Towards an integrated blood pressure self-monitoring solution for stroke/TIA in Ireland: a mixed methods feasibility study for the TASMIN5S IRL randomised controlled trial.

BACKGROUND: Optimising blood pressure (BP) control is one of the most important modifiable risk factors in preventing subsequent stroke where the risk increases by one-third for every 10 mmHg rise in systolic BP. This study evaluated the feasibility and potential effectiveness of blood pressure self-monitoring with planned medication titration, to inform a definitive trial of the intervention, in patients with a previous stroke or transient ischaemic attack (TIA). METHODS: Patients with a history of stroke/TIA and sub-optimal BP control were invited to take part in a mixed methods feasibility study for a randomised controlled trial. Those meeting the inclusion criteria with systolic BP >130 mmHg were randomised to a self-monitoring intervention group or usual care group. The intervention involved self-monitoring BP twice a day for 3 days within a 7-day period, every month, following text message reminders. Treatment escalation, based on a pre-agreed plan by the general practitioner (GP) and patient, was initiated according to the results of these readings. Semi-structured interviews were carried out with patients and clinicians and analysed thematically. RESULTS: Of those identified, 47% (32/68) attended for assessment. Of those assessed, 15 were eligible for recruitment and were consented and randomised to the intervention or control group on a 2:1 basis. Of those randomised, 93% (14/15) completed the study and there were no adverse events. Systolic BP was lower in the intervention group at 3 months. Participants found the intervention acceptable and easy to use. GPs found it easy to incorporate into their practice activity without increasing workload. CONCLUSIONS: TASMIN5S, an integrated blood pressure self-monitoring intervention in patients with a previous stroke/TIA, is feasible and safe to deliver in primary care. A pre-agreed three-step medication titration plan was easily implemented, increased patient involvement in their care, and had no adverse effects. This feasibility study provides important information to inform a definitive trial to determine the potential effectiveness of the intervention in patients post-stroke or TIA. TRIAL REGISTRATION: ISRCTN57946500 . Registered on 12/08/2019.

Methane in aquifers and alluvium overlying a coal seam gas region: Gas concentrations and isotopic differentiation.

The detection and attribution of methane in aquifers overlying oil and gas reservoirs has recently gained increasing attention internationally. The Surat Basin, in the Great Artesian Basin (GAB), Australia, hosts a coal seam gas (CSG) reservoir, with feedlots, town water supply, mines and agriculture that extract groundwater from aquifers that underly and overly the gas reservoir. This study aimed to use a multi-isotopic approach to differentiate biogenic methane generated in situ in GAB aquifers and the Condamine Alluvium, from the biogenic CSG produced from the underlying Walloon Coal Measures reservoir, to understand if gas had migrated or not. Dissolved methane (0.001 to 160 mg/l) and total methane concentrations (up to 91,818 ppmv) were measured using closed sampling methods and were higher than from open direct fill sampling (<0.001 to 25.4 mg/l), especially in gassy bores that contain dissolved methane above 10 to 13 mg/l. The CSG production waters and a gassy overlying aquifer bore had the most depleted water isotopes, and also the most enriched δ13C-DIC indicating strong methanogenesis. The majority of aquifers have isotopic signatures (δ13C-DIC, CH4 and CO2) indicating in situ methane production by primary CO2 reduction or fermentation, distinct from secondary microbial CO2 reduction in the CSG reservoir. Fractionation factors support methane production mainly via CO2 reduction, with fermentation in a subset of aquifer samples. The gas wetness parameters (636 to 20,000) are consistent with mainly microbial gases, with low dissolved ethane (max 0.04 mg/l). The majority of aquifer and alluvium samples in this study are consistent with in situ methane production, not migration, however in several gassy bores the methane source could not be clearly identified. This study is broadly applicable to understanding methane sources in aquifers overlying CSG reservoirs.

Introducing Advanced Paramedics into the rural general practice team in Ireland - general practitioners attitudes.

INTRODUCTION: As Ireland's population increases and chronic disease becomes more prevalent, demand on limited general practice services will increase. Nursing roles within general practice are now considered to be standard, yet alternative allied health professional roles are under explored within an Irish context. Allied health personnel such as Advanced Paramedics (APs) may have the capability to provide support to general practice. AIM: To explore General Practitioners' (GPs) attitudes and opinions of integrating Advanced Paramedics (APs) into rural general practice in Ireland. METHODS: A sequential explanatory mixed methodology was adopted. A questionnaire was designed and distributed to a purposeful sample of GPs attending a rural conference followed by semi-structured interviews. Data was recorded and transcribed verbatim and thematically analysed. RESULTS: In total n = 27 GPs responded to the survey and n = 13 GPs were interviewed. The majority of GPs were familiar with APs and were receptive to the concept of closely collaborating with APs within a variety of settings including out-of-hours services, home visits, nursing homes and even roles within the general practice surgery. CONCLUSION: General Practitioner and Advanced Paramedic clinical practice dovetail within many facets of primary care and emergency care. GPs recognise that current rural models are unsustainable and realise the potential of integrating APs into the general practice team to help support and sustain the future of rural general practice services in Ireland. These interviews provided an exclusive, detailed insight into the world of general practice in Ireland that has not been previously documented in this way.

Exercise Compared to Mindfulness for Physical and Mental Wellbeing in Medical Students.

Aim Physical Activity (PA) and Mindfulness-Based Stress Reduction (MBSR) both have positive effects on medical student well-being. The 'MED-WELL' programme is a curricular intervention that combines PA and education on exercise as medicine. This trial evaluates whether there is a mean difference in outcomes of participants of an exercise intervention, the 'MED-WELL' programme, versus a control group which engages in a MBSR programme. Methods All second-year medical students were voluntarily allocated into the intervention or control group. Data on overall health and well-being, sleep quality, loneliness, current level of PA, and confidence in prescribing exercise as medicine was analysed from both groups at baseline and after eight weeks. Results Within groups the intervention and control groups showed statistically significant improvements in overall well-being (p=0.010, p=0.005 respectively) and in sleep quality (p<0.001, p=0.007 respectively). The intervention group had statistically significant improvements in levels of PA (p=0.003) and confidence in prescribing exercise (p<0.001). However, there were no statistically significant differences in changes in outcome measures between groups. Conclusion This study has shown that participants in an exercise intervention, the 'MED-WELL' programme, had similar improvements in overall wellbeing and sleep quality to those in a control group who participated in a MBSR programme of the same duration.

Increased case-finding and uptake of direct-acting antiviral treatment essential for micro-elimination of hepatitis C among people living with HIV: a national record linkage study.

OBJECTIVES: Micro-elimination of hepatitis C virus (HCV) in people living with HIV (PLHIV) and co-infected with HCV has been proposed as a key contribution to the overall goal of HCV elimination. While other studies have examined micro-elimination in HIV-treated cohorts, few have considered HCV micro-elimination among those not treated for HIV or at a national level. METHODS: Through data linkage of national and sentinel surveillance data, we examined the extent of HCV testing, diagnosis and treatment among a cohort of PLHIV in Scotland identified through the national database of HIV-diagnosed individuals, up to the end of 2017. RESULTS: Of 5018 PLHIV, an estimated 797 (15%) had never been tested for HCV and 70 (9%) of these had undiagnosed chronic HCV. The odds of never having been tested for HCV were the highest in those not on HIV treatment [adjusted odds ratio (aOR) = 7.21, 95% confidence interval (CI): 5.15-10.10). Overall HCV antibody positivity was 11%, and it was at its highest among people who inject drugs (49%). Most of those with chronic HCV (91%) had attended an HCV treatment clinic but only half had been successfully treated (54% for those on HIV treatment, 12% for those not) by the end of 2017. The odds of never having been treated for HCV were the highest in those not on HIV treatment (aOR = 3.60, 95% CI: 1.59-8.15). CONCLUSIONS: Our data demonstrate that micro-elimination of HCV in PLHIV is achievable but progress will require increased effort to engage and treat those co-infected, including those not being treated for their HIV.

Converse Magnetoelectric Composite Resonator for Sensing Small Magnetic Fields.

Magnetoelectric (ME) thin film composites consisting of sputtered piezoelectric (PE) and magnetostrictive (MS) layers enable for measurements of magnetic fields passively, i.e. an AC magnetic field directly generates an ME voltage by mechanical coupling of the MS deformation to the PE phase. In order to achieve high field sensitivities a magnetic bias field is necessary to operate at the maximum piezomagnetic coefficient of the MS phase, harnessing mechanical resonances further enhances this direct ME effect size. Despite being able to detect very small AC field amplitudes, exploiting mechanical resonances directly, implies a limitation to available signal bandwidth along with the inherent inability to detect DC or very low frequency magnetic fields. The presented work demonstrates converse ME modulation of thin film Si cantilever composites of mesoscopic dimensions (25 mm × 2.45 mm × 0.35 mm), employing piezoelectric AlN and magnetostrictive FeCoSiB films of 2 µm thickness each. A high frequency mechanical resonance at about 515 kHz leads to strong induced voltages in a surrounding pickup coil with matched self-resonance, leading to field sensitivities up to 64 kV/T. A DC limit of detection of 210 pT/Hz1/2 as well as about 70 pT/Hz1/2 at 10 Hz, without the need for a magnetic bias field, pave the way towards biomagnetic applications.

Index serum hyaluronic acid independently and accurately predicts mortality in patients with liver disease.

BACKGROUND: Hyaluronic acid is a recognised noninvasive marker of liver fibrosis. However, its prognostic ability has not been extensively studied. AIMS: To investigate the ability of an index serum hyaluronic acid measurement to independently predict transplant-free survival in patients with liver disease of varying aetiology and severity. METHODS: This was a retrospective single-centre cohort study. Serum hyaluronic acid was measured at the discretion of the attending clinicians, in patients attending the liver clinic, to assess disease severity. Patients with a hyaluronic acid measurement between 1995 and 2010 were identified. Patient characteristics at the point of hyaluronic acid measurement were recorded from medical records. Follow-up was from date of index hyaluronic acid measurement to date of death, date of transplant or censor date (July 01, 2015). Primary outcomes were all-cause and liver-related mortality. Kaplan-Meier analysis was used to compare survival in 3 patient groups with hyaluronic acid levels of <100 µg/L, 100-300 µg/L and >300 µg/L. Survival models were constructed using Cox proportional hazard and prediction accuracy was assessed by Harrell's C-statistic. RESULTS: Five hundred and eighty nine patients fulfilled inclusion criteria. Median follow-up was 5.6 years (range 0.1-19.7). Transplant-free survival was significantly different between patients with hyaluronic acid <100 µg/L, 100-300 µg/L and >300 µg/L for liver-related as well as all-cause mortality (P < 0.001). Hyaluronic acid level was an independent predictor of survival (liver-related: HR 1.39, 95% CI 1.20-1.60, P < 0.001; all-cause: HR 1.04, 95% CI 1.02-1.06, P = 0.001). The liver-related prediction accuracy of hyaluronic acid was 0.74 (Standard error 0.03). CONCLUSION: Index hyaluronic acid measurement can accurately and independently predict liver-related and all-cause mortality in patients with liver disease.

Impact of previous hepatitis B infection on the clinical outcomes from chronic hepatitis C? A population-level analysis.

Chronic coinfection with hepatitis C virus (HCV) and hepatitis B virus (HBV) is associated with adverse liver outcomes. The clinical impact of previous HBV infection on liver disease in HCV infection is unknown. We aimed at determining any association of previous HBV infection with liver outcomes using antibodies to the hepatitis B core antigen (HBcAb) positivity as a marker of exposure. The Scottish Hepatitis C Clinical Database containing data for all patients attending HCV clinics in participating health boards was linked to the HBV diagnostic registry and mortality data from Information Services Division, Scotland. Survival analyses with competing risks were constructed for time from the first appointment to decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver-related mortality. Records of 8513 chronic HCV patients were included in the analyses (87 HBcAb positive and HBV surface antigen [HBsAg] positive, 1577 HBcAb positive and HBsAg negative, and 6849 HBcAb negative). Multivariate cause-specific proportional hazards models showed previous HBV infection (HBcAb positive and HBsAg negative) significantly increased the risks of decompensated cirrhosis (hazard ratio [HR]: 1.29, 95% CI: 1.01-1.65) and HCC (HR: 1.64, 95% CI: 1.09-2.49), but not liver-related death (HR: 1.02, 95% CI: 0.80-1.30). This is the largest study to date showing an association between previous HBV infection and certain adverse liver outcomes in HCV infection. Our analyses add significantly to evidence which suggests that HBV infection adversely affects liver health despite apparent clearance. This has important implications for HBV vaccination policy and indications for prioritization of HCV therapy.

Trends in hepatocellular carcinoma incidence and survival among people with hepatitis C: An international study.

This study evaluates trends in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) incidence and survival in three settings, prior to introduction of direct-acting antiviral (DAA) therapies. HCV notifications from British Columbia (BC), Canada; New South Wales (NSW), Australia; and Scotland (1995-2011/2012/2013, respectively) were linked to HCC diagnosis data via hospital admissions (2001-2012/2013/2014, respectively) and mortality (1995-2013/2014/2015, respectively). Age-standardized HCC incidence rates were evaluated, associated factors were assessed using Cox regression, and median survival time after HCC diagnosis was calculated. Among 58 487, 84 529 and 31 924 people with HCV in BC, NSW and Scotland, 734 (1.3%), 1045 (1.2%) and 345 (1.1%) had an HCC diagnosis. Since mid-2000s, HCC diagnosis numbers increased in all jurisdictions. Age-standardized HCC incidence rates remained stable in BC and Scotland and increased in NSW. The strongest predictor of HCC diagnosis was older age [birth <1945, aHR in BC 5.74, 95% CI 4.84, 6.82; NSW 9.26, 95% CI 7.93, 10.82; Scotland 12.55, 95% CI 9.19, 17.15]. Median survival after HCC diagnosis remained stable in BC (0.8 years in 2001-2006 and 2007-2011) and NSW (0.9 years in 2001-2006 and 2007-2013) and improved in Scotland (0.7 years in 2001-2006 to 1.5 years in 2007-2014). Across the settings, HCC burden increased, individual-level risk of HCC remained stable or increased, and HCC survival remained extremely low. These findings highlight the minimal impact of HCC prevention and management strategies during the interferon-based HCV treatment era and form the basis for evaluating the impact of DAA therapy in the coming years.

Topical oxygen therapy promotes the healing of chronic diabetic foot ulcers: a pilot study.

OBJECTIVE: Interventions that can heal or reduce diabetic foot ulcer (DFU) size may reduce the incidence of infection and amputation, and reduce associated social and economic costs. Many chronic wounds exhibit a degree of hypoxia and this leads to a reduction in healing processes including cell division and differentiation, angiogenesis, infection prevention, and collagen production. The aim of this pilot study was to assess the effects of a device supplying continuous oxygen ambulatory therapy on healing in chronic DFUs. METHOD: Patients with chronic DFUs from two tertiary referral hospitals in the UK received treatment with the device. Data were prospectively obtained on wound size using standardised digital images measured by a clinician blinded to the study. Data on device satisfaction and pain were also obtained. RESULTS: We recruited 10 patients, with a mean ulcer duration of 43 weeks (median: 43 weeks) before treatment. By week eight, mean ulcer size had decreased by 51% (median: 53%). Seven of the 10 ulcers were in a healing trajectory, one ulcer present for 56 weeks healed completely, a two-year old ulcer was reduced by more than 50%, and a third, present for 88 weeks, was down to 10% of its original size by the end of the eight-week study. There was also a non-significant trend towards reduction in pain and the device was extremely well tolerated. CONCLUSION: The ambulatory topical oxygen delivery device showed a significant beneficial effect on wound size. This poses practical advantages over currently existing oxygen-based wound therapies such as hyperbaric oxygen therapy due to its continuous oxygen delivery, ease of use, safety and lower cost. The results of this study warrant further review of the device in comparison to standard wound therapies.

Combined skin and muscle vaccination differentially impact the quality of effector T cell functions: the CUTHIVAC-001 randomized trial.

Targeting of different tissues via transcutaneous (TC), intradermal (ID) and intramuscular (IM) injection has the potential to tailor the immune response to DNA vaccination. In this Phase I randomised controlled clinical trial in HIV-1 negative volunteers we investigate whether the site and mode of DNA vaccination influences the quality of the cellular immune responses. We adopted a strategy of concurrent immunization combining IM injection with either ID or TC administration. As a third arm we assessed the response to IM injection administered with electroporation (EP). The DNA plasmid encoded a MultiHIV B clade fusion protein designed to induce cellular immunity. The vaccine and regimens were well tolerated. We observed differential shaping of vaccine induced virus-specific CD4 + and CD8 + cell-mediated immune responses. DNA given by IM + EP promoted strong IFN-γ responses and potent viral inhibition. ID + IM without EP resulted in a similar pattern of response but of lower magnitude. By contrast TC + IM (without EP) shifted responses towards a more Th-17 dominated phenotype, associated with mucosal and epidermal protection. Whilst preliminary, these results offer new perspectives for differential shaping of desired cellular immunity required to fight the wide range of complex and diverse infectious diseases and cancers.

Gasoline cars produce more carbonaceous particulate matter than modern filter-equipped diesel cars.

Carbonaceous particulate matter (PM), comprising black carbon (BC), primary organic aerosol (POA) and secondary organic aerosol (SOA, from atmospheric aging of precursors), is a highly toxic vehicle exhaust component. Therefore, understanding vehicle pollution requires knowledge of both primary emissions, and how these emissions age in the atmosphere. We provide a systematic examination of carbonaceous PM emissions and parameterisation of SOA formation from modern diesel and gasoline cars at different temperatures (22, -7 °C) during controlled laboratory experiments. Carbonaceous PM emission and SOA formation is markedly higher from gasoline than diesel particle filter (DPF) and catalyst-equipped diesel cars, more so at -7 °C, contrasting with nitrogen oxides (NOX). Higher SOA formation from gasoline cars and primary emission reductions for diesels implies gasoline cars will increasingly dominate vehicular total carbonaceous PM, though older non-DPF-equipped diesels will continue to dominate the primary fraction for some time. Supported by state-of-the-art source apportionment of ambient fossil fuel derived PM, our results show that whether gasoline or diesel cars are more polluting depends on the pollutant in question, i.e. that diesel cars are not necessarily worse polluters than gasoline cars.

Review article: hepatitis E-a concise review of virology, epidemiology, clinical presentation and therapy.

BACKGROUND: Hepatitis E virus (HEV) is a leading cause of acute icteric hepatitis and acute liver failure in the developing world. During the last decade, there has been increasing recognition of autochthonous (locally acquired) HEV infection in developed countries. Chronic HEV infection is now recognised, and in transplant recipients this may lead to cirrhosis and organ failure. AIM: To detail current understanding of the molecular biology of HEV, diagnostic and therapeutic strategies and propose future directions for basic science and clinical research. METHODS: PubMed was searched for English language articles using the key words "hepatitis E", "viral hepatitis", "autochthonous infection", "antiviral therapy", "liver transplantation", "acute", "chronic", "HEV", "genotype", "transmission" "food-borne", "transfusion". Additional relevant publications were identified from article reference lists. RESULTS: There has been increasing recognition of autochthonous HEV infection in Western countries, mainly associated with genotype 3. Chronic HEV infection has been recognised since 2008, and in transplant recipients this may lead to cirrhosis and organ failure. Modes of transmission include food-borne transmission, transfusion of blood products and solid organ transplantation. Ribavirin therapy is used to treat patients with chronic HEV infection, but new therapies are required as there have been reports of treatment failure with ribavirin. CONCLUSIONS: Autochthonous HEV infection is a clinical issue with increasing burden. Future work should focus on increasing awareness of HEV infection in the developed world, emphasising the need for clinicians to have a low threshold for HEV testing, particularly in immunosuppressed patients. Patients at potential risk of chronic HEV infection must also be educated and given advice regarding prevention of infection.

Acute liver failure in Scotland: changes in aetiology and outcomes over time (the Scottish Look-Back Study).

BACKGROUND: Acute liver failure is a rare and devastating clinical condition resulting from sudden loss of hepatic parenchyma and metabolic function. The Scottish Liver Transplant Unit (SLTU) offers specialist management and emergency liver transplantation to patients with acute liver failure from across Scotland. AIM: To describe temporal changes in number of admissions, aetiology of acute liver failure, severity of disease at presentation and outcomes over a 22-year period. METHODS: Retrospective analysis of the SLTU database, including all patients admitted with acute liver injury or acute liver failure between November 1992 and March 2014. RESULTS: There has been no change in the number of patients presenting with acute liver injury or failure secondary to paracetamol overdose, but a reduction in the number of admissions with acute liver injury or failure secondary to non paracetamol causes. Over time, disease severity at presentation has not changed in the paracetamol cohort; those with a non paracetamol aetiology have latterly presented with milder hepatic encephalopathy. Spontaneous survival rates improved significantly over time for those patients with acute liver failure due to paracetamol and non paracetamol aetiologies. The most marked improvement in survival is observed in the sickest patients meeting Kings College Hospital poor prognostic criteria. CONCLUSIONS: The number of admissions to the SLTU with acute liver failure is decreasing, due to reduced numbers of non paracetamol cases. Outcomes in this condition are improving, due to improvements in intensive care management and use of liver transplantation, and the increase in survival is most marked in patients meeting Kings College Hospital poor prognostic criteria.

Prognosis of 1169 hepatitis C chronically infected patients with decompensated cirrhosis in the predirect-acting antiviral era.

At a population level, little is known regarding the risk of liver- and nonliver-related mortality and hospitalization and the development of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients with decompensated cirrhosis (DC). This large-scale national record-linkage study estimates these outcomes following first hospital admission for DC. Record-linkages between national HCV diagnosis and clinical databases and the national inpatient hospital episode database and mortality register were conducted to follow-up the disease course of all identified HCV-diagnosed and chronically infected persons. The study population consisted of 1169 HCV chronically infected persons who had a first hospital admission for DC within the period 1994-2013. We observed an overall average annual percentage change of 12.6% in new DC patients (from 63 in 1994-1999 to 541 in 2009-2013), with no evidence for any improvement in the relative risks of liver-related or all-cause death over time. Between 1 January 1994 and 31 May 2014, 722 and 95 DC patients had died of a liver- and a nonliver-related cause, respectively, and 106 patients had a subsequent first admission for HCC. The 5-year cumulative incidence of liver-related mortality, nonliver-related mortality and first subsequent HCC admission was 61.3%, 8.2% and 8.8%, respectively. The health burden in HCV-infected patients associated with development of decompensated cirrhosis has increased dramatically over the last 20 years. Our findings establish the baseline mortality and HCC progression rates in DC patients against which the impact of new antiviral therapies can be measured.