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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., Competing Interests: Competing interests: RCS: Grants/research supports: Sanofi-Aventis Deutschland, Nestle Consultant to Enterobiotix. MC: Consultant: Sanofi, Takeda, Biocodex, Mayoly. SMS: honoraria for teaching for the Laborie Group. SAT: grant support from Takeda. Consultancy fees AstraZeneca, Sanofi-Aventis. Share holder Motilent., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.)

Objective: To investigate whether different anticholinergic drug treatments for overactive bladder have differential risks for incident dementia, in a large representative population of older adults in England., Design: Nested case-control study., Setting: General practices in England providing data to the Clinical Practice Research Datalink (CPRD) GOLD database, with linked patient admission records from secondary care (Hospital Episode Statistics), 1 January 2006 and 16 February 2022., Participants: 170 742 patients aged ≥55 years, with a first reported diagnosis of dementia during the study period, matched by age, sex, and general practice with 804 385 individuals without dementia (controls)., Interventions: Cumulative drug use (defined using total standardised daily dose) of different anticholinergic drugs used for the treatment of an overactive bladder, and a non-anticholinergic drug, mirabegron, in the period 3-16 years before a diagnosis of dementia (or equivalent date in matched controls)., Main Outcome Measures: Odds ratios for onset of dementia associated with the different anticholinergic drugs used for the treatment of an overactive bladder, adjusted for sociodemographic characteristics, clinical comorbidities, and use of other anticholinergic drug treatments., Results: The study population comprised 62.6% women, and median age was 83 (interquartile range 77-87) years. 15 418 (9.0%) patients with dementia and 63 369 (7.9%) controls without dementia had used anticholinergic drugs for the treatment of an overactive bladder in the 3-16 years before diagnosis (or equivalent date for controls). The adjusted odds ratio for dementia associated with the use of any anticholinergic drug used to treat an overactive bladder was 1.18 (95% confidence interval (CI) 1.16 to 1.20), and was higher in men (1.22, 1.18 to 1.26) than women (1.16, 1.13 to 1.19). The risk of dementia was substantially increased with the use of oxybutynin hydrochloride (adjusted odds ratio 1.31, 95% CI 1.21 to 1.42 and 1.28, 1.15 to 1.43 for use of 366-1095 and >1095 total standardised daily doses, respectively), solifenacin succinate (1.18, 1.09 to 1.27 and 1.29, 1.19 to 1.39), and tolterodine tartrate (1.27, 1.19 to 1.37 and 1.25, 1.17 to 1.34). No significant increases in the risk of dementia associated with darifenacin, fesoterodine fumarate, flavoxate hydrochloride, propiverine hydrochloride, and trospium chloride were found. The association between mirabegron, a non-anticholinergic drug, and dementia was variable across the dose categories and might be caused by previous use of anticholinergic drugs for the treatment of an overactive bladder in these individuals., Conclusions: Of the different anticholinergic drugs used to treat an overactive bladder, oxybutynin hydrochloride, solifenacin succinate, and tolterodine tartrate were found to be most strongly associated with the risk of dementia in older adults. This finding emphasises the need for clinicians to take into account the possible long term risks and consequences of the available treatment options for an overactive bladder in older adults, and to consider prescribing alternative treatments that might be associated with a lower risk of dementia., Competing Interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare: support from the National Institute for Health and Care Research (NIHR) School for Primary Care Research for the submitted work; DMA reports research grants from AbbVie, Almirall, Celgene, Eli Lilly, Janssen, Novartis, UCB, and the Leo Foundation, for unrelated projects focused on a different therapeutic area; TD is the regional specialty lead for dementia, NIHR Clinical Research Network East Midlands, and declares previous grant funding from NIHR, Alzheimer's Research UK, and Royal National Institute for Deaf People; at the time of this study, AJA was National Clinical Director for Prescribing for NHS England; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

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., Funding: DART (The Integration and Analysis of Data using Artificial Intelligence to Improve Patient Outcomes with Thoracic Diseases) project, Innovate UK (UK Research and Innovation), QResearch® and grants from the NIHR Biomedical Research Centre (Oxford), John Fell Oxford University Press Research Fund, Cancer Research UK, and the Oxford Wellcome Institutional Strategic Support Fund., Competing Interests: JHC reports grants from National Institute for Health Research, John Fell Oxford University Press Research Fund, Cancer Research U.K. (C5255/A18085), Wellcome Institutional Strategic Support Fund (204826/Z/16/Z) and other research councils, during the conduct of the study. JHC is an unpaid director of QResearch, a not-for-profit organisation which is a partnership between the University of Oxford and EMIS Health who supply the QResearch database used for this work. Until 09 August 2023, JHC had a 50% shareholding in ClinRisk Ltd, co-owning it with her husband, who was an executive director. On 9th August 2023, 100% of the share capital was donated to Endeavour Health Care Charitable Trust and the company renamed to Endeavour Predict Ltd. JHC is an unpaid consultant to Endeavour Predict Ltd and her husband is a non-executive director to cover the transition. The company licences software both to the private sector and to NHS bodies or bodies that provide services to the NHS (through GP electronic health record providers, pharmacies, hospital providers and other NHS providers). This software implements algorithms (including QRISK3) developed from access to the QResearch database during her time at the University of Nottingham. CC reports receiving personal fees from ClinRisk Ltd, outside this work. DRB reports receiving payments for speaking and advice for Astra Zeneca, Roche and MDS., (© 2024 Published by Elsevier Ltd.)

Background: Unintentional injuries are a common cause of morbidity and mortality in the under-5s, but undertaking home safety practices can reduce injury risk. Stay One Step Ahead (SOSA) is an evidence-based standardised home safety programme. This study evaluates the cost-effectiveness of SOSA versus usual care in Nottingham, UK., Methods: Cost-effectiveness analysis from a National Health Service and personal social services perspective. SOSA activity data, injury occurrence and associated short-term healthcare costs were collected within a controlled before-and-after study from 2017 to 2020. The primary outcome was the incremental cost-effectiveness ratio (ICER) per additional home adopting three key safety practices (working smoke alarm, safe poisons storage and fitted stair gate). Secondary outcomes were ICERs per injury avoided and quality-adjusted life-years (QALYs) gained., Results: SOSA costs £30 per child but reduces short-term healthcare expenditure by £42. SOSA increased the number of homes with three key safety practices by 0.02 per child, reduced injuries per child by 0.15 and gained 0.0036 QALYs per child. SOSA was dominant as it was cheaper and more effective than current practice. ICERs were -£590 per additional home deemed safe, -£77 per injury avoided and -£3225 per QALY gained. Focusing on healthcare expenditure alone, SOSA saved £1.39 for every pound spent., Conclusions: SOSA is a cost-saving intervention. Commissioners should consider implementing SOSA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The COVID-19 pandemic and consequent lockdowns had a substantial impact on mental health. Distress and fatigue are highly correlated. However, little is known about the determinants of fatigue in the general population during the pandemic. This study aimed to examine the prevalence and predictors of fatigue during the COVID-19 pandemic in the UK population. Online surveys were completed by a UK community cohort in April 2020 (wave 1), July-September 2020 (wave 2) and November-December 2020 (wave 3). In total, 3097 participants completed the wave 1 survey, and 1385 and 1087 participants (85.4% women) completed wave 2 and 3 surveys respectively. Fatigue was assessed using the Chalder Fatigue Scale at waves 2 and 3. Hair samples were provided by 827 participants (90.6% women) at wave 1 and wave 2, which were analyzed to indicate HairE (stress hormone). The mean total fatigue score during wave 2 was 14.7 (SD = 4.7), significantly higher than pre-pandemic levels observed in the community (mean difference 0.50, p = .003). At wave 2, 614 (44.3%) participants met the case definition for fatigue, only 15.6% of whom indicated that fatigue lasted for more than 6 months (suggesting it had started prior to the pandemic). Predictors of fatigue at wave 3 included being in a risk group, depression and belief in having COVID-19, which explained 23.8% of the variability in fatigue scores. Depression at wave 1 was the only significant predictor of remaining a fatigue case at wave 3. Fatigue was highly prevalent in the UK community during the COVID-19 pandemic and limited people's daily function. Depression and sociodemographic variables were significant predictors of fatigue.