Exercise alone and various combinations of interventions were associated with lower risk of injurious falls compared with usual care. Choice of fall-prevention intervention may depend on patient and caregiver values and preferences.
There is an urgent need to develop new tuberculosis (TB) vaccines to safely and effectively boost Bacille Calmette-Guérin (BCG)-triggered T cell immunity in humans. AdHu5Ag85A is a recombinant human type 5 adenovirus (AdHu5)-based TB vaccine with demonstrated efficacy in a number of animal species, yet it remains to be translated to human applications. In this phase 1 study, we evaluated the safety and immunogenicity of AdHu5Ag85A in both BCG-naïve and previously BCG-immunized healthy adults. Intramuscular immunization of AdHu5Ag85A was safe and well tolerated in both trial volunteer groups. Moreover, although AdHu5Ag85A was immunogenic in both trial volunteer groups, it much more potently boosted polyfunctional CD4(+) and CD8(+) T cell immunity in previously BCG-vaccinated volunteers. Furthermore, despite prevalent preexisting anti-AdHu5 humoral immunity in most of the trial volunteers, we found little evidence that such preexisting anti-AdHu5 immunity significantly dampened the potency of AdHu5Ag85A vaccine. This study supports further clinical investigations of the AdHu5Ag85A vaccine for human applications. It also suggests that the widely perceived negative effect of preexisting anti-AdHu5 immunity may not be universally applied to all AdHu5-based vaccines against different types of human pathogens.
BackgroundAnemia in children continues to be a major public health challenge in most developing countries, particularly in Africa. Anemia in the early stages of life leads to severe negative consequences on the cognitive as well as the growth and development of children, which may persist even after treatment. We examine the prevalence of anemia in under-five children in the Ghanaian population to help inform and serve as a guide to health policies and possible interventions.MethodsData from the 2008 Ghana Demographic and Health Survey (GDHS) was used. Data consists of health, demographic and socio-economic factors. Anemia status was determined using hemoglobin level, and prevalence of childhood anemia along with 95% confidence intervals was provided. We also examined the distribution of prevalence across different age and socio-demographic groups as well as the different regions and sub-regions in Ghana.ResultsThe overall prevalence of anemia in under-five children in Ghana was 78.4% (N = 2168, 95% CI: 76.7-80.2), where 7.8% (N = 2168, 95% CI: 6.6-8.9) of the children had severe anemia, 48.0% (N = 2168, 95% CI: 45.9-50.2) moderate anemia and 22.6% (N = 2168, 95% CI: 20.8-24.4) had mild anemia. The highest prevalence regions were the Upper East, 88.9% (N = 158, 95% CI: 80.9-94.0), and Upper West 88.1% (N = 220, 95% CI: 76.4-94.6). The prevalence was also higher among children under 2 years of age, 85.1% (N = 781, 95% CI: 82.6-87.7) than children 2–5 years of age, 74.8% (N = 1387, 95% CI: 72.5-77.1). No significant difference in prevalence between boys and girls was observed.ConclusionsGiven the high prevalence of childhood anemia observed in Ghana, particularly among those less than 2 years old, and given the negative consequences on their cognitive and behavioral development even in later years, there is an urgent need for effective and efficient public health interventions.
Background/Objectives To examine the comparative effectiveness and safety of cognitive enhancers for Alzheimer's disease (AD). Design Systematic review and Bayesian network metaanalysis (NMA). Setting MEDLINE, EMBASE, Cochrane Library, CINAHL, Ageline (inception–March 2016). Participants Individuals with AD in randomized controlled trials (RCTs), quasi‐RCTs, and nonrandomized studies. Intervention Any combination of donepezil, rivastigmine, galantamine, or memantine. Measurements Two reviewers independently screened titles, abstracts, and full‐texts; abstracted data; and appraised risk of bias. Results Twenty thousand three hundred forty‐three citations were screened, and 142 studies were included (110 RCTs, 21 non‐RCTs, 11 cohort studies). NMA found that donepezil (Mini‐Mental State Examination: mean difference (MD) = 1.39, 95% credible interval (CrI) = 0.53–2.24), donepezil+memantine (2.59, 95% CrI = 0.12–4.98), and transdermal rivastigmine (2.02, 95% CrI = 0.02–4.08) improved cognition more than placebo. NMA found that donepezil (Alzheimer's Disease Assessment Scale–cognitive: MD = −3.29, 95% CrI = −4.57 to −1.99) and galantamine (MD = −2.13, 95% CrI = −3.91 to −0.27) improved cognition more than placebo. NMA found that donepezil+memantine (MD = −5.23, 95% CrI = −8.72 to −1.56) improved behavior more than placebo. NMA found that donepezil (MD = −0.32, 95% CrI = −0.46 to −0.19), donepezil+memantine (MD = −0.57, 95% CrI = −0.95 to −0.21), oral rivastigmine (MD = −0.38, 95% CrI = −0.56 to −0.17), and galantamine (MD = −3.79, 95% CrI = −6.98 to −0.59) improved global status more than placebo. NMA found that galantamine decreased the odds of mortality (odds ratio = 0.56, 95% CrI = 0.36–0.87). No agent increased risk of serious adverse events, falls, or bradycardia. Some increased risk of headache (oral rivastigmine), diarrhea (oral rivastigmine, donepezil), nausea (oral rivastigmine, donepezil, galantamine), and vomiting (oral rivastigmine, donepezil, galantamine). Conclusion An exhaustive review of the literature involving 142 studies demonstrated that cognitive enhancers in general have minimal effects on cognition according to minimal clinically important difference and global ratings. The drugs appear safe, but this must be interpreted cautiously because trial participants may have less comorbidity and fewer adverse effects than those treated with these drugs in clinical practice.
Due to rapid technological advances, various types of genomic and proteomic data with different sizes, formats, and structures have become available. Among them are gene expression, single nucleotide polymorphism, copy number variation, and protein-protein/gene-gene interactions. Each of these distinct data types provides a different, partly independent and complementary, view of the whole genome. However, understanding functions of genes, proteins, and other aspects of the genome requires more information than provided by each of the datasets. Integrating data from different sources is, therefore, an important part of current research in genomics and proteomics. Data integration also plays important roles in combining clinical, environmental, and demographic data with high-throughput genomic data. Nevertheless, the concept of data integration is not well defined in the literature and it may mean different things to different researchers. In this paper, we first propose a conceptual framework for integrating genetic, genomic, and proteomic data. The framework captures fundamental aspects of data integration and is developed taking the key steps in genetic, genomic, and proteomic data fusion. Secondly, we provide a review of some of the most commonly used current methods and approaches for combining genomic data with focus on the statistical aspects.
Objective: Interrupted time series (ITS) designs are robust quasi-experimental designs commonly used to evaluate the impact of interventions and programs implemented in healthcare settings. This scoping review aims to 1) identify and summarize existing methods used in the analysis of ITS studies conducted in health research, 2) elucidate their strengths and limitations, 3) describe their applications in health research and 4) identify any methodological gaps and challenges. Design: Scoping review. Data Sources: Searches were conducted in MEDLINE, JSTOR, PUBMED, EMBASE, CINAHL, Web of Science and the Cochrane Library from inception until September 2017. Study Selection: Studies in health research involving ITS methods or reporting on the application of ITS designs. Data Extraction: Screening of studies was completed independently and in duplicate by two reviewers. One reviewer extracted the data from relevant studies in consultations with a second reviewer. Results of the review were presented with respect to methodological and application areas, and data were summarized using descriptive statistics. Results: A total of 1389 articles were included, of which 98.27% (N=1365) were application papers. Segmented linear regression was the most commonly used method (26%, N=360). A small percentage (1.73%, N=24) were methods papers, of which 11 described either the development of novel methods or improvement of existing methods, 7 adapted methods from other areas of statistics, while 6 provided comparative assessment of conventional ITS methods. Conclusion: A significantly increasing trend in ITS use over time is observed, where its application in health research almost tripled within the last decade. Several statistical methods are available for analyzing ITS data. Researchers should consider the types of data and validate the required assumptions for the various methods. There is a significant methodological gap in ITS analysis involving aggregated data, where analyses involving such data did not account for heterogeneity across patients and hospital settings.
Backgroundolder patients admitted to hospitals are at risk for hospital-acquired morbidity related to immobility. The aim of this study was to implement and evaluate an evidence-based intervention targeting staff to promote early mobilisation in older patients admitted to general medical inpatient units.Methodsthe early mobilisation implementation intervention for staff was multi-component and tailored to local context at 14 academic hospitals in Ontario, Canada. The primary outcome was patient mobilisation. Secondary outcomes included length of stay (LOS), discharge destination, falls and functional status. The targeted patients were aged ≥ 65 years and admitted between January 2012 and December 2013. The intervention was evaluated over three time periods—pre-intervention, during and post-intervention using an interrupted time series design.Resultsin total, 12,490 patients (mean age 80.0 years [standard deviation 8.36]) were included in the overall analysis. An increase in mobilisation was observed post-intervention, where significantly more patients were out of bed daily (intercept difference = 10.56%, 95% CI: [4.94, 16.18]; P < 0.001) post-intervention compared to pre-intervention. Hospital median LOS was significantly shorter during the intervention period (intercept difference = −3.45 days, 95% CI: [−6.67,−0.23], P = 0.0356) compared to pre-intervention. It continued to decrease post-intervention with significantly fewer days in hospital (intercept difference= −6.1, 95% CI: [−11,−1.2]; P = 0.015) in the post-intervention period compared to pre-intervention.Conclusionsthis is a large-scale study evaluating an implementation strategy for early mobilisation in older, general medical inpatients. The positive outcome of this simple intervention on an important functional goal of getting more patients out of bed is a striking success for improving care for hospitalised older patients.
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