What causes the burden of stroke in Scotland? A comparative risk assessment approach linking the Scottish Health Survey to administrative health data

Background: The availability of robust evidence to inform effective public health decision making is becoming increasingly important, particularly in a time of competing health demands and limited resources. Comparative Risk Assessments (CRA) are useful in this regard as they quantify the contribution of modifiable exposures to the disease burden in a population. The aim of this study is to assess the contribution of a range of modifiable exposures to the burden of disease due to stroke, an important public health problem in Scotland. Methods: We used individual-level response data from eight waves (1995–2012) of the Scottish Health Survey linked to acute hospital discharge records from the Scottish Morbidity Record 01 (SMR01) and cause of death records from the death register. Stroke was defined using the International Classification of Disease (ICD) 9 codes 430–431, 433–4 and 436; and the ICD10 codes I60-61 and I63-64 and stroke incidence was defined as a composite of an individual’s first hospitalisation or death from stroke. A literature review identified exposures causally linked to stroke. Exposures were mapped to the layers of the Dahlgren & Whitehead model of the determinants of health and Population Attributable Fractions were calculated for each exposure deemed a significant causal risk of stroke from a Cox Proportional Hazards Regression model. Population Attributable Fractions were not summed as they may add to more than 100% due to the possibility of a person being exposed to more than one exposure simultaneously. Results: Overall, the results suggest that socioeconomic factors explain the largest proportion of incident stroke hospitalisations and deaths, after adjustment for confounding. After DAG adjustment, low education explained 38.8% (95% Confidence Interval 26.0% to 49.4%, area deprivation (as measured by the Scottish Index of Multiple Deprivation) 34.9% (95% CI 26.4 to 42.4%), occupational social class differences 30.3% (95% CI 19.4% to 39.8%), high systolic blood pressure 29.6% (95% CI 20.6% to 37.6%), smoking 25.6% (95% CI 17.9% to 32.6%) and area deprivation (as measured by the Carstairs area deprivation Index) 23.5% (95% CI 14.4% to 31.7%), of incident strokes in Scotland after adjustment. Conclusion: This study provides evidence for prioritising interventions that tackle socioeconomic inequalities as a means of achieving the greatest reduction in avoidable strokes in Scotland. Future work to disentangle the proportion of the effect of deprivation transmitted through intermediate mediators on the pathway between socioeconomic inequalities and stroke may offer additional opportunities to reduce the incidence of stroke in Scotland

Central venous access devices for the delivery of systemic anticancer therapy: an economic evaluation

Objectives: Patients undergoing long-term anti-cancer therapy typically require one of three venous access devices (VADs): HICK, PICC, or PORT. Recent evidence has shown PORT is safer and improves patient satisfaction. However, PORT did not show improvement in quality-adjusted life years (QALYs) and was more expensive. Decisions regarding cost-effectiveness in the UK are typically informed by a cost-per-QALY metric. However, this approach is limited in its ability to capture the full range of relevant outcomes, especially in the context of medical devices. This study assessed the potential cost-effectiveness of HICK, PICC and PORT in routine clinical practice. Methods: Cost-consequence analysis to determine the trade-offs between the following outcomes: complication, infection, non-infection, chemotherapy interruption, unplanned device removals, health utilities, device insertion cost, follow-up cost, and total cost, using data from the CAVA clinical trial. We conducted Value of Implementation analysis of a PORT service. Results: PORT was superior in terms of overall complication rate, compared with both HICK (IRR: 0.422 (95% CI: 0.286 to 0.622)) and PICC (IRR: 0.295 (95% CI: 0.189 to 0.458)) and less likely to lead to an unplanned device removal. There was no difference in chemotherapy interruption or health utilities. Total cost with device in situ was lower on PORT, compared with HICK (£-98.86 (95% CI: -189.20 to -8.53)) and comparable with PICC -£48.57 (95% CI: -164.99 to 67.86)). Value of Implementation analysis found that PORT was likely to be considered cost-effective within the NHS. Conclusion: Decision makers should consider including PORT within the suite of VADs available within in the NHS

What is the potential for plural ownership to support a more inclusive economy? A systematic review protocol

Abstract: Background: The world is facing an unprecedented systemic shock to population health, the economy and society due to the devastating impact of the COVID-19 pandemic. As with most economic shocks, this is expected to disproportionately impact vulnerable groups in society such as those in poverty and those in precarious employment as well as marginalised groups such as women, the elderly, Black, Asian and Minority Ethnic (BAME) groups and those with health conditions. The current literature is rich in normative recommendations on plural ownership as a key building block of an inclusive economy rooted in communities and their needs. There is, however, a need for a rigorous synthesis of the available evidence on what impact (if any) plural ownership may potentially have on the inclusivity of the economy. This review seeks to synthesise and compare the available evidence across the three economic sectors (private, public and third). Methods: We will search eight bibliographic databases (Sociological abstracts, EBSCO Econlit, OVID Embase, OVID Medline, Applied Social Sciences Index and Abstracts (ASSIA), ProQuest Public Health, Web of Science, Research Papers in Economics (Repec) – EconPapers) from the earliest data available in each database until January 2021. Grey literature will be identified from Google (advanced), Google Scholar and 37 organisational websites identified as relevant to the research question. We will include comparative studies of plural ownership from high-income countries that report outcomes on access to opportunities, distribution of benefits, poverty, and discrimination. A bespoke search strategy will be used for each website to account for the heterogeneity in content and search capabilities and will be fully documented. A standardised data extraction template based on the Population-Intervention-Context-Outcome (PICO) template will be developed. We will assess the strength of evidence for different forms of economic ownership identified in relation to the impact of each on the four economic outcomes of interest, paying particular attention to the role of wider contextual factors as they emerge through the evidence. Discussion: The findings of this review are intended to inform policymaking at local, national and international level that prioritises and supports the development of different economic and business models. Systematic review registration: Open Science Framework registration DOI: https://doi.org/10.17605/OSF.IO/BYH5

Venous access devices for the delivery of long-term chemotherapy: the CAVA three-arm RCT

Background: Venous access devices are used for patients receiving long-term chemotherapy. These include centrally inserted tunnelled catheters or Hickman-type devices (Hickman), peripherally inserted central catheters (PICCs) and centrally inserted totally implantable venous access devices (PORTs). Objectives: To evaluate the clinical effectiveness, safety, cost-effectiveness and acceptability of these devices for the central delivery of chemotherapy. Design: An open, multicentre, randomised controlled trial to inform three comparisons: (1) peripherally inserted central catheters versus Hickman, (2) PORTs versus Hickman and (3) PORTs versus peripherally inserted central catheters. Pre-trial and post-trial qualitative research and economic evaluation were also conducted. Setting: This took place in 18 UK oncology centres. Participants: Adult patients (aged ≥ 18 years) receiving chemotherapy (≥ 12 weeks) for either a solid or a haematological malignancy were randomised via minimisation. Interventions: Hickman, peripherally inserted central catheters and PORTs. Primary outcome: A composite of infection (laboratory confirmed, suspected catheter related and exit site infection), mechanical failure, venous thrombosis, pulmonary embolism, inability to aspirate blood and other complications in the intention-to-treat population. Results: Overall, 1061 participants were recruited to inform three comparisons. First, for the comparison of peripherally inserted central catheters (n = 212) with Hickman (n = 212), it could not be concluded that peripherally inserted central catheters were significantly non-inferior to Hickman in terms of complication rate (odds ratio 1.15, 95% confidence interval 0.78 to 1.71). The use of peripherally inserted central catheters compared with Hickman was associated with a substantially lower cost (–£1553) and a small decrement in quality-adjusted life-years gained (–0.009). Second, for the comparison of PORTs (n = 253) with Hickman (n = 303), PORTs were found to be statistically significantly superior to Hickman in terms of complication rate (odds ratio 0.54, 95% confidence interval 0.37 to 0.77). PORTs were found to dominate Hickman with lower costs (–£45) and greater quality-adjusted life-years gained (0.004). This was alongside a lower complications rate (difference of 14%); the incremental cost per complication averted was £1.36. Third, for the comparison of PORTs (n = 147) with peripherally inserted central catheters (n = 199), PORTs were found to be statistically significantly superior to peripherally inserted central catheters in terms of complication rate (odds ratio 0.52, 95% confidence interval 0.33 to 0.83). PORTs were associated with an incremental cost of £2706 when compared with peripherally inserted central catheters and a decrement in quality-adjusted life-years gained (–0.018) PORTs are dominated by peripherally inserted central catheters: alongside a lower complications rate (difference of 15%), the incremental cost per complication averted was £104. The qualitative work showed that attitudes towards all three devices were positive, with patients viewing their central venous access device as part of their treatment and recovery. PORTs were perceived to offer unique psychological benefits, including a greater sense of freedom and less intrusion in the context of personal relationships. The main limitation was the lack of adequate power (54%) in the non-inferiority comparison between peripherally inserted central catheters and Hickman. Conclusions: In the delivery of long-term chemotherapy, peripherally inserted central catheters should be considered a cost-effective option when compared with Hickman. There were significant clinical benefits when comparing PORTs with Hickman and with peripherally inserted central catheters. The health economic benefits were less clear from the perspective of incremental cost per quality-adjusted life-years gained. However, dependent on the willingness to pay, PORTs may be considered to be cost-effective from the perspective of complications averted. Future work: The deliverability of a PORTs service merits further study to understand the barriers to and methods of improving the service. Trial registration: This trial is registered as ISRCTN44504648. Funding: This project was funded by the National Institute for Health Research (NHIR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 47. See the NIHR Journals Library website for further project information

Cediranib combined with carboplatin and paclitaxel in patients with metastatic or recurrent cervical cancer (CIRCCa): a randomised, double-blind, placebo-controlled phase 2 trial

Background: Patients treated with standard chemotherapy for metastatic or relapsed cervical cancer respond poorly to conventional chemotherapy (response achieved in 20–30% of patients) with an overall survival of less than 1 year. High tumour angiogenesis and high concentrations of intratumoural VEGF are adverse prognostic features. Cediranib is a potent tyrosine kinase inhibitor of VEGFR1, 2, and 3. In this trial, we aimed to assess the effect of the addition of cediranib to carboplatin and paclitaxel chemotherapy in patients with metastatic or recurrent cervical cancer. Methods: In this randomised, double-blind, placebo-controlled phase 2 trial, which was done in 17 UK cancer treatment centres, patients aged 18 years or older initially diagnosed with metastatic carcinoma or who subsequently developed metastatic disease or local pelvic recurrence after radical treatment that was not amenable to exenterative surgery were recruited. Eligible patients received carboplatin AUC of 5 plus paclitaxel 175 mg/m2 by infusion every 3 weeks for a maximum of six cycles and were randomised centrally (1:1) through a minimisation approach to receive cediranib 20 mg or placebo orally once daily until disease progression. The stratification factors were disease site, disease-free survival after primary therapy or primary stage IVb disease, number of lines of previous treatment, Eastern Cooperative Oncology Group performance status, and investigational site. All patients, investigators, and trial personnel were masked to study drug allocation. The primary endpoint was progression-free survival. Efficacy analysis was by intention to treat, and the safety analysis included all patients who received at least one dose of study drug. This trial is registered with the ISCRTN registry, number ISRCTN23516549, and has been completed. Findings: Between Aug 19, 2010, and July 27, 2012, 69 patients were enrolled and randomly assigned to cediranib (n=34) or placebo (n=35). After a median follow-up of 24·2 months (IQR 21·9–29·5), progression-free survival was longer in the cediranib group (median 8·1 months [80% CI 7·4–8·8]) than in the placebo group (6·7 months [6·2–7·2]), with a hazard ratio (HR) of 0·58 (80% CI 0·40–0·85; one-sided p=0·032). Grade 3 or worse adverse events that occurred in the concurrent chemotherapy and trial drug period in more than 10% of patients were diarrhoea (five [16%] of 32 patients in the cediranib group vs one [3%] of 35 patients in the placebo group), fatigue (four [13%] vs two [6%]), leucopenia (five [16%] vs three [9%]), neutropenia (10 [31%] vs four [11%]), and febrile neutropenia (five [16%] vs none). The incidence of grade 2–3 hypertension was higher in the cediranib group than in the control group (11 [34%] vs four [11%]). Serious adverse events occurred in 18 patients in the placebo group and 19 patients in the cediranib group. Interpretation: Cediranib has significant efficacy when added to carboplatin and paclitaxel in the treatment of metastatic or recurrent cervical cancer. This finding was accompanied by an increase in toxic effects (mainly diarrhoea, hypertension, and febrile neutropenia)

Hepatitis A, B and C prevalence among transgender women and travestis in five Brazilian capitals between 2019-2021.

OBJECTIVE: To estimate the prevalence and factors associated with hepatitis A, B, and C in transgender women and travestis's networks, in 5 regions of Brazil. METHODS: This cross-sectional study includedtransgender women and travestis in five Brazilian capitals (Campo Grande, Manaus, Porto Alegre, Salvador, and São Paulo), between December/2019 and July/2021. All samples were subjected to detection of serological markers of hepatitis virus A (HAV), B (HBV), and C (HCV) infections through rapid tests and chemiluminescent microparticle immunoassays. Positive samples in the screening tests were submitted to detect HBV DNA and HCV-RNA by real-time PCR and genotyped by Sanger sequencing. RESULTS: Analysis of 1,317 samples showed network prevalence rates of 69.1%, 25.1%, and 1.5% for HAV, HBV, and HCV exposure, respectively. A high susceptibility rate to HBV infection (35.7%) and low prevalence of vaccine response markers (40%) were also observed. Age greater than 26 years, self-declared black/brown skin color, having only primary education, history of incarceration, and use of a condom in the last sexual intercourse with a casual partner were associated with total anti-HAV. Exposure to HBV was associated with age greater than 26 years, self-declared black/brown, history of being a sex worker, and incarceration. Age > 37 years, history of sexual abuse, and frequent alcohol consumption were associated with hepatitis C infection. CONCLUSION: The highest prevalence of HAV in this population was found in the North and Northeast regions, and the prevalence found was higher than that in the general population, suggesting greater vulnerability. The prevalence of HCV infection in our study was similar to that observed in the general population

A polymerase chain reaction (PCR) assay for the detection of inoculum of Sclerotinia sclerotiorum

The development of a polymerase chain reaction (PCR) assay for the detection of inoculum of the plant pathogenic fungus Sclerotinia sclerotiorum is described. The PCR primers were designed using nuclear ribosomal DNA internal transcribed spacer sequences. Specific detection of DNA from S. sclerotiorum was possible even in the presence of a 40-fold excess of DNA from the closely related fungus Botrytis cinerea. PCR products were obtained from suspensions of untreated S. sclerotiorum ascospores alone, but DNA purification was required for detection in the presence of large numbers of B. cinerea conidiospores. Specific detection of inoculum of S. sclerotiorum was possible in field-based air-samples, using a Burkard spore trap, and from inoculated oilseed rape petals. The assay has potential for incorporation into a risk management system for S. sclerotiorum in oilseed rape cropsPeer reviewe

Methods for integrated air sampling and DNA analysis for detection of airborne fungal spores

Integrated air sampling and PCR-based methods for detecting airborne fungal spores, using Penicillium roqueforti as a model fungus, are described, P, roqueforti spores were collected directly into Eppendorf tubes using a miniature cyclone-type air sampler. They were then suspended in 0.1% Nonidet P-40, and counted using microscopy, Serial dilutions of the spores were made. Three methods were used to produce DNA for PCR tests: adding untreated spores to PCRs, disrupting spores (fracturing of spore walls to release the contents) using Ballotini beads, and disrupting spores followed by DNA purification. Three P. roqueforti-specific assays were tested: single-step PCR, nested PCR, and PCR followed by Southern blotting and probing. Disrupting the spores was found to be essential for achieving maximum sensitivity of the assay. Adding untreated spores to the PCR did allow the detection of P, roqueforti, but this was never achieved when fewer than 1,000 spores were added to the PCR, By disrupting the spores, with or without subsequent DNA purification, it was possible to detect DNA from a single spore. When known quantities of P, roqueforti spores were added to air samples consisting of high concentrations of unidentified fungal spores, pollen, and dust, detection sensitivity was reduced. P. roqueforti DNA could not be detected using untreated or disrupted spore suspensions added to the PCRs. However, using purified DNA it was possible to detect 10 P. roqueforti spores in a background of 4,500 other spores. For all DNA extraction methods, nested PCR was more sensitive than single-step PCR or PCR followed by Southern blotting.Peer reviewe

Detection of airborne fungal spores sampled by rotating-arm and Hirst-type spore traps using polymerase chain reaction assays

Conventional methods for detecting airborne fungal spores rely on either optical identification or culturing and can be time consuming or unreliable. A method for purifying DNA from conventional spore samplers and detecting it using polymerase chain reaction (PCR) assays is described. Experiments were done using Penicillium roqueforti. As few as 10 spores could be detected in the PCR and P. roqueforti spores were detected in a background of spores of six other unrelated species. The method successfully detected P. roqueforti spores collected by rotating arm and Hirst-type spore traps in wind tunnel tests. The tests suggested that the detection limit was about 10 spores or less in the PCR. Fungal spores were also detected in air samples collected in Mexico City using fungal consensus primers, with a detection limit of about 200 spores in the PCR. The potential for using PCR-assays in conjunction with impactor samplers is discussed. (C) 2001 Elsevier Science Ltd. All rights reserved.Peer reviewe

How much of the stalled mortality trends in Scotland and England can be attributed to obesity?

OBJECTIVES: The rate of improvement in all-cause mortality rates has slowed in the UK since around 2012. While evidence suggests that UK Government ‘austerity’ policies have been largely responsible, it has been proposed that rising obesity may also have contributed. The aim here was to estimate this contribution for Scotland and England. METHODS: We calculated population attributable fractions (PAFs) resulting from changes in Body Mass Index (BMI) between the mid-1990s and late 2000s for all-cause mortality among 35–89-year olds in 2017–2019. We used BMI data from national surveys (the Scottish Health Survey and the Health Survey for England), and HRs from a meta-analysis of 89 European studies. PAFs were applied to mortality data for 2017–2019 (obtained from national registries), enabling comparison of observed rates, BMI-adjusted rates and projected rates. Uncertainty in the estimates is dominated by the assumptions used and biases in the underlying data, rather than random variation. A series of sensitivity analyses and bias assessments were therefore undertaken to understand the certainty of the estimates. RESULTS: In Scotland, an estimated 10% (males) and 14% (females) of the difference between observed and predicted mortality rates in 2017–2019 may be attributable to previous changes in BMI. The equivalent figures for England were notably higher: 20% and 35%, respectively. The assessments of bias suggest these are more likely to be overestimates than underestimates. CONCLUSIONS: Some of the recent stalled mortality trends in Scotland and England may be associated with earlier increases in obesity. Policies to reduce the obesogenic environment, including its structural and commercial determinants, and reverse the impacts of austerity, are needed