Blood-brain barrier permeable ß-blockers linked to lower risk of Alzheimer's disease in hypertension.

Alzheimer's disease is a neurodegenerative disorder in which the pathological accumulation of amyloid-ß and tau begins years before symptom onset. Emerging evidence suggests that ß-blockers (ß-adrenergic antagonists) increase brain clearance of these metabolites by enhancing CSF flow. Our objective was to determine whether ß-blocker treatments that easily cross the blood-brain barrier reduce the risk of Alzheimer's disease compared to less permeable ß-blockers. Data from the Danish national registers were used to identify a retrospective cohort of individuals with hypertension, and those treated with ß-blockers were included in the analysis. People with indications for ß-blocker use other than hypertension (e.g. heart failure) were only retained in a sensitivity analysis. ß-blockers were divided into three permeability groups: low, moderate and high. We used multivariable cause-specific Cox regression to model the effect of ß-blocker blood-brain barrier permeability on time to dementia outcomes, adjusting for baseline comorbidities, demographics and socioeconomic variables. Death was modelled as a competing risk. The 10-year standardized absolute risk was estimated as the averaged person-specific risks per treatment. In a cohort of 69 081 (median age = 64.4 years, 64.8% female) people treated with ß-blockers for hypertension, highly blood-brain barrier-permeable ß-blockers were associated with reduced risk of Alzheimer's disease versus low permeability ß-blockers (-0.45%, P < 0.036). This effect was specific to Alzheimer's diagnoses and did not extend to dementia in general. Propensity score analysis matching high and low blood-brain barrier-permeable patients also detected a decreased Alzheimer's risk (-0.92%, P < 0.001) in the high permeability group compared to the low, as did a 1-year landmark analysis (-0.57%, P < 0.029) in which events within the first year of follow-up were ignored as likely unrelated to treatment. Our results suggest that amongst people taking ß-blockers for hypertension, treatment with highly blood-brain barrier permeable ß-blockers reduces the risk of Alzheimer's disease compared to low permeability drugs. Our findings support the hypothesis that highly permeable ß-blockers protect against Alzheimer's disease by promoting waste brain metabolite clearance.

Competence of health workers in emergency obstetric care: an assessment using clinical vignettes in Brong Ahafo region, Ghana.

OBJECTIVES: To assess health worker competence in emergency obstetric care using clinical vignettes, to link competence to availability of infrastructure in facilities, and to average annual delivery workload in facilities. DESIGN: Cross-sectional Health Facility Assessment linked to population-based surveillance data. SETTING: 7 districts in Brong Ahafo region, Ghana. PARTICIPANTS: Most experienced delivery care providers in all 64 delivery facilities in the 7 districts. PRIMARY OUTCOME MEASURES: Health worker competence in clinical vignette actions by cadre of delivery care provider and by type of facility. Competence was also compared with availability of relevant drugs and equipment, and to average annual workload per skilled birth attendant. RESULTS: Vignette scores were moderate overall, and differed significantly by respondent cadre ranging from a median of 70% correct among doctors, via 55% among midwives, to 25% among other cadres such as health assistants and health extension workers (p<0.001). Competence varied significantly by facility type: hospital respondents, who were mainly doctors and midwives, achieved highest scores (70% correct) and clinic respondents scored lowest (45% correct). There was a lack of inexpensive key drugs and equipment to carry out vignette actions, and more often, lack of competence to use available items in clinical situations. The average annual workload was very unevenly distributed among facilities, ranging from 0 to 184 deliveries per skilled birth attendant, with higher workload associated with higher vignette scores. CONCLUSIONS: Lack of competence might limit clinical practice even more than lack of relevant drugs and equipment. Cadres other than midwives and doctors might not be able to diagnose and manage delivery complications. Checking clinical competence through vignettes in addition to checklist items could contribute to a more comprehensive approach to evaluate quality of care. TRIAL REGISTRATION NUMBER: NCT00623337.