Interpreting adverse signals in diabetes drug development programs

Detection and interpretation of adverse signals during preclinical and clinical stages of drug development inform the benefit-risk assessment that determines suitability for use in real-world situations. This review considers some recent signals associated with diabetes therapies, illustrating the difficulties in ascribing causality and evaluating absolute risk, predictability, prevention, and containment. Individual clinical trials are necessarily restricted for patient selection, number, and duration; they can introduce allocation and ascertainment bias and they often rely on biomarkers to estimate long-term clinical outcomes. In diabetes, the risk perspective is inevitably confounded by emergent comorbid conditions and potential interactions that limit therapeutic choice, hence the need for new therapies and better use of existing therapies to address the consequences of protracted glucotoxicity. However, for some therapies, the adverse effects may take several years to emerge, and it is evident that faint initial signals under trial conditions cannot be expected to foretell all eventualities. Thus, as information and experience accumulate with time, it should be accepted that benefit-risk deliberations will be refined, and adjustments to prescribing indications may become appropriate. © 2013 by the American Diabetes Association.

Stress, burnout and coping strategies in the emergency and intensive care hospital departments

Doctors and nurses working at the accident and emergency (A&E), and intensive care departments are at risk of burnout. They often spend substantial time in intense interactions with other people, centered on patients? health problems (physical, psychological and social) that may lead to feelings of anger, anxiety and frustration, and eventually to burnout. Burnout is a syndrome of emotional exhaustion, depersonalization and reduced personal accomplishment (Maslach & Jackson, 1981) The purpose of this chapter is to assess work stressors, burnout and stress-coping mechanisms among doctors and nurses at the A&E and intensive care departments. A quantitative design using the survey approach was used to collect data from a sample of 200 participants with a response rate of 71% (n=154) Work stressors were associated with burnout in both doctors and nurses. Workload was the most salient work stressor in the sample. Nurses experienced more stress (M=1.5, SD=0.4) than doctors (M=1.2, SD=0.4) in all the work stressor variables examined. The A&E department was reported as more stressful than the intensive care department. Avoidance-oriented and task-oriented coping were the most and the least frequently reported coping strategies respectively. Additionally, only emotion-oriented coping strategy was significantly different between doctors and nurses, and this strategy was also significantly positively correlated with all the variables in the adapted nursing stress scale, and the three burnout variables. Death and dying was most strongly correlated with emotion-oriented coping. This chapter provides an assessment of stress, burnout and coping experienced by both doctors and nurses within the A&E and intensive care departments. Methods that may mitigate stress in these environments may be adequate staffing, supportive management, stress management programs, as well as improvement in communication strategies between doctors and nurses.

Functional outcomes in the Cleft Care UK study - Part 3:oral health and audiology

OBJECTIVES: To compare oral health and hearing outcomes from the Clinical Standards Advisory Group (CSAG, 1998) and the Cleft Care UK (CCUK, 2013) studies. SETTING AND SAMPLE POPULATION: Two UK-based cross-sectional studies of 5-year-olds born with non-syndromic unilateral cleft lip and palate undertaken 15 years apart. CSAG children were treated in a dispersed model of care with low-volume operators. CCUK children were treated in a centralized, high volume operator system. MATERIALS AND METHODS: Oral health data were collected using a standardized proforma. Hearing was assessed using pure tone audiometry and middle ear status by otoscopy and tympanometry. ENT and hearing history were collected from medical notes and parental report. RESULTS: Oral health was assessed in 264 of 268 children (98.5%). The mean dmft was 2.3, 48% were caries free, and 44.7% had untreated caries. There was no evidence this had changed since the CSAG survey. Oral hygiene was generally good, 96% were enrolled with a dentist. Audiology was assessed in 227 of 268 children (84.7%). Forty-three per cent of children received at least one set of grommets--a 17.6% reduction compared to CSAG. Abnormal middle ear status was apparent in 50.7% of children. There was no change in hearing levels, but more children with hearing loss were managed with hearing aids. CONCLUSIONS: Outcomes for dental caries and hearing were no better in CCUK than in CSAG, although there was reduced use of grommets and increased use of hearing aids. The service specifications and recommendations should be scrutinized and implemented.