Testing for hepatitis C virus infection in UK prisons: what actually happens?

Prisons are a key demographic in the drive to eradicate hepatitis C virus (HCV) as a major public health threat. We have assessed the impact of the recently introduced national opt-out policy on the current status of HCV testing in 14 prisons in the East Midlands (UK). We analysed testing rates pre- and post-introduction of opt-out testing, together with face-to-face interviews with prison healthcare and management staff in each prison.In the year pre-opt-out, 1,972 people in prison (PIP) were tested, compared to 3440 in the year following opt-out. From July 2016 – June 2017, 2706 people were tested, representing 13.5% of all prison entrants (median 16.6%, range 7.6% to 40.7%). Factors correlating with testing rates were: pre-admission location of the PIP (another prison or the community, OR 2.2, 95% CI 1.9-2.3, p less than 0.001); whether the PIP could access healthcare independently of prison officers (OR 1.7, 95% CI 1.5-1.8, p less than 0.001); an absence of out-reach services for HCV treatment (OR 1.3, 95% CI 1.2-1.5, p less than 0.001), whether >50% of PIP reported ease of access to a nurse (OR 2.0, 95% CI 1.8-2.2, p less than 0.001), and whether prison healthcare was supplied by private or NHS providers (OR 1.3, 95% CI 1.2-1.5, p less than 0.001).Testing rates remained far below the minimum national opt-out target of 50%. Inadequacy of healthcare facilities and constraints imposed by adherence to prison regimens were cited by healthcare and management staff at all prisons. Without radical change, the prison estate may be intrinsically incapable of supporting NHSE to deliver the HCV elimination strategy

A randomized trial of an Asthma Internet Self-management Intervention (RAISIN): study protocol for a randomized controlled trial

<b>Background</b><p></p> The financial costs associated with asthma care continue to increase while care remains suboptimal. Promoting optimal self-management, including the use of asthma action plans, along with regular health professional review has been shown to be an effective strategy and is recommended in asthma guidelines internationally. Despite evidence of benefit, guided self-management remains underused, however the potential for online resources to promote self-management behaviors is gaining increasing recognition. The aim of this paper is to describe the protocol for a pilot evaluation of a website 'Living well with asthma' which has been developed with the aim of promoting self-management behaviors shown to improve outcomes.<p></p> <b>Methods</b><p></p> The study is a parallel randomized controlled trial, where adults with asthma are randomly assigned to either access to the website for 12 weeks, or usual asthma care for 12 weeks (followed by access to the website if desired). Individuals are included if they are over 16-years-old, have a diagnosis of asthma with an Asthma Control Questionnaire (ACQ) score of greater than, or equal to 1, and have access to the internet. Primary outcomes for this evaluation include recruitment and retention rates, changes at 12 weeks from baseline for both ACQ and Asthma Quality of Life Questionnaire (AQLQ) scores, and quantitative data describing website usage (number of times logged on, length of time logged on, number of times individual pages looked at, and for how long). Secondary outcomes include clinical outcomes (medication use, health services use, lung function) and patient reported outcomes (including adherence, patient activation measures, and health status).<p></p> <b>Discussion</b><p></p> Piloting of complex interventions is considered best practice and will maximise the potential of any future large-scale randomized controlled trial to successfully recruit and be able to report on necessary outcomes. Here we will provide results across a range of outcomes which will provide estimates of efficacy to inform the design of a future full-scale randomized controlled trial of the 'Living well with asthma' website

The development of the medieval English coronation: From Edgar to Edward II

Thesis (B.A.) in History -- University of Illinois at Urbana-Champaign, 1987.Bibliography: leaves 77-80.Microfiche of typescript. [Urbana, Ill.]: Photographic Services, University of Illinois, U of I Library, [1987]. 2 microfiches (87 frames): negative

A feasibility study of paired Continuous Glucose Monitoring (CGM) intra-partum and in the newborn in pregnancies complicated by Type 1 Diabetes

Aim: To describe the continuous glucose monitoring (CGM) profiles of type 1 diabetes (T1D) offspring in the early neonatal period and its association with maternal intrapartum glucose control. Methods: A prospective observational study of T1D pregnant women and their neonatal offspring. Women had a CGM sensor inserted 2-3 days prior to delivery. Infants had a masked CGM sensor inserted as soon as possible following delivery. Maternal glycaemic outcomes were time-in-target (70-140 mg/dL [3.9-7.8 mmol/L]), hyperglycaemia >140 mg/dL (7.8 mmol/L) and mean CGM glucose during the 24 hours preceding delivery. Neonatal outcomes included lowest recorded blood glucose concentration, and CGM measures (glucose 140 mg/dL (7.8 mmol/L), and 9 (9) % time < 70 mg/dL (3.9 mmol/L) with mean (SD) CGM glucose 113 (9) mg/dL (6.3 [0.7] mmol/L). 15 infants (93.8%) had ≥1 blood glucose concentration < 47 mg/dL (2.6 mmol/L) and five had ≥1 blood glucose concentration < 18 mg/dL (1.0 mmol/L). The mean infant CGM glucose on days 1, 2, and 3 of life was 63 (14), 67 (13), 76 (11) mg/dL (3.5 [0.8], 3.7 [0.7], and 4.2 [0.6] mmol/L). Four infants (25%) spent more than 50% time with CGM glucose levels < 47 mg/dL (2.6 mmol/L) on day 1. Conclusions: CGM detected widespread neonatal hypoglycaemia, even among mothers with good intrapartum glucose control

Feasibility of Automated Insulin Delivery Guided by Continuous Glucose Monitoring in preterm infants

Abstract: Objective: Closed-loop systems have been used to optimise insulin delivery in children with diabetes, but they have not been tested in neonatal intensive care. Extremely preterm infants are prone to hyperglycaemia and hypoglycaemia; both of which have been associated with adverse outcomes. Insulin sensitivity is notoriously variable in these babies and glucose control is time-consuming, with management requiring frequent changes of dextrose-containing fluids and careful monitoring of insulin treatment. We aimed to evaluate the feasibility of closed-loop management of glucose control in these infants. Design and Setting: Single centre feasibility study with a randomized parallel design in a neonatal intensive care unit. Eligibility criteria included birth weight <1200g and <48hours of age. All infants had subcutaneous continuous glucose monitoring for the first week of life, with those in the intervention group receiving closed-loop insulin delivery in a pre-specified window, between 48 and 72hours of age during which time the primary outcome was percentage of time in target (sensor glucose 4-8mmol/l). Results: The mean (SD) gestational age and birth weight of intervention and control study arms were 27.0(2.4) weeks, 962(164) g and 27.5(2.8) weeks, 823(282) g respectively, and were not significantly different. The time in target was dramatically increased from median (IQR) 26%(6, 64) with paper guidance to 91%(78, 99) during closed loop (p<0.001). There were no serious adverse events and no difference in total insulin infused. Conclusions: Closed-loop glucose control based on subcutaneous glucose measurements appears feasible as a potential method of optimizing glucose control in extremely preterm infants.Funding was provided by the Evelyn Trust, the National Institute of Health Research EME Program and the National Institute of Health Research Cambridge Biomedical Research Centre. Medtronic provided the continuous glucose monitoring system and sensors. Medtronic had no role in design of the study, the gathering of data, access to data, preparation of the manuscript or decision to publish the results

Serum phosphate and social deprivation independently predict all-cause mortality in chronic kidney disease

Background: Hyperphosphataemia is linked to cardiovascular disease and mortality in chronic kidney disease (CKD). Outcome in CKD is also affected by socioeconomic status. The objective of this study was to assess the associations between serum phosphate, multiple deprivation and outcome in CKD patients. Methods: All adult patients currently not on renal replacement therapy (RRT), with first time attendance to the renal outpatient clinics in the Glasgow area between July 2010 and June 2014, were included in this prospective study. Area socioeconomic status was assessed as quintiles of the Scottish Index of Multiple Deprivation (SIMD). Outcomes were all-cause and cardiovascular mortality and commencement of RRT. Results: The cohort included 2950 patients with a median (interquartile range) age 67.6 (53.6–76.9) years. Median (interquartile range) eGFR was 38.1 (26.3–63.5) ml/min/1.73 m 2 , mean (±standard deviation) phosphate was 1.13 (±0.24) mmol/L and 31.6 % belonged to the most deprived quintile (SIMD quintile I). During follow-up 375 patients died and 98 commenced RRT. Phosphate &#8805;1.50 mmol/L was associated with all-cause (hazard ratio (HR) 2.51; 95 % confidence interval (CI) 1.63-3.89) and cardiovascular (HR 5.05; 95 % CI 1.90–13.46) mortality when compared to phosphate 0.90–1.09 mmol/L in multivariable analyses. SIMD quintile I was independently associated with all-cause mortality. Phosphate did not weaken the association between deprivation index and mortality, and there was no interaction between phosphate and SIMD quintiles. Neither phosphate nor SIMD predicted commencement of RRT. Conclusions Multiple deprivation and serum phosphate were strong, independent predictors of all-cause mortality in CKD and showed no interaction. Phosphate also predicted cardiovascular mortality. The results suggest that phosphate lowering should be pursued regardless of socioeconomic status

Population pharmacokinetics of a single daily intramuscular dose of gentamicin in children with severe malnutrition

Article published in Journal of Antimicrobial ChemotherapyObjectives: The World Health Organization recommends that all children admitted with severe malnutrition should routinely receive parenteral ampicillin and gentamicin; despite this, mortality remains high. Since this population group is at risk of altered volume of distribution, we aimed to study the population pharmacokinetics of once daily gentamicin (7.5 mg/kg) in children with severe malnutrition and to evaluate clinical factors affecting pharmacokinetic parameters. Methods: Thirty-four children aged 0.5–10 years were studied. One hundred and thirty-two gentamicin concentrations (median of four per patient), drawn 0.4–24.6 h after administration of the intramuscular dose, were analysed. The data were fitted by a two-compartment model using the population package NONMEMw. Results: Gentamicin was rapidly absorbed and all concentrations measured within the first 2 h after administration were >8 mg/L (indicating that satisfactory peak concentrations were achieved). Ninetyeight percent of samples measured more than 20 h after the dose were <1 mg/L. The best model included weight, and it was found that high base deficit, high creatinine concentration and low temperature (all markers of hypovolaemic shock) reduced clearance (CL/F). Weight influenced volume of the central (V1/F) and peripheral (V2/F) compartments, and high base deficit reduced V2/F and intercompartmental CL (Q/F). Interindividual variability in CL was 26%, in V1/F 33% and in V2/F and Q/F was 52%. Individual estimates of CL/F ranged from 0.02 to 0.16 (median 0.10) L/h/kg and those of Vss/F from 0.26 to 1.31 (median 0.67) L/kg. Initial half-lives had a median of 1.4 h and elimination half-lives and a median of 14.9 h. Excessive concentrations were observed in one patient who had signs of renal impairment and shock. Conclusions: Although a daily dose of 7.5 mg/kg achieves satisfactory gentamicin concentrations in the majority of patients, patients with renal impairment and shock may be at risk of accumulation with 24 hourly dosing. Further studies of gentamicin pharmacokinetics in this group are now needed to inform future international guideline recommendations

Risk factors of ischemic stroke and subsequent outcome in hemodialysis patients

Background and purpose: End stage renal disease (ESRD) requiring hemodialysis (HD) carries up to a 10-fold greater risk of stroke than normal renal function. Knowledge concerning risk factors and management strategies derived from the general population may not be applicable to those with ESRD. We studied a large ESRD population to identify risk factors and outcomes for stroke. Methods: All adult patients receiving HD for ESRD from 01/01/2007 to 31/12/2012 were extracted from the electronic patient record. Variables associated with stroke were identified by survival analysis; demographic, clinical, imaging and dialysis related variables were assessed and case-fatality determined. Follow-up was until 31/12/2013. Results: 1382 patients were identified (mean age 60.5 years, 58.5% male). The prevalence of AF was 21.2% and 59.4% were incident HD patients. 160 (11.6%) experienced a stroke during 3471 patient-years of follow-up (95% ischemic). Stroke incidence was 41.5/1000 patient-years in prevalent and 50.1/1000 patient-years in incident HD patients. Factors associated with stroke on regression analysis were prior stroke, diabetes and age at starting renal replacement therapy. AF was not significantly associated with stroke and warfarin did not affect stroke risk in warfarin treated patients. Fatality was 18.8% at 7, 26.9% at 28 and 56.3% 365 days after stroke.&lt;p&gt;&lt;/p&gt; Conclusions: Incidence of stroke is high in patients with ESRD on HD with high case-fatality. Incident HD patients had the highest stroke incidence. Many, but not all, important risk factors commonly associated with stroke in the general population were not associated with stroke in patients receiving HD

A ROLE FOR RESEARCH IN INITIAL TEACHER EDUCATION ADMISSIONS: A CASE STUDY FROM ONE CANADIAN UNIVERSITY

This article argues for the importance of broad and on-going research to support initial or pre-service teacher education program admissions. Examples from a large initial teacher education program at one Canadian university illustrate the contributions of research to the evaluation and refinement of admission processes. These examples include anonymous surveys and confidential interviews of current pre-service teachers about their experiences of answering application questions about their social identity, how they decided to apply to and attend the program, and their expectations of teacher education and teaching. Research studies about the perspectives of and agreement among the application raters are also discussed. Finally, how the operational needs of the admission processes shape the research agenda and the emerging research findings in turn shape the admission processes is explored

Identification of Klebsiella capsule synthesis loci from whole genome data.

Klebsiella pneumoniae is a growing cause of healthcare-associated infections for which multi-drug resistance is a concern. Its polysaccharide capsule is a major virulence determinant and epidemiological marker. However, little is known about capsule epidemiology since serological typing is not widely accessible and many isolates are serologically non-typeable. Molecular typing techniques provide useful insights, but existing methods fail to take full advantage of the information in whole genome sequences. We investigated the diversity of the capsule synthesis loci (K-loci) among 2503 K. pneumoniae genomes. We incorporated analyses of full-length K-locus nucleotide sequences and also clustered protein-encoding sequences to identify, annotate and compare K-locus structures. We propose a standardized nomenclature for K-loci and present a curated reference database. A total of 134 distinct K-loci were identified, including 31 novel types. Comparative analyses indicated 508 unique protein-encoding gene clusters that appear to reassort via homologous recombination. Extensive intra- and inter-locus nucleotide diversity was detected among the wzi and wzc genes, indicating that current molecular typing schemes based on these genes are inadequate. As a solution, we introduce Kaptive, a novel software tool that automates the process of identifying K-loci based on full locus information extracted from whole genome sequences (https://github.com/katholt/Kaptive). This work highlights the extensive diversity of Klebsiella K-loci and the proteins that they encode. The nomenclature, reference database and novel typing method presented here will become essential resources for genomic surveillance and epidemiological investigations of this pathogen