Local ancestry at APOE modifies Alzheimer's disease risk in Caribbean Hispanics

IntroductionAlthough the relationship between APOE and Alzheimer's disease (AD) is well established in populations of European descent, the effects of APOE and ancestry on AD risk in diverse populations is not well understood.MethodsLogistic mixed model regression and survival analyses were performed in a sample of 3067 Caribbean Hispanics and 3028 individuals of European descent to assess the effects of APOE genotype, local ancestry, and genome-wide ancestry on AD risk and age at onset.ResultsAmong the Caribbean Hispanics, individuals with African-derived ancestry at APOE had 39% lower odds of AD than individuals with European-derived APOE, after adjusting for APOE genotype, age, and genome-wide ancestry. While APOE E2 and E4 effects on AD risk and age at onset were significant in the Caribbean Hispanics, they were substantially attenuated compared with those in European ancestry individuals.DiscussionThese results suggest that additional genetic variation in the APOE region influences AD risk beyond APOE E2/E3/E4.     

Low-dose l-isoproterenol versus salbutamol in hospitalized pediatric patients with severe acute exacerbation of asthma: A double-blind,randomized controlled trial

BackgroundAlthough the guidelines in most countries do not recommend continuous inhalation of l-isoproterenol to treat pediatric patients with acute severe exacerbation of asthma, lower dose of l-isoproterenol has been widely used in Japan. To determine whether the efficacy of low-dose l-isoproterenol was superior to that of salbutamol, we conducted a double-blind, randomized controlled trial.MethodsHospitalized patients aged 1–17 years were eligible if they had severe asthma exacerbation defined by the modified pulmonary index score (MPIS). Patients were randomly assigned (1:1) to receive inhalation of l-isoproterenol (10 μg/kg/h) or salbutamol (500 μg/kg/h) for 12 hours via a large-volume nebulizer with oxygen. The primary outcome was the change in MPIS from baseline to 3 hours after starting inhalation. Trial registration number UMIN000001991.ResultsFrom December 2009 to October 2013, 83 patients (42 in the l-isoproterenol group and 41 in the salbutamol group) were enrolled into the study. Of these, one patient in the l-isoproterenol group did not receive the study drug and was excluded from the analysis. Compared with salbutamol, l-isoproterenol reduced MPIS more rapidly. Mean (SD) changes in MPIS at 3 hours were −2.9 (2.5) in the l-isoproterenol group and −0.9 (2.3) in the salbutamol group (difference −2.0, 95% confidence interval −3.1 to −0.9; P < 0.001). Adverse events occurred in 1 (2%) and 11 (27%) patients in the l-isoproterenol and salbutamol groups, respectively (P = 0.003). Hypokalemia and tachycardia occurred only in the salbutamol group.ConclusionsLow-dose l-isoproterenol has a more rapid effect with fewer adverse events than salbutamol.     

Invasive pneumococcal disease in children under 16 years of age: Incomplete rebound in incidence after the maximum effect of PCV13 in 2012/13 in Germany

ObjectiveTo identify a potential nadir of the impact of pneumococcal conjugate vaccination (PCV) in infancy on invasive pneumococcal diseases (IPD) in children under 16 in Germany.MethodsActive surveillance on IPD based on two independent data sources with capture-recapture correction for underreporting. Annual incidence rates by age group, serotypes, site of infection, and relative incidence reduction compared to pre-vaccination period (1997–2001) at nadir and for the most recent season are reported. We calculated vaccine coverage at the age of 24 months using health insurance claims data.Results96–97% of children had received at least two doses of PCV since 2009. The maximum impact on overall IPD incidence was achieved in 2012/13 (−48% [95% CI: −55%; −39%]) with a rebound to −26% [95% CI: −36%; −16%] in 2015/16. Non-PCV13 serotypes accounted for 84.1% of the IPD cases in 2015/16. The most frequent non-PCV serotypes in IPD in 2014/15 and 2015/16 were 10A, 24F, 15C, 12F, 38, 22F, 23B, and 15B. The impact at nadir was highest in children 0–1 years of age both in meningitis and non-meningitis cases, whereas the impact for other age groups was higher for meningitis cases. The rebound mainly pertained to non-meningitis cases.ConclusionThe maximum impact of pneumococcal conjugate vaccination has been attained and signs of a rebound are apparent. Sustained surveillance for IPD in children is warranted to assess whether these trends will continue. There may be a need for vaccines using antigens common to all serotypes.     

The Impact of Age of Transfer on Outcomes in the Transition From Pediatric to Adult Health Systems: A Systematic Review of Reviews

PurposeInternational guidance on health-care transition has existed for over a decade; however, many unanswered questions remain. This systematic review of reviews aimed to answer the question: is a later age of transfer from pediatric to adult health care associated with improved health and health service outcomes?MethodsWe included systematic reviews which considered at least one long-term condition and provided outcome data from adult services. Methodology of primary studies was not an exclusion criterion. We searched multiple databases and conducted an initial search in May 2015 which was repeated in May 2017. All reviews were assessed for quality using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) tool. Reviews that scored less than 22 were excluded.ResultsInitial searches identified 6,149 papers. Forty-three reviews met exclusion and inclusion criteria, and 15 reviews also met quality criteria. With one exception, primary studies from reviews which only considered quantitative evidence found that a delayed age of transfer resulted in improved outcomes. Qualitative and mixed-methods evidence supported the view that age 18 was an appropriate time of transfer.ConclusionWe found moderate evidence that models of transition which transfer young people in late adolescence or early adulthood can improve transition outcomes and patient satisfaction.     

Parents' drinking motives and problem drinking predict their children's drinking motives,alcohol use and substance misuse

The aim of the current study was to test the direct and indirect influence of parents' drinking motives and problem drinking on their children's drinking motives, alcohol use and substance misuse. Cross-sectional analysis of parent and child drinking patterns and motives, derived from the nationally representative Drinkaware Monitor panel survey. The sample comprised a total of 148 couples of parents and child. Path analysis revealed that children's alcohol use and substance misuse were influenced by their own drinking motives and parents' problem drinking. Parents' conformity motives were linked to their children's conformity motives. Finally, parental drinking problems mediated the effect of their coping motives on their childrens' alcohol use and substance misuse. In conclusion, parental drinking styles relate to their children's alcohol use and substance misuse through problem drinking and drinking motives.     

Who will become my co-residents? The role of attractiveness of institutional care in the changing demand for long-term care institutions

BackgroundIn several OECD countries the percentage of people over 80 in LTC institutions has been declining for more than a decade, despite population ageing. The standard model to explain healthcare utilization, the Andersen model, cannot explain this trend. We extend the Andersen model by including proxies for the relative attractiveness of community living compared to institutional care. Using longitudinal data on long-term care use in the Netherlands from 1996 to 2012, we examine to what extent a decline in institutional care is associated with changes in perceived attractiveness of institutional LTC care compared to community living.MethodsWith a Blinder–Oaxaca decomposition regression, we decomposed the difference in admission to LTC institutions between the period 1996–1999 and 2009–2012 into a part that accounts for differences in predictors of the Andersen model and an “unexplained” part, and investigate whether the perceived attractiveness of institutional care reduces the size of the unexplained part.ResultsWe find that factors related to the perceived attractiveness of institutional care compared to community living explains 12.8% of the unexplained negative time trend in admission rates over the total period (1996–2012), and 19.1–19.2% over shorter time frames.DiscussionOur results show that changes in the perceived attractiveness of institutional LTC may explain part of the decline in demand for institutional care. Our findings imply that policies to encourage community living may have a self-reinforcing effect.