarding the study's potential scientific limitations as well as some of the administrative aspects of its conduct. Now, almost 30 years since the implementation of the AFHS and nearly a decade since the final follow up examinations, an appraisal of the study indicates that the results of the AFHS do not provide evidence of disease in the Ranch Hand veterans caused by their elevated levels of exposure to Agent Orange.     

Braden scale for pressure ulcer risk predicts rehabilitation placement after pancreatic resection

BackgroundPatients undergoing pancreatic resection frequently require rehabilitation facilities after hospital discharge. We evaluated the predictive role of validated markers of frailty on rehabilitation facility placement to identify patients who may require this service.MethodsSingle-center retrospective cohort study of patients who underwent pancreatic resection from 2010 to 2015. 90-day morbidity and mortality were calculated. Postoperative validated markers of frailty (Activities of Daily Living scale, Braden scale [assesses pressure ulcer risk, lower scores = higher risk] and Morse fall scale) were evaluated via multivariate regression to identify predictors of discharge to rehabilitation facility.Results470 patients with complete data were included. Mean age was 62 and 49.2% were male. Postoperative median length of stay (LOS) was 8 (IQR 7–10). 92 (19.66%) patients were discharged to rehabilitation facilities and 138 (29.49%) patients were readmitted within 90 days. On multivariate analysis, age, sex, LOS > 8 days, inpatient Comprehensive Complication Index (CCI) and initial Braden scale were predictive of rehabilitation placement.ConclusionA marker of frailty routinely collected daily by nursing staff, the Braden scale, is available to help surgeons predict the need for postoperative rehabilitation placement after pancreatic resection. Engaging discharge planning services for at-risk patients may help prevent delayed hospital discharge and should be further evaluated.