Adjusted indices of multiple deprivation to enable comparisons within and between constituent countries of the UK including an illustration using mortality rates

OBJECTIVES: Social determinants can have a major impact on health and as a consequence substantial inequalities are seen between and within countries. The study of inequalities between countries relies on having accurate and consistent measures of deprivation across the country borders. However, in the UK most socioeconomic deprivation measures are not comparable between countries. We give a method of adjusting the Indices of Multiple Deprivation (IMD) for use across the UK, describe the deprivation of each UK country, and show the problems introduced by naïvely using country-specific deprivation measures in a UK-wide analysis of mortality rates. SETTING/PARTICIPANTS: 42 148 geographic areas covering the population of the UK. OUTCOME MEASURES: Adjusted IMD scores based on the income and employment domains of country-specific IMD scores, adjusting for the contribution of other domains. The mortality rate among people aged under 75 years standardised to the UK age structure was compared between country-specific and UK-adjusted IMD quintiles. RESULTS: Of the constituent countries of the UK, Northern Ireland was the most deprived with 37% of the population living in areas in the most deprived fifth of the UK, followed by Wales with 22% of the population living in the most deprived fifth of the UK. England and Scotland had similar levels of deprivation. Deprivation-specific mortality rates were similar in England and Wales. Northern Ireland had lower mortality rates than England for each deprivation group, with similar differences for each group. Scotland had higher mortality rates than England for each deprivation group, with larger differences for more deprived groups. CONCLUSIONS: Analyses of between-country and within-country inequalities by socioeconomic position should use consistent measures; failing to use consistent measures may give misleading results. The published adjusted IMD scores we describe allow consistent analysis across the UK

A retrospective cohort study assessing patient characteristics and the incidence of cardiovascular disease using linked routine primary and secondary care data

This is the final version. Available from the publisher via the DOI in this record.Objectives: Data linkage combines information from several clinical data sets. The authors examined whether coding inconsistencies for cardiovascular disease between components of linked data sets result in differences in apparent population characteristics. Design: Retrospective cohort study. Setting: Routine primary care data from 40 Scottish general practitioner (GP) surgeries linked to national hospital records. Participants: 240 846 patients, aged 20 years or older, registered at a GP surgery. Outcomes: Cases of myocardial infarction, ischaemic heart disease and stroke (cerebrovascular disease) were identified from GP and hospital records. Patient characteristics and incidence rates were assessed for all three clinical outcomes, based on GP, hospital, paired GP/hospital (similar diagnoses recorded simultaneously in both data sets) or pooled GP/hospital records (diagnosis recorded in either or both data sets). Results: For all three outcomes, the authors found evidence (p<0.05) of different characteristics when using different methods of case identification. Prescribing of cardiovascular medicines for ischaemic heart disease was greatest for cases identified using paired records (p≤0.013). For all conditions, 30-day case fatality rates were higher for cases identified using hospital compared with GP or paired data, most noticeably for myocardial infarction (hospital 20%, GP 4%, p=0.001). Incidence rates were highest using pooled GP/hospital data and lowest using paired data. Conclusions: Differences exist in patient characteristics and disease incidence for cardiovascular conditions, depending on the data source. This has implications for studies using routine clinical data

Improved protocols for functional analysis in the pathogenic fungus Aspergillus flavus

<p>Abstract</p> <p>Background</p> <p>An available whole genome sequence for <it>Aspergillus flavus </it>provides the opportunity to characterize factors involved in pathogenicity and to elucidate the regulatory networks involved in aflatoxin biosynthesis. Functional analysis of genes within the genome is greatly facilitated by the ability to disrupt or mis-express target genes and then evaluate their result on the phenotype of the fungus. Large-scale functional analysis requires an efficient genetic transformation system and the ability to readily select transformants with altered expression, and usually requires generation of double (or multi) gene deletion strains or the use of prototrophic strains. However, dominant selectable markers, an efficient transformation system and an efficient screening system for transformants in <it>A. flavus </it>are absent.</p> <p>Results</p> <p>The efficiency of the genetic transformation system for <it>A. flavus </it>based on uracil auxotrophy was improved. In addition, <it>A. flavus </it>was shown to be sensitive to the antibiotic, phleomycin. Transformation of <it>A. flavus </it>with the <it>ble </it>gene for resistance to phleomycin resulted in stable transformants when selected on 100 μg/ml phleomycin. We also compared the phleomycin system with one based on complementation for uracil auxotrophy which was confirmed by uracil and 5-fluoroorotic acid selection and via transformation with the <it>pyr4 </it>gene from <it>Neurospora crassa </it>and <it>pyrG </it>gene from <it>A. nidulans </it>in <it>A. flavus </it>NRRL 3357. A transformation protocol using <it>pyr4 </it>as a selectable marker resulted in site specific disruption of a target gene. A rapid and convenient colony PCR method for screening genetically altered transformants was also developed in this study.</p> <p>Conclusion</p> <p>We employed phleomycin resistance as a new positive selectable marker for genetic transformation of <it>A. flavus</it>. The experiments outlined herein constitute the first report of the use of the antibiotic phleomycin for transformation of <it>A. flavus</it>. Further, we demonstrated that this transformation protocol could be used for directed gene disruption in <it>A. flavus</it>. The significance of this is twofold. First, it allows strains to be transformed without having to generate an auxotrophic mutation, which is time consuming and may result in undesirable mutations. Second, this protocol allows for double gene knockouts when used in conjunction with existing strains with auxotrophic mutations.</p> <p>To further facilitate functional analysis in this strain we developed a colony PCR-based method that is a rapid and convenient method for screening genetically altered transformants. This work will be of interest to those working on molecular biology of aflatoxin metabolism in <it>A. flavus</it>, especially for functional analysis using gene deletion and gene expression.</p

ACE inhibitor and angiotensin receptor-II antagonist prescribing and hospital admissions with acute kidney injury:a longitudinal ecological study

BACKGROUND: ACE Inhibitors (ACE-I) and Angiotensin-Receptor Antagonists (ARAs) are commonly prescribed but can cause acute kidney injury (AKI) during intercurrent illness. Rates of hospitalization with AKI are increasing. We aimed to determine whether hospital AKI admission rates are associated with increased ACE-I/ARA prescribing. METHODS AND FINDINGS: English NHS prescribing data for ACE-I/ARA prescriptions were matched at the level of the general practice to numbers of hospital admissions with a primary diagnosis of AKI. Numbers of prescriptions were weighted for the demographic characteristics of general practices by expressing prescribing as rates where the denominator is Age, Sex, and Temporary Resident Originated Prescribing Units (ASTRO-PUs). We performed a mixed-effect Poisson regression to model the number of admissions for AKI occurring in each practice for each of 4 years from 1/4/2007. From 2007/8-2010/11, crude AKI admission rates increased from 0.38 to 0.57 per 1000 patients (51.6% increase), and national annual ACE-I/ARA prescribing rates increased by 0.032 from 0.202 to 0.234 (15.8% increase). There was strong evidence (p<0.001) that increases in practice-level prescribing of ACE-I/ARA over the study period were associated with an increase in AKI admission rates. The increase in prescribing seen in a typical practice corresponded to an increase in admissions of approximately 5.1% (rate ratio = 1.051 for a 0.03 per ASTRO-PU increase in annual prescribing rate, 95%CI 1.047-1.055). Using the regression model we predict that 1,636 (95%CI 1,540-1,780) AKI admissions would have been avoided if prescribing rates were at the 2007/8 level, equivalent to 14.8% of the total increase in AKI admissions. CONCLUSION: In this ecological analysis, up to 15% of the increase in AKI admissions in England over a 4-year time period is potentially attributable to increased prescribing of ACE-I and ARAs. However, these findings are limited by the lack of patient level data such as indication for prescribing and patient characteristics

How do people with diabetes describe their experiences in primary care? Evidence from 85,760 patients with self-reported diabetes from the English General Practice Patient Survey.

OBJECTIVE: Developing primary care is an important current health policy goal in the U.S. and England. Information on patients' experience can help to improve the care of people with diabetes. We describe the experiences of people with diabetes in primary care and examine how these experiences vary with increasing comorbidity. RESEARCH DESIGN AND METHODS: Using data from 906,578 responders to the 2012 General Practice Patient Survey (England), including 85,760 with self-reported diabetes, we used logistic regressions controlling for age, sex, ethnicity, and socioeconomic status to analyze patient experience using seven items covering three domains of primary care: access, continuity, and communication. RESULTS: People with diabetes were significantly more likely to report better experience on six out of seven primary care items than people without diabetes after adjusting for age, sex, ethnicity, and socioeconomic status (adjusted differences 0.88-3.20%; odds ratios [ORs] 1.07-1.18; P < 0.001). Those with diabetes and additional comorbid long-term conditions were more likely to report worse experiences, particularly for access to primary care appointments (patients with diabetes alone compared with patients without diabetes: OR 1.22 [95% CI 1.17-1.28] and patients with diabetes plus three or more conditions compared with patients without diabetes: OR 0.87 [95% CI 0.83-0.91]). CONCLUSIONS: People with diabetes in England report primary care experiences that are at least as good as those without diabetes for most domains of care. However, improvements in primary care are needed for diabetes patients with comorbid long-term conditions, including better access to appointments and improved communication.Diabetes UKThis is the author accepted manuscript. The final version is available from the American Diabetes Association via http://dx.doi.org/10.2337/dc14-109

The accuracy of diagnostic coding for acute kidney injury in England - a single centre study.

BACKGROUND: Acute kidney injury (AKI) is an independent risk factor for mortality and is responsible for a significant burden of healthcare expenditure, so accurate measurement of its incidence is important. Administrative coding data has been used for assessing AKI incidence, and shows an increasing proportion of hospital bed days attributable to AKI. However, the accuracy of coding for AKI and changes in coding over time have not been studied in England. METHODS: We studied a random sample of admissions from 2005 and 2010 where ICD-10 code N17 (acute renal failure) was recorded in the administrative coding data at one acute NHS Foundation Trust in England. Using the medical notes and computerised records we examined the demographic and clinical details of these admissions. RESULTS: Against a 6.3% (95% CI 4.8-7.9%) increase in all non-elective admissions, we found a 64% increase in acute renal failure admissions (95% CI 41%-92%, p < 0.001) in 2010 compared to 2005. Median age was 78 years (IQR 72-87), 11-25% had a relevant pre-admission co-morbidity and 64% (55-73%) were taking drugs known to be associated with AKI. Over both years, 95% (91-99%) of cases examined met the Kidney Disease: Improving Global Outcomes criteria for AKI. CONCLUSIONS: Patients with hospital admissions where AKI has been coded are elderly with multiple co-morbidities. Our results demonstrate a high positive predictive value of coding data for a clinical diagnosis of AKI, with no suggestion of marked changes in coding of AKI between 2005 and 2010.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Nanosecond pulsed electric field thresholds for nanopore formation in neural cells.

The persistent influx of ions through nanopores created upon cellular exposure to nanosecond pulse electric fields (nsPEF) could be used to modulate neuronal function. One ion, calcium (Ca(2+)), is important to action potential firing and regulates many ion channels. However, uncontrolled hyper-excitability of neurons leads to Ca(2+) overload and neurodegeneration. Thus, to prevent unintended consequences of nsPEF-induced neural stimulation, knowledge of optimum exposure parameters is required. We determined the relationship between nsPEF exposure parameters (pulse width and amplitude) and nanopore formation in two cell types: rodent neuroblastoma (NG108) and mouse primary hippocampal neurons (PHN). We identified thresholds for nanoporation using Annexin V and FM1-43, to detect changes in membrane asymmetry, and through Ca(2+) influx using Calcium Green. The ED50 for a single 600 ns pulse, necessary to cause uptake of extracellular Ca(2+), was 1.76  kV/cm for NG108 and 0.84  kV/cm for PHN. At 16.2  kV/cm, the ED50 for pulse width was 95 ns for both cell lines. Cadmium, a nonspecific Ca(2+) channel blocker, failed to prevent Ca(2+) uptake suggesting that observed influx is likely due to nanoporation. These data demonstrate that moderate amplitude single nsPEF exposures result in rapid Ca(2+) influx that may be capable of controllably modulating neurological function

Forage Systems to Optimize Agronomic and Economic Performance in Organic Dairy Systems

Organic dairy production in the USA is growing, but most forage systems research focuses on conventional production practices. As a result, organic dairy producers have limited science-based information to assist with farm and livestock management. The objective of this project was to use a multi-faceted approach to determine the ideal species mixtures for organic dairy production as well as document forage quality, forage yield, soil characteristics, milk production and milk quality during the grazing season. The forages studied ranged from a single species monoculture to a four species mixture of warm and cool season grasses and legumes. Nine distinct forage systems were seeded into small plots at the University of Tennessee and University of Kentucky research farms using organic practices. These plots were monitored for three years for yield, quality, species composition, and soil characteristics. The four best performing forage systems were planted in small paddocks on organic dairy farms in Tennessee and Kentucky to evaluate forage yield, forage quality, seasonality of production, and suitability for on-farm milk production. The superior forage system was established on a 4 ha paddock and compared the existing forage system used by each of the dairy farms. These larger paddocks allowed continued measurements of forage yield and quality, as well as measurements of milk production, milk quality, and grazing behaviour of the animals. The information from this project is currently being incorporated into a total farm management system for organic dairy producers in the Southeastern USA