Life expectancy inequalities in Wales before COVID-19: an exploration of current contributions by age and cause of death and changes between 2002 and 2018.

OBJECTIVES: The COVID-19 pandemic in Wales and the UK has highlighted significant and historic inequalities in health between social groups. To better understand the composition of these inequalities and inform planning after the pandemic, we undertook a decomposition of life expectancy inequalities between the most and least deprived quintiles for men and women by age and cause of death and explored trends between 2002 and 2018. STUDY DESIGN: Statistical decomposition of life expectancy inequalities by age and cause of death using routine population mortality datasets. METHODS: We used routine statistics from the Office for National Statistics for the period 2002-2018 on population and deaths in Wales stratified by age, gender, Welsh Index of Multiple Deprivation (WIMD) 2019 quintile and cause of death, categorised by International Classification of Disease, version 10, code into 15 categories of public health relevance. We aggregated data to 3-year rolling figures to account for low numbers of events in some groups annually. Next, we estimated life expectancy at birth by quintile, gender and period using life table methods. Lastly, we performed a decomposition analysis using the Arriaga method to identify the specific disease categories and ages at which excess deaths occur in more disadvantaged areas to highlight potential areas for action. RESULTS: Life expectancy inequalities between the most and least WIMD quintiles rose for both genders between 2002 and 2018: from 4.69 to 6.02 years for women (an increase of 1.33 years) and from 6.34 to 7.42 years for men (an increase of 1.08 years). Exploratory analysis of these trends suggested that the following were most influential for women: respiratory disease (1.50 years), cancers (1.36 years), circulatory disease (1.35 years) and digestive disease (0.51 years). For men, the gap was driven by circulatory disease (2.01 years), cancers (1.39 years), respiratory disease (1.25 years), digestive disease (0.79 years), drug- and alcohol-related conditions (0.54 years) and external causes (0.54 years). Contributions for women from respiratory disease, cancers, dementia and drug- and alcohol-related conditions appeared to be increasing, while among men, there were rising contributions from respiratory, digestive and circulatory disease. CONCLUSIONS: Life expectancy inequalities in Wales remain wide and have been increasing, particularly among women, with indications of worsening trends since 2010 following the introduction of fiscal austerity. As agencies recover from the pandemic, these findings should be considered alongside any resumption of services in Wales or future health and public policy.

Direct observation of muonium reacting with uncapped gold nanoparticles in porous silica and nature of the final state.

We report the reaction of muonium (Mu = [µ+e-]), a light isotopic analog of hydrogen, with uncapped gold nanoparticles embedded in mesoporous silica. Using the radio-frequency muon spin rotation (RF-µSR) technique, we directly observe and characterize the resulting final state on the nanoparticle surface, showing conclusively its diamagnetic nature. The magnetic environment experienced by the reacted muons is only weakly perturbed compared to that of muons in a silica reference, consistent with the surface of the gold nanoparticles being metallic and non-magnetic. We demonstrate the potential of RF-µSR for the investigation of the surface properties of nanoparticles and show the feasibility of Knight shift measurements of muons on metal surfaces.

Harmonizing influenza primary-care surveillance in the United Kingdom: piloting two methods to assess the timing and intensity of the seasonal epidemic across several general practice-based surveillance schemes.

General Practitioner consultation rates for influenza-like illness (ILI) are monitored through several geographically distinct schemes in the UK, providing early warning to government and health services of community circulation and intensity of activity each winter. Following on from the 2009 pandemic, there has been a harmonization initiative to allow comparison across the distinct existing surveillance schemes each season. The moving epidemic method (MEM), proposed by the European Centre for Disease Prevention and Control for standardizing reporting of ILI rates, was piloted in 2011/12 and 2012/13 along with the previously proposed UK method of empirical percentiles. The MEM resulted in thresholds that were lower than traditional thresholds but more appropriate as indicators of the start of influenza virus circulation. The intensity of the influenza season assessed with the MEM was similar to that reported through the percentile approach. The MEM pre-epidemic threshold has now been adopted for reporting by each country of the UK. Further work will continue to assess intensity of activity and apply standardized methods to other influenza-related data sources.

Effectiveness of trivalent seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2012/13 end of season results.

The effectiveness of the 2012/13 trivalent seasonal influenza vaccine (TIV) was assessed using a test-negative case-control study of patients consulting primary care with influenza-like illness in the United Kingdom. Strain characterisation was undertaken on selected isolates. Vaccine effectiveness (VE) against confirmed influenza A(H3N2), A(H1N1) and B virus infection, adjusted for age, sex, surveillance scheme (i.e. setting) and month of sample collection was 26% (95% confidence interval (CI): -4 to 48), 73% (95% CI: 37 to 89) and 51% (95% CI: 34 to 63) respectively. There was an indication, although not significant, that VE declined by time since vaccination for influenza A(H3N2) (VE 50% within three months, 2% after three months, p=0.25). For influenza A(H3N2) this is the second season of low VE, contributing to the World Health Organization (WHO) recommendation that the 2013/14 influenza vaccine strain composition be changed to an A(H3N2) virus antigenically like cell-propagated prototype 2012/13 vaccine strain (A/Victoria/361/2011). The lower VE seen for type B is consistent with antigenic drift away from the 2012/13 vaccine strain. The majority of influenza B viruses analysed belong to the genetic clade 2 and were antigenically distinguishable from the 2012/13 vaccine virus B/Wisconsin/1/2010 clade 3. These findings supported the change to the WHO recommended influenza B vaccine component for 2013/14.

The emerging role of community sentinel surveillance in the understanding of the clinical features and epidemiology of acute Mycoplasma pneumoniae infection.

Retrospective analysis of 3984 test results for the detection of Mycoplasma pneumoniae performed between 2009 and 2013 in Wales was undertaken. Analysis of the clinical presentation of positive cases suggested that mild respiratory infection was common in the community and appeared to coincide with increased hospitalizations. Symptomatic infection was more prevalent in men, with a median age of 22.6 years (range <1-88 years), and 40% of hospitalized cases presented with pneumonia. Inclusion of M. pneumonia nucleic acid amplification tests (NAATs) into routine respiratory NAAT screens will increase the understanding of the epidemiology and clinical spectrum of acute infections in the wider population.

A randomized, placebo-controlled phase 2 study of ganitumab or conatumumab in combination with FOLFIRI for second-line treatment of mutant KRAS metastatic colorectal cancer.

BACKGROUND: Targeted agents presently available for mutant KRAS metastatic colorectal cancer (mCRC) are bevacizumab and aflibercept. We evaluated the efficacy and safety of conatumumab (an agonistic monoclonal antibody against human death receptor 5) and ganitumab (a monoclonal antibody against the type 1 insulin-like growth factor receptor) combined with standard FOLFIRI chemotherapy as a second-line treatment in patients with mutant KRAS mCRC. PATIENTS AND METHODS: Patients with mutant KRAS metastatic adenocarcinoma of the colon or rectum refractory to fluoropyrimidine- and oxaliplatin-based chemotherapy were randomized 1 : 1 : 1 to receive intravenous FOLFIRI plus conatumumab 10 mg/kg (Arm A), ganitumab 12 mg/kg (Arm B), or placebo (Arm C) Q2W. The primary end point was progression-free survival (PFS). RESULTS: In total, 155 patients were randomized. Median PFS in Arms A, B, and C was 6.5 months (HR, 0.69; P = 0.147), 4.5 months (HR, 1.01; P = 0.998), and 4.6 months, respectively; median overall survival was 12.3 months (HR, 0.89; P = 0.650), 12.4 months (HR, 1.27; P = 0.357), and 12.0 months; and objective response rate was 14%, 8%, and 2%. The most common grade ≥3 adverse events in Arms A/B/C included neutropenia (30%/25%/18%) and diarrhea (18%/2%/10%). CONCLUSIONS: Conatumumab, but not ganitumab, plus FOLFIRI was associated with a trend toward improved PFS. Both combinations had acceptable toxicity.

Effectiveness of seasonal 2012/13 vaccine in preventing laboratory-confirmed influenza infection in primary care in the United Kingdom: mid-season analysis 2012/13.

The early experience of the United Kingdom (UK) is that influenza B has dominated the influenza 2012/13 season. Overall trivalent influenza vaccine (TIV) adjusted vaccine effectiveness (VE) against all laboratory-confirmed influenza in primary care was 51% (95% confidence interval (CI): 27% to 68%); TIV adjusted VE against influenza A alone or influenza B alone was 49% (95% CI: -2% to 75%) and 52% (95% CI: 23% to 70%) respectively. Vaccination remains the best protection against influenza.

Vaccine effectiveness of 2011/12 trivalent seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: evidence of waning intra-seasonal protection.

The 2011/12 season was characterised by unusually late influenza A (H3N2) activity in the United Kingdom (UK). We measured vaccine effectiveness (VE) of the 2011/12 trivalent seasonal influenza vaccine (TIV) in a test-negative case­control study in primary care. Overall VE against confirmed influenza A (H3N2) infection, adjusted for age, surveillance scheme and month, was 23% (95% confidence interval (CI): -10 to 47). Stratified analysis by time period gave an adjusted VE of 43% (95% CI: -34 to 75) for October 2011 to January 2012 and 17% (95% CI: -24 to 45) for February 2012 to April 2012. Stratified analysis by time since vaccination gave an adjusted VE of 53% (95% CI: 0 to 78) for those vaccinated less than three months, and 12% (95% CI: -31 to 41) for those vaccinated three months or more before onset of symptoms (test for trend: p=0.02). For confirmed influenza B infection, adjusted VE was 92% (95% CI: 38 to 99). A proportion (20.6%) of UK influenza A(H3N2) viruses circulating in 2011/12 showed reduced reactivity (fourfold difference in haemagglutination inhibition assays) to the A/Perth/16/2009 2011/12 vaccine component, with no significant change in proportion over the season. Overall TIV protection against influenza A(H3N2) infection was low, with significant intraseasonal waning.

Age-specific vaccine effectiveness of seasonal 2010/2011 and pandemic influenza A(H1N1) 2009 vaccines in preventing influenza in the United Kingdom.

An analysis was undertaken to measure age-specific vaccine effectiveness (VE) of 2010/11 trivalent seasonal influenza vaccine (TIV) and monovalent 2009 pandemic influenza vaccine (PIV) administered in 2009/2010. The test-negative case-control study design was employed based on patients consulting primary care. Overall TIV effectiveness, adjusted for age and month, against confirmed influenza A(H1N1)pdm 2009 infection was 56% (95% CI 42-66); age-specific adjusted VE was 87% (95% CI 45-97) in <5-year-olds and 84% (95% CI 27-97) in 5- to 14-year-olds. Adjusted VE for PIV was only 28% (95% CI -6 to 51) overall and 72% (95% CI 15-91) in <5-year-olds. For confirmed influenza B infection, TIV effectiveness was 57% (95% CI 42-68) and in 5- to 14-year-olds 75% (95% CI 32-91). TIV provided moderate protection against the main circulating strains in 2010/2011, with higher protection in children. PIV administered during the previous season provided residual protection after 1 year, particularly in the <5 years age group.

Design and commissioning of a high magnetic field muon spin relaxation spectrometer at the ISIS pulsed neutron and muon source.

The high magnetic field (HiFi) muon instrument at the ISIS pulsed neutron and muon source is a state-of-the-art spectrometer designed to provide applied magnetic fields up to 5 T for muon studies of condensed matter and molecular systems. The spectrometer is optimised for time-differential muon spin relaxation studies at a pulsed muon source. We describe the challenges involved in its design and construction, detailing, in particular, the magnet and detector performance. Commissioning experiments have been conducted and the results are presented to demonstrate the scientific capabilities of the new instrument.

Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is a chronic and slowly progressive disease for which biomarkers may be able to provide a more rapid indication of therapeutic responses to therapy than is currently available; this could accelerate and facilitate OA drug discovery and development programs. The goal of this document is to provide a summary and guide to the application of in vitro (biochemical and other soluble) biomarkers in the development of drugs for OA and to outline and stimulate a research agenda that will further this goal. METHODS: The Biomarkers Working Group representing experts in the field of OA biomarker research from both academia and industry developed this consensus document between 2007 and 2009 at the behest of the Osteoarthritis Research Society International Federal Drug Administration initiative (OARSI FDA initiative). RESULTS: This document summarizes definitions and classification systems for biomarkers, the current outcome measures used in OA clinical trials, applications and potential utility of biomarkers for development of OA therapeutics, the current state of qualification of OA-related biomarkers, pathways for biomarker qualification, critical needs to advance the use of biomarkers for drug development, recommendations regarding practices and clinical trials, and a research agenda to advance the science of OA-related biomarkers. CONCLUSIONS: Although many OA-related biomarkers are currently available they exist in various states of qualification and validation. The biomarkers that are likely to have the earliest beneficial impact on clinical trials fall into two general categories, those that will allow targeting of subjects most likely to either respond and/or progress (prognostic value) within a reasonable and manageable time frame for a clinical study (for instance within 1-2 years for an OA trial), and those that provide early feedback for preclinical decision-making and for trial organizers that a drug is having the desired biochemical effect. As in vitro biomarkers are increasingly investigated in the context of specific drug treatments, advances in the field can be expected that will lead to rapid expansion of the list of available biomarkers with increasing understanding of the molecular processes that they represent.

Two waves of pandemic influenza A(H1N1) 2009 in Wales--the possible impact of media coverage on consultation rates, April-December 2009.

In the United Kingdom, the influenza A(H1N1) 2009 pandemic had a distinct two-wave pattern of general practice consultations for influenza-like illness (ILI). We describe the epidemiology of the influenza pandemic in Wales between April and December 2009 using integrated data from a number of independent sources: GP surveillance, community virology surveillance, hospital admissions and deaths, and media enquiries monitoring. The first wave peaked in late July at 100 consultations per 100,000 general practice population and attracted intensive media coverage. The positivity rate for the A(H1N1)2009 influenza did not exceed 25% and only 44 hospitalisations and one death were recorded. By contrast, the second wave peaked in late October and although characterised by lower ILI consultation rates (65 consultations per 100,000 general practice population) and low profile media activity, was associated with much higher positivity rates for pandemic influenza A(H1N1)2009 (60%) and substantially more hospital admissions (n=379) and deaths (n=26). The large number of ILI-related consultations during the first wave in Wales probably reflected the intensive media activity rather than influenza virus circulating in the community. Data from community surveillance schemes may therefore have considerably overestimated the true incidence of influenza. This has implications for the future interpretation of ILI surveillance data and their use in policy making, and underlines the importance of using integrated epidemiological, virological and hospital surveillance data to monitor influenza activity.

Electric-field-enhanced neutralization of deep centers in GaAs.

The charge dynamics of hydrogenlike centers in semi-insulating GaAs have been studied by muon spin resonance in the presence of electric field and RF excitation. Electric-field-enhanced neutralization of deep electron and hole traps by track-induced hot carriers results in an increase of the excess electron's or hole's lifetimes. Similar processes may take place in semiconductor devices working at high voltages and/or under irradiation. As a consequence of the deep traps neutralization, the muonium (mu{+} + e{-}) center can capture a hole.

Influenza immunisation uptake in carers.

In 2005 the United Kingdom departments of health added 'carers' to the list of people that should be offered seasonal influenza immunisation by their general practice. We surveyed a sample of carers registered for care assistance with the charity Crossroads Caring for Carers. Over half (58%) were not aware that they are eligible for free influenza immunisation. Young carers without a chronic disease, were least likely to be offered immunisation and least likely to be immunised.

Dynamics and reactivity of positively charged muonium in heavily doped Si:B and comparisons with hydrogen.

The detailed dynamics of the positively charged muonium (Mu+) in heavily doped p-type Si:B is reported. Below 200 K, Mu+ is static and isolated, and is located in a stretched Si-Si bond. Above approximately 200 K, Mu+ diffuses incoherently. At temperatures higher than 300 K, the Mu+-B- complex is formed while above 520 K, it starts to dissociate. There is significant enhancement of the diffusion of Mu+ in Si compared to H+ and D+-this is attributed to its smaller mass.

Biological monitoring for trimethylbenzene exposure: a human volunteer study and a practical example in the workplace.

This paper presents data from both a human volunteer study looking at exposure to 1,3,5-trimethylbenzene (TMB) and an occupational hygiene study of a printing firm using screen wash containing technical grade TMB. The biomarkers measured were TMB in blood and breath, and urinary dimethylbenzoic acids (DMBAs). The volunteer (N = 4) study showed that TMB was rapidly absorbed into the bloodstream reaching a mean level of 0.85 micromol l(-1) during a 4 h exposure to 25 p.p.m. TMB. There was little decline 1 h post-exposure possibly indicating storage of TMB in adipose tissue. Breath TMB levels peaked within an hour of exposure commencing and averaged 137 nmol l(-1) during exposure. Elimination of TMB in breath was biphasic with an initial half-life of 60 min. Peak excretion of urinary DMBA occurred 4-8 h after the end of exposure and averaged 40 mmol mol(-1) creatinine. Elimination of DMBA in urine was biphasic with half-lives of 13 and 60 h indicating that accumulation of body burden throughout the working week is likely if exposure is repeated. The occupational hygiene study demonstrated an excellent correlation between personal air TMB levels and post-shift urinary DMBA levels (r = 0.997) collected on the third working day. The regression equation from this study indicates that 8 h exposure to 25 p.p.m. TMB would result in a urinary DMBA level of 206 mmol mol(-1) creatinine. All workers showed pre-shift levels of DMBA from exposure to TMB on previous days. Both urinary DMBA and breath TMB levels can be used as biomarkers of TMB exposure. Urine samples should be taken post-shift towards the end of the working week as significant body burden accumulation throughout the working week can be expected. Breath sampling is more suited to task or single-shift monitoring.

Suspicion, resistance, tokenism and mutiny: problematic dynamics relevant to the implementation of clinical supervision in nursing.

In this paper I will discuss some of the more common pitfalls inherent in attempts to introduce clinical supervision to hospital wards or community teams. I will consider pre-existing relationships and how these may, if unexamined and unaccounted for, result in clinical supervision becoming less than optimally effective. Drawing upon the theory of Transactional Analysis, in particular the concept of 'psychological distance', I consider four possible interpersonal dynamics and examine how these may impact upon the implementation of clinical supervision. These problematic dynamics can result in undue resistance, suspicion, tokenism or interpersonal difficulties. Finally, I will consider ways in which the aforementioned problems may be addressed and their effects minimized through the use of co-operative contracting.

Evidence for weak itinerant long-range magnetic correlations in UGe2.

Positive muon spin relaxation measurements performed on the ferromagnet UGe2 reveal, in addition to the well-known localized 5f-electron density responsible for the bulk magnetic properties, the existence of itinerant quasistatic magnetic correlations. Their critical dynamics is well described by the conventional dipolar Heisenberg model. These correlations involve small magnetic moments.