Explore the vast range of titles available.

Background Promoting integrated care is a key goal of the NHS Long Term Plan to improve population respiratory health, yet there is limited data-driven evidence of its effectiveness. The Morecambe Bay Respiratory Network is an integrated care initiative operating in the North-West of England since 2017. A key target area has been reducing referrals to outpatient respiratory clinics by upskilling primary care teams. This study aims to explore space-time patterns in referrals from general practice in the Morecambe Bay area to evaluate the impact of the initiative. Methods Data on referrals to outpatient clinics and chronic respiratory disease patient counts between 2012-2020 were obtained from the Morecambe Bay Community Data Warehouse, a large store of routinely collected healthcare data. For analysis, the data is aggregated by year and small area geography. The methodology comprises of two parts. The first explores the issues that can arise when using routinely collected primary care data for space-time analysis and applies spatio-temporal conditional autoregressive modelling to adjust for data complexities. The second part models the rate of outpatient referral via a Poisson generalised linear mixed model that adjusts for changes in demographic factors and number of respiratory disease patients. Results The first year of the Morecambe Bay Respiratory Network was not associated with a significant difference in referral rate. However, the second and third years saw significant reductions in areas that had received intervention, with full intervention associated with a 31.8% (95% CI 17.0-43.9) and 40.5% (95% CI 27.5-50.9) decrease in referral rate in 2018 and 2019, respectively. Conclusions Routinely collected data can be used to robustly evaluate key outcome measures of integrated care. The results demonstrate that effective integrated care has real potential to ease the burden on respiratory outpatient services by reducing the need for an onward referral. This is of great relevance given the current pressure on outpatient services globally, particularly long waiting lists following the COVID-19 pandemic and the need for more innovative models of care.

Background Outpatient services in the UK, and in particular outpatient neurology services, are under considerable pressure with an ever-increasing gap between capacity and demand. To improve services, we first need to understand the current situation. This study aims to explore the patterns of appointment type seen in outpatient neurology, in order to identify potential opportunities for change. Methods We use State Sequence Analysis (SSA) on routinely collected data from a single neurology outpatient clinic. SSA is an exploratory methodology which allows patterns within sequences of appointments to be discovered. We analyse sequences of appointments for the 18 months following a new appointment. Using SSA we create groups of similar appointment sequence patterns, and then analyse these clusters to determine if there are particular sequences common to different diagnostic categories. Results Of 1315 patients 887 patients had only one appointment. Among the 428 patients who had more than one appointment a 6 monthly cycle of appointments was apparent. SSA revealed that there were 11 distinct clusters of appointment sequence patterns. Further analysis showed that there are 3 diagnosis categories which have significant influence over which cluster a patient falls into: seizure/epilepsy, movement disorders, and headache. Conclusions Neurology outpatient appointment sequences show great diversity, but there are some patterns which are common to specific diagnostic categories. Information about these common patterns could be used to inform the structure of future outpatient appointments.

Background Approximately 900,000 MRI brain scans are performed annually in the United Kingdom alone, with incidental findings frequently encountered. One of the most prevalent findings is white matter hyperintensities (WMHs). WMHs often indicate cerebral small vessel disease (cSVD) but can also be associated with migraine and demyelination. Prospective population studies have already confirmed a high prevalence of WMHs in elderly patients. In younger patients, or when the radiological burden is low, WMHs are commonly considered non-specific. Routinely collected data represents a valuable resource to facilitate further study. We aimed to describe the prevalence of WMHs in a direct to scan referral population and to understand associations with age, demographics, performance status and referral criteria. Methods We performed a service evaluation of our local two-week wait suspected central nervous system cancer pathway to understand the association between age, demographics, performance status, referral criteria, imaging outcomes and both the prevalence and radiological characteristics of WMHs. Analysis was performed using R version 4.1.3. Results We identified 1033 patients, referred over a 30-month period. Mean patient age was 51.3±18.3 years with 65% females. As expected, WMHs were present on 89.7% of scans in patients aged over 80, with 98.1% of these consistent with cSVD upon review by an experienced neuroradiologist. We show an important association between WMHs deemed representative of cSVD and both performance status and levels of deprivation. However, WMHs were also present in approximately 1 in 5 patients under 50 years old and were typically deemed non-specific. Our analysis showed prevalence of WMH, its radiological burden and likelihood of WMHs being attributed to cSVD all increased with age. It is therefore feasible to consider that these changes may represent early cSVD. Conclusions We demonstrate a prevalence of radiological cSVD comparable to the wider literature in elderly patients whilst highlighting the potential underestimation of cSVD in the younger population, in whom further study of WMHs is required. There is potential for routinely collected data to define the prevalence and characteristics of radiological cSVD more accurately whilst facilitating further research.

By impairing both function and survival, the severe reduction in oxygen availability associated with high-altitude environments is likely to act as an agent of natural selection. We used genomic and candidate gene approaches to search for evidence of such genetic selection. First, a genome-wide allelic differentiation scan (GWADS) comparing indigenous highlanders of the Tibetan Plateau (3,200-3,500 m) with closely related lowland Han revealed a genome-wide significant divergence across eight SNPs located near EPAS1. This gene encodes the transcription factor HIF2α, which stimulates production of red blood cells and thus increases the concentration of hemoglobin in blood. Second, in a separate cohort of Tibetans residing at 4,200 m, we identified 31 EPAS1 SNPs in high linkage disequilibrium that correlated significantly with hemoglobin concentration. The sex-adjusted hemoglobin concentration was, on average, 0.8 g/dL lower in the major allele homozygotes compared with the heterozygotes. These findings were replicated in a third cohort of Tibetans residing at 4,300 m. The alleles associating with lower hemoglobin concentrations were correlated with the signal from the GWADS study and were observed at greatly elevated frequencies in the Tibetan cohorts compared with the Han. High hemoglobin concentrations are a cardinal feature of chronic mountain sickness offering one plausible mechanism for selection. Alternatively, as EPAS1 is pleiotropic in its effects, selection may have operated on some other aspect of the phenotype. Whichever of these explanations is correct, the evidence for genetic selection at the EPAS1 locus from the GWADS study is supported by the replicated studies associating function with the allelic variants.

Coverage of many routine childhood vaccinations in Afghanistan is low and declining. For instance, only 60% of eligible children received doses of the pentavalent vaccine in 2013-18, and this fell to 51% in 2022/23. To help explain the underlying causes behind this trend, this study aims to identify socio-demographic factors relating to caregivers whose children are either entirely unvaccinated or only partially vaccinated. A secondary analysis of Multi Indictor Cluster survey (MICS) 2022/23 data was conducted that focused on the level of vaccination children had received by the time they reach their first birthday. Children were categorized into unvaccinated, under-vaccinated, and fully vaccinated groups and binary and multinomial logistic regression models were fitted with household characteristics included as explanatory variables. The study data comprised 6,178 children aged 12-23 months with a predominance of rural areas (76.2%). In the multinomial analysis, children from Pashto-speaking households had significantly higher odds of being unvaccinated (OR = 3.54, 95% CI: 2.62-4.79) and under-vaccinated (OR = 2.19, 95% CI: 1.74-2.75) compared with those who were fully vaccinated. Maternal education was found to be highly significant, with children whose mothers had no formal education found to be more likely to be under vaccinated (69.1% unvaccinated/under-vaccinated) compared to those with primary education (41.9% unvaccinated/under-vaccinated, adjusted odds ratio: 0.59. 95% CI: 0.43-0.81). Children from the richest households had a full vaccination rate of 55.9% and were less likely to be unvaccinated than fully vaccinated (adjusted odds ratio: 0.22, 95% CI: 0.14-0.35). Full vaccination coverage is low, with approximately one-third of Afghan children aged 12-23 months receiving complete vaccine schedules. However, this study shows that rates vary significantly with a range of cultural, economic, and educational factors. These findings suggest that improving maternal healthcare access and education, along with focused outreach in specific demographic groups, may be effective in enhancing immunization coverage.

Recent years have seen a rise in digital interventions to improve coordination between care homes and NHS services, supporting remote sharing of data on the health of care home residents. Such interventions were key components in the response to the COVID-19 pandemic. This paper presents findings from the qualitative component of an evaluation of an implementation of the HealthCall Digital Care Homes application, across sites in northern England. The purpose of this qualitative component was to explore issues round feasibility, appropriacy, and acceptability. The implementation commenced prior to the pandemic and continued throughout. Semi-structured, qualitative interviews were held with stakeholders. Interviews were conducted remotely (October 2020 -June 2021). Data were analysed via a reflexive thematic analysis then mapped against Normalization Process Theory (NPT) constructs (coherence, collective action, cognitive participation, and reflexive monitoring) providing a framework to assess implementation success. Thirty-five participants were recruited: 16 care home staff, six NHS community nurses, five relatives of care home residents, four HealthCall team members, three care home residents, and one local authority commissioner. Despite facing challenges such as apprehension towards digital technology among care home staff, the application was viewed positively across stakeholder groups. The HealthCall team maintained formal and informal feedback loop with stakeholders. This resulted in revisions to the intervention and implementation. Appropriate training and problem solving from the HealthCall team and buy-in from care home and NHS staff were key to achieving success across NPT constructs. While this implementation appears broadly successful, establishing rapport and maintaining on-going support requires significant time, financial backing, and the right individuals in place across stakeholder groups to drive implementation and intervention evolution. The digital literacy of care home staff requires encouragement to enhance their readiness for digital interventions. The COVID-19 pandemic has pushed this agenda forward. Problems with stability across the workforce within care homes need to be addressed to avoid skill loss and support embeddedness of digital interventions.

CYP2A6 metabolically inactivates nicotine. Faster CYP2A6 activity is associated with heavier smoking and higher lung cancer risk. The CYP2A6 gene is polymorphic, including functional structural variants (SV) such as gene deletions (CYP2A6*4), duplications (CYP2A6*1 × 2), and hybrids with the CYP2A7 pseudogene (CYP2A6*12, CYP2A6*34). SVs are challenging to genotype due to their complex genetic architecture. Our aims were to develop a reliable protocol for SV genotyping, functionally phenotype known and novel SVs, and investigate the feasibility of CYP2A6 SV imputation from SNP array data in two ancestry populations. European- (EUR; n = 935) and African- (AFR; n = 964) ancestry individuals from smoking cessation trials were genotyped for SNPs using an Illumina array and for CYP2A6 SVs using Taqman copy number (CN) assays. SV-specific PCR amplification and Sanger sequencing was used to characterize a novel SV. Individuals with SVs were phenotyped using the nicotine metabolite ratio, a biomarker of CYP2A6 activity. SV diplotype and SNP array data were integrated and phased to generate ancestry-specific SV reference panels. Leave-one-out cross-validation was used to investigate the feasibility of CYP2A6 SV imputation. A minimal protocol requiring three Taqman CN assays for CYP2A6 SV genotyping was developed and known SV associations with activity were replicated. The first domain swap CYP2A6-CYP2A7 hybrid SV, CYP2A6*53, was identified, sequenced, and associated with lower CYP2A6 activity. In both EURs and AFRs, most SV alleles were identified using imputation (>70% and >60%, respectively); importantly, false positive rates were <1%. These results confirm that CYP2A6 SV imputation can identify most SV alleles, including a novel SV.

Background Care homes (long-term care facilities) were profoundly impacted early in the COVID-19 pandemic, both in terms of resident mortality and restrictions for infection control. This study investigated the impact on the emotional well-being of care home staff of challenges faced at this time, and the strategies used to manage them. Methods Semi-structured interviews conducted October 2020-June 2021 with care home staff and health service staff working with them explored the impact of the early waves of the COVID-19 pandemic (March 2020-June 2021). Interview data were analysed using reflexive thematic analysis. Results Interview participants were 16 care home staff and 10 health service staff. Analysis generated four key themes: 1)Anxiety and distress, 2)Overwhelming workload, 3)Pulling through; and 4)Resilience in a time of crisis. Care home staff experienced Anxiety and distress due to uncertainty of what to expect; witnessing illness and deaths of residents; concerns regarding their own health, and sometimes feeling their work was under-recognised. They also experienced an Overwhelming workload due to infection control measures, caring for sick residents and reduction in external healthcare support. Our theme of Pulling through reflects the peer support and problem-solving strategies with which care home staff managed the impact of the pandemic, along with a sense of responsibility and meaning towards their work. An overarching theme of Resilience in a time of crisis drew on the other three themes and describes how many staff managed, maintained, and often increased their work despite the challenges of the pandemic. Participants also described increasing emotional fatigue as the pandemic continued. Conclusions This paper builds on literature on the emotional impact of the pandemic on care home staff, also exploring ways that staff responded to this impact. These findings can help inform planning for future crises including disease outbreaks, and raise important questions for further work to develop pandemic preparedness in care homes and beyond. They also raise wider questions about the current cultural status of care work, which may have exposed care home staff to greater risk of distress, and which contrasts with the professionalism and responsibility shown by staff in response to pandemic challenges.

Background Early in the COVID-19 pandemic, care homes (long-term care facilities) globally were severely impacted in many ways, including end-of-life care and death of residents. They experienced significantly elevated mortality rates amongst residents, compounded by restrictions on support from external healthcare and specialist palliative care providers. Family access to dying residents was often severely restricted. This paper explores experiences of deaths, dying and end-of-life care in care homes during the first year of the pandemic (Spring 2020–2021). Methods As part of a wider study of experiences in care homes in Northern England during the early pandemic, we conducted semi-structured interviews with care home staff (16), residents (3), family members (5) and health service staff (10). Interviews were analysed using reflexive thematic analysis, this secondary analysis focusing on experiences of death and dying over the period. Results Thematic analysis generated three key themes: (1) Preparing for large scale deaths : Care home staff reported a sense of foreboding at requirements to prepare for large scale resident deaths, sometimes feeling left with minimal external support to manage this, and uneasy about the rapid roll-out of emergency care planning to residents; (2) Balancing support and policing visiting during the terminal phase : The requirement to restrict access for family members when their relatives were dying was experienced as distressing for both family members and care home staff; and, (3) Distress surrounding deaths for staff and families : Care home staff were distressed by the frequency and speed of deaths that they witnessed when their care home had a COVID-19 outbreak. Family separation near time of death was a source of distress for everyone involved, with suggestions that this led to regrets in bereavement for family members, and moral distress in staff. Conclusions The experience of death and dying in care homes in the early waves of the COVID-19 pandemic was extremely challenging for care home staff and family members. Our analysis suggests that the ramifications of stringent visitation policies and the consequent distress may shape experiences in bereavement. Monitoring for longer term consequences, such as prolonged grief and moral injury, should be a priority.

Nicotine is inactivated by the polymorphic CYP2A6 enzyme to cotinine and then to 3′hydroxycotinine. The Nicotine Metabolite Ratio (NMR; 3′hydroxycotinine/cotinine) is a heritable nicotine metabolism biomarker, varies with sex and ancestry, and influences smoking cessation and disease risk. We conducted sex-stratified genome-wide association studies of the NMR in European American (EA) and African American (AA) smokers (NCT01314001, NCT00666978). In EA females (n = 389) and males (n = 541), one significant (P < 5e−8) chromosome 19 locus was found (top variant: rs56113850, CYP2A6 (intronic), for C vs. T: females: beta = 0.67, P = 7.5e−22, 21.8% variation explained; males: beta = 0.75, P = 1.2e−37, 26.1% variation explained). In AA females (n = 503) and males (n = 352), the top variant was found on chromosome 19 but differed by sex (females: rs11878604, CYP2A6 (~ 16 kb 3′), for C vs. T: beta = − 0.71, P = 6.6e−26, 16.2% variation explained; males: rs3865454, CYP2A6 (~ 7 kb 3′), for G vs. T: beta = 0.64, P = 1.9e−19, 18.9% variation explained). In AA females, a significant region was found on chromosome 12 (top variant: rs12425845: P = 5.0e−9, TMEM132C (~ 1 Mb 5′), 6.1% variation explained) which was not significant in AA males. In AA males, significant regions were found on chromosomes 6 (top variant: rs9379805: P = 4.8e−9, SLC17A2 (~ 8 kb 5′), 8.0% variation explained) and 16 (top variant: rs77368288: P = 3.5e−8, ZNF469 (~ 92 kb 5′), 7.1% variation explained) which were not significant in AA females. Further investigation of these associations outside of chromosome 19 is required, as they did not replicate. Understanding how sex and ancestry influence nicotine metabolism genetics may improve personalized approaches for smoking cessation and risk prediction for tobacco-related diseases.