Objective:We examined the independent risk of incident comorbidities associated with prescribed oral paracetamol, NSAIDs and opioids and their interaction and mediation with OA. Methods:Exposure of these analgesics and the association with nine systemic groups of incident comorbidities were examined in this 5-year cohort study of 261 273 people with incident OA and 261 273 age-, sex- and practice-matched controls (no OA) in the large UK primary care database. A propensity score-adjusted time-varying exposure analysis was undertaken using multivariable Cox models to estimate the hazard ratios (HRs) for incident comorbidities associated with OA and analgesics. Interaction was defined when the combined term for OA and analgesic was significant. The proportion of the risk associated with OA mediated by analgesics was also calculated. Results:The mean age of the cohort was 60 years and 57.7% were female. NSAIDs and opioids were independently associated with all comorbidities. Paracetamol interacted with OA leading to an extra risk of renal comorbidities [multiplicative HR (mHR) 1.14 (95% CI 1.06, 1.22)]. NSAIDs and opioids interacted with OA with extra risk of cardiovascular [mHR 1.05 (95% CI 1.01, 1.11) and mHR 1.06 (95% CI 1.02, 1.11)] and endocrine [mHR 1.11 (95% CI 1.05, 1.17) and mHR 1.08 (95% CI 1.02, 1.13)] comorbidities. About 16% and 7% risk from OA to psychological comorbidities were indirectly mediated by NSAIDs and opioids, respectively. Conclusion:Our findings suggest that in people with OA, analgesic prescriptions may be associated with increased risk of certain incident comorbidities, particularly in long-term use.

BACKGROUND:Menopause, marked by hormonal decline and menstrual cessation, is associated with various symptoms. Socio-demographic and behavioural factors may influence symptom type and severity. Understanding these associations can inform better symptom management. OBJECTIVES:To identify factors associated with the presence and severity of menopausal symptoms through systematic review and meta-analysis. SEARCH STRATEGY:We searched Medline, Embase, CINAHL and Cochrane for studies on demographic, behavioural, or health factors linked to vasomotor, vaginal dryness and joint symptoms in women aged 40-60. SELECTION CRITERIA:Studies reporting odds ratios or raw numbers for symptom presence or severity were included. DATA COLLECTION AND ANALYSIS:Studies were combined for meta-analysis, reporting odds ratios and 95% confidence intervals. Quality assessment was performed to quantify the risk of bias. RESULTS:Of 9228 screened articles, 61 were meta-analysed. Compared with White women, Black women had higher odds of vasomotor symptom presence (OR 1.65, 1.41-1.94) and severity (OR 1.91, 1.10-3.29), and vaginal dryness presence (OR 1.27, 1.10-1.47), while Asian had lower vasomotor symptom presence and severity (OR 0.40, 0.22-0.72; OR 0.55, 0.53-0.56). Higher education (OR 1.31, 1.09-1.56), high income (OR 1.41, 1.01-1.97) and depression (OR 2.36, 1.51-3.70) were associated with increased presence of vasomotor symptoms. Smoking and obesity were associated with both presence (OR 1.63, 1.30-2.04 and 1.35, 1.02-1.78) and severity (OR 1.56, 1.07-2.27 and 1.42, 1.11-1.83) of vasomotor symptoms. CONCLUSION:Socio-demographic and behavioural factors, including ethnicity, education, income, smoking, obesity and depression, influence menopausal symptoms, highlighting the need for personalised care. TRIAL REGISTRATION:PROSPERO number: CRD42023459154.

Background:Osteoarthritis (OA) is associated with some comorbidities. However, the consistency of the associations across different countries is unclear. We analysed relationships between OA and 61 comorbidities before and after diagnosis using data from four European primary care databases: the UK, the Netherlands, Sweden, and Spain. Methods:The multinational ComOA study combined case-control and cohort designs in people aged ≥18 years using large primary care records databases in each country. The study population consisted of incident OA cases, and age and sex matched controls without OA. We reported adjusted odds ratios (aOR) and adjusted hazard ratios (aHR) after adjusting for other covariates. Pooled proportions with comorbidities, ORs and HRs were estimated using random effect methods for congruency evidence. Congruency was present if the results of all the countries favoured in one direction. Findings:The four databases included 845,373 OA cases and 2,556,243 matched controls combined for prospective and retrospective studies. The percentage of women varied from 41.7% (808,725/1,936,792) in Spain to 64.0% (254,930/398,143) in the Netherlands. Mean age at diagnosis of OA was lowest in the UK (59.8 years, SD 12.8), and highest in the Netherlands (65.8 years, SD 12.2). Retrospectively, 10 out of 33 comorbidities studied by all four countries showed congruent associations with OA such as, fibromyalgia (aOR 1.93; 95% CI 1.49-2.49), polymyalgia rheumatica (aOR 1.44; 95% CI 1.31-1.58), and chronic back pain (aOR 1.42; 95% CI 1.32-1.53). Prospectively, three of eight conditions studied by all four countries showed congruent, i.e., depression (aHR 1.11; 95% CI 1.07-1.16), osteoporosis (aHR 1.05; 95% CI 1.01-1.09), and hypertension (aHR 1.05; 95% CI 1.02-1.09). Additionally, contingency was also observed between retrospective and prospective studies for sleep problem, migraine, asthma, eczema, and benign prostatic hypertrophy. Interpretation:OA is associated with some long-term conditions across Europe, despite different population structures and health systems. Further research is needed to understand the mechanisms shared between OA and comorbidities for these associations, especially those congruent across nations. Funding:This work was supported by Foundation for Research in Rheumatology (FOREUM) grant The Swedish Research Council, Governmental funding of clinical research within the national health services (ALF), and The Swedish Rheumatism Association. CM is funded by the National Institute for Health Research (NIHR) Applied Research Collaboration West Midlands, the National Institute for Health Research (NIHR) School for Primary Care Research and a National Institute for Health Research (NIHR) Research Professorship in General Practice.

OBJECTIVE:To identify factors associated with HRT uptake among women. DESIGN:A systematic review and meta-analysis to identify factors associated with HRT uptake. SETTING:Retrospective and prospective cohort studies, case-control studies and cross-sectional studies from any country and in any language. POPULATION:The study population was women aged 40-60 years old. METHODS:We searched Medline, Embase, CINAHL and Cochrane databases to identify studies reporting associations between demographic, behavioural or health-related factors and HRT uptake. Studies were selected if they reported numbers or odds ratios of the factors and HRT uptake. Studies were combined for meta-analysis, reporting odds ratios and 95% confidence intervals. Quality assessment was performed to quantify the risk of bias. MAIN OUTCOME MEASURES:HRT uptake, defined as 'ever' versus 'never' users. RESULTS:5124 papers were identified for title and abstract screening; 136 full texts were screened; 53 were included in meta-analyses. HRT uptake was 53% lower in Black (OR 0.47, 0.30-0.73) compared to White women. Diabetes, obesity and history of stroke or venous thromboembolism were associated with lower HRT uptake (OR 0.71, 0.59-0.85; 0.67, 0.56-0.81; 0.75, 0.63-0.89; 0.78, 0.74-0.0.83 respectively). Osteoporosis and depression were associated with higher HRT uptake (OR 1.64, 1.10-2.45 and 1.69, 1.17-2.43, respectively). CONCLUSIONS:There are differences in HRT uptake by ethnicity and health characteristics. However, findings are not generalisable globally. Our results could aid healthcare professionals and policymakers to address the gaps in HRT uptake and promote healthcare equity.

Abstract Aims The Falls Management Exercise (FaME) programme, delivered over 24 weeks, reduces falls in randomised controlled trials and ‘real world’ delivery, but some services deliver shorter, adapted FaME programmes. We investigated the ‘real-world’ effectiveness of FaME delivered for 12 or 24 weeks across three UK regions. Methods Design: prospective cohort study. Participants: 1,601 FaME programme attendees (median age 79.5 years), of whom 873 had follow-up data recorded. Setting: 14 provider organisations in Greater Manchester, Devon and the East Midlands. Procedure: Participant data were collected by FaME providers at baseline and up to 24 weeks later. Outcomes: Timed up-and-go (TUG); Short Falls Efficacy Scale-International (Short FES-I); at least one self-reported fall, and number of self-reported falls, in the past 3 months. Analysis: Univariate before-and-after tests; multivariable multilevel logistic, linear, Poisson, negative binomial regression. Results At final follow-up (≤24 weeks), compared to baseline, the odds of a self-reported fall within 3 months (Odds ratio 0.16 [95% confidence interval [CI] 0.10 to 0.25], p <.001) and TUG time had decreased (difference-between-paired-medians -1.0 (95% CI -1.50 to -1.0), p <.001). Short FES-I scores had not significantly changed. Twenty-four- rather than 12-week programmes were associated with faster TUG times (mean difference -3.31 seconds [95% CI -5.97 to -0.65]) and reduced concerns about falling (mean Short FES-I difference -2.00 [95% CI -3.65 to -0.34], p = 0.018), but no significant difference in the odds of a self-reported fall or number of falls within 3 months. Conclusions FaME programmes of both 12 and 24-weeks were associated with improved functional mobility and reduced falls. Participants who attended 24-, rather than 12-week, programmes had significantly greater improvements in functional mobility and reduced concerns about falling. Due to follow-up data missingness, the study was not adequately powered to detect differences in falls risk or rate between 12 and 24-week programmes.

There is a complex relationship between pain and mood disorders, and interactions between opioids and antidepressants can affect the effectiveness and adverse effects of these medicines when taken together. However, little is known about the scale of co-prescription for these medicines. We used routinely collected primary care data from the Clinical Practice Research Datalink to describe the extent of opioid and antidepressant co-prescribing in over 4.3 million adults in England. Linked data included deprivation information and hospital episode statistics admitted patient care data to improve completeness of ethnicity information. We identified all primary care prescriptions of opioids and antidepressants between 2010 and 2019 and counted if an opioid and antidepressant prescription overlapped, and if so, for how long. People were censored at the first date of a record of cancer, terminal illness, heart failure or opioid misuse. There were 4,355,694 people included in the study population. Of these, 304,029 (7.0

OBJECTIVES:In response to high levels of demand for primary medical services in England, characterized by longer appointment waiting times and delayed referrals, the Government developed its National Health Service (NHS) Primary Care Recovery Plan. A key component of the plan is Pharmacy First (PF), which involves participating community pharmacies supplying prescription-only medicine after consultation with a pharmacist for seven common conditions: earache, uncomplicated urinary tract infections in women, sore throat, sinusitis, impetigo, shingles, and infected insect bites. The study aims to evaluate the implementation of the PF service and its impact on the volume of prescribing, case mix of General Practitioner consultations, accident and emergency department and other hospital use, equity of access, and cost for different groups of patients in different contexts, as well as its acceptability and fidelity. METHODS:A 36-month, mixed methods evaluation with five elements, namely evidence synthesis, semi-structured interviews, focus groups, quantitative analysis of impacts before and after implementation (e.g. using interrupted time series analysis) using routine data, and an economic evaluation. Findings will be synthesized and interpreted using the Consolidated Framework for Implementation Research supplemented by Proctor's Implementation Outcomes Framework. CONCLUSIONS:The evaluation should have service level, policy, professional, and research impact both in England and beyond. This includes generating evidence to show: whether PF contributes to improving primary healthcare access, assessing the quality of antimicrobial use, identifying the scope for refinements to PF, and, overall, informing better implementation of PF. The findings will also provide robust evidence to enable policymakers to determine how to enhance the role of community pharmacy in England in the future. Furthermore, the evaluation will develop a data dashboard, and the methods and codes used to interrogate it (though not the patient data), will be made publicly available that could support other similar evaluations in England and internationally.

BACKGROUND:Sotrovimab is a neutralising monoclonal antibody (nMAB) currently available to treat extremely clinically vulnerable COVID-19 patients in England. Trials have shown it to have mild to moderate side effects, however, evidence regarding its safety in real-world settings remains insufficient. METHODS:Descriptive and multivariable logistic regression analyses were conducted to evaluate uptake, and a self-controlled case series analysis performed to measure the risk of hospital admission (hospitalisation) associated with 49 pre-specified suspected adverse outcomes in the period 2-28 days post-Sotrovimab treatment among eligible patients treated between December 11, 2021 and May 24, 2022. RESULTS:Here we show that among treated and untreated eligible individuals, the mean ages (54.6 years, SD: 16.1 vs 54.1, SD: 18.3) and sex distribution (women: 60.9% vs 58.1%; men: 38.9% vs 41.1%) are similar. There are marked variations in uptake between ethnic groups, which is higher amongst individuals categorised ethnically as Indian (15.0%; 95%CI 13.8, 16.3), Other Asian (13.7%; 95%CI 11.9, 15.8), white (13.4%; 95%CI 13.3, 13.6), and Bangladeshi (11.4%; 95%CI 8.8, 14.6); and lower amongst Black Caribbean individuals (6.4%; 95%CI 5.4, 7.5) and Black Africans (4.7%; 95%CI 4.1, 5.4). We find no increased risk of any of the suspected adverse outcomes in the period 2-28 days post-treatment. CONCLUSIONS:We find no safety signals of concern for possible adverse outcomes in the period 2-28 days post treatment with Sotrovimab. However, there is evidence of unequal uptake of Sotrovimab treatment across ethnic groups.

Electronic health records are increasingly used to conduct pregnancy-related research as pregnant women are under-represented in research. Creating a register of pregnancies by combining data from primary and secondary care will further facilitate research in pregnancy. This work describes the construction of an algorithm to create a unified pregnancy cohort in the QResearch database during the emergency phase of the COVID-19 pandemic. National primary care records in the QResearch® database were linked to patient-level data from Hospital Episode Statistics (HES) datasets. Females aged 15-50 years with a pregnancy outcome recorded between 30 December 2020 and 30 September 2022 were included. Pregnancy (delivery/loss) episodes were identified and cohort demographics reported using a three-stage algorithm. Pregnancy start dates were derived using a combination of HES and primary care data, or individually estimated where no corresponding date could be identified. 266,758 women with 279,027 pregnancies are captured in the register. 232,673 pregnancies (83.4

BACKGROUND:Antipsychotic treatments require physical health monitoring (PHM), especially among children and young people (CYP). OBJECTIVE:For CYP aged 5-17, to investigate recorded indications for antipsychotics prescribing and first-treatment durations, and, for psychosis, bipolar disorder, autism spectrum disorder (ASD) and Tourette's syndrome, recorded levels of PHM for CYP with antipsychotics prescriptions and those without. METHODS:All CYP registered with QResearch English general practices between 2006 and 2021 were considered. To quantify PHM, 2158 CYP with antipsychotics prescriptions and 22 151 CYP with a condition but no prescriptions were followed for 2 years. FINDINGS:47% (2363) of CYP with antipsychotics prescriptions had a recorded mental health condition of interest (of which 62% were ASD). 19% (921) had no relevant indication. For patients with ASD and Tourette syndrome, top quartiles for initial exposure to antipsychotics were >10 months. Recorded PHM was generally low, with over 50% of CYP showing no blood test during the 2-year follow-up. CONCLUSIONS:Coverage of best practice is uneven across the condition-related national CYP guidelines, and this requires improvement. However, we suspect some apparently poor adherence to best practice also derives from treatment complexities and associated data flows leading to gaps in the encoded general practice data. To audit more exactly clinical practice against guidelines, we propose qualitative studies, targeted to cover the full range of local circumstances, nationally. CLINICAL IMPLICATIONS:General practices should be encouraged to prioritise encoding of all treatment data. Development of one central gold-standard set of recommendations for antipsychotics use could encourage better adherence levels across conditions.

Study Objectives:To examine whether there is a temporal association between sleep disturbance and multimorbidity. Methods:We performed a cross-sectional and longitudinal observational analysis in people aged 40 years or more, recruited from the knee pain and related health in the community cohort study. The primary exposure was the Sleep Problems Index II score in tertiles measured at baseline. The primary outcome was count of chronic conditions developed in 5 years. Pain, low mood, and anxiety were measured at 2 years as mediators. Poisson regression was used to calculate adjusted relative risk and 95% confidence intervals. Results:We included 4488 participants in the cross-sectional analysis at baseline and 1941 in the 5-year longitudinal analysis. At baseline, the adjusted relative risks for prevalent multimorbidity were 1 (reference) for tertile 1, 1.09 (95% confidence interval; 1.01-1.18) for tertile 2, and 1.21 (95% confidence interval; 1.11-1.32) for tertile 3 of the sleep disturbance score (p for trend <.001). Of the total association between sleep disturbance and multimorbidity, 14 per cent (95% confidence interval; 9% to 19%) were mediated by pain and 7 per cent (95% confidence interval; 2% to 13%) by low mood. In the 5 year follow-up, the adjusted relative risk for incident multimorbidity were 1 (reference) for tertile 1, 1.12 (95% confidence interval; 0.98-1.28) for tertile 2, and 1.25 (95% confidence interval; 1.06-1.47) for tertile 3 (p for trend .007). Of the total association between sleep disturbance and multimorbidity, 10 per cent (95% confidence interval; 2% to 18%) was mediated by pain. Conclusions:Sleep disturbance is associated with multimorbidity. The association is dose-dependent, temporal, and partially mediated by pain.

Background Lung cancer is a leading cause of mortality, yet disparities in lung cancer across different sociodemographic groups in the UK remain unclear. This study investigates ethnicity and sociodemographic disparities and differences in lung cancer in a nationally representative English cohort, aiming to highlight inequalities and promote equitable access to diagnostic advancements. Methods We conducted a population-based cohort study using health care records from QResearch, a large primary care database in England. The study included adults aged 25 and over, spanning the period of 2005-2019. Lung cancer incidence rates were calculated using age-standardized methods. Multinomial logistic regression was applied to assess associations between ethnicity/sociodemographic factors and diagnostic characteristics (histological type, stage, and cancer grade), adjusting for confounders. Findings From a cohort of over 17.5 million people, we identified disparities in incidence rates across ethnic groups from 2005 to 2019. Analysis of 84,253 lung cancer cases revealed that younger woman and Individuals of Indian, other Asian, Black African, Caribbean and Chinese backgrounds had a significantly higher risks of adenocarcinoma compared with squamous cell carcinoma than their White counterparts (relative risk ratios [RRR] spanning from 1.52 (95% CI 1.18-1.94) to 2.69 (95% CI 1.43-5.05). Men and current smokers were more likely to be diagnosed at an advanced stage than women and never smokers (RRR: 1.72 [95% CI 1.56-1.90]-2.45 [95% CI 2.16-2.78]). Socioeconomic deprivation was associated with higher risks of moderate or poorly differentiated adenocarcinoma compared with well differentiated (RRRs between 1.35 [CI: 1.02-1.79] and 1.37 [1.05-1.80]). Interpretation Our study highlights significant differences in lung cancer incidence and in lung cancer diagnostic characteristics related to ethnicity, deprivation and other demographic factors. These findings have important implications for the provision of equitable screening and prevention programmes to mitigate health inequalities. Copyright (c) 2024 Published by Elsevier Ltd.

[This corrects the article DOI: 10.1016/j.ocarto.2023.100414.].

Objective To quantify prescribing of hormone replacement therapy (HRT) in women aged 40-60 years by type of HRT and length of use, and to determine sociodemographic factors associated with receiving a HRT prescription.Design Population based cohort study.Setting QResearch database of primary care practices in England, 1 January 2013 to 13 July 2023, and patient electronic health records for prescribing information .Participants 1 978 348 women aged 40-60 years at any time over a 10 year period.Main outcome measures Overall uptake of two or more prescriptions of the same type of HRT in women of menopausal age, length of use, and association between ethnic group, deprivation, and geographical region and receiving a HRT prescription before and during the eight years since implementation of National Institute for Health and Care Excellence (NICE) guidance on the menopause in 2015 in the UK.Results The cohort comprised 1 978 348 women with a mean age of 49.4 years, and 76.2% were white women. Overall, 379 911 (19.2%) women received two or more HRT prescriptions. Combination HRT formulations in one prescription were the most frequently prescribed (62.4% of those prescribed HRT), with 43.3% receiving oral and 26.3% transdermal formulations. Mean age at first prescription was 49.8 years. Rates for two or more prescriptions of HRT were higher in white women (22.6%) than in other ethnic groups, ranging from 8.9% in Caribbean women to 3.9% in black African women. Prescription rates decreased with increasing social deprivation, from 24.2% in the most affluent to 10.9% in the most deprived groups. London had lower prescription rates (11.7%) than other regions (all >19%). Multivariable Cox regression showed that non-white ethnic groups had significantly lower HRT prescription rates (hazard ratios 0.85-0.92, P<0.001), and each increase in social deprivation group was associated with lower HRT prescription rates (hazard ratio for the most deprived group 0.92, 95% confidence interval 0.92 to 0.93, P<0.001).Conclusions This study identified differences in HRT prescribing in England based on ethnic group, socioeconomic status, and geographical location. White women and those in more affluent neighbourhoods were more likely to receive HRT than non-white women and those in more deprived areas. These findings suggest potential inequities that require further exploration.

ABSTRACT:Our aim was to investigate relative contributions of central and peripheral mechanisms to knee osteoarthritis (OA) diagnosis and their independent causal association with knee OA. We performed longitudinal analysis using data from UK-Biobank participants. Knee OA was defined using International Classification of Diseases manual 10 codes from participants' hospital records. Central mechanisms were proxied using multisite chronic pain (MCP) and peripheral mechanisms using body mass index (BMI). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated, and proportional risk contribution (PRC) was estimated from receiver-operator-characteristic (ROC) analysis. To estimate the causal effects, we performed 2-sample multivariable Mendelian Randomisation (MR) analysis. We selected genetic instruments from the largest Genome Wide Association Study of BMI (N = 806,834) and MCP (N = 387,649) and estimated the instruments genetic associations with knee OA in the largest available dataset (62,497 cases and 333,557 control subjects). The multivariable MR was performed using modified inverse-variance weighting methods. Of the 203,410 participants, 6% developed knee OA. Both MCP (OR 1.23, 95% CI; 1.21-1.24) and BMI (1.10, 95% CI; 1.10-1.11) were associated with knee OA diagnosis. The PRC was 6.9% (95% CI; 6.7%-7.1%) for MCP and 21.9% (95% CI; 21.4%-22.5%) for BMI; the combined PRC was 38.8% (95% CI; 37.9%-39.8%). Body mass index and MCP had independent causal effects on knee OA (OR 1.76 [95% CI, 1.64-1.88] and 1.83 [95% CI, 1.54-2.16] per unit change, respectively). In conclusion, peripheral risk factors (eg, BMI) contribute more to the development of knee OA than central risk factors (eg, MCP). Peripheral and central factors are independently causal on knee OA.

QR4 is a new cardiovascular disease (CVD) risk score developed and evaluated in 16.9 million people that has better performance than other commonly used CVD risk scores. It includes nine new risk factors associated with increased risk of developing CVD (for example, a heart attack or stroke) over the next 10 years.

Electronic health records can be used to facilitate research in pregnancy. This work describes the construction of a novel algorithm to create a unified pregnancy cohort in the QResearch database, during the initial phases of the COVID-19 pandemic, for England. National GP records in the QResearch® database were linked to patient-level data from Hospital Episode Statistics (HES) datasets. Females aged 15-50 years with a pregnancy recorded between December 2020 and September 2022 were included. Pregnancy (delivery/loss) episodes were identified and cohort demographics reported using a three-stage algorithm. 266,758 women with 279,027 pregnancies were identified. 232,673 pregnancies (83%) resulted in a delivery (99.6% live births and 0.4% stillbirths). 46,354 (17%) pregnancies resulted in a pregnancy loss. Pregnancy losses were highest amongst those of Caribbean (23.1%; n=781) ethnicity and lowest in those of Pakistani ethnicity (14.4%, n=1,579). The QResearch Pregnancy Register offers a useful and adaptable resource for future research on pregnancy exposures, outcomes, and events.

BACKGROUND:Colonic motility in constipation can be assessed non-invasively using MRI. OBJECTIVE:To compare MRI with high-resolution colonic manometry (HRCM) for predicting treatment response. DESIGN:Part 1: 44 healthy volunteers (HVs), 43 patients with irritable bowel syndrome with constipation (IBS-C) and 37 with functional constipation (FC) completed stool diaries and questionnaires and underwent oral macrogol (500-1000 mL) challenge. Whole gut transit time (WGTT), segmental colonic volumes (CV), MRI-derived Motility Index and chyme movement by 'tagging' were assessed using MRI and time to defecation after macrogol recorded. Left colonic HRCM was recorded before and after a 700 kcal meal. Patients then proceeded to Part 2: a randomised cross-over study of 10-days bisacodyl 10 mg daily versus hyoscine 20 mg three times per day, assessing daily pain and constipation. RESULTS:Part 1: Total CVs median (range) were significantly greater in IBS-C (776 (595-1033)) and FC (802 (633-951)) vs HV (645 (467-780)), p<0.001. Patients also had longer WGTT and delayed evacuation after macrogol. IBS-C patients showed significantly reduced tagging index and less propagated pressure wave (PPW) activity during HRCM versus HV. Compared with FC, IBS-C patients were more anxious and reported more pain. Abnormally large colons predicted significantly delayed evacuation after macrogol challenge (p<0.02), impaired manometric meal response and reduced pain with bisacodyl (p<0.05).Part 2: Bisacodyl compared with hyoscine increased bowel movements but caused more pain in both groups (p<0.03). CONCLUSION:An abnormally large colon is an important feature in constipation which predicts impaired manometric response to feeding and treatment responses. HRCM shows that IBS-C patients have reduced PPW activity. TRIAL REGISTRATION NUMBER:The study was preregistered on ClinicalTrials.gov, Reference: NCT03226145.

Background: Associations of osteoarthritis (OA) with different comorbidities have gained attention recently. However, there is no literature on the congruency across different large primary care settings. Objectives: We examined the associations of OA with 61 different comorbidities diagnosed before and after the first diagnosis of OA in four different European primary care settings from the United Kingdom, the Netherlands, Sweden, and Spain. We tested the congruency and incongruency of the findings across these four countries. Congruency was present if the results of all the centres were significant and favoured in one direction. Methods: The multicentre ComOA study(1) combined case-control and cohort studies for a total of 3,401,616 people aged 18 or above from four countries’ large primary care records in the UK (CPRD GOLD, n= 518,000), Netherlands (IPCI, n=398,143), Sweden (Skane, n=548,681), and Spain (SIDIAP, n=1,936,792). The study population consisted of incident OA cases and age, sex, and practice matched controls without OA. We examined bidirectional association of 61 comorbidities with OA using case-control and cohort methodology, reported as odds ratios (OR) and hazard ratios (HR) and adjusting for other covariates. Pooled proportions with comorbidities, ORs and HRs were estimated using random effect methods. Results: Four databases had 845,373 OA cases and 2,556,243 controls. Of 61 comorbidities, all centres examined 33 and 8 conditions in both retrospective and prospective analyses, respectively. The percentage of women participants varied from 41.6% in SIDIAP to 64.0% in IPCI. Mean age at the diagnosis of OA was lowest in CPRD GOLD (59.8 years, SD12.8), and highest in IPCI (65.8 years, SD 12.19). In people with OA the pooled prevalence (%) of the top conditions which were higher than matched controls were: chronic back pain (43.8; 95% CI: 33.0-54.8), hypertension (34.3; 95% CI 26.4-42.6), allergy (21.2; 95% CI 10.3-34.6), cataract (16.0; 95%CI 9.6-23.6), vertigo (13.8; 95% CI 13.7-13.9), depression (12.8; 95%CI 8.2-18.6), and diabetes (12.8; 95%CI 9.3-16.8). Of 33 comorbidities studied retrospectively, 10 showed congruent evidence of association with OA across the four countries. The three leading comorbidities before the diagnosis of OA were fibromyalgia (OR 1.93; 95% CI 1.49-2.49), polymyalgia (1.44; 95% CI 1.31-1.58), and chronic back pain (1.42; 95% CI 1.32-1.53). (Figure 1) 32 of 61 comorbidities showed congruent evidence of association prospectively by at least three centres. (Figure 2) The three leading comorbidities developed after the diagnosis of OA were fibromyalgia (HR: 1.42; 95% CI 1.29-1.56), rheumatoid arthritis (HR: 1.27; 95% CI 1.20-1.35), and polymyalgia (HR: 1.24; 95% CI 1.20-1.27). Non-congruent evidence was found for 14 chronic conditions, either retrospectively or prospectively, such as heart failure, diabetes, dementia, and chronic obstructive pulmonary disease (COPD). Conclusion: OA is associated with a large number of chronic conditions, especially for painful musculoskeletal conditions, across different countries in Europe, despite different population structures and health systems. Further research is needed to establish the causal association. REFERENCES: [1] Swain S, Kamps A, Runhaar J, et al Comorbidities in osteoarthritis (ComOA): a combined cross-sectional, case–control and cohort study using large electronic health records in four European countries. BMJ Open 2022;12:e052816. doi: 10.1136/bmjopen-2021-052816.GERD- Gastroesophageal reflux disease; COPD- Chronic obstructive pulmonary diseases. Pooled hazard ratio was calculated using the ‘random effect’ model for conditions having results from three or more centres. Acknowledgements: We thank the Patient Research Participants (PRP) members Jenny Cockshull, Stevie Vanhegan, and Irene Pitsillidou for their involvement since the beginning of the project. We would like to thank the FOREUM for financially supporting the research. Financial disclosure- This work was supported by Foundation for Research in Rheumatology (FOREUM) grant (2019-2022), The Swedish Research Council (2020-01103), Governmental funding of clinical research within the national health services (ALF), and The Swedish Rheumatism Association. CM is funded by the National Institute for Health Research (NIHR) Applied Research Collaboration West Midlands and the National Institute for Health Research (NIHR) School for Primary Care. Disclosure of Interests: Subhashisa Swain: None declared, Carol Coupland: None declared, Anne Kamps: None declared, Jos Runhaar: None declared, Andrea Dell’Isola: None declared, Christian Mallen: None declared, Chang-Fu Kuo: None declared, Michael Doherty: None declared, Daniel Prieto-Alhambra Prof. Prieto-Alhambra’s research group has received grant support from Amgen, Chesi-Taylor, Novartis, and UCB Biopharma. His department has received advisory or consultancy fees from Amgen, Astellas, AstraZeneca, Johnson, and Johnson, and UCB Biopharma and fees for speaker services from Amgen and UCB Biopharma., Martin Englund: None declared, S.M.A. Bierma-Zeinstra: None declared, Weiya Zhang: None declared.Figure 1Associations between comorbidities and OA before the diagnosis of OA in UK, Netherlands, Sweden and Spain Figure 2Associations between OA and comorbidities after the diagnosis of OA in UK, Netherlands, Sweden and Spain.