Designing a primary care pharmacist-led review for people treated with opioids for persistent pain: a multi-method qualitative study.

BACKGROUND: Opioids are frequently prescribed for persistent non-cancer pain despite limited evidence of long-term effectiveness and risk of harm. Evidence-based interventions to address inappropriate opioid prescribing are lacking. AIM: To explore perspectives of people living with persistent pain to understand barriers and facilitators in reducing opioids in the context of a pharmacist-led primary care review, and identify review components and features for optimal delivery. DESIGN & SETTING: Primary care multi-method qualitative study. METHOD: Adults with experience of persistent pain and taking opioids participated in semi-structured interviews (n=15, 73% female) and an online discussion forum (n=31). The Theoretical Domains Framework (TDF) provided a framework for data collection and thematic analysis, involving deductive analysis to TDF domains, inductive analysis within-domains to generate subthemes, and subtheme comparison to form across-domain overarching themes. The behaviour change technique taxonomy v.1 and motivational behaviour change technique classification system were used to systematically map themes to behaviour change techniques to identify potential review components and delivery features. RESULTS: 32 facilitator and barrier subthemes for patients reducing opioids were identified across 13 TDF domains. These combined into six overarching themes: learning to live with pain, opioid reduction expectations, assuming a medical model, pharmacist-delivered reviews, pharmacist-patient relationship and patient engagement. Subthemes mapped to 21 unique behaviour change techniques, yielding 17 components and five delivery features for the proposed PROMPPT review. CONCLUSION: This study generated theoretically-informed evidence for design of a practice pharmacist-led PROMPPT review. Future research will test the feasibility and acceptability of the PROMPPT review and pharmacist training.

Bayesian profile regression for clustering analysis involving a longitudinal response and explanatory variables.

The identification of sets of co-regulated genes that share a common function is a key question of modern genomics. Bayesian profile regression is a semi-supervised mixture modelling approach that makes use of a response to guide inference toward relevant clusterings. Previous applications of profile regression have considered univariate continuous, categorical, and count outcomes. In this work, we extend Bayesian profile regression to cases where the outcome is longitudinal (or multivariate continuous) and provide PReMiuMlongi, an updated version of PReMiuM, the R package for profile regression. We consider multivariate normal and Gaussian process regression response models and provide proof of principle applications to four simulation studies. The model is applied on budding yeast data to identify groups of genes co-regulated during the Saccharomyces cerevisiae cell cycle. We identify 4 distinct groups of genes associated with specific patterns of gene expression trajectories, along with the bound transcriptional factors, likely involved in their co-regulation process.

Exploring the potential extended role of community pharmacy in the management of osteoarthritis: A multi-methods study with pharmacy staff and other healthcare professionals.

INTRODUCTION: Osteoarthritis is the commonest form of chronic joint pain, which patients often self-manage before seeking healthcare advice. Patients frequently seek advice from community pharmacies, and a recent policy has recommended integrating community pharmacies into long-term condition pathways. This study explored community pharmacy teams' (CPs) and other healthcare professionals' (HCPs) views on community pharmacies providing an extended role for osteoarthritis management, identifying potential barriers and facilitators to this. METHODS: A multi-methods study comprising surveys of CPs and other HCPs, followed by qualitative interviews. Descriptive statistics were used in an exploratory analysis of the survey data. Qualitative data were analysed using reflexive thematic analysis and the identified barriers and facilitators were mapped to the Theoretical Domains Framework. RESULT: CPs and other HCPs in the surveys and interviews reported that an extended role for osteoarthritis management could include: a subjective assessment, explaining the joint problem and its treatment, medication management and support for self-care. There was less consensus on diagnosing the problem as OA and completing an objective assessment. A key facilitator was training to deliver the role, whilst barriers were high workload and lack of access to General Practitioner medical records. DISCUSSION: Acceptable elements of an extended community pharmacy role for osteoarthritis centre around the provision of information, advice on medication and supported self-management. CONCLUSION: CPs are well placed to contribute towards evidenced-based osteoarthritis management. Feasibility testing of delivering the extended role is needed and future implementation requires training for CPs and raising public awareness of the extended role.

REST: a preoperative tailored sleep intervention for patients undergoing total knee replacement - feasibility study for a randomised controlled trial.

OBJECTIVES: To test the feasibility of a randomised controlled trial (RCT) of a novel preoperative tailored sleep intervention for patients undergoing total knee replacement. DESIGN: Feasibility two-arm two-centre RCT using 1:1 randomisation with an embedded qualitative study. SETTING: Two National Health Service (NHS) secondary care hospitals in England and Wales. PARTICIPANTS: Preoperative adult patients identified from total knee replacement waiting lists with disturbed sleep, defined as a score of 0-28 on the Sleep Condition Indicator questionnaire. INTERVENTION: The REST intervention is a preoperative tailored sleep assessment and behavioural intervention package delivered by an Extended Scope Practitioner (ESP), with a follow-up phone call 4 weeks postintervention. All participants received usual care as provided by the participating NHS hospitals. OUTCOME MEASURES: The primary aim was to assess the feasibility of conducting a full trial. Patient-reported outcomes were assessed at baseline, 1-week presurgery, and 3 months postsurgery. Data collected to determine feasibility included the number of eligible patients, recruitment rates and intervention adherence. Qualitative work explored the acceptability of the study processes and intervention delivery through interviews with ESPs and patients. RESULTS: Screening packs were posted to 378 patients and 57 patients were randomised. Of those randomised, 20 had surgery within the study timelines. An appointment was attended by 25/28 (89%) of participants randomised to the intervention. Follow-up outcomes measures were completed by 40/57 (70%) of participants presurgery and 15/57 (26%) postsurgery. Where outcome measures were completed, data completion rates were 80% or higher for outcomes at all time points, apart from the painDETECT: 86% complete at baseline, 72% at presurgery and 67% postsurgery. Interviews indicated that most participants found the study processes and intervention acceptable. CONCLUSIONS: This feasibility study has demonstrated that with some amendments to processes and design, an RCT to evaluate the clinical and cost-effectiveness of the REST intervention is feasible. TRIAL REGISTRATION NUMBER: ISRCTN14233189.

Polypharmacy in atrial fibrillation: A prospective analysis of mortality and ischemic stroke using the Clinical Practice Research Datalink.

Background: Observational studies of polypharmacy and the risk of death or stroke in individuals with atrial fibrillation (AF) have produced inconsistent findings. By using propensity score matching (PSM) and Cox regression, this study aimed to determine whether polypharmacy (five to nine medicines) in the 3 months following AF diagnosis, is associated with an increased risk of death or ischemic stroke, compared to non-polypharmacy (one to four medicines). Methods: A prospective cohort study using data from the Clinical Practice Research Datalink (2006-2019). Data from 23 629 individuals with AF were analyzed. Cox regression models were adjusted for age, gender, morbidities, obesity, alcohol, smoking, and wealth. In the PSM models, cases and controls with near identical health profiles were selected from the study pool. The risk of death and stroke were presented as hazard ratios (HRs) with 95% confidence intervals (CIs). Results: 68.9% (n = 16 271) of the participants had polypharmacy. PSM showed that polypharmacy was associated with an increased risk of death during follow-up (HR 1.32; 95% CI: 1.19-1.47, p < .01), but not ischemic stroke (HR 0.84; 95% CI: 0.69-1.02, p = .08). Conclusion: Polypharmacy was associated with an increased risk of death during follow-up, but not ischemic stroke, in individuals with AF. The effects of comorbidity and other confounding factors were reduced by using PSM. This study focused on the overall medication burden; however, further research is needed to identify which specific medications in polypharmacy regimens increase the risk of mortality in AF. These findings could inform prescribing practices in the future.

Grant funding among underrepresented minority and women urologists at academic institutions.

INTRODUCTION: Grant funding to Urology has decreased over the last decade. Documented lack of gender and race diversity at the faculty level raises concerns for funding disparities. This study sought to characterize disparities based upon race and gender in National Institutes of Health (NIH) funding data to Urologic faculty. METHODS AND MATERIALS: Data from 145 ACGME accredited Urology residency programs incorporating faculty gender and underrepresented in medicine (URiM) status was utilized. The NIH Research Portfolio Online Report Tool was queried between 1985 and 2023 for grants related to current Urology faculty. URiM status, gender, years of practice, academic rank, and Doximity residency program rank were factors in multivariable analysis. RESULTS: A total of 2,131 faculty were included. Three hundred one Urologists received 793 urologic grants for a total of $993,919,052 in funding. By race, grants were awarded to: White 72.9%, Asian 21.8%, Hispanic 3.0%, Black 2.1%. Men received 708 grants (89.3%) worth $917,083,475 total. Women received 85 grants (10.7%) worth $76,835,577 total. Likelihood of being awarded a grant was significantly associated with non-URiM status (p < 0.001) and men (p < 0.0001). On multivariable analysis, Doximity rank (p < 0.001) and academic rank (p < 0.001) were significant predictors of receiving a grant; male gender, URiM status, and years of practice were not. Academic rank was also a significant predictor of number of grants received (p = 0.04) and total funding (p = 0.04); years of practice, Doximity rank, URiM status, and gender were not. CONCLUSIONS: NIH grants were more likely awarded to higher ranked faculty from higher Doximity ranked institutions with no differences based on URiM status or gender.

Mental health in the COVID-19 pandemic: A longitudinal analysis of the CLoCk cohort study.

BACKGROUND: Little is known about the long-term mental health consequences of the pandemic in children and young people (CYP), despite extremely high levels of exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus and the disruption to schooling and leisure activities due to the resultant restrictions. There are mixed findings from systematic reviews of how the pandemic affected CYP's mental health, which may be due to heterogeneous methods and poor quality studies. Most, but not all, suggest deterioration in mental health but population level studies may obscure the differing experiences of subgroups. The study questions are: (i) are there subgroups of CYP with distinct mental health profiles over the course of the second year of the Coronavirus Disease 2019 (COVID-19) pandemic (between April 2021 and May 2022); and (ii) do vulnerability factors influence CYP's mental health trajectories. METHODS AND FINDINGS: A matched longitudinal cohort study of non-hospitalised test-positive and test-negative 11- to 17-year-old CYP in England were recruited from the UK Health Security Agency having undergone PCR testing for COVID-19. They completed the Strengths and Difficulties Questionnaire (SDQ) at least twice over a 12-month follow-up period. Overall, 8,518 of 17,918 (47.5%) CYP who returned their first SDQ at 3 or 6 months post-testing were included in the analytical sample. Associations between age, sex, ethnicity, socioeconomic status (SES), and an educational health and care plan (EHCP, indicating special educational needs) on SDQ score trajectories were examined separately, after adjusting for PCR test result. Findings from multilevel mixed-effects linear regression model showed that on average mental health symptoms as measured by the total SDQ score increased over time (B = 0.11 (per month), 95% CI = 0.09 to 0.12, p < 0.001) although this increase was small and not clinically significant. However, associations with time varied by age, such that older participants reported greater deterioration in mental health over time (B = 0.12 (per month), 95% CI = 0.10 to 0.14 for 15 to 17y; 0.08 (95% CI = 0.06 to 0.10) for 11 to 14y; pinteraction = 0.002) and by sex, with greater deterioration in girls. Children with an EHCP experienced less deterioration in their mental health compared to those without an EHCP. There was no evidence of differences in rate of change in total SDQ by ethnicity, SES, or physical health. Those with worse prior mental health did not appear to be disproportionately negatively affected over time. There are several limitations of the methodology including relatively low response rates in CLoCk and potential for recall bias. CONCLUSIONS: Overall, there was a statistically but not clinically significant decline in mental health during the pandemic. Sex, age, and EHCP status were important vulnerability factors that were associated with the rate of mental health decline, whereas ethnicity, SES, and prior poor physical health were not. The research highlights individual factors that could identify groups of CYP vulnerable to worsening mental health.

Co-development and testing of an extended community pharmacy model of service delivery for managing osteoarthritis: protocol for a sequential, multi-methods study (PharmOA).

BACKGROUND: Osteoarthritis is a common, painful and disabling long-term condition. Delivery of high-quality guideline-informed osteoarthritis care that successfully promotes and maintains supported self-management is imperative. However, osteoarthritis care remains inconsistent, including under use of core non-pharmacological approaches of education, exercise and weight loss. Community pharmacies are an accessible healthcare provider. United Kingdom government initiatives are promoting their involvement in a range of long-term conditions, including musculoskeletal conditions. It is not known what an enhanced community pharmacy role for osteoarthritis care should include, what support is needed to deliver such a role, and whether it would be feasible and acceptable to community pharmacy teams. In this (PharmOA) study, we aim to address these gaps, and co-design and test an evidence-based extended community pharmacy model of service delivery for managing osteoarthritis. METHODS: Informed by the Theoretical Domains Framework, Normalisation Process Theory, and the Medical Research Council (MRC) framework for developing complex interventions, we will undertake a multi-methods study involving five phases: 1. Systematic review to summarise currently available evidence on community pharmacy roles in supporting adults with osteoarthritis and other chronic (non-cancer) pain. 2. Cross-sectional surveys and one-to-one qualitative interviews with patients, healthcare professionals and pharmacy staff to explore experiences of current, and potential extended community pharmacy roles, in delivering osteoarthritis care. 3. Stakeholder co-design to: a) agree on the extended role of community pharmacies in osteoarthritis care; b) develop a model of osteoarthritis care within which the extended roles could be delivered (PharmOA model of service delivery); and c) refine existing tools to support community pharmacies to deliver extended osteoarthritis care roles (PharmOA tools). 4. Feasibility study to explore the acceptability and feasibility of the PharmOA model of service delivery and PharmOA tools to community pharmacy teams. 5. Final stakeholder workshop to: a) finalise the PharmOA model of service delivery and PharmOA tools, and b) if applicable, prioritise recommendations for its wider future implementation. DISCUSSION: This novel study paves the way to improving access to and availability of high-quality guideline-informed, consistent care for people with osteoarthritis from within community pharmacies.

Children and young people's reported contact with professional services for mental health concerns: a secondary data analysis.

Children and young people's mental health services have been under increasing pressure following COVID-19. Understanding, for which channels help is sought from, will highlight services needing support. This study aims to explore the professional services that parents of children, and young people get help from when they have a concern for the child's/their mental health. Secondary analysis of data is taken from Mental Health of Children and Young People in England Survey, 2017. 7608 reports of mental health-related contact with professional services from parents of 5-16 year-olds and self-reports from young people aged 17-19 were available. Service contact was reported by Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnosis, age, gender and ethnicity. Less than two-thirds of children and young people with a DSM-V diagnosis (63.5% (95% CI 58.6-68.1) aged 5-10, and 64.0% (95% CI 59.4-68.4) aged 11-16) reported contact with any professional services. The figure was lower for those aged 17-19; 50.1% (95% CI 42.8-58.2), p = 0.005. Children and young people aged 5-16 from Black (11.7%; 95% CI 2.4-41.4), Asian (55.1%; 95% CI 34.7-73.9) and Mixed (46.0%; 95% CI 32.4-60.3) ethnic groups reported less contact with professional services compared to those from the White group (66.9%; 95% CI 63.5-70.2). Patterns of service access during the three main educational stages aid with understanding service need during childhood. These lower levels of reported service access for young people aged 17-19 with a DSM-V diagnosis and those in ethnic minority groups demand further investigation.

Same sex-attraction as a predictor of suicide and self-harm behaviours: The role of bullying and social support.

Sexual minority youth are at higher risk of self-harming than heterosexual adolescents. Understanding why sexual minority youth are more vulnerable to poor mental health and identifying factors that might buffer against this risk is important for developing targeted interventions. We used the Millennium Cohort Study to investigate whether same-sex attraction at age 14 is associated with suicide attempts and self-harm at age 17. Additionally, we tested whether bullying victimisation might mediate any observed associations, and whether social support might protect against any increased risk. Sexual minority youth were 2.44 times more likely to attempt suicide and 2.59 times more likely to self-harm aged 17. There was no evidence for an association between greater social support and lower levels of self-harm. However, greater social support in sexual minority youth is associated with reduced risk for suicide attempt. Bullying partially mediated the relationship between same-sex attraction and mental health. Greater levels in bullying in sexual minority youth were associated with 1.32 times higher risk for suicide and 1.30 times higher risk for self-harm. Social support was not associated with reduced risk of suicide attempt or self-harm among bullied sexual minority youth. Sexual minority youth in the UK are at higher risk for suicide attempt and self-harm. To address this disparity, health and educational practitioners should understand this heightened risk for poor mental health, and address bullying as one risk factor. Further interventions are needed to assist sexual minority youth beyond social support provision through friends and family.

Risk of new onset and persistent psychopathology in children with long-term physical health conditions: a population-based cohort study.

Children and young people (CYP) with long-term physical health conditions (pLTCs) have increased risk of psychopathology compared to physically healthier peers. We explored risk factors for new onset and persistent psychiatric disorders in CYP with pLTCs compared to CYP without pLTCs. This 3-year follow-up study involved a UK representative sample of CYP from the British Child and Adolescent Mental Health Surveys (N = 7804). We examined potential baseline predictors of new onset and persistent psychiatric disorders at follow-up in four groups of children based on the presence of any physical and/or any psychiatric conditions at baseline. Psychiatric disorders were assessed using standardised multi-informant diagnostic assessment. Separate multivariable binary logistic regressions were conducted for each group. In CYP with pLTCs, rented housing (aOR = 1.42, 95% CI 1.01 to 1.99), non-traditional family structure (aOR = 2.08, 95% CI 1.42 to 3.05), increased parental distress (aOR = 1.09, 95% CI 1.04 to 1.14), and greater peer relationship difficulties (aOR = 1.29, 95% CI 1.19 to 1.39) predicted future psychiatric disorder. Only peer relationship difficulties predicted persistent disorder (aOR = 1.27, 95% CI 1.17 to 1.38) in this group. A greater number of factors predicted the onset of psychiatric disorder in CYP with pLTCs compared to physically healthier peers and similarly, a higher number of factors predicted persistent disorder in CYP without pLTCs. CYP with pLTCs might comprise a group with different vulnerabilities, some of which are potentially tractable and may be useful indicators of patients who require preventable or management interventions.

Neuroinflammation is linked to dementia risk in Parkinson's disease.

The development of dementia is a devastating aspect of Parkinson's disease (PD), affecting nearly half of patients within 10 years post-diagnosis. For effective therapies to prevent and slow progression to PD dementia (PDD), the key mechanisms that determine why some people with PD develop early dementia, while others remain cognitively unaffected, need to be understood. Neuroinflammation and tau protein accumulation have been demonstrated in post-mortem PD brains, and in many other neurodegenerative disorders leading to dementia. However, whether these processes mediate dementia risk early on in the PD disease course is not established. To this end, we used PET neuroimaging with 11C-PK11195 to index neuroinflammation and 18F-AV-1451 for misfolded tau in early PD patients, stratified according to dementia risk in our 'Neuroinflammation and Tau Accumulation in Parkinson's Disease Dementia' (NET-PDD) study. The NET-PDD study longitudinally assesses newly-diagnosed PD patients in two subgroups at low and high dementia risk (stratified based on pentagon copying, semantic fluency, MAPT genotype), with comparison to age- and sex-matched controls. Non-displaceable binding potential (BPND) in 43 brain regions (Hammers' parcellation) was compared between groups (pairwise t-tests), and associations between BPND of the tracers tested (linear-mixed-effect models). We hypothesized that people with higher dementia risk have greater inflammation and/or tau accumulation in advance of significant cognitive decline. We found significantly elevated neuroinflammation (11C-PK11195 BPND) in multiple subcortical and restricted cortical regions in the high dementia risk group compared with controls, while in the low-risk group this was limited to two cortical areas. The high dementia risk group also showed significantly greater neuroinflammation than the low-risk group concentrated on subcortical and basal ganglia regions. Neuroinflammation in most of these regions was associated with worse cognitive performance (Addenbrooke's Cognitive Examination-III score). Overall neuroinflammation burden also correlated with serum levels of pro-inflammatory cytokines. In contrast, increases in 18F-AV-1451 (tau) BPND in PD versus controls were restricted to subcortical regions where off-target binding is typically seen, with no relationship to cognition found. Whole-brain 18F-AV-1451 burden correlated with serum phosphorylated tau181 levels. Although there was minimal regional tau accumulation in PD, regional neuroinflammation and tau burden correlated in PD participants, with the strongest association in the high dementia risk group, suggesting possible co-localization of these pathologies. In conclusion, our findings suggest that significant regional neuroinflammation in early PD might underpin higher risk for PDD development, indicating neuroinflammation as a putative early modifiable aetiopathological disease factor to prevent or slow dementia development using immunomodulatory strategies.

Pre-existing musculoskeletal pain and its association with mortality in newly diagnosed co-morbid conditions: an electronic health record cohort study.

Objective: Musculoskeletal pain is a common risk factor for co-morbid conditions and might increase the risk of poor outcomes. The objective was to determine whether patients with pre-existing musculoskeletal pain have an increased risk for mortality following a new diagnosis of a co-morbid condition. Methods: Patients aged ≥45 years with a new diagnosis of acute coronary syndrome (ACS), stroke, cancer, dementia or pneumonia recorded in a UK electronic primary care database linked to hospital and mortality records were examined. The association of mortality with musculoskeletal pain (inflammatory conditions, OA and regional pain) was determined. Results: The sample size varied from 128 649 (stroke) to 406 289 (cancer) by cohort, with 22-31% having pre-existing musculoskeletal conditions. In the ACS cohort, there was a higher rate of mortality for all musculoskeletal types. There were also higher unadjusted mortality rates in patients with inflammatory arthritis compared with those without musculoskeletal pain in the stroke, cancer and dementia cohorts and for patients with OA in the stroke and cancer cohorts. After adjustment for the number of prescribed medications and age, the increased risk of mortality remained only for patients with inflammatory arthritis in the ACS cohort (adjusted hazard ratio = 1.07; 95% CI 1.03, 1.10). Conclusion: Older adults with inflammatory arthritis and OA have increased risk of mortality when they develop a new condition, which seems to be related to the prescription of multiple medicines. Pre-existing musculoskeletal pain is an indicator of a complex patient who is at risk of poorer outcomes at the onset of new illnesses.

Molecular Architecture of Salmonella Typhimurium Virus P22 Genome Ejection Machinery.

Bacteriophage P22 is a prototypical member of the Podoviridae superfamily. Since its discovery in 1952, P22 has become a paradigm for phage transduction and a model for icosahedral viral capsid assembly. Here, we describe the complete architecture of the P22 tail apparatus (gp1, gp4, gp10, gp9, and gp26) and the potential location and organization of P22 ejection proteins (gp7, gp20, and gp16), determined using cryo-EM localized reconstruction, genetic knockouts, and biochemical analysis. We found that the tail apparatus exists in two equivalent conformations, rotated by ∼6° relative to the capsid. Portal protomers make unique contacts with coat subunits in both conformations, explaining the 12:5 symmetry mismatch. The tail assembles around the hexameric tail hub (gp10), which folds into an interrupted ß-propeller characterized by an apical insertion domain. The tail hub connects proximally to the dodecameric portal protein and head-to-tail adapter (gp4), distally to the trimeric tail needle (gp26), and laterally to six trimeric tailspikes (gp9) that attach asymmetrically to gp10 insertion domain. Cryo-EM analysis of P22 mutants lacking the ejection proteins gp7 or gp20 and biochemical analysis of purified recombinant proteins suggest that gp7 and gp20 form a molecular complex associated with the tail apparatus via the portal protein barrel. We identified a putative signal transduction pathway from the tailspike to the tail needle, mediated by three flexible loops in the tail hub, that explains how lipopolysaccharide (LPS) is sufficient to trigger the ejection of the P22 DNA in vitro.

A novel stabilization mechanism accommodating genome length variation in evolutionarily related viral capsids.

Tailed bacteriophages are one of the most numerous and diverse group of viruses. They store their genome at quasi-crystalline densities in capsids built from multiple copies of proteins adopting the HK97-fold. The high density of the genome exerts an internal pressure, requiring a maturation process that reinforces their capsids. However, it is unclear how capsid stabilization strategies have adapted to accommodate the evolution of larger genomes in this virus group. Here we characterized a novel capsid reinforcement mechanism in two evolutionary-related actinobacteriophages that modifies the length of a stabilization protein to accommodate a larger genome while maintaining the same capsid size. We used cryo-EM to reveal that capsids contained split hexamers of HK97-fold proteins with a stabilization protein in the chasm. The observation of split hexamers in mature capsids was unprecedented, so we rationalized this result mathematically, discovering that icosahedral capsids can be formed by all split or skewed hexamers as long as their T-number is not a multiple of three. Our results suggest that analogous stabilization mechanisms can be present in other icosahedral capsids, and they provide a strategy for engineering capsids accommodating larger DNA cargoes as gene delivery systems.

Does Having a Sibling Affect Autistic People's Empathy?

This study examined whether autistic people with siblings score higher on measures of empathy than those without siblings. Cohorts of autistic children (n = 939; mean age = 7.35 years (SD = 2.15)) and autistic adults (n = 736; mean age = 37 years (SD = 12.39)) from the Cambridge Autism Research Database (CARD) were each divided into two groups: with or without siblings. Empathy was measured using the children version of the Empathy Quotient (EQ) (parent-report) for children. For adults, the EQ (self-report version) and the Reading the Mind in the Eyes Test (RMET) were used. Contrary to the hypothesis, autistic children without siblings scored higher on EQ than those with siblings (t(283.70) = 4.20, p < .001; d = 0.50). In adults, there was no difference between autistic adults with and without siblings on both measures, but there was an interaction effect between sex and group on the RMET (f(1732) = 4.10, p = 0.04): whilst autistic males without siblings on average scored lower than females, autistic males with siblings on average performed similarly to females. Future research should investigate the possible effect of siblings on autistic males' empathy performance in a larger cohort of autistic individuals. Children's empathic abilities may be underestimated by their parents when they have siblings due to a contrast effect.

Relationship between deprivation, and the uptake and use of the common ailments service in community pharmacies in Wales.

OBJECTIVES: Since 2013 community pharmacies in Wales have been commissioned to provide a common ailments service (CAS), providing pharmacy medicine without charge to patients. In the first review of national pharmacy data, this study aimed to describe the relationship between provision of CAS and deprivation. METHODS: A retrospective observational study, using CAS claims data from April 2022 to March 2023 collected as part of routine service delivery. Consultation data were matched to the index of multiple deprivation (IMD) decile of the providing pharmacy. Linear regression was used to describe the correlation between CAS claims data and IMD deciles of the pharmacy postcode. KEY FINDINGS: In the study period, 239 028 consultations were recorded. More than twice as many consultations were carried out in pharmacies located in the most deprived decile (33 950) than in pharmacies in the least deprived decile (14 465). Linear regression demonstrated a significant correlation r(10) = -0.927, P < 0.001. There was a strong relationship between greater numbers of consultations and greater deprivation of the pharmacy postcode (R2 = 0.887). This significant correlation with deprivation was also found in the majority of individual conditions. There was no significant correlation between deprivation decile and the number of consultations per patient. CONCLUSIONS: Community pharmacies offer a key resource for tackling health inequalities. Patients in those areas with the greatest need are those most likely to use the CAS in pharmacies and receive the care they need. Commissioning services like this naturally supports deprived communities, through a combination of patient behaviours, location, and accessibility.

Brain Growth Charts for Quantitative Analysis of Pediatric Clinical Brain MRI Scans with Limited Imaging Pathology.

Background Clinically acquired brain MRI scans represent a valuable but underused resource for investigating neurodevelopment due to their technical heterogeneity and lack of appropriate controls. These barriers have curtailed retrospective studies of clinical brain MRI scans compared with more costly prospectively acquired research-quality brain MRI scans. Purpose To provide a benchmark for neuroanatomic variability in clinically acquired brain MRI scans with limited imaging pathology (SLIPs) and to evaluate if growth charts from curated clinical MRI scans differed from research-quality MRI scans or were influenced by clinical indication for the scan. Materials and Methods In this secondary analysis of preexisting data, clinical brain MRI SLIPs from an urban pediatric health care system (individuals aged ≤22 years) were scanned across nine 3.0-T MRI scanners. The curation process included manual review of signed radiology reports and automated and manual quality review of images without gross pathology. Global and regional volumetric imaging phenotypes were measured using two image segmentation pipelines, and clinical brain growth charts were quantitatively compared with charts derived from a large set of research controls in the same age range by means of Pearson correlation and age at peak volume. Results The curated clinical data set included 532 patients (277 male; median age, 10 years [IQR, 5-14 years]; age range, 28 days after birth to 22 years) scanned between 2005 and 2020. Clinical brain growth charts were highly correlated with growth charts derived from research data sets (22 studies, 8346 individuals [4947 male]; age range, 152 days after birth to 22 years) in terms of normative developmental trajectories predicted by the models (median r = 0.979). Conclusion The clinical indication of the scans did not significantly bias the output of clinical brain charts. Brain growth charts derived from clinical controls with limited imaging pathology were highly correlated with brain charts from research controls, suggesting the potential of curated clinical MRI scans to supplement research data sets. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Ertl-Wagner and Pai in this issue.

Estimating the direct healthcare utilization and cost of musculoskeletal pain among people with comorbidity: a retrospective electronic health record study.

OBJECTIVE: To investigate the impact of pre-existing painful musculoskeletal conditions on healthcare utilization and costs among patients with five common conditions: acute coronary syndrome (ACS), stroke, cancer, dementia and pneumonia. METHODS: Using primary and secondary care services data from electronic health records, a negative binomial regression model was used to compare resource use while a two-part model was used to compare costs across the five conditions, between those with and without a pre-existing musculoskeletal pain. RESULTS: The study included 760,792 patients (144,870 with ACS, 121,208 with stroke, 231,702 with cancer, 134,638 with dementia, and 128,374 with pneumonia) in the complete case analysis. Pre-existing musculoskeletal pain had an incident rate ratio of above one for most healthcare resources over the follow-up period and an adjusted additional mean cumulative total healthcare costs per patient of £674.59 (95%CI 570.30 to 778.87) for ACS; £613.34 (95%CI 496.87 to 729.82) for stroke; £459.26 (95%CI 376.60 to 541.91) for cancer; and £766.23 (95%CI 655.06 to 877.39) for dementia over five years after diagnosis; and £200.85 (95%CI 104.16 to 297.55) for pneumonia over one year after diagnosis compared to those without musculoskeletal pain. CONCLUSION: This study highlights that individuals with painful musculoskeletal conditions have higher healthcare utiliszation and costs than those without painful musculoskeletal conditions. Given the high occurrence of musculoskeletal pain in patients with other conditions, effective management strategies are needed to reduce the burden on healthcare resources.