Do large-scale hospital- and system-wide interventions improve patient outcomes: a systematic review

BackgroundWhile health care services are beginning to implement system-wide patient safety interventions, evidence on the efficacy of these interventions is sparse. We know that uptake can be variable, but we do not know the factors that affect uptake or how the interventions establish change and, in particular, whether they influence patient outcomes. We conducted a systematic review to identify how organisational and cultural factors mediate or are mediated by hospital-wide interventions, and to assess the effects of those factors on patient outcomes.MethodsA systematic review was conducted and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Database searches were conducted using MEDLINE from 1946, CINAHL from 1991, EMBASE from 1947, Web of Science from 1934, PsycINFO from 1967, and Global Health from 1910 to September 2012. The Lancet, JAMA, BMJ, BMJ Quality and Safety, The New England Journal of Medicine and Implementation Science were also hand searched for relevant studies published over the last 5 years. Eligible studies were required to focus on organisational determinants of hospital- and system-wide interventions, and to provide patient outcome data before and after implementation of the intervention. Empirical, peer-reviewed studies reporting randomised and non-randomised controlled trials, observational, and controlled before and after studies were included in the review.ResultsSix studies met the inclusion criteria. Improved outcomes were observed for studies where outcomes were measured at least two years after the intervention. Associations between organisational factors, intervention success and patient outcomes were undetermined: organisational culture and patient outcomes were rarely measured together, and measures for culture and outcome were not standardised.ConclusionsCommon findings show the difficulty of introducing large-scale interventions, and that effective leadership and clinical champions, adequate financial and educational resources, and dedicated promotional activities appear to be common factors in successful system-wide change

Design and development of a new flowable and photocurable lactide and caprolactone-based polymer for bone repair and augmentation

With a global aging population, there is a high demand for new biomaterials that provide regenerative or fixation modalities following a bone injury. Here, the design and development of newly synthesised poly(l-lactic acid)-dimethacrylate (PLLA-DM) and poly(caprolactone-co-fumarate)-dimethacrylate (PCF-DM) monomer systems serves to address some of the main medical challenges and requirements of surgeons during application and better postoperative outcomes of new bone-healing biomaterials. Synthesis of PLLA-DM and PCF-DM via ring opening polymerisation (ROP) and polycondensation routes led to low MW ‘flowable’ and resorbable monomers that polymerise in-situ at up to 6 mm curing depth. Tensile testing of photocured PLLA-DM/PCF-DM formulations at strain rate 0.05 s−1, revealed elastic moduli of 4.4 ± 0.5 to 11.7 ± 2.5 (SD) GPa, with ultimate tensile strength ranging between 29.7 ± 4.9 to 76.1 ± 13.5 (SD) MPa. Resazurin-based metabolic activity studies via an indirect contact method involving Saos-2 osteoblast-like cell lines revealed enhanced cytocompatibility with metabolic activity of treated Saos-2 cells increasing by up to 20% compared with respective untreated control groups. Attachment of Saos-2 cells on PLLA-DM/PCF-DM specimen surfaces revealed cellular structures such as filopodia extending beyond lamellipodia, indicative of remarkable cell adhesion and favouring colonization. The initial development of the polymer chemistry presented here provides the potential for the design and further development towards a new resorbable biomaterial with enhanced mechanical properties for bone repair and augmentation involving both orthopaedic (bone cement) and restorative dentistry applications

Mapping the Origins of Luminescence in ZnO Nanowires by STEM-CL

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jpclett.8b03286.In semiconductor nanowires, understanding both the sources of luminescence (excitonic recombination, defects, etc.) and the distribution of luminescent centers (be they uniformly distributed, or concentrated at structural defects or at the surface) is important for synthesis and applications. We develop scanning transmission electron microscopy−cathodoluminescence (STEM-CL) measurements, allowing the structure and cathodoluminescence (CL) of single ZnO nanowires to be mapped at high resolution. Using a CL pixel resolution of 10 nm, variations of the CL spectra within such nanowires in the direction perpendicular to the nanowire growth axis are identified for the first time. By comparing the local CL spectra with the bulk photoluminescence spectra, the CL spectral features are assigned to internal and surface defect structures. Hyperspectral CL maps are deconvolved to enable characteristic spectral features to be spatially correlated with structural features within single nanowires. We have used these maps to show that the spatial distribution of these defects correlates well with regions that show an increased rate of nonradiative transitions

The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat

PURPOSE: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene. Migalastat, a pharmacological chaperone, binds to specific mutant forms of α-galactosidase A to restore lysosomal activity. METHODS: A pharmacogenetic assay was used to identify the α-galactosidase A mutant forms amenable to migalastat. Six hundred Fabry disease-causing mutations were expressed in HEK-293 (HEK) cells; increases in α-galactosidase A activity were measured by a good laboratory practice (GLP)-validated assay (GLP HEK/Migalastat Amenability Assay). The predictive value of the assay was assessed based on pharmacodynamic responses to migalastat in phase II and III clinical studies. RESULTS: Comparison of the GLP HEK assay results in in vivo white blood cell α-galactosidase A responses to migalastat in male patients showed high sensitivity, specificity, and positive and negative predictive values (≥0.875). GLP HEK assay results were also predictive of decreases in kidney globotriaosylceramide in males and plasma globotriaosylsphingosine in males and females. The clinical study subset of amenable mutations (n = 51) was representative of all 268 amenable mutations identified by the GLP HEK assay. CONCLUSION: The GLP HEK assay is a clinically validated method of identifying male and female Fabry patients for treatment with migalastat

Host choice and multiple blood feeding behaviour of malaria vectors and other anophelines in Mwea rice scheme, Kenya

<p>Abstract</p> <p>Background</p> <p>Studies were conducted between April 2004 and February 2006 to determine the blood-feeding pattern of <it>Anopheles </it>mosquitoes in Mwea Kenya.</p> <p>Methods</p> <p>Samples were collected indoors by pyrethrum spay catch and outdoors by Centers for Disease Control light traps and processed for blood meal analysis by an Enzyme-linked Immunosorbent Assay.</p> <p>Results</p> <p>A total of 3,333 blood-fed <it>Anopheles </it>mosquitoes representing four <it>Anopheles </it>species were collected and 2,796 of the samples were assayed, with <it>Anopheles arabiensis </it>comprising 76.2% (n = 2,542) followed in decreasing order by <it>Anopheles coustani </it>8.9% (n = 297), <it>Anopheles pharoensis </it>8.2% (n = 272) and <it>Anopheles funestus </it>6.7% (n = 222). All mosquito species had a high preference for bovine (range 56.3–71.4%) over human (range 1.1–23.9%) or goat (0.1–2.2%) blood meals. Some individuals from all the four species were found to contain mixed blood meals. The bovine blood index (BBI) for <it>An. arabiensis </it>was significantly higher for populations collected indoors (71.8%), than populations collected outdoors (41.3%), but the human blood index (HBI) did not differ significantly between the two populations. In contrast, BBI for indoor collected <it>An. funestus </it>(51.4%) was significantly lower than for outdoor collected populations (78.0%) and the HBI was significantly higher indoors (28.7%) than outdoors (2.4%). Anthropophily of <it>An. funestus </it>was lowest within the rice scheme, moderate in unplanned rice agro-ecosystem, and highest within the non-irrigated agro-ecosystem. Anthropophily of <it>An. arabiensis </it>was significantly higher in the non-irrigated agro-ecosystem than in the other agro-ecosystems.</p> <p>Conclusion</p> <p>These findings suggest that rice cultivation has an effect on host choice by <it>Anopheles </it>mosquitoes. The study further indicate that zooprophylaxis may be a potential strategy for malaria control, but there is need to assess how domestic animals may influence arboviruses epidemiology before adapting the strategy.</p

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

The Role of organisational and cultural factors in the implementation of systemwide interventions in acute hospitals to improve patient outcomes : protocol for a systematic literature review

Introduction: Little is known about the role of the organisational culture in the success and sustainability of the hospital-wide interventions, and how local culture affects patient outcomes in acute hospitals. Methods and analysis: A systematic literature review will be conducted to identify organisational factors influencing hospital-wide interventions and patient outcomes. A search of English language articles will be performed in MEDLINE, CINAHL, EMBASE, Web of Science, PsychInfo and Global Health databases using Medical Subject Headings and keywords. Randomised controlled trials, quasi-randomised trials, controlled before and after design studies and interrupted timeseries analysis studies will be included. 'Grey literature' will be excluded, however peer-reviewed journals that are likely to publish relevant studies (JAMA, BMJ, BMJ Quality and Safety, Lancet and New England Journal of Medicine and Implementation Science) will be hand searched for the last 5 years. Two reviewers will independently undertake a title and abstract review using inclusion and exclusion criteria. Studies will be excluded only after discussion between at least two reviewers, who will assess and agree on the inclusion, risk of bias and quality rating of the studies. One author will extract summary descriptive data from these studies; the other author will review this documentation for accuracy and completeness. Results: It is likely that the studies will be heterogeneous in nature, therefore a narrative synthesis of the findings will be conducted. Conclusions: We will discuss characteristics of the studies and stratify the results according to the type of hospital-wide interventions, organisational factors associated with them and outcomes measured.5 page(s