Benchmarking quality of care using patient reported outcome measure data for patients presenting with musculoskeletal conditions in primary care GP practices.

BACKGROUND: Patient Reported Outcome Measures (PROMs) evaluate health status from a patient perspective. They can be used to support care at a patient level but also collectively to review quality of care across care providers. Vast amounts of patients with musculoskeletal (MSK) conditions present to General Practice (GP) primary care practitioners each year. Variation in patient outcomes in this setting however has not been reported. OBJECTIVE: To identify variation in patient outcomes measured using the musculoskeletal health questionnaire (MSK-HQ) PROM for adults presenting to 20 GP practices in the UK with MSK conditions. METHODS: A secondary analysis of the STarT MSK cluster randomised controlled trial dataset. A standardised case-mix adjustment model, adjusting for condition complexity co-variates, was used to calculate predicted 6-month follow-up MSK-HQ scores, and used to compare adjusted and un-adjusted health gain (n = 868). Patient MSK-HQ change outcomes were aggregated to practice level and boxplots used to display outlier GP practices for un-adjusted and adjusted outcomes. RESULTS: Substantial variation in patient outcomes was seen across the 20 practices, even after case-mix adjustment, with mean change in MSK-HQ scores ranging from 6 to 12 points. Boxplots displaying un-adjusted outcomes showed one negative GP practice outlier and two positive outliers. However, the boxplots displaying case-mix adjusted outcomes showed no negative outliers, with two practices remaining as positive outliers, and one practice additionally becoming a positive outlier. CONCLUSION: This study showed a two-fold GP practice variation in patient outcomes measured using the MSK-HQ PROM. To our knowledge it is the first study to demonstrate that (a) a standardised case-mix adjustment method can be used to fairly compare patient health outcome variation in GP care, and (b) that case-mix adjustment changes benchmarking findings with regards to provider performance and outlier identification. This has important implications for identifying best practice exemplars and thereby helping to improve the quality of MSK primary care in the future

Increased proinflammatory responses from asthmatic human airway smooth muscle cells in response to rhinovirus infection

BACKGROUND: Exacerbations of asthma are associated with viral respiratory tract infections, of which rhinoviruses (RV) are the predominant virus type. Airway smooth muscle is important in asthma pathogenesis, however little is known about the potential interaction of RV and human airway smooth muscle cells (HASM). We hypothesised that rhinovirus induction of inflammatory cytokine release from airway smooth muscle is augmented and differentially regulated in asthmatic compared to normal HASM cells. METHODS: HASM cells, isolated from either asthmatic or non-asthmatic subjects, were infected with rhinovirus. Cytokine production was assayed by ELISA, ICAM-1 cell surface expression was assessed by FACS, and the transcription regulation of IL-6 was measured by luciferase activity. RESULTS: RV-induced IL-6 release was significantly greater in HASM cells derived from asthmatic subjects compared to non-asthmatic subjects. This response was RV specific, as 5% serum- induced IL-6 release was not different in the two cell types. Whilst serum stimulated IL-8 production in cells from both subject groups, RV induced IL-8 production in only asthmatic derived HASM cells. The transcriptional induction of IL-6 was differentially regulated via C/EBP in the asthmatic and NF-κB + AP-1 in the non-asthmatic HASM cells. CONCLUSION: This study demonstrates augmentation and differential transcriptional regulation of RV specific innate immune response in HASM cells derived from asthmatic and non-asthmatics, and may give valuable insight into the mechanisms of RV-induced asthma exacerbations

Associations between post-traumatic stress disorders and psychotic symptom severity in adult survivors of developmental trauma: a multisite cross-sectional study in the UK and South Korea

BACKGROUND: Childhood maltreatment is a risk factor for the development of post-traumatic stress disorders and psychosis. However, the association between post-traumatic stress disorder (PTSD), including complex PTSD, and psychotic symptoms is unknown. We investigated whether the presence of PTSD and complex PTSD was associated with psychotic symptom severity within survivors of developmental trauma. METHODS: As part of the Investigating Mechanisms underlying Psychosis Associated with Childhood Trauma (IMPACT) study, from Aug 20, 2020, to Jan 24, 2021, and from Sept 9, 2022, to Feb 21, 2023, using study advertisement on online platforms we recruited adult (≥18 years) participants who had experienced developmental trauma without a psychiatric diagnosis in the UK and South Korea. We measured whether participants met diagnostic thresholds for PTSD and complex PTSD using the self-reported International Trauma Questionnaire, and psychotic symptoms using the self-reported Community Assessment of Psychic Experiences. We used linear regression, adjusting for sociodemographic variables such as age, sex, ethnicity, educational attainment, and socioeconomic status, to examine whether there was an association between PTSD and complex PTSD and psychotic symptoms. The study is registered in the UK (University College London Research Ethics Committee [14317/001] and the National Health Service Research Ethics Committee [22/YH/0096]) and South Korea (Institutional Review Board of Seoul National University Bundang Hospital [B-2011-648-306]), and is ongoing. FINDINGS: Of the 2675 participants who took part in the study, 1273 had experienced developmental trauma and were included in the study in the UK (n=475) and South Korea (n=798), comprising 422 (33%) men and 851 (67%) women with a mean age of 26·9 years (SD 6, range 18-40), mostly of White British (n=328) or South Korean (n=798) ethnicity. We found no significant association between PTSD and psychotic symptom severity (total severity β=-2·40 [SE 3·28], p=0·47), compared with participants who did not meet PTSD or complex PTSD caseness. We found a significant relationship between complex PTSD and psychotic symptom severity (total severity β=22·62 [SE 1·65], p<0·0001), including for positive (β=12·07 [SE 0·99], p<0·0001) and negative symptoms (β=10·5 [SE 0·95], p<0·0001), compared with participants who did not meet PTSD or complex PTSD caseness. INTERPRETATION: Health systems must assess individuals with previous developmental trauma for complex PTSD and treat those affected. These individuals should also be assessed for psychotic symptoms, and if necessary, preventative measures should be taken to reduce risk of conversion. Further work should assess whether treating complex PTSD modifies the risk of conversion to psychosis. FUNDING: UKRI Future Leaders Fellowship, British Medical Association Margaret Temple Award for Schizophrenia Research, and the National Research Foundation of Korea-Korea Government

Mendelian randomization with fine-mapped genetic data: choosing from large numbers of correlated instrumental variables

Mendelian randomization uses genetic variants to make causal inferences about the effect of a risk factor on an outcome. With fine-mapped genetic data, there may be hundreds of genetic variants in a single gene region any of which could be used to assess this causal relationship. However, using too many genetic variants in the analysis can lead to spurious estimates and inflated Type 1 error rates. But if only a few genetic variants are used, then the majority of the data is ignored and estimates are highly sensitive to the particular choice of variants. We propose an approach based on summarized data only (genetic association and correlation estimates) that uses principal components analysis to form instruments. This approach has desirable theoretical properties: it takes the totality of data into account and does not suffer from numerical instabilities. It also has good properties in simulation studies: it is not particularly sensitive to varying the genetic variants included in the analysis or the genetic correlation matrix, and it does not have greatly inflated Type 1 error rates. Overall, the method gives estimates that are not so precise as those from variable selection approaches (such as using a conditional analysis or pruning approach to select variants), but are more robust to seemingly arbitrary choices in the variable selection step. Methods are illustrated by an example using genetic associations with testosterone for 320 genetic variants to assess the effect of sex hormone-related pathways on coronary artery disease risk, in which variable selection approaches give inconsistent inferences.Stephen Burgess and Verena Zuber are supported by Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 204623/Z/16/Z). Jemma C Hopewell is supported by a British Heart Foundation Basic Science Research Fellowship (grant number FS/14/55/30806)

Extended spectrum β-lactamase-and AmpC β-lactamase-producing Enterobacterales associated with urinary tract infections in the New Zealand community: A case-control study.

(c) The Author/sOBJECTIVES: To assess whether having a pet in the home is a risk factor for community-acquired urinary tract infections associated with extended spectrum β-lactamase (ESBL)- or AmpC β-lactamase (ACBL)- producing Enterobacterales. METHODS: An unmatched case-control study was conducted between August 2015 and September 2017. Cases (n=141) were people with community-acquired urinary tract infection (UTI) caused by ESBL- or ACBL- producing Enterobacterales. Controls (n=525) were recruited from the community. A telephone questionnaire on pet ownership, and other factors was administered, and associations were assessed using logistic regression. RESULTS: Pet ownership was not associated with ESBL- or ACBL-producing Enterobacterales related human UTIs. A positive association was observed for recent antimicrobial treatment, travel to Asia in the previous year, and a doctor's visit in the previous six months. Among isolates with an ESBL-/ACBL-producing phenotype 126/134 (94%) were Escherichia coli, with sequence type (ST) 131 being the most common (47/126). CONCLUSIONS: Companion animals in the home were not found to be associated with ESBL- or ACBL-producing Enterobacterales related community-acquired UTI in New Zealand. Risk factors included overseas travel, recent antibiotic use, and doctor visits.Published onlin

Forms of Structuralism: Bourbaki and the Philosophers

In this paper, we argue that, contrary to the view held by most philosophers of mathematics, Bourbaki’s technical conception of mathematical structuralism is relevant to philosophy of mathematics. In fact, we believe that Bourbaki has captured the core of any mathematical structuralism

A highly efficacious pediculicide based on dimeticone: Randomized observer blinded comparative trial

BACKGROUND: Infestation with the human head louse (Pediculus humanus capitis) occurs worldwide. Existing treatment options are limited, and reports of resistance to commonly used pediculicides have been increasing. In this trial we assessed the efficacy of a product containing a high (92%) concentration of the silicone oil dimeticone (identical in composition to NYDA(R)), as compared to a 1% permethrin lotion. METHODS: Randomized, controlled, observer blinded clinical trial. Participants were recruited from a poor urban neighbourhood in Brazil where pediculosis capitis was highly prevalent. To minimize reinfestation during the trial, participants (145 children aged 5-15 years with head lice infestations) were transferred to a holiday resort outside the endemic area for a period of 9 days. Two applications of dimeticone or 1% permethrin were done, seven days apart. Outcome measures were defined as cure (absence of vital head lice) after first application and before and after second applications, degree of itching, cosmetic acceptability, and clinical pathology. RESULTS: Overall cure rates were: day 2 - dimeticone 94.5% (95% CI: 86.6% - 98.5%) and permethrin 66.7% (95% CI: 54.6% - 77.3%; p < 0.0001); day 7 - dimeticone 64.4% (95% CI: 53.3% - 75.3%) and permethrin 59.7% (95% CI: 47.5% - 71.1%; p = 0.5); day 9 - dimeticone 97.2% (95% CI: 90.3% - 99.7%) and permethrin 67.6% (95% CI: 55.4%-78.2%); p < 0.0001). Itching was reduced similarly in both groups. Cosmetic acceptability was significantly better in the dimeticone group as compared to the permethrin group (p = 0.01). Two mild product-related incidents occurred in the dimeticone group. CONCLUSION: The dimeticone product is a safe and highly efficacious pediculicide. Due to its physical mode of action (interruption of the lice's oxygen supply of the central nervous system), development of resistance is unlikely. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15117709

Large N and Bosonization in Three Dimensions

Bosonization is normally thought of as a purely two-dimensional phenomenon, and generic field theories with fermions in D>2 are not expected be describable by local bosonic actions, except in some special cases. We point out that 3D SU(N) gauge theories on R^{1,1} x S^{1}_{L} with adjoint fermions can be bosonized in the large N limit. The key feature of such theories is that they enjoy large N volume independence for arbitrary circle size L. A consequence of this is a large N equivalence between these 3D gauge theories and certain 2D gauge theories, which matches a set of correlation functions in the 3D theories to corresponding observables in the 2D theories. As an example, we focus on a 3D SU(N) gauge theory with one flavor of adjoint Majorana fermions and derive the large-N equivalent 2D gauge theory. The extra dimension is encoded in the color degrees of freedom of the 2D theory. We then apply the technique of non-Abelian bosonization to the 2D theory to obtain an equivalent local theory written purely in terms of bosonic variables. Hence the bosonized version of the large N three-dimensional theory turns out to live in two dimensions.Comment: 30 pages, 2 tables. v2 minor revisions, references adde