The utilisation of health research in policy-making: Concepts, examples and methods of assessment

The importance of health research utilisation in policy-making, and of understanding the mechanisms involved, is increasingly recognised. Recent reports calling for more resources to improve health in developing countries, and global pressures for accountability, draw greater attention to research-informed policy-making. Key utilisation issues have been described for at least twenty years, but the growing focus on health research systems creates additional dimensions. The utilisation of health research in policy-making should contribute to policies that may eventually lead to desired outcomes, including health gains. In this article, exploration of these issues is combined with a review of various forms of policy-making. When this is linked to analysis of different types of health research, it assists in building a comprehensive account of the diverse meanings of research utilisation. Previous studies report methods and conceptual frameworks that have been applied, if with varying degrees of success, to record utilisation in policy-making. These studies reveal various examples of research impact within a general picture of underutilisation. Factors potentially enhancing utilisation can be identified by exploration of: priority setting; activities of the health research system at the interface between research and policy-making; and the role of the recipients, or 'receptors', of health research. An interfaces and receptors model provides a framework for analysis. Recommendations about possible methods for assessing health research utilisation follow identification of the purposes of such assessments. Our conclusion is that research utilisation can be better understood, and enhanced, by developing assessment methods informed by conceptual analysis and review of previous studies

Asymptotically Tight Bounds for Performing BMMC Permutations on Parallel Disk Systems

This paper presents asymptotically equal lower and upper bounds for the number of parallel I/O operations required to perform bit-matrix-multiply/complement (BMMC) permutations on the Parallel Disk Model proposed by Vitter and Shriver. A BMMC permutation maps a source index to a target index by an affine transformation over GF(2), where the source and target indices are treated as bit vectors. The class of BMMC permutations includes many common permutations, such as matrix transposition (when dimensions are powers of 2), bit-reversal permutations, vector-reversal permutations, hypercube permutations, matrix reblocking, Gray-code permutations, and inverse Gray-code permutations. The upper bound improves upon the asymptotic bound in the previous best known BMMC algorithm and upon the constant factor in the previous best known bit-permute/complement (BPC) permutation algorithm. The algorithm achieving the upper bound uses basic linear-algebra techniques to factor the characteristic matrix for the BMMC permutation into a product of factors, each of which characterizes a permutation that can be performed in one pass over the data. The factoring uses new subclasses of BMMC permutations: memoryload-dispersal (MLD) permutations and their inverses. These subclasses extend the catalog of one-pass permutations. Although many BMMC permutations of practical interest fall into subclasses that might be explicitly invoked within the source code, this paper shows how to quickly detect whether a given vector of target addresses specifies a BMMC permutation. Thus, one can determine efficiently at run time whether a permutation to be performed is BMMC and then avoid the general-permutation algorithm and save parallel I/Os by using the BMMC permutation algorithm herein

Distinct Effects of Two HIV-1 Capsid Assembly Inhibitor Families That Bind the Same Site within the N-Terminal Domain of the Viral CA Protein

The emergence of resistance to existing classes of antiretroviral drugs necessitates finding new HIV-1 targets for drug discovery. The viral capsid (CA) protein represents one such potential new target. CA is sufficient to form mature HIV-1 capsids in vitro, and extensive structure-function and mutational analyses of CA have shown that the proper assembly, morphology, and stability of the mature capsid core are essential for the infectivity of HIV-1 virions. Here we describe the development of an in vitro capsid assembly assay based on the association of CA-NC subunits on immobilized oligonucleotides. This assay was used to screen a compound library, yielding several different families of compounds that inhibited capsid assembly. Optimization of two chemical series, termed the benzodiazepines (BD) and the benzimidazoles (BM), resulted in compounds with potent antiviral activity against wild-type and drug-resistant HIV-1. Nuclear magnetic resonance (NMR) spectroscopic and X-ray crystallographic analyses showed that both series of inhibitors bound to the N-terminal domain of CA. These inhibitors induce the formation of a pocket that overlaps with the binding site for the previously reported CAP inhibitors but is expanded significantly by these new, more potent CA inhibitors. Virus release and electron microscopic (EM) studies showed that the BD compounds prevented virion release, whereas the BM compounds inhibited the formation of the mature capsid. Passage of virus in the presence of the inhibitors selected for resistance mutations that mapped to highly conserved residues surrounding the inhibitor binding pocket, but also to the C-terminal domain of CA. The resistance mutations selected by the two series differed, consistent with differences in their interactions within the pocket, and most also impaired virus replicative capacity. Resistance mutations had two modes of action, either directly impacting inhibitor binding affinity or apparently increasing the overall stability of the viral capsid without affecting inhibitor binding. These studies demonstrate that CA is a viable antiviral target and demonstrate that inhibitors that bind within the same site on CA can have distinct binding modes and mechanisms of action

Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio)

Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells in the presence of ototoxic drugs. Dimethyl sulfoxide (DMSO) is typically used as a solvent for many pharmacological agents in sensory hair cell cytotoxicity assays. Serendipitously, we found that DMSO potentiated the effects of cisplatin and killed more sensory hair cells than treatment with cisplatin alone. Yet, DMSO alone did not kill hair cells. We did not observe the synergistic effects of DMSO with the ototoxic aminoglycoside antibiotic neomycin. Cisplatin treatment with other commonly used organic solvents (i.e. ethanol, methanol, and polyethylene glycol 400) also did not result in increased cell death compared to cisplatin treatment alone. Thus, caution should be exercised when interpreting data generated from small molecule screens since many compounds are dissolved in DMSO.National Institutes of Health (U.S.) (DC010998)National Institutes of Health (U.S.) (NIH DC010231)Harvard College (1780- )Sarah Fuller Foundation for Little Deaf Childre

Primary Prevention of First-Ever Stroke in Primary Health Care: A Clinical Practice Study Based on Medical Register Data in Sweden

Background. The aim of this study was to investigate whether established risk factors for stroke in patients admitted to health care for first-ever stroke had been detected and treated in primary health care. Methods. In a retrospective study in Nacka municipality, Stockholm County, Sweden, with about 70 000 inhabitants, we included all men and women admitted to health care due to first-ever stroke between October 1999 and March 2001. Data on 187 such patients, with a mean age of 75 years, were obtained from medical registers. Main outcome measures were detection and treatment of risk factors for stroke including hypertension, diabetes, atrial fibrillation, smoking, alcohol abuse, and overweight/obesity. Results. In a majority of patients seen in primary health care with hypertension and diabetes, those risk factors were detected and treated (75.6% and 75.0%, resp.). Fewer patients with atrial fibrillation received treatment (60.9%). Treatment of lifestyle factors was difficult to assess because of lack of data in the medical records. Conclusions. Primary prevention of stroke in primary health care needs to be improved, especially when atrial fibrillation and lifestyle-related risk factors are present. Health policies need to target not only the public, but also general practitioners and other health care professionals

Levelling off of prevalence of obesity in the adult population of Sweden between 2000/01 and 2004/05

<p>Abstract</p> <p>Background</p> <p>The escalating global epidemic of obesity is of worldwide concern because of its association with several chronic diseases and premature mortality. Some subgroups seem to be more affected than others. The aim of this study was to examine whether the mean BMI (adjusted for age) and the prevalence of obesity (adjusted for all the explanatory variables) changed between 2000/01 and 2004/05 in different subgroups of the Swedish population.</p> <p>Methods</p> <p>This study compared two cross-sectional, nationwide random samples of persons aged 16 to 84 years: the first from 2000/01 (5515 men, 5838 women) and the second from 2004/05 (4681 men, 4821 women). After stratification by gender, a logistic regression model was applied to analyse possible changes in mean BMI and the prevalence of obesity between 2000/01 and 2004/05.</p> <p>Results</p> <p>Total mean BMI remained almost unchanged between 2000/01 and 2004/05 for both men and women. The prevalence of obesity increased slightly in both men and women, but not significantly (from 9.7 to 10.8% and from 9.6 to 10.2%, respectively). The prevalence of obesity in 2004/05 was especially high in some subgroups: men aged 45-54 (14.3%) or 55-64 (16.5%), women aged 65-74 (15.9%) or 75-84 (16.8%), men and women of middle educational level (15.6% and 14.4%, respectively), male former smokers (13.4%), and men from small towns or rural areas (13.1%).</p> <p>Conclusions</p> <p>Although the mean BMI and obesity were almost unchanged in the Swedish adult population between 2000/01 and 2004/05, obesity levels in Sweden remained unacceptably high, especially in certain subgroups. Primary and secondary intervention actions should strive to decrease the prevalence of obesity in Sweden.</p

A life course examination of the physical environmental determinants of physical activity behaviour: A “Determinants of Diet and Physical Activity” (DEDIPAC) umbrella systematic literature review.

Background: Participation in regular physical activity is associated with a multitude of health benefits across the life course. However, many people fail to meet PA recommendations. Despite a plethora of studies, the evidence regarding the environmental (physical) determinants of physical activity remains inconclusive. Objective: To identify the physical environmental determinants that influence PA across the life course. Methods: An online systematic literature search was conducted using MEDLINE, ISI Web of Science, Scopus and SPORTDiscus. The search was limited to studies published in English (January 2004 to April 2016). Only systematic literature reviews (SLRs) and meta-analyses (MAs) of observational studies, that investigated the association between physical determinants and physical activity outcomes, were eligible for inclusion. The extracted data were assessed on the importance of determinants, strength of evidence and methodological quality. Results: The literature search identified 28 SLRs and 3 MAs on 67 physical environmental characteristics potentially related to physical activity that were eligible for inclusion. Among preschool children, a positive association was reported between availability of backyard space and outdoor toys/equipment in the home and overall physical activity. The availability of physical activity programs and equipment within schools, and neighbourhood features such as pedestrian and cyclist safety structure were positively associated with physical activity in children and adolescents. Negative street characteristics, for example, lack of sidewalks and streetlights, were negatively associated with physical activity in adults. Inconsistent associations were reported for the majority of reviewed determinants in adults. Conclusion: This umbrella SLR provided a comprehensive overview of the physical environment determinants of physical activity across the life course and has highlighted, particularly amongst youth, a number of key determinants that may be associated with overall physical activity. Given the limited evidence drawn mostly from cross-sectional studies, longitudinal studies are needed to further explore these associations

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: a comparative risk assessment

Background High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods We used data for exposure to risk factors by country, age group, and sex from pooled analyses of populationbased health surveys. We obtained relative risks for the eff ects of risk factors on cause-specifi c mortality from metaanalyses of large prospective studies. We calculated the population attributable fractions for- each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the eff ects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specifi c population attributable fractions by the number of disease-specifi c deaths. We obtained cause-specifi c mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the fi nal estimates. Findings In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10\ub78 million deaths, 95% CI 10\ub71\u201311\ub75) of deaths from these diseases in 2010 were attributable to the combined eff ect of these four metabolic risk factors, compared with 67% (7\ub71 million deaths, 6\ub76\u20137\ub76) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined eff ects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing eff ect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the globalresponse to non-communicable diseases