Contribution of avoidable mortality to life expectancy inequalities in Wales: a decomposition by age and by cause between 2002 and 2020.

OBJECTIVES: To explore the contribution of avoidable mortality to life expectancy inequalities in Wales during 2002-2020. DESIGN: Observational study. SETTING: Wales, 2002-20, including early data from the COVID-19 pandemic. METHODS: We used routine statistics for 2002-2020 on population and deaths in Wales stratified by age, sex, deprivation quintile and cause of death. We estimated the contribution of avoidable causes of death and specific age-categories using the Arriaga decomposition method to highlight priorities for action. RESULTS: Life expectancy inequalities rose 2002-20 amongst both sexes, driven by serial decreases in life expectancy amongst the most deprived quintiles. The contributions of amenable and preventable mortality to life expectancy inequalities changed relatively little between 2002 and 2020, with larger rises in non-avoidable causes. Key avoidable mortality conditions driving the life expectancy gap in the most recent period of 2018-2020 for females were circulatory disease, cancers, respiratory disease and alcohol- and drug-related deaths, and also injuries for males. CONCLUSIONS: Life expectancy inequalities widened during 2002-20, driven by deteriorating life expectancy in the most deprived quintiles. Sustained investment in prevention post-COVID-19 is needed to address growing health inequity in Wales; there remains a role for the National Health Service in ensuring equitable healthcare access to alongside wider policies that promote equity.

First steps in PROMs and PREMs collection in Wales as part of the prudent and value-based healthcare agenda.

PURPOSE: Patients are experts in their own health and should be treated as equal partners in their care. Patient-reported outcome measures (PROMs) are an effective way of gathering patient feedback and can facilitate effectiveness and cost-effectiveness analysis to improve decision making and service improvement. The PROMs, PREMs & Effectiveness Programme was initiated in 2016 and aimed to develop an electronic platform to facilitate collection of PROMs and Patient-reported experience measures (PREMs) from secondary care patients across Wales. METHODS: We worked with all Health Boards in Wales, the NHS Wales Informatics Service (NWIS), and Cedar (a healthcare technology research centre) to identify and meet technical requirements to develop a platform which is fit for purpose. Patient groups were included throughout the development to gather feedback and for extensive testing. Clinical teams helped identify the most appropriate tools, with licences, translations and electronic formatting issues being managed centrally. RESULTS: The developed platform is integrated with patient administration systems minimising the need for manual input, with processes in place to allow automatic collection triggers according to nationally agreed schedules. We have over 30 nationally agreed PROMs 'pathways' with over 110,000 PROMs collected to date. Responses are fed back to clinicians via the electronic patient record and to each health board via feeds to the national data warehouse, making data easily accessible to different teams, maximising use and application. DISCUSSION: The national platform has provided a co-ordinated approach to PROMs collection in Wales, offering an effective means of communicating with patients outside the traditional clinic visit.

C-H Functionalization of Commodity Polymers.

Synthetic manipulation of polymer substrates is one of the oldest and most reliable methods to increase the functional diversity of soft materials. Modifying the chemical structure of polymers that are already produced on a commodity scale leverages the current high-volume and low-cost production of commodity plastics for the discovery of modern materials. A myriad of polymer C-H functionalization methods have been developed which enable the modification of material properties on both a laboratory and industrial scale. More recently, driven by advances in C-H activation, photoredox catalysis, and radical chemistry, chemoselective approaches have emerged as a means to impart precise functionality onto commodity polymer substrates. This Review discusses the historical significance of and contemporary advances in the C-H functionalization of commodity polymers. The conceptual approach outlined herein presents exciting new directions for the field, including increasing the value of otherwise pervasive materials, uncovering entirely new material properties, and a viable path to upcycle post-consumer plastic waste.

Comparison of an Unlabeled Probe High-Resolution Melting Analysis Assay (HRMA) for Factor V Leiden 1691 G/A Mutation to a Fluorogenic 5' Nuclease PCR Hydrolysis Assay.

BACKGROUND: The clinically significant Factor V Leiden (FVL) point mutation (1691 G/A) causes replacement of Arg with Gln (glutamine), preventing activated protein C from inactivating Factor V leading to a lengthened clotting process. Individuals with the Factor V Leiden mutations have an increased risk for venous thrombosis. The aim of this study is to compare an unlabeled probe high-resolution melting analysis (HRMA) assay for Factor V Leiden mutation to a TaqMan hydrolysis assay (fluorogenic 5' nuclease PCR hydrolysis assay). HRMA is a post-PCR, homogenous, closed-tube system for the detection of sequence variants. Post-PCR, the amplicons are heated gradually until the melting temperature is reached and the fluorescent dye unbinds from the amplicon and exhibits low fluorescence. A melt-curve analysis is generated that is characteristic of a particular sequence variant. Therefore, HRMA allows for comparison of one base changes in genetic sequences based on their differences in melting rate. METHODS: Blood samples were collected in EDTA tubes and DNA extracted using the Roche MagNaPure. Reactions of both HRMA and TaqMan were carried out on 3 controls (1691 G/G, 1691 G/A, and 1691 G/G and G/A) and 20 samples. RESULTS: The genotypes for 3 reference controls purchased from Coriell (F5 1691 G/G, FVL 1691 G/A, and Heterozygote 1691 G/G and G/A) were confirmed by both the HRMA and TaqMan FVL assays. All 20 samples were confirmed to be F5 1691 G/G by both HRMA and TaqMan assays. CONCLUSIONS: Comparing the results of the unlabeled probe HRMA FVL assay with a real-time TaqMan probe end point genotyping assay resulted in 100% sensitivity and 100% specificity for both assays.

The copper active site of CBM33 polysaccharide oxygenases.

The capacity of metal-dependent fungal and bacterial polysaccharide oxygenases, termed GH61 and CBM33, respectively, to potentiate the enzymatic degradation of cellulose opens new possibilities for the conversion of recalcitrant biomass to biofuels. GH61s have already been shown to be unique metalloenzymes containing an active site with a mononuclear copper ion coordinated by two histidines, one of which is an unusual τ-N-methylated N-terminal histidine. We now report the structural and spectroscopic characterization of the corresponding copper CBM33 enzymes. CBM33 binds copper with high affinity at a mononuclear site, significantly stabilizing the enzyme. X-band EPR spectroscopy of Cu(II)-CBM33 shows a mononuclear type 2 copper site with the copper ion in a distorted axial coordination sphere, into which azide will coordinate as evidenced by the concomitant formation of a new absorption band in the UV/vis spectrum at 390 nm. The enzyme's three-dimensional structure contains copper, which has been photoreduced to Cu(I) by the incident X-rays, confirmed by X-ray absorption/fluorescence studies of both aqueous solution and intact crystals of Cu-CBM33. The single copper(I) ion is ligated in a T-shaped configuration by three nitrogen atoms from two histidine side chains and the amino terminus, similar to the endogenous copper coordination geometry found in fungal GH61.

Delivering value-based healthcare for people with diabetes in a national publicly funded health service: Lessons from Ireland and Wales.

The term value-based healthcare (VBHC) describes an approach to the organization and delivery of care that emphasizes reducing the cost of care while improving outcomes. This involves increased investment earlier in the care pathway e.g., in the prevention, timely diagnosis, and screening for complications in order to maximize the overall impact of care. Key elements of VBHC include the collection and interpretation of relevant data to drive quality improvement and appropriateness of care, a focus on a continuum of care from prevention through to complications, an awareness of the financial drivers of the cost of care and a recognition that meaningful outcomes of care are those that are important to patients. Although VBHC has its origins in North America and has mostly been applied to private health systems, the principles can also be applied to national health services. In publicly funded health systems, where resources are finite, VBHC initiatives aim to eliminate ineffective care that has no beneficial impact or added value for patients and to optimize patient outcomes by delivering care that meets the changing healthcare needs of a population over time. The National Health Service in Wales has established a VBHC Office and has begun to realize the benefits of adopting VBHC approaches. The Irish Health Service Executive (HSE) can learn from the approaches used in Wales. In this paper we explore some of the principles of VBHC through case studies from Ireland and Wales highlighting how national health services are using VBHC to achieve improvement in outcomes for people living with diabetes.

Value of improving patient safety: health economic considerations for rapid response systems-a rapid review of the literature and expert round table.

OBJECTIVES: Failure to rescue deteriorating patients in hospital is a well-researched topic. We aimed to explore the impact of safer care on health economic considerations for clinicians, providers and policymakers. DESIGN: We undertook a rapid review of the available literature and convened a round table of international specialists in the field including experts on health economics and value-based healthcare to better understand health economics of clinical deterioration and impact of systems to reduce failure to rescue. RESULTS: Only a limited number of publications have examined the health economic impact of failure to rescue. Literature examining this topic lacked detail and we identified no publications on long-term cost outside the hospital following a deterioration event. The recent pandemic has added limited literature on prevention of deterioration in the patients' home.Cost-effectiveness and cost-efficiency are dependent on broader system effects of adverse events. We suggest including the care needs beyond the hospital and loss of income of patients and/or their informal carers as well as sickness of healthcare staff exposed to serious adverse events in the analysis of adverse events. They are likely to have a larger health economic impact than the direct attributable cost of the hospital admission of the patient suffering the adverse event. Premorbid status of a patient is a major confounder for health economic considerations. CONCLUSION: In order to optimise health at the population level, we must limit long-term effects of adverse events through improvement of our ability to rapidly recognise and respond to acute illness and worsening chronic illness both in the home and the hospital.

Value-based healthcare: is it the way forward?

It is undeniable that the NHS, our universal healthcare system, is struggling to meet the needs and expectations of a population that is very different from its inception in 1948. Costs are rising inexorably and, yet, patient experience of their healthcare is often not what we would want it to be. Inequities still exist, both in terms of access to care and clinical outcome. As we spend more and more, surprisingly little is known about the extent to which we are meeting the healthcare goals and outcomes that really matter to patients. Equally, clinical teams are stretched and facing burnout as we emerge slowly from the pandemic. Meanwhile, value-based healthcare has gathered momentum worldwide as a lens through which to examine these problems. But does it provide helpful solutions? This article examines the strengths and limitations of value-based healthcare and its application in the UK context.

The Challenge of maintaining good health outcomes for all during the COVID-19 pandemic-a view from family medicine in Wales, UK.

This article addresses the issue of maintaining essential healthcare services throughout the pandemic and beyond. It suggests a key role for the use of patient-reported outcomes.

Clinical Risk Prediction Scores in Coronavirus Disease 2019: Beware of Low Validity and Clinical Utility.

Several risk stratification tools were developed to predict disease progression in coronavirus disease 2019, with no external validation to date. We attempted to validate three previously published risk-stratification tools in a multicenter study. Primary outcome was a composite outcome of development of severe coronavirus disease 2019 disease leading to ICU admission or death censored at hospital discharge or 30 days. We collected data from 169 patients. Patients were 73 years old (59-82 yr old), 66 of 169 (39.1%) were female, 57 (33.7%) had one comorbidity, and 80 (47.3%) had two or more comorbidities. Area under the receiver operating characteristic curve (95% CI) for the COVID-GRAM score was 0.636 (0.550-0.722), for the CALL score 0.500 (0.411-0.589), and for the nomogram 0.628 (0.543-0.714).

Upcycling aromatic polymers through C-H fluoroalkylation.

The unique properties imparted by planar, rigid aromatic rings in synthetic polymers make these macromolecules useful in a range of applications, including disposable packaging, aerospace materials, flexible electronics, separation membranes, and engineering thermoplastics. The thermal and chemical stability of aromatic polymers, however, makes it difficult to alter their bulk and/or surface properties and results in challenges during recycling. In response, we report a platform approach for the C-H functionalization of aromatic polymers by taking advantage of their innate reactivity with electrophilic radical intermediates. The method uses mild reaction conditions to photocatalytically generate electrophilic fluoroalkyl radicals for the functionalization of an array of commercially relevant polyaromatic substrates, including post-industrial and post-consumer plastic waste, without altering their otherwise attractive thermomechanical properties. The density of fluorination, and thus the material properties, is tuned by either increasing the reagent concentration or incorporating longer perfluoroalkyl species. Additionally, the installation of versatile chemical functionality to aromatic polymers is demonstrated through the addition of a bromodifluoromethyl group, which acts as an initiator for atom transfer radical polymerization (ATRP) grafting of vinyl polymers. The method described herein imparts new and versatile chemical functionality to aromatic polymers, enabling an efficient approach to diversify the properties of these otherwise recalcitrant commodity plastics and demonstrating a viable pathway to upcycle post-consumer plastic waste.

Defining an International Standard Set of Outcome Measures for Patients With Hip or Knee Osteoarthritis: Consensus of the International Consortium for Health Outcomes Measurement Hip and Knee Osteoarthritis Working Group.

OBJECTIVE: To define a minimum Standard Set of outcome measures and case-mix factors for monitoring, comparing, and improving health care for patients with clinically diagnosed hip or knee osteoarthritis (OA), with a focus on defining the outcomes that matter most to patients. METHODS: An international working group of patients, arthroplasty register experts, orthopedic surgeons, primary care physicians, rheumatologists, and physiotherapists representing 10 countries was assembled to review existing literature and practices for assessing outcomes of pharmacologic and nonpharmacologic OA therapies, including surgery. A series of 8 teleconferences, incorporating a modified Delphi process, were held to reach consensus. RESULTS: The working group reached consensus on a concise set of outcome measures to evaluate patients' joint pain, physical functioning, health-related quality of life, work status, mortality, reoperations, readmissions, and overall satisfaction with treatment result. To support analysis of these outcome measures, pertinent baseline characteristics and risk factor metrics were defined. Annual outcome measurement is recommended for all patients. CONCLUSION: We have defined a Standard Set of outcome measures for monitoring the care of people with clinically diagnosed hip or knee OA that is appropriate for use across all treatment and care settings. We believe this Standard Set provides meaningful, comparable, and easy to interpret measures ready to implement in clinics and/or registries globally. We view this set as an initial step that, when combined with cost data, will facilitate value-based health care improvements in the treatment of hip and knee OA.

Self management of haemodialysis for End Stage Renal Disease: a systematic review.

BACKGROUND: Exploring self management in End Stage Renal Disease is extremely important for patients as they encounter several challenges including ongoing symptoms, complex treatments and restrictions, uncertainty about life and a dependency on technology, all of which impact upon their autonomy particularly after commencement of haemodialysis. OBJECTIVE: To summarise the effects of nursing interventions which effect selfmanagement of haemodialysis for patients with End Stage Renal Disease. SEARCH STRATEGY: Search terms were chosen after reviewing text words and MeSH terms in relevant articles and databases. An extensive search of the literature from 1966 to June 2009 was conducted across a range of health databases including Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, PsycINFO and Web of Science. Further studies were identified from reference lists of all retrieved studies. SELECTION CRITERIA: We considered randomised controlled trials that compared interventions to improve self management of haemodialysis in patients with ESRD. In the absence of RCTs, comparative studies without randomisation as well as before and after studies were considered for inclusion. METHODOLOGICAL QUALITY: Study reports selected for retrieval were assessed by two independent reviewers for methodological quality prior to inclusion in the review using the standardised critical appraisal instruments for the Joanna Briggs Institute System for the Unified Management, Assessment and Review of Information package (SUMARI). DATA COLLECTION AND ANALYSIS: Data was extracted using the JBI data extraction tool for evidence of effectiveness independently by pairs of review authors. The evidence was reported in narrative summaries due to heterogeneity of the interventions of the studies. RESULTS AND CONCLUSIONS: Five randomised controlled trials were included in the review. Overall, the evidence found that psychosocial and educational interventions influenced self management of haemodialysis in this patient population. IMPLICATIONS FOR PRACTICE: There is evidence to suggest that implementing the following interventions may be effective in improving self management for patients with End Stage Renal Disease undergoing haemodialysis. IMPLICATIONS FOR RESEARCH: The design and interventions of future studies with statistically significant results should be replicated to allow for study comparisons, data analyses and the translation of results into clinical practice. There is a need for randomised controlled trials to include longer term, follow up data collection of the included interventions to show effectiveness of interventions over time.

Identification of a novel tubulin-destabilizing protein related to the chaperone cofactor E.

Factors that regulate the microtubule cytoskeleton are critical in determining cell behavior. Here we describe the function of a novel protein that we term E-like based on its sequence similarity to the tubulin-specific chaperone cofactor E. We find that upon overexpression, E-like depolymerizes microtubules by committing tubulin to proteosomal degradation. Our data suggest that this function is direct and is based on the ability of E-like to disrupt the tubulin heterodimer in vitro. Suppression of E-like expression results in an increase in the number of stable microtubules and a tight clustering of endocellular membranes around the microtubule-organizing center, while the properties of dynamic microtubules are unaffected. These observations define E-like as a novel regulator of tubulin stability, and provide a link between tubulin turnover and vesicle transport.