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Background: People with severe mental illness (SMI) such as schizophrenia and bipolar disorder are at a substantially higher risk of premature death in that they die between 10 and 20 years earlier than the general population. Cardiovascular disease (CVD) and diabetes are the main potentially avoidable contributors to early death. Research that explores the experiences of people with SMI highlights their struggles in engaging with health professionals and accessing effective and timely interventions for physical health conditions. A consequence of such struggles to navigate and access physical healthcare results in many people with SMI relying heavily on support provided by informal carers (e.g., family members, close friends). Despite this, the experiences of informal carers, and the roles they undertake in relation to supporting the physical health and psychotropic medication use of people with SMI, remains under-researched. Aims: To explore the impacts of providing care for physical health in severe mental illness on informal carers. Method: Thematic analysis of semi-structured interviews with eight informal carers of people with SMI in United Kingdom (UK) national health services. Results: Informal carers played an active part in the management of the patient's conditions and shared their illness experience. Involvement of informal carers was both emotional and practical and informal carers' own lives were affected in ways that were sometimes deeply profound. Informal carers were involved in both 'looking after' the patient from the perspective of doing practical tasks such as collecting dispensed medication from a community pharmacy (caring for) and managing feelings and emotions (caring about). Conclusions: Providing care for the physical health of someone with SMI can be understood as having two dimensions - 'caring for' and 'caring about'. The findings suggest a bidirectional relationship between these two dimensions, and both have a cost for the informal carer. With appropriate support informal carers could be more actively involved at all stages of care without increasing their burden. This should be with an awareness that carers may minimise the information they share about their own needs and impacts of their role to spare the person they care and themselves any distress. [ABSTRACT FROM AUTHOR]

Interval breast cancers (IBCs) are cancers diagnosed between screening episodes. Understanding the biological differences between IBCs and screen-detected breast-cancers (SDBCs) has the potential to improve mammographic screening and patient management. We analysed and compared the genomic landscape of 288 IBCs and 473 SDBCs by whole genome sequencing of paired tumour-normal patient samples collected as part of the UK 100,000 Genomes Project. Compared to SDBCs, IBCs were more likely to be lobular, higher grade, and triple negative. A more aggressive clinical phenotype was reflected in IBCs displaying features of genomic instability including a higher mutation rate and number of chromosomal structural abnormalities, defective homologous recombination and TP53 mutations. We did not however, find evidence to indicate that IBCs are associated with a significantly different immune response. While IBCs do not represent a unique molecular class of invasive breast cancer they exhibit a more aggressive phenotype, which is likely to be a consequence of the timing of tumour initiation. This information is relevant both with respect to treatment as well as informing the screening interval for mammography. [ABSTRACT FROM AUTHOR]

What Is New and Objectives: Older people from ethnic minorities experience the intersectionality of age and ethnicity in relation to complex medication management and polypharmacy. Minority ethnic groups in the United Kingdom are at risk of poor medication management because factors such as cultural beliefs, language barriers, lack of knowledge of how the healthcare system works may affect their ability to safely manage their medications. The aim of this systematic review was to review the literature focussing on medication management in the older population amongst ethnic minority communities in United Kingdom. Methods: The review was conducted and reported according to methods in the Cochrane Handbook and in the PRISMA 2020 statement using databases such as EMBASE, ASSIA, MEDLINE, PsychINFO and others. Studies conducted in the United Kingdom on individuals over 60 years of age and from a minority ethnic background were included. A thematic analysis was used to synthesize the results. Results and Discussion: Nine studies (eight from initial searches, one from a search update in 2021) met the inclusion criteria. Three main themes were identified: misbeliefs around medications, poor health literacy, communication and education as possible intervention to improve medication management. Misbeliefs around long‐term illnesses exert a negative impact on medication management. Poor health literacy around medications influences patients' adherence to treatments. Poor communication is perceived as barrier to successful medication management. Despite extensive searching, the team identified a limited number of studies and a lack of intersectional studies focussing on minority ethnic groups and the older population. What is New and Conclusion: Our findings suggest tailored education as a possible intervention to improve medication management amongst these minority groups. Future research should look at recruiting participants from specific ethnic groups and from rural as well as urban areas to explore how medication management operates in different areas of the United Kingdom. [ABSTRACT FROM AUTHOR]

Background: Informal carers play an important role in the care of patients with mental illness. Little is known of the relationship experience of the patient and their informal carer (caring dyad) as the context for the intersection between physical and mental health. Aim: This study aimed to explore the impact of comorbid cardiometabolic risk (CMR), metabolic syndrome (MetS) and related diseases and severe mental illness (SMI) on the caring dyad. Design: Between October 2018 and March 2020, we conducted 11 in‐depth semi‐structured interviews across 6 adult caring dyads, interviewing each individual separately. Setting: Dyads were recruited within the United Kingdom; informal carers were nominated by the patient as a person who provided a significant amount of support. Variable Being Studied: Participants were asked about the impacts of illness and caring on daily life. Data Analysis: Data were analysed at the dyad level using thematic analysis, comparing and contrasting responses from each individual. Results: Themes were identified: enhanced closeness, dissonance and balance within the caring dyad. Discussion and Conclusions: This study uses a particular population of patients with comorbid CMR factors, MetS and related diseases and SMI and their informal carers to explore the relevance and utility of caring dyads as an analytical framework to inform practice and policy. Future interventions should consider factors impacting on dyadic relationships to formulate effective and sustainable dyadic care and treatment to improve health outcomes for both patients with SMI and their informal carers. Patient/Public Involvement: In this study, patients and informal carers were participants. Topic guides were piloted with a patient and informal carer. [ABSTRACT FROM AUTHOR]

Introduction: We have previously reported rates of diagnosis of male hypogonadism in United Kingdom (UK) general practices. We aimed to identify factors associated with testosterone prescribing in UK general practice. Methods: We determined for 6741 general practices in England, the level of testosterone prescribing in men and the relation between volume of testosterone prescribing and (1) demographic characteristics of the practice, (2) % patients with specific comorbidities and (3) national GP patient survey results. Results: The largest volume (by prescribing volume) agents were injectable preparations at a total cost in the 12‐month period 2018/19 of £8,172,519 with gel preparations in second place: total cost £4,795,057. Transdermal patches, once the only alternative to testosterone injections or implants, were little prescribed: total cost £222,022. The analysis accounted for 0.27 of the variance in testosterone prescribing between general practices. Thus, most of this variance was not accounted for by the analysis. There was a strong univariant relation (r =.95, P <.001) between PDE5‐I prescribing and testosterone prescribing. Other multivariant factors independently linked with more testosterone prescribing were as follows: HIGHER proportion of men with type 2 diabetes(T2DM) on target control (HbA1c ≤ 58 mmol/mol) and HIGHER overall practice rating on the National Patient Survey for good experience, while non‐white ethnicity and socio‐economic deprivation were associated with less testosterone prescribing. There were a number of comorbidity factors associated with less prescribing of testosterone (such as T2DM, hypertension and stroke/TIA). Conclusion: Our analysis has indicated that variation between general practices in testosterone prescribing in a well developed health economy is only related to small degree (r2 = 0.27) to factors that we can define. This suggests that variation in amount of testosterone prescribed is largely related to general practitioner choice/other factors not studied and may be amenable to measures to increase knowledge/awareness of male hypogonadism, with implications for men's health. [ABSTRACT FROM AUTHOR]

It is proposed that, through restriction to individuals delineated as high risk, polygenic risk scores (PRSs) might enable more efficient targeting of existing cancer screening programmes and enable extension into new age ranges and disease types. To address this proposition, we present an overview of the performance of PRS tools (ie, models and sets of single nucleotide polymorphisms) alongside harms and benefits of PRS-stratified cancer screening for eight example cancers (breast, prostate, colorectal, pancreas, ovary, kidney, lung, and testicular cancer). For this modelling analysis, we used age-stratified cancer incidences for the UK population from the National Cancer Registration Dataset (2016–18) and published estimates of the area under the receiver operating characteristic curve for current, future, and optimised PRS for each of the eight cancer types. For each of five PRS-defined high-risk quantiles (ie, the top 50%, 20%, 10%, 5%, and 1%) and according to each of the three PRS tools (ie, current, future, and optimised) for the eight cancers, we calculated the relative proportion of cancers arising, the odds ratios of a cancer arising compared with the UK population average, and the lifetime cancer risk. We examined maximal attainable rates of cancer detection by age stratum from combining PRS-based stratification with cancer screening tools and modelled the maximal impact on cancer-specific survival of hypothetical new UK programmes of PRS-stratified screening. The PRS-defined high-risk quintile (20%) of the population was estimated to capture 37% of breast cancer cases, 46% of prostate cancer cases, 34% of colorectal cancer cases, 29% of pancreatic cancer cases, 26% of ovarian cancer cases, 22% of renal cancer cases, 26% of lung cancer cases, and 47% of testicular cancer cases. Extending UK screening programmes to a PRS-defined high-risk quintile including people aged 40–49 years for breast cancer, 50–59 years for colorectal cancer, and 60–69 years for prostate cancer has the potential to avert, respectively, a maximum of 102, 188, and 158 deaths annually. Unstratified screening of the full population aged 48–49 years for breast cancer, 58–59 years for colorectal cancer, and 68–69 years for prostate cancer would use equivalent resources and avert, respectively, an estimated maximum of 80, 155, and 95 deaths annually. These maximal modelled numbers will be substantially attenuated by incomplete population uptake of PRS profiling and cancer screening, interval cancers, non-European ancestry, and other factors. Under favourable assumptions, our modelling suggests modest potential efficiency gain in cancer case detection and deaths averted for hypothetical new PRS-stratified screening programmes for breast, prostate, and colorectal cancer. Restriction of screening to high-risk quantiles means many or most incident cancers will arise in those assigned as being low-risk. To quantify real-world clinical impact, costs, and harms, UK-specific cluster-randomised trials are required. The Wellcome Trust. [ABSTRACT FROM AUTHOR]

• The current minimum point prevalence for all skeletal muscle channelopathies is 1.99/100 000. • The minimum point prevalence of myotonia congenita is 1.13/100 000; for paramyotonia congenita/sodium channel myotonia is 0.35/100 000, for hypoPP/hyperPP is 0.41/100 000 and for Andersen Tawil Syndrome is 0.1/100 000. • Next generation sequencing as well as increased referral rates have been primary contributors to the almost doubled point prevalence rate from 1.12/100 000 to 1.99/100 000. We provide an up-to-date and accurate minimum point prevalence of genetically defined skeletal muscle channelopathies which is important for understanding the population impact, planning for treatment needs and future clinical trials. Skeletal muscle channelopathies include myotonia congenita (MC), sodium channel myotonia (SCM), paramyotonia congenita (PMC), hyperkalemic periodic paralysis (hyperPP), hypokalemic periodic paralysis (hypoPP) and Andersen- Tawil Syndrome (ATS). Patients referred to the UK national referral centre for skeletal muscle channelopathies and living in UK were included to calculate the minimum point prevalence using the latest data from the Office for National Statistics population estimate. We calculated a minimum point prevalence of all skeletal muscle channelopathies of 1.99/100 000 (95% CI 1.981–1.999). The minimum point prevalence of MC due to CLCN1 variants is 1.13/100 000 (95% CI 1.123–1.137), SCN4A variants which encode for PMC and SCM is 0.35/100 000 (95% CI 0.346 – 0.354) and for periodic paralysis (HyperPP and HypoPP) 0.41/100 000 (95% CI 0.406–0.414). The minimum point prevalence for ATS is 0.1/100 000 (95% CI 0.098–0.102). There has been an overall increase in point prevalence in skeletal muscle channelopathies compared to previous reports, with the biggest increase found to be in MC. This can be attributed to next generation sequencing and advances in clinical, electrophysiological and genetic characterisation of skeletal muscle channelopathies. [ABSTRACT FROM AUTHOR]

The primary webometric method for estimating the online impact of an organization is to count links to its website. Link counts have been available from commercial search engines for over a decade but this was set to end by early 2012 and so a replacement is needed. This article compares link counts to two alternative methods:URL citations and organization title mentions. New variations of these methods are also introduced.The three methods are compared against each other usingYahoo!.Two of the three methods (URL citations and organization title mentions) are also compared against each other using Bing. Evidence from a case study of 131 UK universities and 49 US Library and Information Science (LIS) departments suggests that Bing's Hit Count Estimates (HCEs) for popular title searches are not useful for webometric research but that Yahoo!'s HCEs for all three types of search and Bing's URL citation HCEs seem to be consistent. For exact URL counts the results of all three methods in Yahoo! and both methods in Bing are also consistent. Four types of accuracy factors are also introduced and defined: search engine coverage, search engine retrieval variation, search engine retrieval anomalies, and query polysemy. [ABSTRACT FROM AUTHOR]

The article explores on the effectiveness of electronic health records in Great Britain. It examines the sustainability of present healthcare systems in many industrialised countries such as Great Britain. Quantification of value of healthcare through cost-effectiveness determining the incremental costs related to health care outcomes improvement, is also emphasized.

Colorectal carcinoma (CRC) is a common cause of mortality 1 , but a comprehensive description of its genomic landscape is lacking 2-9 . Here we perform whole-genome sequencing of 2,023 CRC samples from participants in the UK 100,000 Genomes Project, thereby providing a highly detailed somatic mutational landscape of this cancer. Integrated analyses identify more than 250 putative CRC driver genes, many not previously implicated in CRC or other cancers, including several recurrent changes outside the coding genome. We extend the molecular pathways involved in CRC development, define four new common subgroups of microsatellite-stable CRC based on genomic features and show that these groups have independent prognostic associations. We also characterize several rare molecular CRC subgroups, some with potential clinical relevance, including cancers with both microsatellite and chromosomal instability. We demonstrate a spectrum of mutational profiles across the colorectum, which reflect aetiological differences. These include the role of Escherichia coli pks+ colibactin in rectal cancers 10 and the importance of the SBS93 signature 11-13 , which suggests that diet or smoking is a risk factor. Immune-escape driver mutations 14 are near-ubiquitous in hypermutant tumours and occur in about half of microsatellite-stable CRCs, often in the form of HLA copy number changes. Many driver mutations are actionable, including those associated with rare subgroups (for example, BRCA1 and IDH1), highlighting the role of whole-genome sequencing in optimizing patient care., (© 2024. The Author(s).)

Purpose: The COVID-19 pandemic has impacted healthcare systems globally, little is known about the trauma patterns during a national lockdown. The aim of this study is to delineate the trauma patterns and outcomes at Aintree University Teaching Hospital level 1 Major Trauma Centre (MTC) during the COVID-19 lockdown imposed by the U.K. government., Methods: A retrospective cohort study data from the Merseyside and Cheshire Trauma Audit and Research Network database were analysed. The 7-week 'lockdown period' was compared to a 7-week period prior to the lockdown and also to an equivalent 7-week period corresponding to the previous year., Results: A total of 488 patients were included in the study. Overall, there was 37.6% and 30.0% reduction in the number of traumatic injuries during lockdown. Road traffic collisions (RTC) reduced by 42.6% and 46.6%. RTC involving a car significantly reduced during lockdown, conversely, bike-related RTC significantly increased. No significant changes were noted in deliberate self-harm, trauma severity and crude mortality during lockdown. There was 1 mortality from COVID-19 infection in the lockdown cohort., Conclusion: Trauma continues during lockdown, our MTC has continued to provide a full service during lockdown. However, trauma patterns have changed and departments should adapt to balance these alongside the COVID-19 pandemic. As the U.K. starts its cautious transition out of lockdown, trauma services are required to be flexible during changes in national social restrictions and changing trauma patterns. COVID-19 and lockdown state were found to have no significant impact on survival outcomes for trauma.

Objective: To evaluate the impact of faecal immunochemical testing (FIT) prioritisation to mitigate the impact of delays in the colorectal cancer (CRC) urgent diagnostic (2-week-wait (2WW)) pathway consequent from the COVID-19 pandemic., Design: We modelled the reduction in CRC survival and life years lost resultant from per-patient delays of 2-6 months in the 2WW pathway. We stratified by age group, individual-level benefit in CRC survival versus age-specific nosocomial COVID-19-related fatality per referred patient undergoing colonoscopy. We modelled mitigation strategies using thresholds of FIT triage of 2, 10 and 150 µg Hb/g to prioritise 2WW referrals for colonoscopy. To construct the underlying models, we employed 10-year net CRC survival for England 2008-2017, 2WW pathway CRC case and referral volumes and per-day-delay HRs generated from observational studies of diagnosis-to-treatment interval., Results: Delay of 2/4/6 months across all 11 266 patients with CRC diagnosed per typical year via the 2WW pathway were estimated to result in 653/1419/2250 attributable deaths and loss of 9214/20 315/32 799 life years. Risk-benefit from urgent investigatory referral is particularly sensitive to nosocomial COVID-19 rates for patients aged >60. Prioritisation out of delay for the 18% of symptomatic referrals with FIT >10 µg Hb/g would avoid 89% of these deaths attributable to presentational/diagnostic delay while reducing immediate requirement for colonoscopy by >80%., Conclusions: Delays in the pathway to CRC diagnosis and treatment have potential to cause significant mortality and loss of life years. FIT triage of symptomatic patients in primary care could streamline access to colonoscopy, reduce delays for true-positive CRC cases and reduce nosocomial COVID-19 mortality in older true-negative 2WW referrals. However, this strategy offers benefit only in short-term rationalisation of limited endoscopy services: the appreciable false-negative rate of FIT in symptomatic patients means most colonoscopies will still be required., Competing Interests: Competing interests: ML has received honoraria from Pfizer, EMD Merck Serono and Roche for speaking honoraria unrelated to this work. ML has received an unrestricted educational grant from Pfizer for research unrelated to this work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)