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Background: Persons with COVID-19 may experience limitations in daily functioning and can be referred to occupational therapy., Objectives: To evaluate changes in daily functioning, cognitive complaints, fatigue and self-management of persons with COVID-19 who received occupational therapy in primary care.To get insights in the volume and duration of occupational therapy., Design: A pre-post observational cohort study from October 2020 until April 2021., Setting: Fifty-eight occupational therapy practices in primary care throughout the Netherlands participated with 68 occupational therapists., Participants: 228 adults (≥18 years) with COVID-19, referred to occupational therapy, gave informed consent and participated in the pre-post evaluation. The mean age was 49 years (SD 13) and 79% of the patients was female. The most frequently reported complaints included fatigue and cognitive complaints., Interventions: Occupational therapy using Dutch guidelines for occupational therapy in clients with COVID-19., Outcome Measures: Performance and satisfaction with performance using the Canadian Occupational Performance Measure (COPM); the impact of Cognitive Complaints on Participation (CoCo-P); and daily activities, self-management and perceived contribution of occupational therapy using the Patient Reported Outcome Measure for Occupational Therapy (PROM-OT)., Results: COPM-performance score improved with a mean difference of 2.9 points (95% CI 2.7 to 3.2), and COPM-satisfaction score improved with 3.2 points (95% CI 2.9 to 3.5). CoCo-P score improved with a mean difference of 20.9 points (95% CI from 14.4 to 27.4), and PROM-OT improved with 42.8 points (95% CI from 40.2 to 45.4). Participants received a median of seven sessions of occupational therapy (IQR 5-10) with a median duration of 18 weeks (IQR 12-25). They valued the contribution of occupational therapy to their improved functioning with a mean score of 8 (SD 1.4) and recommended this to others with a mean score of 9 (SD 1.2)., Conclusions: Persons with COVID-19 who received occupational therapy in primary care improved significantly in daily functioning and highly valued occupational therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Type 2 diabetes mellitus (T2DM) is a complex metabolic disease with several treatment options. Some glucagon-like peptide 1 receptor agonists (GLP-1 RAs) approved by the European Medicines Agency include dulaglutide, subcutaneous (s.c.) semaglutide, and oral semaglutide. This study examines dulaglutide and semaglutide dosing patterns for T2DM in France and Italy., Methods: IQVIA Longitudinal Prescription Data identified adults with T2DM prescribed dulaglutide or semaglutide between August 1, 2020 and December 31, 2022. Cohort 1 (incident) and cohort 2 (prevalent) users were followed for 12 months., Results: In France and Italy, 255,571 and 350,853 patients, respectively, received at least one study GLP-1 RA. Most dulaglutide-naïve patients in France (62%) and approximately half in Italy (49%) started on 1.5 mg and remained on this dose for up to 12 months (France: 66% cohort 1, 88% cohort 2; Italy: 73% cohort 1, 87% cohort 2). In cohort 1, s.c. semaglutide users mostly started on 0.25 mg (France, 78%; Italy, 61%). At 12 months, s.c. semaglutide 1.0 mg was most prescribed (France: 58% cohort 1, 75% cohort 2; Italy: 59% cohort 2), with cohort 1 in Italy mostly receiving 0.5 mg (57%). Most oral semaglutide users in Italy started on 3.0 mg (78% cohort 1; 68% cohort 2), which was increased to 7.0 mg (62% cohort 1) and 14.0 mg (48% cohort 2) at 12 months., Conclusions: GLP-1 RA dosing patterns, although similar between France and Italy, were heterogeneous over time. As oral semaglutide and higher dulaglutide doses are recent to the market, additional real-world evidence is required to evaluate utilization patterns. Graphical abstract available for this article., (© 2024. The Author(s).)

Introduction: In female patients diagnosed with gynaecological cancer, the main priority is treating cancer itself. However, a significant number of these patients develop lower limb lymphoedema (LLL), with its incidence strongly influenced by the diagnostic cut-off (a difference in leg circumference between both legs of 5% or 10%). LLL significantly impacts patients' quality of life (QoL) due to functional impairment, the daily time investment required for treatment, financial costs and affected body image. Additionally, it increases the risk of cellulitis, often leading to hospitalisation for intravenous antibiotics. Timely recognition and acknowledgement of symptoms are crucial first steps in improving the QoL for these women. LLL is a common and irreversible complication following treatment for gynaecological cancer. Despite its clinical significance, there are limited prospective studies investigating LLL incidence, risk factors, early detection and clinical course in this patient population. Therefore, the objective of this observational cohort study is to investigate the incidence rate of stage 0-1 or stage 2-3 LLL based on the International Society of Lymphology criteria in the first 2 years after gynaecological cancer treatment. The embedded randomised control study (RCT) examines the added value of prophylactic compression garments (class II) to standard care in preventing irreversible lymphoedema after gynaeco-oncological therapy., Methods and Analysis: In June 2022, two university hospitals in Belgium initiated a multicentre observational cohort study, which also includes an embedded RCT. The study aims to enrol 400 patients before they begin cancer treatment or within 14 days of starting chemotherapy, radiotherapy or surgery. This cohort will be followed for up to 2 years. The embedded RCT will focus on patients who develop clinical lymphoedema stage 0-1 within the first 12 months following their initial cancer treatment. A total of 196 patients will be randomised into two groups: the intervention group (98 patients), receiving usual care plus prophylactic compression garments (compression class 2 (CCL2): 23-32 mm Hg), and the control group (98 patients), receiving only usual care. The RCT aims to assess the impact of adding prophylactic compression garments to standard care on further deterioration. Assessments will be conducted at baseline, and at 3, 12 and 24 months after initial cancer treatment. An additional assessment (T-visit) will be provided if there is a transition to LLL stage 0-1 or from stage 0-1 to stage 2-3 LLL, based on follow-up findings or patient initiative, using the predictive value of a validated self-report lower extremity questionnaire. This questionnaire is part of a lymph diary app provided to all patients. The primary outcome of the observational study is to determine the incidence rate of stage 0-1 or stage 2-3 LLL in the first 2 years after gynaecological cancer treatment. The primary outcome of the RCT is to evaluate the effect of wearing CCL2 preventive garments to avoid progression to higher-stage lymphoedema in patients who develop LLL within 1 year of treatment. Key secondary outcomes of the observational study include the timing of the development of LLL, risk factors for developing LLL and the impact of LLL on QoL and sexuality, as well as the evaluation of screening and diagnostic tools. The secondary outcomes of the RCT include tolerance and compliance with wearing the preventive compressive garments, the impact of the garments on limb volume and the patient's time and financial investment., Ethics and Dissemination: The study was approved by the Ethics Committee of the two academic hospitals: the University Hospital of Ghent in September 2021 and the University Hospital of Leuven in December 2021. Approval has been granted for the study protocol, informed consent forms and other related documents by the main Ethics Committee of Ghent (BC-09915) and the local Ethics Committee of Leuven (S65724). All patients will provide written informed consent before participating in the trial. The results will be shared through peer-reviewed journals and presentations., Trial Registration Number: NCT05469945., 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.)

Introduction: Daratumumab, lenalidomide, and dexamethasone (DRd) and bortezomib, lenalidomide, and dexamethasone (VRd) are the only preferred treatment regimens for patients with transplant-ineligible (TIE) newly diagnosed multiple myeloma (NDMM). As there are no randomized head-to-head studies of DRd versus VRd, this analysis aimed to compare real-world time-to-next-treatment (TTNT) or death in this population., Methods: Patients with NDMM who received front-line (FL) DRd or VRd were identified from the Acentrus database (January 1, 2018 to May 31, 2023). Those with a record of a stem cell transplant or aged < 65 years were excluded to limit analysis to the TIE population. Inverse probability of treatment weighting was used to balance baseline patient characteristics. A doubly robust Cox proportional hazards model was used to compare TTNT or death between cohorts., Results: A total of 149 and 494 patients who initiated DRd and VRd, respectively, were identified. After weighting (weighted N DRd  = 302, weighted N VRd  = 341), cohorts had similar baseline characteristics. Of these, 98 (32.4%) DRd and 175 (51.2%) VRd patients either received a subsequent line of therapy or died, with a median TTNT or death of 37.8 months in the DRd cohort and 18.7 months in the VRd cohort (hazard ratio: 0.58, 95% confidence interval: 0.35, 0.81; p < 0.001)., Conclusion: Treatment of TIE NDMM patients with DRd led to a significantly longer TTNT or death compared to VRd, evidenced by a 42% risk reduction, supporting the effectiveness of DRd over VRd as FL treatment in this patient population., (© 2024 Janssen Scientific Affairs, LLC. Cancer Medicine published by John Wiley & Sons Ltd.)

Background/aim: In several studies, Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have been reported to increase hemoglobin (Hb) levels. In a study in which Hb levels were compared between patients who received SGLT2i and dipeptidyl peptidase-4 inhibitors, some patients exhibited increased Hb levels (>1.0 g/dl), whereas some exhibited unchanged Hb levels. Notably, several factors may influence the Hb-increasing effect of SGLT2i. This study aimed to analyze the factors influencing the Hb-increasing effect of SGLT2i., Patients and Methods: Type 2 diabetes patients were divided into three groups: SGLT2i (SGLT2i only group, n=36), those receiving a combination of SGLT2i and angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) (SGLT2i+ACEi/ARBs group, n=32), and those not receiving these drugs (control group, n=49). We retrospectively analyzed Hb changes in these groups. Kaplan-Meier curves compared Hb changes from SGLT2i initiation to day 63, with an Hb increase defined as ≥0.5 g/dl. In addition, sex, age, ACEi/ARBs, estimated glomerular filtration rate, and hematocrit levels were analyzed using Cox proportional hazards as factors influencing Hb-increasing events., Results: Hb-increasing event rates were 61%, 41%, and 20% in the SGLT2i only, SGLT2i+ACEi/ARBs, and control groups, respectively. The Kaplan-Meier curves showed significantly higher Hb-increasing event rates in the SGLT2i only group than in the control and SGLT2i+ACEi/ARBs groups. In the Cox proportional hazards model, ACEi/ARBs use was associated with a 39% reduction in the incidence of Hb-increasing events., Conclusion: SGLT2i exhibit a Hb-increasing effect, which may be reduced by ACEi/ARBs., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Research Question: What is the relationship between antral follicle count (AFC) and chronological age, and what are the expected values for AFC?, Design: This was a retrospective cohort study at a specialist gynaecological ultrasound centre in London, UK. Women presenting to a gynaecology diagnostic unit for investigation of symptoms or routine check-up, and undergoing transvaginal ultrasound (TVUS) examinations, between 1 January 2017 and 22 September 2022 were included in this study., Results: In total, 8821 TVUS records from 7573 patients were analysed. The relationship between AFC and age was estimated to develop an AFC nomogram independent of the stage in the menstrual cycle. AFC corresponding to the 10 th , 25 th , 50 th , 75 th and 90 th centiles for each patient and age group were calculated. Both nomogram and condition-specific populations displayed a Gaussian relationship between AFC and age. For the nomogram population (scans n = 4256, patients n = 3821), a peak median AFC of 30 was observed between 21-23 years of age. The AFC distribution of the group with previous ovarian cystectomy (scans n = 534, patients n = 443) was found to be significantly different compared with the nomogram population (P < 0.0001). However, the same did not hold true for those on hormonal contraception (scans n = 566, patients n = 534) (P = 0.43)., Conclusions: An AFC nomogram reporting median and interquartile values for AFC by chronological age across the reproductive years was developed. This is a useful tool for providing counselling for those undergoing ovarian reserve assessments, and can be taken any time in the menstrual cycle, including in women on hormonal contraceptives or who have undergone previous ovarian cystectomy., (Copyright © 2024. Published by Elsevier Ltd.)

Aim: To establish trust in real-world evidence (RWE) derived from CareLink Personal (CP), Medtronic's data management system for MiniMed system users, we show that this database and its analyses strictly adhere to the principles of RWE., Methods: The methodology is applicable to all MiniMed iterations. We described every step from raw data to predefined outcomes. In addition, we showed CP's fitness-for-research by the below metrics (using last year's MiniMed 780G system data as a case study): representative population, relevant endpoints, appropriate granularity, high data completeness, high data representativity and consistency in results., Results: The process from raw data to outcomes has been validated, and metrics/logics adhere to established definitions. Over 95% of users have a CP account; with 96% providing consent, this allows the use of >91% of the census population. There is no rationale for an over-representation of a specific phenotype among users not included. CP includes >50 endpoints, including 'International Consensus on Time in Range' based metrics. Data are recorded at 5-min intervals (maximum 288 per day), and on average there were 263 data points per person per day. Ninety-nine per cent of uploads were automated. For the last year, only 1 in 6 users had a data gap >1 day, and 1 in 50 had a gap >1 week. The time in range from in-silico studies was similar to that of real-world studies from different geographies and with ever growing populations., Conclusion: RWE from CP adheres to the principles of RWE and can serve as robust evidence on the performance and safety of MiniMed systems., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objectives: To investigate the utilization and costs of non-insulin glucose-lowering drugs (GLDs) in Australia from 2013 to 2023., Materials and Methods: We conducted a retrospective analysis of the Australian Pharmaceutical Benefits Scheme (PBS) administrative dataset of 118 727 494 GLD prescriptions. The main outcome measures were the annual number of GLD prescriptions dispensed, accounting for type 2 diabetes mellitus (T2DM) prevalence and healthcare system costs, adjusted for inflation., Results: Utilization of GLDs doubled from 6.4 million prescriptions in 2013 to 15.6 million in 2023. The average annual percent increase in utilization was 8.1%, compared to the average annual increase in prevalence of T2DM of 1.8%. The biggest change was in sodium-glucose cotransporter-2 (SGLT2) inhibitors, for which there was an average annual increase in utilization of 59.4% (95% confidence interval [CI] 51.7%, 68.2%; p < 0.05) from 2014 (first full year of PBS listing), followed by glucagon-like peptide-1 receptor agonists (GLP-1RAs), which showed an increase of 31.4% (95% CI 28.5%, 33.8%; p < 0.05) annually (2013 to 2023). Dipeptidyl peptidase-4 inhibitor utilization tripled, with an average annual increase of 10.9% (95% CI 8.1%, 13.8%; p < 0.05), but this plateaued from 2020. Metformin utilization increased by 4.7% (95% CI 2.0%, 6.9%; p < 0.05) annually. In contrast, sulphonylurea, glitazone and acarbose utilization declined. Total GLD costs increased threefold over the same period. Despite only accounting for 11.7% of utilization, GLP-1RAs contributed to 35% of the costs., Conclusion: Utilization of GLDs doubled, and associated costs tripled over the past 11 years, with no sign of either utilization or costs plateauing, predominantly due to increased GLP-1RA and SGLT2 inhibitor prescribing., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To investigate the independent contributions of glycated haemoglobin (HbA1c) reduction and weight loss to clinical outcomes in patients with type 2 diabetes (T2D) treated with antidiabetic drugs, including glucagon-like peptide-1 receptor agonists (GLP-1RAs)., Materials and Methods: This observational, retrospective cohort study used deidentified electronic health record-derived data from patients evaluated at the Cleveland Clinic (1 January 2000-31 December 2020). Cohort A included 8876 patients with newly diagnosed T2D treated with any of six antidiabetic drug classes. Cohort B included 4161 patients with T2D initiating GLP-1RA treatment. The effects of body mass index (BMI) and HbA1c reduction, variability, and durability on clinical outcomes were investigated., Results: In Cohort A, each 1% BMI reduction was associated with 3%, 1%, and 4% reduced risk of heart failure (p = 0.017), hypertension (p = 0.006), and insulin initiation (p = 0.001), respectively. Each 1% (~11 mmol/mol) HbA1c reduction was associated with 4% and 29% reduced risk of hypertension (p = 0.041) and insulin initiation (p = 0.001), respectively. In Cohort B, each 1% BMI reduction was associated with 4% and 3% reduced risk of cardiovascular disease (p = 0.008) and insulin initiation (p = 0.002), respectively. Each 1% (~11 mmol/mol) HbA1c reduction was associated with 4% and 16% reduced risk of chronic kidney disease (p = 0.014) and insulin initiation (p = 1 × 10 -4 ), respectively. Lower BMI variability and greater BMI durability were associated with decreased risk of clinical outcomes in both cohorts., Conclusions: Antidiabetic medication-associated, and specifically GLP-1RA-associated, weight loss and HbA1c reductions independently reduce real-world clinical outcome risk., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To estimate healthcare resource utilization (HCRU) and healthcare costs by body mass index (BMI) in a UK cohort and to explore how this varied by defined BMI strata., Materials and Methods: This retrospective open cohort study used Discover, a linked primary and secondary electronic health records database covering 2.7 million individuals. Adults were stratified by BMI as: overweight (25-<30 kg/m 2 ); obesity class I (30-<35 kg/m 2 ); obesity class II (35-<40 kg/m 2 ); or obesity class III (≥40 kg/m 2 ). Cost data, comprising primary care, secondary care (inpatient admissions, outpatient appointments and emergency room visits) and prescriptions, were reported for 2015-2019., Results: Overall, 1 008 101 individuals were overweight, 278 782 had obesity class I; 80 621 had obesity class II, and 42 642 had obesity class III. Healthcare costs and HCRU events per person per year increased over time (2015: £851-£1321 and 10.6-13.4 events; 2019: £1143-£1871 and 11.4-14.9 events), and were higher for each successive BMI group. Groups with chronic kidney disease or cardiovascular disease incurred particularly high costs. In 270 493 individuals with obesity in 2019, more than 72% of total healthcare costs were incurred by the highest cost quintile, which had a higher mean age and more obesity-related complications (ORCs) than lower cost quintiles., Conclusions: The economic impact of obesity could be alleviated by weight management support based on unmet need, to limit the effects of BMI progression and ORC development., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

This observational study aimed to investigate associations between dietary live microbe intake and mortality, as well as biological aging. Adults from the 1999-2018 National Health and Nutrition Examination Survey were categorized into low, medium, and high dietary live microbe groups. Foods with medium and high live microbe content were aggregated into a medium-high consumption category. The outcomes included all-cause, cardiovascular, and cancer mortality, along with biological age (BA) acceleration assessed by the Klemera-Doubal method (KDM) and PhenoAge. Multiple regression analyses and mediation analyses were conducted to assess associations, adjusting for potential confounders. A total of 34 133 adults were included in our analyses. Over an average follow-up period of 9.92 years, 5 462 deaths occurred. In multivariate adjusted models, every 100 g of medium-high group foods consumed was associated with reduced all-cause mortality (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.91 to 0.97, p < .001) and cardiovascular mortality (HR 0.91, 95% CI 0.86 to 0.96, p < .001), but not with cancer mortality (HR 1.01, 95% CI 0.95 to 1.07, p = .768). Every 100 g medium-high group foods consumption was associated with decreased KDM-BA acceleration (fully adjusted regression coefficient -0.09, 95% CI -0.15 to -0.04, p = .001) and PhenoAge acceleration (fully adjusted regression coefficient -0.07, 95% CI -0.11 to -0.03, p < .001). Mediation analysis showed that BA acceleration partially mediated live microbes-mortality associations. Our results suggest that higher dietary live microbe intake is associated with lower mortality risk and slower biological aging. However, further research is needed to verify these findings., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aim: To assess the prevalence of individual obesity-related complications (ORCs) and multimorbidity (≥ 1, ≥ 2 and ≥ 3 ORCs), and multimorbidity-associated healthcare costs, over 10 years., Methods: This retrospective open cohort study used Discover, a UK database of linked primary and secondary electronic health records. Adults were stratified by body mass index (BMI; overweight: 25-< 30 kg/m 2 ; obesity class I: 30-< 35 kg/m 2 ; obesity class II: 35-< 40 kg/m 2 ; obesity class III: ≥ 40 kg/m 2 ). Outcomes by year since baseline were assessed for serial cross sections across the study period (1 January 2004 to 31 December 2019; the index date was the date of first eligible BMI measurement)., Results: Across 1 410 146 individuals (overweight: 1 008 101; obesity class I: 278 782; obesity class II: 80 621; obesity class III: 42 642), ORC prevalence was higher in successive BMI groups, and increases over time were generally greater for obesity relative to overweight. In those with ORC multimorbidity, both higher BMI and the presence of more ORCs were associated with higher annual per-person healthcare costs. Costs increased over time in those individuals with obesity and one or more ORC, as well as in those with obesity and two or more ORCs., Conclusions: Higher BMI was associated with higher baseline ORC prevalence and a greater increase in ORC prevalence over time, and with higher healthcare costs in those with multimorbidity. To reduce the burden of overweight and obesity on patients and healthcare systems, the presence, number and type of ORCs should be considered in developing effective, targeted prevention and management care pathways., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Nonsuicidal self-injury (NSSI) is highly prevalent in adolescents and young adults worldwide. It is linked to a broad variety of mental disorders and an increased suicide risk. Despite its high prevalence, research on the underlying mechanisms and on potential risk and resilience factors for maintaining or quitting NSSI remains scarce. This manuscript presents an overview of the "Self-injury: Treatment-Assessment-Recovery" (STAR) collaboration, which aimed to address these gaps., Methods: We investigated the natural course of NSSI as well as its social, psychological, and neurobiological predictors (observational study; OS). OS data collection occurred at four timepoints (baseline [T0], 4 [post, T1], 12 [follow-up (FU), T2], and 18 [FU, T3] months after baseline) for the NSSI group, which was compared to a healthy control (HC) group at T0 only. Online self-report was used at all timepoints, while semi-structured interviews (face-to-face (f2f)) were conducted at T0 and T3. At T0 only, we conducted ecological momentary assessment and neurobiological investigations. Here, we present the general methodology and sample characteristics of the completed OS including the f2f subprojects, while other subprojects are not within the scope of this paper., Sample Description: The OS sample consists of 343 participants at T0 (180 NSSI, 163 HC). Mean age in the NSSI group (T0) was 18.1 years (SD = 2.09, range: 15-25), gender-related data is available for 166: 156 = female, 7 = male, 3 = transgender, 10 = not disclosed). In the HC group, mean age (T0) was 19.1 years (SD = 2.35, range: 15-25) (142 = female, 21 = male). At T1, 128 (71.11%) of the NSSI participants completed the questionnaires, at T2 125 (69.44%) and at T3 104 (57.78%). In the fMRI subproject, 126 adolescents participated (NSSI = 66, HC = 60, 100% female; mean age (T0): NSSI = 18.10 years, SD = 2.21; HC = 19.08, SD = 2.36)., Conclusion: Understanding predictors is of utmost importance for adequate diagnosis and intervention for NSSI. Our OS applied a multimodal investigation of social, psychological, and neurobiological parameters and is the largest sample of adolescents with NSSI to date including follow-up assessments. As health care providers require specific knowledge to develop new treatments, we believe that our in-depth assessments can potentially enhance care for youths engaging in NSSI., (© 2024. The Author(s).)

Background: Despite programmatic protocolised care and structured support, considerable variation is observed in completeness of registration and achieving targets of cardiovascular risk management (CVRM) between individual GPs in the Netherlands., Aim: To determine whether completeness of registration and achieved targets of cardiovascular risk factors improves with practice visitation., Design & Setting: Observational study utilising the care group's database (2016-2019), comparing changes in registration and achieved targets in non-visited practices and visited practices., Method: We compared completeness scores of registration and scores of targets achieved before visitation and 1 year after visitation. Data were analysed on patient level and GP level. Separate analyses were performed among GPs who were ranked in the lower 25% of score distributions., Results: We observed no clinically relevant improvements in completeness of registration and targets achieved in 2017, 2018, and 2019 that could be attributed to visitations in the previous year, both on individual patient level and on aggregated level per general practice. In practices ranked in the lower 25% of the distribution, improvements over time were clinically relevant and larger than the overall changes. Yet, these findings were irrespective of the number of practice visitations., Conclusion: Practice visitations in our setting did not seem to lead to improvements in practice performance, nor in completeness of registration of risk factors or in reaching predefined target goals for cardiovascular risk factors., (Copyright © 2024, The Authors.)

Purpose: Physical activity is safe and feasible for individuals with metastatic cancer and may support symptom management. We investigated the extent to which individuals with metastatic cancer are meeting the World Health Organisation (WHO) moderate-vigorous physical activity (MVPA) guideline, factors associated with meeting the guideline, and perceptions about physical activity and receiving physical activity advice., Methods: Data were from UK adults with metastatic breast, prostate, or colorectal cancer who completed the Healthy Lifestyle After Cancer survey (N = 588). Self-reported clinical, demographic, and physical activity (Godin Leisure-Time Exercise Questionnaire) data were collected. Logistic regression models assessed whether clinical and demographic factors were associated with meeting the MVPA guideline., Results: Most (59%) individuals with metastatic cancer were not meeting the WHO guideline of 150 min of MVPA per week. Adjusting for cancer type, the odds of meeting the MVPA guideline were lower for unemployed individuals (OR = 0.47, 95% CI = 0.23-0.77) and ethnic minorities (OR = 0.44, 95% CI = 0.22-0.89), but higher for those with a university education (OR = 1.89, 95% CI = 1.0-3.57). Most (63.5%) participants felt they should be doing more physical activity. However, 70.1% did not receive any physical activity advice or support, despite 73.6% wanting to receive it., Conclusion: People with metastatic cancer may need further support to address inadequate levels of physical activity. The differences observed between demographic sub-groups suggest this may be more beneficial for those less likely to engage in physical activity., Implications for Cancer Survivors: Individuals with metastatic cancer are likely to benefit from increased physical activity support, which considers the needs of diverse demographic groups., (© 2024. The Author(s).)

Aims: This study aimed to explore the effect of discontinuation of long-term spironolactone treatment on markers of kidney function in individuals with type 2 diabetes (T2D) at high risk of kidney disease enrolled in the Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria (PRIORITY) study., Materials and Methods: An observational study following the nested randomised part of the PRIORITY study was conducted. A total of 115 individuals with T2D and normoalbuminuria but high risk for progression based on urinary proteomics, randomised to daily spironolactone (n = 50) or placebo (n = 65) for a median of 2.5 years, were re-examined approximately 6 weeks after the final visit in the PRIORITY study. Primary endpoint was relative change in geometric mean of urinary albumin-creatinine ratio (UACR) between the final visit in PRIORITY (baseline) and follow-up. Secondary endpoints were change in estimated glomerular filtration rate (eGFR), systolic blood pressure (SBP) and serum potassium., Results: No change in UACR was observed in neither the spironolactone (geometric mean change: 17%; 95% CI -12, 55; p = 0.28) nor the placebo (5%; 95% CI -13, 26; p = 0.63) group at follow-up. No difference in UACR between the groups was observed at follow-up (relative difference in geometric mean: 11%, 95% CI -26, 67; p = 0.60). For eGFR and SBP, an increase after discontinuation of spironolactone was observed, as well as for SBP after placebo discontinuation. Potassium levels were lower after discontinuation of spironolactone, but higher after placebo discontinuation (all p < 0.05)., Conclusions: UACR did not change after discontinuation of long-term treatment with spironolactone. However, an increase in eGFR was observed supporting a haemodynamic effect of spironolactone in the kidneys., (© 2024 John Wiley & Sons Ltd.)

Background: Understanding public opinions about emerging tobacco products is important to inform future interventions and regulatory decisions. Heated tobacco products (HTPs) are an emerging tobacco product category promoted by the tobacco industry as a "better alternative" to combustible cigarettes. Philip Morris International's IQOS is leading the global HTP market and recently has been subject to important policy events, including the US Food and Drug Administration's (FDA) modified-risk tobacco product (MRTP) authorization (July 2020) and the US import ban (November 2021). Although limited in their legal implications outside the United States, these policy events have been quoted in global news outlets and Philip Morris International's promotional communications, showing how they may potentially impact global tobacco regulation. Given the impending return of IQOS to the US market, understanding how the policy events were received through social media discourse will provide valuable insights to inform global tobacco control policy., Objective: This study aims to examine HTP-related social media discourse around important policy events., Methods: We analyzed HTP-related posts on Twitter during the time period that included IQOS's MRTP authorization in the United States and the US import ban, examining personal testimonial, news/information, and direct marketing/retail tweets separately. We also examined how the tweets discussed health and policy. A total of 10,454 public English tweets (posted from June 2020 to December 2021) were collected using HTP-related keywords. We randomly sampled 2796 (26.7%) tweets and conducted a content analysis. We used pairwise co-occurrence analyses to evaluate connections across themes., Results: Tweet volumes peaked around IQOS-related policy events. Among all tweets, personal testimonials were the most common (1613/2796, 57.7%), followed by news/information (862/2796, 30.8%) and direct marketing/retail (321/2796, 11%). Among personal testimonials, more tweets were positive (495/1613, 30.7%) than negative (372/1613, 23.1%), often comparing the health risks of HTPs with cigarettes (402/1613, 24.9%) or vaping products (252/1613, 15.6%). Approximately 10% (31/321) of the direct marketing/retail tweets promoted international delivery, suggesting cross-border promotion. More than a quarter of tweets (809/2796, 28.9%) discussed US and global policy, including misinterpretation about IQOS being a "safer" tobacco product after the US FDA's MRTP authorization. Neutral testimonials mentioning the IQOS brand (634/1613, 39.3%) and discussing policy (378/1613, 23.4%) showed the largest pairwise co-occurrence., Conclusions: Results suggest the need for careful communication about the meaning of MRTP authorizations and relative risks of tobacco products. Many tweets expressed HTP-favorable opinions referring to reduced health risks, even though the US FDA has denied marketing of the HTP with reduced risk claims. The popularity of social media as an information source with global reach poses unique challenges in health communication and health policies. While many countries restrict tobacco marketing via the web, our results suggest that retailers may circumvent such regulations by operating overseas., (©Minji Kim, Julia Vassey, Dongmei Li, Artur Galimov, Eileen Han, Matthew G Kirkpatrick, Cassandra A Stanton, Jenny E Ozga, Sarah Lee, Jennifer B Unger. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 24.10.2024.)

Background: Avelumab first-line maintenance treatment was approved for patients with advanced urothelial carcinoma (aUC) without progression following platinum-based chemotherapy (PBC), based on the results from the JAVELIN Bladder 100 phase 3 trial., Objective: To report the results from AVENANCE, a real-world study of avelumab first-line maintenance treatment., Design, Setting, and Participants: This is a retrospective and prospective, noninterventional study (NCT04822350). Eligible patients with aUC without progression on first-line PBC were enrolled at 82 centers in France between July 2021 and May 2022. The effectiveness population included 595 patients. The median follow-up was 26.3 mo., Intervention: Previous, ongoing, or planned avelumab first-line maintenance treatment., Outcome Measurements and Statistical Analysis: Overall survival (OS) from avelumab initiation (primary endpoint) and safety were evaluated., Results and Limitations: The median age was 73.0 yr, and performance status was 0/1 in 91% of patients and ≥2 in 9.3%. The most common prior first-line chemotherapy regimen was carboplatin plus gemcitabine (61%). At data cutoff (December 7, 2023), the median duration of avelumab treatment was 5.6 mo, 125 patients remained on avelumab, and 55% had received second-line treatment. The median OS from avelumab initiation was 21.3 mo (95% confidence interval [CI], 17.6-24.6), and the median progression-free survival was 5.7 mo (95% CI, 5.2-6.5). In exploratory analyses of this population without disease progression on PBC, the median OS from the start of first-line PBC was 26.5 mo overall, and in subgroups that received second-line enfortumab vedotin (n = 55) or PBC (n = 79), it was 41.5 and 24.5 mo, respectively., Conclusions: Real-world data from AVENANCE confirm the effectiveness and safety of avelumab first-line maintenance treatment in a heterogeneous population, supporting its recommendation for cisplatin-eligible and cisplatin-ineligible patients with aUC who are progression free after first-line PBC. In an exploratory analysis, a small subgroup that received a treatment sequence of first-line PBC without disease progression followed by avelumab first-line maintenance and second-line enfortumab vedotin had a median OS of >3 yr., Patient Summary: A French real-world study, called AVENANCE, looked at avelumab maintenance treatment in people with advanced urothelial cancer whose tumor disappeared, shrank, or stopped growing with chemotherapy. Overall, results were consistent with those seen in a previous clinical trial, and on average, people treated with avelumab maintenance lived for 26.5 mo from the start of chemotherapy. Analyses of different groups of people found that survival varied, with people living for an average of 18-42 mo depending on what treatment they received after they finished avelumab treatment., (Copyright © 2024. Published by Elsevier B.V.)

Background: Frailty often requires intensive care, and the admission outcomes of frail patients are often poor. However, owing to the lack of reliable diagnostic indicators, quickly identifying frailty is challenging. The present study aimed to explore the associations of the platelet/high-density lipoprotein cholesterol ratio (PHR; a novel inflammatory indicator) with frailty and all-cause mortality., Methods: The present study analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Frailty was assessed on the basis of the 49-item Frailty Index. The associations of the PHR with frailty and long-term survival prognosis were explored through weighted logistic regression, weighted restricted cubic spline (RCS), and weighted Cox regression, with adjustments for demographic factors, lifestyle, blood lipids, medication history, and complications. In addition, subgroup and interaction analyses were conducted. Finally, several sensitivity analyses were performed., Results: A total of 15,615 adult participants were included, with 7,928 women (53.63%) and an average age of 60.76 years. After fully adjusting for confounding variables, the prevalence of frailty in the highest PHR quartile group of was significantly greater than that in the lowest quartile group (OR: 1.23, 95% CI: 1.04-1.47; P = 0.02). The RCS showed that the inflection point was 166.7. Before and after the inflection point, the PHR was negatively associated (OR: 0.88, 95% CI: 0.80-0.97, P = 0.01) and positively associated (OR: 1.10, 95% CI: 1.02-1.19, P = 0.01) with frailty, respectively. Subgroup analysis suggested that the association between PHR and frailty was stronger in women than in men. A total of 5,544 frail participants were included in the survival analysis. The RCS revealed that the PHR was associated with the all-cause mortality risk of frail participants in a U-shaped manner, with an inflection point of 240.4. Before and after the inflection point, the PHR decreased (HR: 0.89, 95% CI: 0.81-0.97, P = 0.01) and the all-cause mortality risk increased (HR: 1.08, 95% CI: 1.02-1.14, P = 0.01), respectively., Conclusion: The present study suggests that there is a J-shaped association between PHR and frailty in the adult population of the United States and that the association between the PHR and frailty is stronger in women. In addition, the PHR has a U-shaped relationship with the all-cause mortality risk of frail patients., (© 2024. The Author(s).)

Background: The relationship between socioeconomic status (SES) and stroke remains controversial, and the underlying mediator is unclear. This study aimed to assess the causal relationship of SES with stroke and its subtypes and to identify potential modifiable risk factors responsible for this relationship., Methods: The study included 372,437 participants from the UK Biobank. Over an average period of 12.13 years, 6,457 individuals (2.7%) were recorded as having experienced a stroke. Cox proportional hazards model was used to determine the relationship between SES (average annual household income before tax and age at the end of full-time education) and stroke, ischemic stroke, and hemorrhagic stroke. Two-sample Mendelian randomization (MR) was employed to assess the causal relationship between SES and stroke and its subtypes. Furthermore, network MR was utilized to evaluate the potential mediating role of modifiable risk factors for stroke in this causal relationship., Results: After adjusting for factors such as sociodemographic characteristics, health behaviors, health status, and past medical history, participants in the second highest income group showed the lowest risk of stroke, with a hazard ratio (HR) of 0.780 (95% confidence interval [CI]: 0.702-0.866), and for ischemic stroke, the HR was 0.701 (95% CI: 0.618-0.795). Those who completed full-time education at the latest age group(>18 years) had the lowest risk of stroke (HR: 0.906, 95% CI: 0.830-0.988) and ischemic stroke (HR: 0.897, 95% CI: 0.811-0.992). MR analysis showed that higher income and education were both associated with a lower risk of stroke (income: inverse-variance-weighted odds ratio [OR IVW ] =0.796, 95% CI: 0.675-0.940, education: OR IVW  = 0.631, 95% CI: 0.557-0.716) and ischemic stroke (income: OR IVW  = 0.813, 95% CI: 0.684-0.966, education: OR IVW  = 0.641, 95% CI: 0.559-0.735). Additionally, hypertension had the highest mediating effect on this relationship. It accounted for 57.12% of the effect of income on stroke, 51.24% on ischemic stroke, and 27% and 24% for education., Conclusion: Higher SES was associated with a lower risk of stroke and ischemic stroke, and hypertension had the highest mediating effect on this causal relationship. The results have significant public health implications, emphasizing the importance of early intervention to reduce the risk of stroke in low SES populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Malnutrition is a complication of chronic kidney disease (CKD). Whether malnutrition, assessed via the geriatric nutritional risk index (GNRI), is associated with the incidence and risk of CKD in older individuals remains unclear., Methods: Data from the National Health and Nutrition Examination Survey and the UK Biobank database were used. Older participants over 60 years old with available data for GNRI assessment and CKD diagnosis were enrolled. Logistic regression models and Cox regression models were used to assess associations between the geriatric nutritional risk index and the risk of and mortality associated with CKD., Results: This study enrolled 13,162 participants from the NHANES and 66,326 participants from the UK Biobank. We identified 6,135 and 16,662 CKD patients in the NHANES and UK Biobank, respectively, with the majority being male (74% in the NHANES and 52% in the UK Biobank). The average age of CKD patients was 72.3 (SD 7.2) years in the NHANES and 64.9 (SD 2.9) years in the UK Biobank. The median follow-up times of older CKD patients were 81 months and 162 months in the NHANES and UK Biobank, respectively. According to the cross-sectional analysis, individuals with a lower GNRI had an increased likelihood of having CKD, with odds ratios of 1.38 (95% CI: 1.05-1.80, P = 0.020) in the NHANES and 2.35 (95% CI: 1.89-2.92, P < 0.001) in the UK Biobank. According to our analysis of the risk of incident CKD in the UK Biobank, a lower GNRI was associated with a greater incidence of CKD (HR: 1.11, 95% CI: 1.04-1.18; P = 0.002). According to the analysis of the risk of mortality, a lower GNRI was associated with an increased risk of death among older CKD patients (NHANES: HR: 1.69, 95% CI: 1.13-2.53, P = 0.011; UK Biobank: HR: 2.28, 95% CI: 1.94-2.69, P < 0.001)., Conclusion: Malnutrition assessed by the GNRI was significantly and independently associated with the incidence of CKD. Moreover, CKD patients with malnutrition also have a high risk of mortality., (© 2024. The Author(s).)

Objective: To examine the wealth-related disparities in modern contraceptives use among women in Papua New Guinea., Design: We performed a cross-sectional analysis of the 2016-2018 Papua New Guinea Demographic and Health Survey data. We included 11 618 women of reproductive age in our final analysis. Percentages were used to present the results on utilisation of modern contraceptives. A concentration curve was used to summarise the cumulative use of modern contraceptives by wealth index (ranked into groups: richest, richer, middle, poorer and poorest). We used a decomposition analysis to estimate the contributions of individual factors towards wealth-related inequality in modern contraceptives use. We estimated the slope index of inequality (SII) and the relative index of inequality (RII) in modern contraceptive utilisation to provide summary evidence of inequality., Setting: Papua New Guinea., Participants: Women aged 15-49 years., Outcome Measure: Modern contraceptives utilisation., Results: Overall, 27.5% of Papua New Guinea women used modern contraceptives. The concentration curve showed that the use of modern contraceptives was highly concentrated among women of the richest household wealth index as the concentration curve lies below the equality line. The SII (0.210, CI 0.182 to 0.239) indicates that the richest group uses more modern contraceptives. The RII depicts a relative difference of 2.044 between the richest and the poorest women in the use of modern contraceptives., Conclusions: Our study has shown that modern contraceptives use among women in Papua New Guinea is low. Women from the richest household wealth index group had the highest propensity to use modern contraceptives in comparison with those from poorer homes. The Ministry of Health and other organisations must design and carry out initiatives aimed at enhancing the availability of and use of modern contraceptives among women from less affluent backgrounds., 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.)

Objectives: Investigate associations between body height and cardiovascular disease risk factors at several time points in women and men across educational levels in Norway., Design: Population-based longitudinal study., Setting: The Tromsø Study, a population-based study with six surveys conducted between 1979 and 2016 in the municipality of Tromsø, Norway., Primary and Secondary Outcome Measures: Body height, systolic blood pressure, diastolic blood pressure, serum total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and self-reported educational level., Participants: 23 512 women and men (49.6% women), aged 30-49 years at first participation in The Tromsø Study. Participants who attended more than one survey contributed with repeated measurements for blood pressure and lipids.Blood pressure and lipid values were used as dependent variables in sex specific age-adjusted linear mixed models. Body height at first participation was the independent variable, while survey time point and educational level were used as covariates., Results: Overall effect models showed inverse associations between body height and systolic blood pressure (reg. coefficients: -0.88 (95% CI -1.1, -0.6)), diastolic blood pressure (-0.41 (95% CI -0.6, -0.3)), serum total cholesterol (-0.12 (95% CI -0.1, -0.1)) and triglycerides (-0.06 (95% CI -0.1, -0.0)) in women. Inverse associations between body height and lipid variables were also observed in men (serum total cholesterol: -0.12 (95% CI -0.1, -0.1) triglycerides -0.05 (95% CI -0.1, -0.0)). Regression coefficients for associations between body height and cardiovascular risk factors varied across surveys. Overall, there were no associations between body height and cardiovascular risk factors based on educational level and survey., Conclusion: The overall effect models support previous findings of inverse associations between body height and cardiovascular risk factors in women, and inverse associations between body height and lipids in men. Our study showed varied degrees of associations between body height and cardiovascular risk factors at different time points in Norway., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: The primary objective of this study was to assess caregivers' perceptions of feeding practices (breastfeeding and complementary feeding) and diet diversity among children aged 12-59 months in a rural district of South India. The secondary objective was to identify potential predictors of these perceptions and diet diversity., Design: An analytical cross-sectional study was performed from March 2023 to May 2023., Setting: In a rural district of Tamil Nadu, South India., Participants: This study included 301 mothers/caregivers of children between 12 and 59 months of age in a rural district of Tamil Nadu. The research gathered demographic information from caregivers, including details such as age, educational background, occupation, relationship with the child and place of residence. Additionally, the caregivers' perspectives were evaluated through a questionnaire focused on breastfeeding/complementary feeding, and the diet diversity of the children was also assessed., Outcome Measures: The primary outcome was the perceptions of mothers/caregivers of children between 12 and 59 months of age about breastfeeding/complementary feeding practices, and the diet diversity of the children was measured. Additionally, predictors associated with these perceptions were evaluated through regression analysis., Results: In the present study, 188 (62.5%) and 179 (59.5%) of the participants had good perceptions of breastfeeding practices and complementary feeding practices, respectively. This binomial regression revealed that subjects with unstable occupations (adjusted OR=2.24, 95% CI 1.25 to 4.01), schooling (7.71, 95% CI 2.73 to 8.9) and higher education (38.32, 95% CI 4.63 to 316.85) had increased chances of having good perceptions of breastfeeding practices. Subjects with unstable occupations (0.23, 95% CI 0.06 to 0.85), stable occupations (0.13, 95% CI 0.04 to 0.51), schooling (0.43, 95% CI 0.25 to 0.74), higher education (0.15, 95% CI 0.04 to 0.50) and increased birth weights (2.54, 95% CI 1.35 to 4.78) had increased chances of having good perceptions of complementary feeding practices (p<0.05). This study revealed that 86.4% of the children had adequate diet diversity., Conclusion: The study revealed that most caregivers, particularly mothers, possess a strong understanding of breastfeeding and complementary feeding practices, with education and occupation exerting a notable influence. However, there is a crucial necessity to translate this knowledge into practical applications to effectively obtain feeding indicators., 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.)

Background: The Netherlands is one of few countries worldwide which has used the bivalent HPV vaccine for girls-only for over a decade. This allows assessment of vaccine effectiveness (VE) against female genital HPV DNA-positivity of this vaccine in an observational post-licencing real-world setting. Additionally, it is unclear whether catch-up vaccination campaigns result in similar VE as routine vaccination. Therefore, type-specific and grouped VE were assessed and compared for women who had been eligible for catch-up vaccination at 13-16 years with those who had been eligible for routine vaccination at 12 years., Methods: PASSYON is a Dutch biennial repeated cross-sectional (2011-2021) study among sexual health clinic clients aged 16-24 years old. Women provided self-collected vaginal samples, questionnaires on demographics and sexual behaviour were administered, and women self-reported HPV vaccination status. Samples were analysed using a PCR-based assay (SPF 10 -LiPA 25 ). Type-specific and grouped VE estimates, adjusted with propensity score stratification, were assessed against genital positivity for 14 HPV types. VE for targeted and non-targeted genotypes were compared between women who had been eligible for the catch-up and those who had been eligible for routine vaccination., Results: The study included 4488 female participants who had been eligible for HPV vaccination and provided genital swabs (1561 eligible for catch-up, 2927 for routine vaccination). Very high VE against genital HPV-16 and HPV-18 was observed (resp. 93.5% and 89.5%) and significant cross-protection against six other genotypes (HPV-31/33/35/45/52/58), varying from 18.0% (HPV-52) to 79.6% (HPV-45). VE estimates were comparable between women who had been eligible for the catch-up campaign and those eligible for routine vaccination: VE HPV-16/HPV-18: 92.2% (95%CI: 87.9-94.9) vs. 91.8% (95%CI: 86.0-95.2)., Conclusions: In real-world settings, the VE of bivalent vaccine is high against targeted genotypes, with cross-protection against 6 other genotypes. Catch-up campaigns up to age 16 years can be as effective as routine vaccination at age 12, although it is recommendable to provide HPV vaccination at an age at which most are likely not sexually active yet. This may inform countries considering catch-up campaigns when introducing or extending the use of HPV vaccination within their national immunisation programmes., (© 2024. The Author(s).)

Background: The growth of patient and public involvement in clinical research highlights the paucity of literature on operational practices that ensure the success of large, patient-centered outcomes trials. The authors' objective was to identify tools launched by the Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer (CISTO) study team to determine their effectiveness in maximizing patient enrollment in this observational, pragmatic trial., Methods: The primary outcomes for this study were patient screening and enrollment across 36 CISTO study sites. The operational strategies included CISTOquestion email correspondence and All Sites Meetings, specifically poll performance data from meetings, and a nonanonymized feedback survey about the CISTO study's management practices. Effectiveness was measured using correlation analysis with patient cohort data, including screenings, enrollments, post-hoc exclusions, and the post-hoc exclusion rate., Results: Average screenings and enrollment rose after the implementation of CISTOquestion in April 2021, with the average number of screenings rising from 7.42 to 26.8 patients per month and enrollment rising from 3.76 to 16 patients per month. Use of CISTOquestion was correlated strongly with increased patient screenings and enrollment across all study sites. Eighty-three percent of sites with above-average post-hoc exclusion rates (≥0.092) sent below the average number of CISTOquestion inquiries. Poll performance and survey data revealed that all survey respondents who used CISTOquestion found that it was a valuable and accessible resource., Conclusions: Of the several operational tools implemented within the CISTO study that aimed to improve patient enrollment, CISTOquestion, a centralized email for addressing eligibility questions, was most beneficial to overall patient accrual., (© 2024 American Cancer Society.)

Background: Musculoskeletal alterations causing reduced range of motion of the ankle joint are common in children with cerebral palsy (CP). Objective measurements of passive joint resistance and three-dimensional skeletal muscle volume and muscle architecture can lead to a comprehensive understanding of which factors influence joint range of motion., Research Question: To investigate the relation between the passive dorsiflexion of the ankle joint, biomechanical contributing factors to the passive joint resistance, and muscular architectural properties of the triceps surae muscle in children with CP., Methods: In this cross-sectional observational study, 14 children with spastic CP (bilateral: 5, unilateral: 9, Gross Motor Function Classification System (GMFCS) level I:11, II:3) naïve to intramuscular tone reducing treatment, and 14 TD children were included. The passive dorsiflexion of the ankle was measured with a goniometer. Passive joint resistance and related parameters were estimated based on a biomechanical model and measurements using a motorized device, the Neuroflexor. Three-dimensional muscle architecture was quantified with diffusion tensor magnetic resonance imaging (DT-MRI)., Results: In the CP group, the median [min, max] passive dorsiflexion was decreased in the most affected leg (MAL) compared to the less affected leg (LAL) (2.5° [-25°, 20°] vs. 12.5° [5°, 30°], p = 0.001). The stiffness coefficient (Nm/rad) in the MAL was significantly higher in children with CP compared to TD children (7.10 [3.39, 62.00] vs. 2.82 [1.24, 10.46], p = 0.015). Muscle architecture properties did not differ between CP and TD, except for pennation angle in the medial gastrocnemius (MG) of the MAL (CP 17.64° (2.29) vs. TD 21.46° (3.20), p = 0.017). The stiffness coefficient, in the MAL, correlated negatively to passive dorsiflexion (r s =-0.638) and pennation angle in medial gastrocnemius (r s =-0.964), and the non-linear coefficient (Non-linear 1) correlated negatively to the fascicle length of the medial gastrocnemius (r s =-0.857)., Conclusion: This study shows that stiffness of the plantarflexors is related to decreased passive dorsiflexion of the ankle and muscle structure of the MG in high-functioning children with spastic CP. Assessments of how dynamic components as well as microscopic muscle alterations contribute to joint stiffness in the plantarflexors in individuals with CP are warranted., Trial Registration: Retrospectively registered in ClinicalTrials.gov, NCT05447299. Observational study. Study start: 2019-01-15, register date: 2022-07-01., (© 2024. The Author(s).)

Background: Adverse pregnancy outcomes have reached epidemic proportions in recent years with serious health ramifications, especially for diverse cancers risk. Therefore, we carried out an umbrella review to systematically evaluate the validity and strength of the data and the extent of potential biases of the established association between adverse pregnancy outcomes and cancers risk in both mother and offspring., Methods: PubMed, Embase, and Web of Science databases were searched from inception until 18 January 2024. Meta-analyses of observational studies investigating the relationship between adverse pregnancy outcomes and multiple cancers risk in both mother and offspring were included. Evidence certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. The protocol for this umbrella review was prospectively registered in PROSPERO (CRD42023470544)., Results: The search identified 129 meta-analyses of observational studies and 42 types of cancer. Moderate certainty of evidence, exhibiting statistical significance, has been observed linking per kilogram increase in birth weight to a heightened risk of breast cancer (OR = 1.07, 95% CI = 1.02-1.12), prostate cancer (OR = 1.02, 95% CI = 1.00-1.05), leukemia (OR = 1.18, 95% CI = 1.13-1.23), and acute lymphoblastic leukemia in offspring (OR = 1.18, 95% CI = 1.12-1.23); rubella infection during pregnancy to an increased risk of leukemia in offspring (OR = 2.79, 95% CI = 1.16-6.71); and a linear dose-response association between an increase in the proportion of optimal birth weight and an elevated risk of acute lymphoblastic leukemia in offspring (OR = 1.16, 95% CI = 1.09-1.24), respectively., Conclusions: Although some adverse pregnancy outcomes have clinically promising associations with risk of several cancers in both mother and offspring, it is essential to conduct additional research to solidify the evidence, evaluate causality, and ascertain clinical utility., (© 2024. The Author(s).)

Background: Despite strong evidence for maintaining blood pressure (BP) < 130/80 for secondary stroke prevention, there have been many barriers toward achieving this goal. The purpose of this pilot study was to assess the feasibility of a new physician-led BP telemedicine program on the improvement of BP and medication compliance in stroke survivors., Methods: We prospectively enrolled patients with a history of stroke and hypertension into this BP telemedicine program where participants were paired with a physician for one-on-one counseling. Participants submitted daily recordings of their BP as well as completed surveys assessing the usability of the program (Marshfield Usability Survey) and medication compliance (Morisky Medication Adherence Scale). A repeated measures ANOVA was utilized to examine differences in BP recordings at enrollment, 3 months, and 6 months., Results: Due to an interruption of external funding only 27 patients were ultimately enrolled (4/25/22-10/15/23). There were significant differences over time for both systolic (p = 0.022) and diastolic (p = 0.007) BP, however these differences were seen only between the enrollment and 6-month timepoint in follow-up testing. Participants rated the program highly favorably across multiple categories, commenting on the ease of using the program and feeling confident in the system. There was also an observed reduction in reported barriers to taking medications., Conclusion: This pilot program demonstrated the feasibility of managing BP using a telemedicine approach. A minimum of 6 months was required to see significant differences in BP as well as trends toward improvements in medication compliance. These results have an impact in how similar remote programs should be designed for future evaluations of this patient population., Competing Interests: Declaration of competing interest A. Singer and R. Tennant are both physician consultants for the DailyDoctor telemedicine platform, but were not involved in the study design, analysis, or interpretation of the results of this study. M. Howard, J. Buncom, M. Castillo, and V. Rajasekhar are employees of the DailyDoctor telemedicine platform, however were not involved in the analysis or interpretation of the results of this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Prior studies have presented paradoxical results regarding the association of uric acid-lowering drugs (ULDs) therapy with cognition and dementia. We aimed to explore this correlation. In this observational study, we extracted and analyzed the data from the National Health and Nutrition Examination Survey (NHANES) database and the FDA Adverse Event Reporting System (FAERS) database to investigate the association of ULDs with cognitive function and dementia. Two-simple Mendelian randomization (MR) and multivariable MR (MVMR) analyses were conducted to evaluate the causal associations of ULDs for all common types of dementia, including Alzheimer's disease (AD), vascular dementia (VD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). In the NHANES database, regardless of whether ULDs were included only or adjusted for covariates, the linear regression models did not find a correlation between ULDs and three cognitive tests (all p > 0.05). In the FAERS database, the dementia signal in ULDs lost significance after stepwise constraints (the lower limit of proportional reporting ratio lower than 1). In the two-sample MR analysis, allopurinol was associated with an increased risk of VD (OR = 123.747, p = 0.002), and a positive causal relationship was found between uricosuric drugs and AD (OR = 1.003, p = 0.003). However, the significance disappeared after adjusting for risk factors of dementia (p > 0.05). This study indicates that ULDs may not be related to an increase or decrease risk of cognition function and dementia, including all common types of dementia (AD, VD, FTD, and DLB)., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Novel technologies, such as ecological momentary assessment (EMA) and wearable biosensor wristwatches, are increasingly being used to assess outcomes and mechanisms of change in psychological treatments. However, there is still a dearth of information on the feasibility and acceptability of these technologies and whether they can be reliably used to measure variables of interest., Objective: Our objectives were to assess the feasibility and acceptability of incorporating these technologies into dialectical behavior therapy and conduct a pilot evaluation of whether these technologies can be used to assess emotion regulation processes and associated problems over the course of treatment., Methods: A total of 20 adults with borderline personality disorder were enrolled in a 6-month course of dialectical behavior therapy. For 1 week out of every treatment month, participants were asked to complete EMA 6 times a day and to wear a biosensor watch. Each EMA assessment included measures of several negative affect and suicidal thinking, among other items. We used multilevel correlations to assess the contemporaneous association between electrodermal activity and 11 negative emotional states reported via EMA. A multilevel regression was conducted in which changes in composite ratings of suicidal thinking were regressed onto changes in negative affect., Results: On average, participants completed 54.39% (SD 33.1%) of all EMA (range 4.7%-92.4%). They also wore the device for an average of 9.52 (SD 6.47) hours per day and for 92.6% of all days. Importantly, no associations were found between emotional state and electrodermal activity, whether examining a composite of all high-arousal negative emotions or individual emotional states (within-person r ranged from -0.026 to -0.109). Smaller changes in negative affect composite scores were associated with greater suicidal thinking ratings at the subsequent timepoint, beyond the effect of suicidal thinking at the initial timepoint., Conclusions: Results indicated moderate overall compliance with EMA and wearing the watch; however, there was no concurrence between EMA and wristwatch data on emotions. This pilot study raises questions about the reliability and validity of these technologies incorporated into treatment studies to evaluate emotion regulation mechanisms., (© Shireen L Rizvi, Allison K Ruork, Qingqing Yin, April Yeager, Madison E Taylor, Evan M Kleiman. Originally published in JMIR Mental Health (https://mental.jmir.org).)

Aim: To evaluate the association of metformin continuation with relapse of diabetes after metabolic bariatric surgery (MBS) in patients with type 2 diabetes and obesity who achieved an HbA1c level of less than 6.5%., Materials and Methods: This observational, retrospective cohort study included Clalit Health Service members aged 24 years or older with obesity and diabetes, who were treated with metformin, underwent MBS during 2005-2020 and achieved an HbA1c level of less than 6.5% up to 6 months after surgery (index date). Patients who continued metformin treatment (> 2 prescriptions filled, n = 122) after the index date were matched (1:2) on age, sex and HbA1c level at index date and compared with those who stopped treatment (no filled prescriptions, n = 244). The outcome was relapse of diabetes as measured by an HbA1c level of 6.5% or higher (yes/no)., Results: The two matched groups maintained a mean HbA1c level of less than 6.5% during the follow-up (mean ~ 5 years). An adjusted Cox proportional hazards model revealed no significant association of metformin continuation after MBS with relapse of diabetes (adjusted hazard ratio = 1.70, 95% confidence interval: 0.98-2.94). No significant differences were observed between the two groups in weight loss and filled prescriptions for other diabetes medications during the follow-up period., Conclusions: Among individuals living with obesity and diabetes who achieved diabetes remission post-MBS, metformin continuation was not associated with relapse of diabetes. This lack of an association indicates that metformin did not provide an additional benefit for maintaining glycaemic control or weight reduction during an average of 5 years postsurgery., (© 2024 John Wiley & Sons Ltd.)

Introduction: Urban youth are experiencing increasing mental health problems due to diverse personal, social and environmental concerns. Youths' detachment from natural environments, including green and blue spaces, may intensify such issues further. Contact with nature can benefit mental health and promote pro-environmental behaviour (PEB). Yet, only a few studies assess these relationships among the youth usually ignoring effects of living in diverse urban contexts, and everyday nature experiences. ECO-MIND will investigate whether urban youth's dynamic greenspace exposure and their mental models about nature connectedness explain the associations between greenspace exposure, mental health and PEB in multiple urban contexts., Methods and Analysis: We will collect data from university students from the Global South (ie, Dhaka, Kampala) and Global North cities (ie, Utrecht). Participants aged 18-24 will be recruited through stratified random sampling. We will use geographic ecological momentary assessment to assess respondents' everyday experiences and exposure to greenspaces. Our definition of greenspace exposure will be based on the availability, accessibility and visibility of greenspaces extracted from satellite and street view images. We will administer a baseline questionnaire to participants about mental health, nature connectedness and PEB characteristics. Further, we will ask participants to build mental models to show their perception of nature connectedness. Finally, we will fit partial least square structural equation models and multi-level models to our longitudinal geographic momentary assessment data., Ethics and Dissemination: The study was approved by the Ethical Review Board of the Utrecht University (Geo S-23221). Informed consent must be given freely, without coercion and based on a clear understanding of the participation in the study. Findings will be disseminated in peer-reviewed journals and at conferences. Furthermore, we will implement public engagement activities (eg, panel discussion) to share results among local stakeholders and policymakers and cocreate policy briefs., 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.)

Background: Lung cancer, predominantly non-small cell lung cancer (NSCLC), remains a formidable challenge, necessitating an in-depth understanding of evolving treatment paradigms. The Italian Lung Cancer Observational Study (LUCENT) addresses this need by investigating the outcomes of patients with early and locally advanced lung cancer in Italy., Objective: With a focus on real-world data and patient registries, this study aims to provide comprehensive insights into clinical, psychosocial, and economic impacts, contributing to informed decision-making in health care., Methods: LUCENT is a prospective observational multicenter cohort study enrolling patients eligible for minimally invasive manual, robot-assisted, or traditional open surgery. The study will develop a web-based registry to collect longitudinal surgical, oncological, and socioeconomic outcome data. The primary objectives include performance assessment through the establishment of national benchmarks based on risk-adjusted outcomes and processes of care indicators. The secondary objectives encompass economic and psychosocial impact assessments of innovative technologies and treatment pathways. The multicenter design ensures a diverse and representative study population., Results: The evolving landscape of NSCLC treatment necessitates a nuanced approach with consideration of the dynamic shifts in therapeutic strategies. LUCENT strives to fill existing knowledge gaps by providing a platform for collecting and analyzing real-world data, emphasizing the importance of patient-reported outcomes in enhancing the understanding of the disease. By developing a web-based registry, the study not only facilitates efficient data collection but also addresses the limitations of traditional methods, such as suboptimal response rates and costs associated with paper-and-pencil questionnaires. Recruitment will be conducted from January 01, 2024, to December 31, 2026. Follow-up will be performed for a minimum of 2 years. The study will be completed in the year 2028., Conclusions: LUCENT's potential implications are substantial. Establishing national benchmarks will enable a thorough evaluation of outcomes and care processes, guiding clinicians and policymakers in optimizing patient management. Furthermore, the study's secondary objectives, focusing on economic and psychosocial impacts, align with the contemporary emphasis on holistic cancer care. Insights gained from this study may influence treatment strategies, resource utilization, and patient well-being, thereby contributing to the ongoing refinement of lung cancer management., Trial Registration: ClinicalTrials.gov NCT05851755; https://clinicaltrials.gov/study/NCT05851755. ISRCTN 67197140; https://www.isrctn.com/ISRCTN67197140., International Registered Report Identifier (irrid): PRR1-10.2196/57183., (©Luca Bertolaccini, Oriana Ciani, Marco Lucchi, Francesco Zaraca, Alessandro Bertani, Roberto Crisci, Lorenzo Spaggiari, LUCENT Study Group. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 08.10.2024.)

Background: The procedures used to assess the methodological quality and risk of bias (RoB) of systematic reviews of observational dental studies have not been investigated. The purpose of this research was to examine the way that authors of systematic reviews of epidemiological observational studies published in dentistry conducted the methodological assessment of those primary studies. In the present article, we aimed to assess the characteristics and the level of reporting of tools used to assess the methodologies of these reviews., Methods: We searched Scopus and the Web of Science from their inceptions to June 2023 for systematic reviews with meta-analyses of observational studies published in dentistry. Document selection and data extraction were performed in duplicate and independently by two authors. In a random sample of 10% of the systematic reviews, there was an agreement of more than 80% between the reviewers; data selection and extraction were conducted in the remaining 90% of the sample by one author. Data on the article and systematic review characteristics were extracted and recorded for descriptive reporting., Results: The search in the two databases resulted in the inclusion of 3,214 potential documents. After the elimination of duplicates and the application of the eligibility criteria, a total of 399 systematic reviews were identified and included. A total of 368 systematic reviews reported a methodological tool, of which 102 used the Newcastle-Ottawa scale. Additionally, 76 systematic reviews stated the use of a modified methodological tool. Information about the approach of assessing the methodological quality or RoB of primary studies but reporting no tool or tool name occurred in 25 reviews., Conclusions: The majority of authors of systematic reviews of epidemiological observational studies published in dentistry reported the tools used to assess the methodological quality or RoB of the included primary studies. Modifying existing tools to meet the individual characteristics of various studies should be considered., (© 2024. The Author(s).)

Background: Worldwide, atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in adults and poses a significant burden to patients, physicians, and healthcare systems. We developed a quality of care score based on the Atrial Fibrillation Better Care pathway recommended by the European Society of Cardiology and the European Heart Rhythm Association guidelines. This is a 14-point score that we have termed the MAGIC score(Management of Atrial Fibrillation in Integrated Care and General Practice)., Objective: The objective of this pilot study was to develop and test a quality of care score for patients with permanent AF in general practice., Methods: An observational cross-sectional pilot study was undertaken. Proportionate sampling was used across 11 practices from the Ireland East practice-based research network. The GPs completed a report form on each patient by undertaking a retrospective chart review. Eleven practices participated with a total of 1855 patients with AF. We received data on 153 patients., Results: The main findings were that no patient met all 14 guideline based recommendations. The mean MAGIC score was 11.3. Points were most commonly deducted because the creatinine clearance and HAS-BLED score were not recorded, and the patient was not on the correct dose of oral anti-coagulation., Conclusion: This study demonstrates the feasibility of using a quality of care score to measure the quality of AF management in general practice. This scoring system, which is based on internationally recognized quality of care markers, highlights key areas that can be targeted with quality improvement intervention., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: Acute pancreatitis (AP) is an inflammatory disease with multiple etiologies, and the emergence of complications. Between 0.1-5% of cases are attributed to drugs. The absence of specific characteristics complicates the diagnosis and treatment of drug-induced AP. Reviewing patients admitted with the diagnosis of drug-induced AP can provide information and improve its management., Patients and Methods: This is a descriptive, observational, and retrospective study. All patients admitted to the Hospital Universitari de Bellvitge between June 2007 and March 2023 with suspected drug-induced AP were included. The data were obtained from the hospital pharmacovigilance program database., Results: Thirty-eight patients with suspected drug-induced AP were identified, representing 0.62% of all adverse drug reactions (n=6.085). Of these, 65.8% (n=25) had a single suspected drug. The median latency period for the onset of adverse drug reactions was 160.5 days (IQR: 18-582 days), and the median hospital stay was 5 days (IQR: 3-7 days). Fifty-nine suspected drugs were identified, involving 26 active principles. Azathioprine and atorvastatin were the most frequent, with 9 cases each (15.2%), followed by enalapril with 8 cases (13.6%). Drug etiology was assessed in 23 cases (60.5%), and the suspected drug was discontinued in all cases. There was one fatal case documented (2.63%)., Conclusion: This study can contribute to better understanding of drug-induced pancreatitis episodes. We propose a diagnostic algorithm that includes the assessment of the drug as a possible cause., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Background: While traditional medicine (TM) is employed by a significant portion of the global population for managing health issues, clinical guidelines and state recommendations often overlook this practice. The aim of this study was to describe the frequency of use of TM to control 3 metabolic risk factors (MRF): hypertension, hypercholesterolemia, and hyperglycaemia; and the sociodemographic, economic, and clinical characteristics associated with the use of TM., Methods: Cross-sectional descriptive study that analyses data obtained from a representative population survey in 2 health districts, one urban in the south of Quito and another in a forested rural area with diverse ethnic groups in Esmeraldas, Ecuador. We include 602 individuals with at least one MRF. We calculated the proportion of people reporting the regular use of TM (herbal or traditional remedy) to control their MRF and we assessed potential associations with sociodemographic, economic, and clinical characteristics with a multivariable logistic regression model., Results: In two very different sociocultural contexts in Ecuador we found that use of TM to control MRF was frequent (39.4% in Esmeraldas, 31.1% in Quito), frequently in combination with CM. There is a notable percentage of people, 33.9% in Esmeraldas and 39.0% in Quito, who did not take any treatment for their MRF, and the remainder used CM alone. In both settings, an individual's education lever was significantly associated with TM use. Whereas in Quito individuals with higher education more frequently treated their MRF with TM (aOR 2.04, 95% CI 1.03-3.90), in the rural, hard-to-reach context of Esmeraldas, it was more frequent among people with no formal schooling (aOR: 3.76; 95%CI 1.59-8.88), as well as those of younger age (aOR by year: 0.97; 95% CI 0.95-0.99) and afro ethnicity (aOR: 2.13; 95%CI 1.02-4.45)., Conclusion: Traditional medicine is used by a significant proportion of the population in Ecuador, highlighting the need for a more accessible and intercultural healthcare approach. The health system should ensure access to the necessary information and resources for the management of their metabolic risk factors., (© 2024. The Author(s).)

The difference in restricted mean survival time has been increasingly used as an alternative measure to the hazard ratio in survival analysis. Although some statistical methods have been developed for estimating the difference in restricted mean survival time adjusted for measured confounders in observational studies, the impact of unmeasured confounding on the estimate has rarely been assessed. We develop a novel sensitivity analysis for the estimate of the difference in restricted mean survival time with respect to unmeasured confounding. After formulating the sensitivity analysis problem as an optimization problem, we explain how to obtain the sensitivity range of the difference in restricted mean survival time efficiently and assess its uncertainty using the percentile bootstrap confidence interval. Analytic results are provided for some important survival settings. Simulation studies show that the proposed methods perform well in various settings. We illustrate the proposed sensitivity analysis method by analyzing data from the German Breast Cancer Study Group study., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Real-world evidence on locally advanced or metastatic urothelial carcinoma (la/mUC) management in Spain is limited. This study describes patient characteristics, treatment patterns, survival, and health care resource utilization (HCRU) in this population., Methods/patients: This retrospective observational study included all adults with a first diagnosis/record of la/mUC (index date) from January 2015 to June 2020 at nine university hospitals in Spain. Data were collected up to December 31, 2020 (end of study), death, or loss to follow-up. Patient characteristics, treatment patterns, median overall survival (OS) and progression-free survival (PFS) from index date (Kaplan-Meier estimates), and disease-specific HCRU were described., Results: Among 829 patients, median age at diagnosis was 71 years; 70.2% had ≥ 1 comorbidity, and 52.5% were eligible for cisplatin. Median follow-up was 12.7 months. Most (84.7%) patients received first-line systemic treatment; of these, 46.9% (n = 329) received second-line and 16.6% (n = 116) received third-line therapy. Chemotherapy was the most common treatment in all lines of therapy, followed by programmed cell death protein 1/ligand 1 inhibitors. Median (95% confidence interval) OS and PFS were 18.8 (17.5-21.5) and 9.9 (8.9-10.5) months, respectively. Most patients required ≥ 1 outpatient visit (71.8%), inpatient admission (56.6%), or emergency department visit (56.5%)., Conclusions: Therapeutic patterns were consistent with Spanish guideline recommendations. Chemotherapy had a role in first-line treatment of la/mUC in Spain during the study period. However, the disease burden remains high, and new first-line treatments recommended in the latest European guidelines should be made available to patients in Spain., (© 2024. The Author(s).)

Aims: Hospitalizations for adverse drug reactions (ADR-HA) have increased over the last decade, but the impact of ADR-HA has rarely been evaluated. The aim of this study was to estimate the economic burden of ADR-HA in France., Methods: A partial economic evaluation from the viewpoint of French public health insurance was performed, based on a previous pharmacovigilance study (IATROSTAT) performed in 2018 in public hospital medical units. The cost included direct medical costs, collected retrospectively, from the French hospital discharge database. The economic burden was estimated by calculating the total cost per ADR-HA patient (cost of hospital stays, additional daily cost of specific stays, such as in a resuscitation, intensive care or continuous surveillance unit, drug products and medical devices in addition to Healthcare Resource Group-based tariffs, and specific outpatient consultations and other clinical and technical medical procedures, over 3 months as from the first day of ADR-HA). The robustness of the results was assessed using a one-way deterministic sensitivity analysis of cost factors applying tariffs from 2023 instead of 2018., Results: According to the 2018 tariffs (vs. 2023), the mean total cost per patient with ADR-HA was estimated at €5208 ± €3719 (vs. €5974 ± €4232) ranging from €514 to €23 355 (vs. €618 to €27 380). The total cost for 196 patients with ADR-HA admitted to a sample of French public hospitals was estimated at €1 020 549 (vs. €1 170 960). It could be estimated at €1.3 billion at the national level., Conclusions: In addition to the increase in the number of expensive drugs, the ageing population and polypharmacy, the economic impact of serious ADR-HA weighs heavily on healthcare spending., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: The creation of large language models (LLMs) such as ChatGPT is an important step in the development of artificial intelligence, which shows great potential in medical education due to its powerful language understanding and generative capabilities. The purpose of this study was to quantitatively evaluate and comprehensively analyze ChatGPT's performance in handling questions for the National Nursing Licensure Examination (NNLE) in China and the United States, including the National Council Licensure Examination for Registered Nurses (NCLEX-RN) and the NNLE., Objective: This study aims to examine how well LLMs respond to the NCLEX-RN and the NNLE multiple-choice questions (MCQs) in various language inputs. To evaluate whether LLMs can be used as multilingual learning assistance for nursing, and to assess whether they possess a repository of professional knowledge applicable to clinical nursing practice., Methods: First, we compiled 150 NCLEX-RN Practical MCQs, 240 NNLE Theoretical MCQs, and 240 NNLE Practical MCQs. Then, the translation function of ChatGPT 3.5 was used to translate NCLEX-RN questions from English to Chinese and NNLE questions from Chinese to English. Finally, the original version and the translated version of the MCQs were inputted into ChatGPT 4.0, ChatGPT 3.5, and Google Bard. Different LLMs were compared according to the accuracy rate, and the differences between different language inputs were compared., Results: The accuracy rates of ChatGPT 4.0 for NCLEX-RN practical questions and Chinese-translated NCLEX-RN practical questions were 88.7% (133/150) and 79.3% (119/150), respectively. Despite the statistical significance of the difference (P=.03), the correct rate was generally satisfactory. Around 71.9% (169/235) of NNLE Theoretical MCQs and 69.1% (161/233) of NNLE Practical MCQs were correctly answered by ChatGPT 4.0. The accuracy of ChatGPT 4.0 in processing NNLE Theoretical MCQs and NNLE Practical MCQs translated into English was 71.5% (168/235; P=.92) and 67.8% (158/233; P=.77), respectively, and there was no statistically significant difference between the results of text input in different languages. ChatGPT 3.5 (NCLEX-RN P=.003, NNLE Theoretical P<.001, NNLE Practical P=.12) and Google Bard (NCLEX-RN P<.001, NNLE Theoretical P<.001, NNLE Practical P<.001) had lower accuracy rates for nursing-related MCQs than ChatGPT 4.0 in English input. English accuracy was higher when compared with ChatGPT 3.5's Chinese input, and the difference was statistically significant (NCLEX-RN P=.02, NNLE Practical P=.02). Whether submitted in Chinese or English, the MCQs from the NCLEX-RN and NNLE demonstrated that ChatGPT 4.0 had the highest number of unique correct responses and the lowest number of unique incorrect responses among the 3 LLMs., Conclusions: This study, focusing on 618 nursing MCQs including NCLEX-RN and NNLE exams, found that ChatGPT 4.0 outperformed ChatGPT 3.5 and Google Bard in accuracy. It excelled in processing English and Chinese inputs, underscoring its potential as a valuable tool in nursing education and clinical decision-making., (© Zelin Wu, Wenyi Gan, Zhaowen Xue, Zhengxin Ni, Xiaofei Zheng, Yiyi Zhang. Originally published in JMIR Medical Education (https://mededu.jmir.org).)

Background: Minimal pleural fluid is often seen incidentally on chest MRI. However, its prevalence and clinical characteristics remain unknown., Methods: This retrospective observational study included 2726 participants who underwent comprehensive medical check-ups for screening, including chest CT and MRI, and transthoracic echocardiography between March 2018 and February 2019. Pleural fluid on MRI was manually measured for maximum thickness. Its distribution, change over time, and relevance to participant characteristics were analyzed. The pulmonary function data of 82 participants and their associations with fluid were also analyzed., Results: Of the 2726 participants (mean age ± standard deviation, 59 ± 11 years), 2009 (73.7%) had minimal pleural fluid (thickness, 1-9 mm) on either side, with right-sided fluid being more frequent than left-sided fluid (P < 0.001). Negligible changes in fluid thickness were observed one year later. The following parameters were associated with less fluid: age, ≥65 years (P < 0.001); male sex (P = 0.006); current smoking (P < 0.001); body mass index, ≥25 kg/m 2 (P < 0.001); and mean arterial pressure, ≥100 mmHg (P = 0.01), whereas a ratio between early mitral inflow velocity and mitral annular early diastolic velocity>14 was associated with more fluid (P = 0.01). The presence of fluid was an independent explanatory variable for a higher percentage of predicted vital capacity (P = 0.048)., Conclusions: MRI was highly sensitive in detecting minimal pleural fluid. Pleural fluid found on MRI for health screening was assumed to be physiological and fluid thickness at the steady state might be variable among participants depending on age, sex, smoking habits, body shape, blood pressure, and cardiac diastolic capacity., Competing Interests: Declaration of competing interest T. Yoshikawa belongs to the Department of Computational Diagnostic Radiology and Preventive Medicine, which is sponsored by HIMEDIC, Inc. and Siemens Japan K.K; KF, HM, TK, T. Yamaguchi, AS, NY and HK have no conflict of interest., (Copyright © 2024 The Author. Published by Elsevier B.V. All rights reserved.)

Background: Abnormal lipid metabolism is linked to intervertebral disc degeneration (IVDD), sciatica, and low back pain (LBP), but it remains unclear whether targeted interventions can prevent these issues. This study investigated the causal effects of lipid-lowering drug use on IVDD, sciatica, and LBP development., Methods: Single-nucleotide polymorphisms (SNPs) linked to total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and non-high-density-lipoprotein cholesterol (non-HDL-C) were obtained from the Global Lipids Genetics Consortium's genome-wide association study (GWAS). Genes near HMGCR, PCSK9, and NPC1L1 were selected to represent therapeutic inhibition targets. Using Mendelian randomization (MR) focusing on these drug targets, we identified causal effects of PCSK9, HMGCR, and NPC1L1 on the risk of developing IVDD, sciatica, and LBP, with coronary heart disease risk serving as a positive control. Using summary data from Mendelian randomization (SMR) analysis, we evaluated potential therapeutic targets for IVDD, sciatica, and LBP through protein quantitative trait loci (pQTL). The genetic associations with IVDD, sciatica, LBP, and coronary heart disease were derived from FinnGen (discovery) and UK Biobank (replication). Additionally, a cross-sectional observational study was performed using data from the National Health and Nutrition Examination Survey (NHANES) to further investigate the connection between LBP and statin use, with a sample size of 4343 participants. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to assess the outcomes., Results: The NHANES-based cross-sectional study indicated that non-statin use was associated with an increased risk of developing LBP (OR = 1.29, 95% CI [1.04, 1.59], P = 0.019). Moreover, Inverse-variance weighting (IVW) analysis revealed that NPC1L1-mediated reductions in TC, LDL-C, and non-HDL-C concentrations were associated with a decreased risk of developing IVDD (P = 9.956E-03; P = 3.516E-02; P = 1.253E-04). Similarly, PCSK9-mediated reductions in LDL-C and TC concentrations were linked to a lower risk of developing sciatica (P = 3.825E-02; P = 2.709E-02). Sensitivity analysis confirmed the stability and reliability of the MR results. MST1 (macrophage stimulating 1) levels was inversely associated with IVDD, sciatica, and LBP risks., Conclusion: The results of cross-sectional study suggested that non-use of statins was positively correlated with LBP. The results of Mendelian randomization study suggest that NPC1L1 could lower the risk of developing IVDD by reducing TC, LDL-C, and non-HDL-C levels. Additionally, PCSK9 may reduce the risk of developing sciatica by lowering LDL-C and TC levels. In contrast, HMGCR appears to have no significant effect on IVDD, sciatica, or LBP development. Nonetheless, further research is needed to verify these preliminary results. MST1 warrants further exploration as a potential therapeutic target. It is necessary to do further research to validate these findings., (© 2024. The Author(s).)

Background: Chronic obstructive pulmonary disease affects nearly 400 million worldwide - over a million in the United Kingdom - and is the third leading cause of death. However, there is limited understanding of what prompts a diagnosis, how long this takes from symptom onset and the different approaches to clinical management by primary care professionals., Objectives: Map out the clinical management and National Health Service contacts from symptom presentation to chronic obstructive pulmonary disease diagnosis and first acute exacerbation of chronic obstructive pulmonary disease in three time periods; construct risk prediction for first acute exacerbation of chronic obstructive pulmonary disease., Design: Retrospective cohort study and cross-sectional survey., Setting: Primary care., Participants: Patients with incident chronic obstructive pulmonary disease aged > 35 years in England., Interventions: None., Main Outcome Measures: First acute exacerbation of chronic obstructive pulmonary disease., Data Sources: Clinical Practice Research Datalink Aurum; new online survey., Results: Forty thousand five hundred and seventy-seven patients were diagnosed between April 2006 and March 2007 (cohort 1), 48,249 between April 2016 and March 2017 (cohort 2) and 4752 between March and August 2020 (cohort 3). The mean (standard deviation) age was 68.3 years (12.0); 47.3% were female. Around three-quarters were diagnosed in primary care, with a slight fall in cohort 3. Compliance with National Institute for Health and Care Excellence diagnostic guidelines was slightly higher in cohorts 2 and 3 for all patients; 35.8% (10.0% in the year before diagnosis) had all four elements met for all cohorts combined. Multilevel modelling showed considerable between-practice variation in spirometry. The survey on the charity website had 156 responses by chronic obstructive pulmonary disease patients. Many respondents had not heard of the condition, hoped the symptoms would go away and identified various healthcare-related barriers to earlier diagnosis. Clinical Practice Research Datalink analysis showed notable changes in post-diagnosis prescribing from cohort 1 to 2, such as increases in long-acting muscarinic antagonist (21.7-46.3%). Triple therapy rose from 2.9% in cohort 2 to 11.1% in cohort 3. Documented pulmonary rehabilitation rose from just 0.8% in cohort 1 to 13.7% in cohort 2 and 20.9% in cohort 3. For all patients combined, the median time to first acute exacerbation of chronic obstructive pulmonary disease in patients who had one was 1.4 years in cohorts 1 and 2. Acute exacerbation of chronic obstructive pulmonary disease prediction models identified some consistent predictors, such as age, deprivation, severity, comorbidities, post-diagnosis spirometry and annual review. Models without post-diagnosis general practitioner actions had a c -statistic of around 0.70; the highest c -statistic was 0.81, for cohort 2 with post-diagnosis general practitioner actions and 6-month follow-up. All models had good calibration. The three most important predictors in terms of their population attributable risks were being a current smoker and offered smoking cessation advice (32.8%), disease severity (30.6%) and deprivation (15.4%). The highest population attributable risks for variables with adjusted hazard ratios < 1 were chronic obstructive pulmonary disease review (-27.3%) and flu vaccination (-26.6%)., Limitations: Symptom recording and chronic obstructive pulmonary disease diagnosis vary between practice; predicted forced expiratory volume in 1 second had many missing values., Conclusions: There has been some improvement over time in chronic obstructive pulmonary disease diagnosis and management, with large changes in prescribing, though patient and system barriers to further improvement exist. Data available to general practitioners cannot generate risk prediction models with sufficient accuracy., Future Work: It will be important to expand the COVID-era cohort with longer follow-up and augment general practitioner data for better prediction., Study Registration: This study is registered as Researchregistry.com: researchregistry4762., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 17/99/72) and is published in full in Health and Social Care Delivery Research ; Vol. 12, No. 43. See the NIHR Funding and Awards website for further award information.

Objectives: To explore the within-person fluctuations of fatigue in systemic sclerosis and its association with negative affect, positive affect, pain, perceived exertion of physical activity and quality of sleep., Methods: We performed an ecological momentary assessment study in adult patients with a clinical diagnosis of systemic sclerosis. During 14 days, patients completed daily assessments of fatigue severity, negative affect, positive affect, pain, quality of sleep and perceived exertion of physical activity at four fixed time points. The day-to-day fluctuations in fatigue were quantified by the intra-individual variance and probability of acute change, capturing the magnitude and frequency of clinical relevant within-person day-to-day fluctuations, respectively. Using multilevel models, the within-person association between fatigue and the daily assessments were analysed., Results: Fifty-seven patients with systemic sclerosis participated. The mean (standard deviation) intra-individual variance was 1.08 (0.42) and the probability of acute change was mean (standard deviation) 0.40 (0.14), ranging from 0.08 to 0.77. For fatigue, a within-person variation of 51% was observed. Multilevel analyses showed that higher average levels and daily increases in negative affect, pain and perceived exertion of physical activity were associated with more fatigue, while the opposite was observed for positive affect and quality of sleep. Positive affect demonstrated the strongest association with fatigue fluctuations., Conclusion: This is the first quantitative study showing that fatigue in systemic sclerosis is characterized by a dynamic course and that approximately half of the day-to-day fluctuations within persons are clinically meaningful. Furthermore, our results indicate that integrating activities with positive impact on mood into fatigue treatment strategies might reduce the frequency of fatigue fluctuations., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.C.V. received honorary as speaker from Boehringer Ingelheim, Bristol-Myers Squibb, GSK, Janssen, MSD, Novartis and Roche, as consultant from Boehringer Ingelheim and Janssen, Grant/research and received support from Research grants from Boehringer Ingelheim, Janssen, Ferrer and Galapagos, none on the subject of this study. J.E.V. received honorary as speaker from Eli Lilly, but this is not pertaining to this study. The remaining authors have declared no conflicts of interest., (© The Author(s) 2024.)

Purpose: We investigated whether a 52-gene signature was associated with transplant-free survival and other clinically meaningful outcomes in patients with idiopathic pulmonary fibrosis (IPF) in the IPF-PRO Registry, which enrolled patients who were and were not taking antifibrotic therapy., Methods: The 52-gene risk signature was implemented to classify patients as being at "high risk" or "low risk" of disease progression and mortality. Transplant-free survival and other outcomes were compared between patients with a low-risk versus high-risk signature., Results: The 52-gene signature classified 159 patients as at low risk and 86 as at high risk; in these groups, respectively, 56.6% and 51.2% used antifibrotic therapy at enrollment. Among those taking antifibrotic therapy, patients with a low-risk versus high-risk signature were at decreased risk of death, a composite of lung transplant or death, and a composite of decline in DLco % predicted > 15%, lung transplant, or death. Similar results were observed in the overall cohort., Conclusions: These data suggest that the 52-gene signature can be used in patients with IPF treated with antifibrotic therapy to distinguish patients at higher risk of disease progression and mortality., (© 2024. The Author(s).)

Background: The comparative effectiveness of selective serotonin reuptake inhibitors (SSRIs) has been subjected to relatively little research. However, a recent study based on target trial emulation suggested that sertraline may be more effective than escitalopram., Aims: To investigate whether sertraline, citalopram, and escitalopram differ in their effectiveness-assessed via the risk of psychiatric hospital admission and suicide following treatment initiation. The choice to focus on sertraline, citalopram, and escitalopram was made to limit confounding by indication, as the Danish depression treatment guideline from 2007 specifically listed these three SSRIs as first choice., Method: We conducted a target trial emulation based on data from Danish registers. We identified all individuals that initiated treatment for depression with sertraline, citalopram, or escitalopram in the period from January 1, 2007, to March 1, 2019. These individuals were followed until psychiatric hospital admission or suicide (separate analyses), death, 1 year after treatment initiation or end of data. Cox proportional hazards regression adjusted for relevant baseline covariates was performed to emulate randomized treatment allocation, comparing the rate of psychiatric hospital admission and suicide for individuals treated with sertraline (used as reference), citalopram or escitalopram, respectively. For escitalopram, we conducted a sensitivity analysis excluding data from the period during which the drug was sold under patent, as the price of the drug during that time likely entailed a different prescription pattern, increasing the risk of ("patent-related") confounding by indication., Results: We identified 56,865, 118,145, and 31,083 individuals initiating treatment with sertraline, citalopram, and escitalopram, respectively. Using sertraline as reference, the adjusted hazard rate ratio (aHRR) for psychiatric admission was 0.98 (95% CI = 0.91-1.05) for citalopram and 1.21 (95% CI = 1.10-1.32) for escitalopram. Notably, in the sensitivity analysis only including patients initiating treatment after the escitalopram patent had expired, the increased risk of psychiatric hospital admission associated with escitalopram treatment was no longer present (aHRR = 0.98, 95% CI = 0.82-1.18). The results of the analyses of suicide were inconclusive, due to few outcome events., Conclusions: Sertraline, citalopram, and escitalopram do not seem to have differential effectiveness in the treatment of depression. Taking potential patent-related, time varying, confounding by indication (via severity) into account is critical for pharmacoepidemiological studies, including those employing target trial emulation., (© 2024 The Author(s). Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Aim: Non-randomized studies on bariatric surgery have reported large reductions in mortality within 6-12 months after surgery compared with non-surgical patients. It is unclear whether these findings are the result of bias., Study Design and Setting: We searched PubMed to identify all non-randomized studies investigating the effect of bariatric surgery on all-cause mortality compared with non-surgical patients. We assessed these studies for potential confounding and time-related biases. We conducted bias analyses to quantify the effect of these biases., Results: We identified 21 cohort studies that met our inclusion criteria. Among those, 11 were affected by immortal time bias resulting from the misclassification or exclusion of relevant follow-up time. Five studies were subject to potential confounding bias because of a lack of adjustment for body mass index (BMI). All studies used an inadequate comparator group that lacked indications for bariatric surgery. Bias analyses to correct for potential confounding from BMI shifted the effect estimates towards the null [reported hazard ratio (HR): 0.78 vs. bias-adjusted HR: 0.92]. Bias analyses to correct for the presence of immortal time also shifted the effect estimates towards the null (adjustment for 2-year wait time: reported HR: 0.57 vs. bias-adjusted HR: 0.81)., Conclusion: Several important sources of bias were identified in non-randomized studies of the effectiveness of bariatric surgery versus non-surgical comparators on mortality. Future studies should ensure that confounding by BMI is accounted for, considering the choice of the comparator group, and that the design or analysis avoids immortal time bias from the misclassification or exclusion., (© 2024 John Wiley & Sons Ltd.)