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The role of biomarkers in risk-based early detection of lung cancer may enable screening to become cost effective and widely accessible. EarlyCDT-Lung is an example of such a blood-based autoantibody biomarker which may improve accessibility to Low dose Computed Tomography (LDCT) screening for those at highest risk. We randomized 12 208 individuals aged 50-75 at high risk of developing lung cancer to either the test or to standard clinical care. Outcomes were ascertained from Register of Deaths and Cancer Registry. Cox proportional hazards models were used to estimate the hazard ratio of the rate of deaths from all causes and lung cancer. Additional analyses were performed for cases of lung cancer diagnosed within two years of the initial test. After 5 years 326 lung cancers were detected (2.7% of those enrolled). The total number of deaths reported from all causes in the intervention group was 344 compared to 388 in the control group. There were 73 lung cancer deaths in the intervention arm and 90 in the controls (Adjusted HR 0.789 (0.636, 0.978). An analysis of cases of lung cancer detected within 2 years of randomization in the intervention group showed that there were 34 deaths from all causes and 29 from lung cancer. In the control group there were 56 deaths with 49 from lung cancer. In those diagnosed with lung cancer within 2 years of randomization the hazard ratio for all cause mortality was 0.615 (0.401,0.942) and for lung cancer 0.598 (0.378, 0.946). Further large-scale studies of the role of biomarkers to target lung cancer screening, in addition to LDCT, are likely to provide additional value., Competing Interests: F.M. Sullivan reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. F.S. Mair reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. W. Anderson has nothing to disclose. C. Chew has nothing to disclose. A. Dorward has nothing to disclose. J. Haughney has nothing to disclose. F. Hogarth reports grants from the Scottish Government Health and Social Care Directorate of the Chief Scientist Office and from Oncimmune, during the conduct of the study. D. Kendrick has nothing to disclose. R. Littleford reports grants from the Scottish Government Health and Social Care Directorate of the Chief Scientist Office and Oncimmune, during the conduct of the study. A. McConnachie reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. C. McCowan has nothing to disclose. N. McMeekin reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. M. Patel has nothing to disclose. P. Rauchhaus reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. L. Ritchie has nothing to disclose. J. Robertson reports other funding from Oncimmune, during the conduct of the study; and other funding from Oncimmune, outside the study. J. Robertson was a founder of Oncimmune, a company spun out from the University of Nottingham based on his academic research. Between 2003 and 2013 he was Chief Scientific Officer of Oncimmune and a Director of the company. During this time, he was responsible for the original drafting of the ECLS protocol. Since 2013 he has had no involvement in the science or management of the company. He has been and remains a shareholder in the company. J. Sarvesvaran has nothing to disclose. H. Sewell reports other funding from Oncimmune, outside the submitted work; and was an external member of the Oncimmune Scientific Advisory Board from 2006 to 2013. T. Taylor reports grants, nonfinancial support and other funding from Oncimmune, grants and personal fees from the Chief Scientist Office for Scotland, and grants and nonfinancial support from the Scottish Government, outside the submitted work. S. Treweek reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study. K. Vedhara has nothing to disclose. S. Schembri reports grants from Oncimmune and the Scottish Government Health and Social Care Directorate of the Chief Scientist Office, during the conduct of the study., (Copyright: © 2025 Sullivan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Despite the recovery advantages of minimally invasive surgical techniques, delayed return of gut function after colectomy is a common barrier to timely discharge from hospital., Objective: To evaluate the effect of 2% perioperative intravenous lidocaine infusion on return of gut function after elective minimally invasive colon resection., Design, Setting, and Participants: The ALLEGRO trial was a randomized, placebo-controlled, double-blind trial conducted in 27 UK hospitals. A total of 590 adults scheduled for elective minimally invasive colon resection for benign or malignant disease were randomized 1:1 to 2% intravenous lidocaine or saline placebo. Enrollment occurred from August 13, 2018, to April 11, 2023, with a pause in recruitment from March 20, 2020, through July 6, 2020; final follow-up was on August 10, 2023., Interventions: The intervention patients received 2% intravenous lidocaine administered as 1.5-mg/kg bolus at induction of anesthesia followed by 1.5 mg/kg/h for 6 or 12 hours. Control patients received 0.9% saline placebo for 6 or 12 hours., Main Outcomes and Measures: The primary outcome was the proportion of patients with return of gut function at 72 hours after surgery, defined by the GI-3 composite end point of tolerating diet (ingestion of food and drink without significant nausea or vomiting for 3 consecutive meals) and passage of flatus or stool. There were 11 secondary outcomes, including time to GI-3 recovery, time to GI-2 recovery (tolerance of oral diet and passage of stool), prolonged postoperative ileus, postoperative nausea and vomiting score, Overall Benefit of Analgesia Score, postoperative opioid consumption, Quality of Recovery-15, quality of life (EuroQol 5-Dimension 5-Level), enhanced recovery protocol adherence, time to meeting medically defined criteria for discharge, and time to patient self-assessed readiness for discharge., Results: The trial enrolled 590 patients (295 intervention, 295 control); after 33 postrandomization exclusions, 557 patients were included (279 intervention, 278 control; 249 female patients [44.7%]; mean [SD] age, 66 [10.9] years); 532 (96%) received the randomized treatment. Return of gut function as defined by the GI-3 composite outcome was achieved at 72 hours by 160 patients (57.3%) in the intravenous lidocaine group vs 164 patients (59.0%) in the placebo group (adjusted absolute difference, -1.9% [95% CI, -8.0% to 4.2%]; relative risk, 0.97 [95% CI, 0.88 to 1.07]). There was no significant difference between the intervention and control groups in any of the 11 secondary end points., Conclusions and Relevance: Among patients undergoing elective minimally invasive colon resection, perioperative administration of 2% intravenous lidocaine did not improve return of gut function at 72 hours., Trial Registration: isrctn.org Identifier: ISRCTN52352431.

Objective: Identification of patients with head-and-neck malignancies who are especially vulnerable to malnutrition is critical for optimizing outcomes. The objectives are; to correlate Bioelectrical-impendence-analysis (BIA) parameters with Subjective-Global-Assessment (SGA) scores, and determine the association of BIA parameters with common perioperative complications in patients undergoing head-and-neck surgery., Study Design: Patients underwent formal SGA scoring and BIA preoperatively in a multidisciplinary allied health clinic., Settings: This is a cohort study of 61 patients with head-and-neck malignancies who were admitted for elective surgery from 2018 to 2019 in a tertiary hospital in Singapore., Methods: BIA was performed using the Bodystat Quadscan 4000. Kruskal-Wallis rank sum tests and were performed for associations between SGA and BIA parameters. Wilcoxon rank sum tests and multivariable logistic regression models (Firth's bias reduction method) were performed to evaluate associations between BIA parameters and perioperative complications. Receiver-operating-characteristic (ROC) curves were plotted for determination of optimal cut-off values of phase angle and Wellness marker in detecting malnutrition and perioperative pneumonia using Youden's-Index (YI)., Results: 45 males and 16 females with median age of 62 were included in the study. Significant differences were observed in Wellness Marker ( P  = .006) and phase angle ( P  = .008) among patients in the 3 SGA categories. The Wellness Marker ( P  = .02) was associated with perioperative pneumonia in the univariate analysis. No significant differences were observed for other perioperative complications studied., Conclusion: BIA shows promise as a preoperative tool, in conjunction with SGA, to detect malnutrition in patients undergoing surgery for head-and-neck malignancies and highlight patients at risk of developing perioperative pneumonia., Competing Interests: None., (© 2025 The Author(s). OTO Open published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: Acceptance and Commitment Therapy (ACT) has been found to be beneficial for individuals dealing with chronic pain. The theoretical mechanisms of change proposed by ACT are based on the Hexaflex model. To comprehensively reflect this model, the Multidimensional Psychological Flexibility Inventory (MPFI) and Psy-Flex have been developed. The study aimed to adapt the MPFI-24 and the Psy-Flex for Spanish-speaking populations with chronic pain and to examine their dimensionality, internal consistency, convergent validity and incremental validity., Methods: This cross-sectional study involved 309 Spanish-speaking adults with chronic pain who completed an online survey. The majority of the participants were women (88.3%). The ages ranged from 18 to 79 years., Results: Factor analysis showed that the Spanish version of the MPFI-24 has 12 factors, consisting of six flexibility and six inflexibility factors, similar to the original version, but lacking second-order general factors. The Psy-Flex demonstrated a single-factor structure, maintaining the general factor of psychological flexibility seen in the original version. The MPFI-24 showed good internal consistency and adequate convergent validity, with the exception of the Acceptance and Experiential Avoidance subscales. The Psy-Flex showed good internal consistency and convergent validity. Notably, both the MPFI-24 and Psy-Flex scores significantly explained additional variance in psychological distress beyond other ACT-related measures of Hexaflex processes; however, only the Psy-Flex explained pain interference., Conclusions: The Spanish adaptations of the MPFI-24 and Psy-Flex are valid and reliable instruments for assessing the Hexaflex model processes in Spanish-speaking adults with chronic pain., Significance Statement: Practitioners and researchers in chronic pain will find the Spanish versions of the MPFI-24 and the Psy-Flex here, along with recommendations for their use and scoring based on a robust psychometric rationale. It should be noted that these measures surpass the Chronic Pain Acceptance Questionnaire (CPAQ) and the Psychological Inflexibility in Pain Scale (PIPS), which are considered gold standards in chronic pain assessment., (© 2024 The Author(s). European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

Objectives: Traditional methods for medical device post-market surveillance often fail to accurately account for operator learning effects, leading to biased assessments of device safety. These methods struggle with non-linearity, complex learning curves, and time-varying covariates, such as physician experience. To address these limitations, we sought to develop a machine learning (ML) framework to detect and adjust for operator learning effects., Materials and Methods: A gradient-boosted decision tree ML method was used to analyze synthetic datasets that replicate the complexity of clinical scenarios involving high-risk medical devices. We designed this process to detect learning effects using a risk-adjusted cumulative sum method, quantify the excess adverse event rate attributable to operator inexperience, and adjust for these alongside patient factors in evaluating device safety signals. To maintain integrity, we employed blinding between data generation and analysis teams. Synthetic data used underlying distributions and patient feature correlations based on clinical data from the Department of Veterans Affairs between 2005 and 2012. We generated 2494 synthetic datasets with widely varying characteristics including number of patient features, operators and institutions, and the operator learning form. Each dataset contained a hypothetical study device, Device B, and a reference device, Device A. We evaluated accuracy in identifying learning effects and identifying and estimating the strength of the device safety signal. Our approach also evaluated different clinically relevant thresholds for safety signal detection., Results: Our framework accurately identified the presence or absence of learning effects in 93.6% of datasets and correctly determined device safety signals in 93.4% of cases. The estimated device odds ratios' 95% confidence intervals were accurately aligned with the specified ratios in 94.7% of datasets. In contrast, a comparative model excluding operator learning effects significantly underperformed in detecting device signals and in accuracy. Notably, our framework achieved 100% specificity for clinically relevant safety signal thresholds, although sensitivity varied with the threshold applied., Discussion: A machine learning framework, tailored for the complexities of post-market device evaluation, may provide superior performance compared to standard parametric techniques when operator learning is present., Conclusion: Demonstrating the capacity of ML to overcome complex evaluative challenges, our framework addresses the limitations of traditional statistical methods in current post-market surveillance processes. By offering a reliable means to detect and adjust for learning effects, it may significantly improve medical device safety evaluation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To perform an economic evaluation to determine whether or not teledermatology (TD) units in primary care (PC) centers offer an alternative in terms of cost-utility and cost per quality-adjusted life years (QALYs) to conventional dermatology consultations (face-to-face dermatology [F-F/D]) at the hospital from the perspective of the Public Health System (PHS) and the patients., Methods: This is a randomized, controlled, nonblinded, and multicenter study. During 6 months, data from 450 patients (TD: 225 vs. F-F/D: 225) were collected. From both perspectives, costs, quality of life, and costs per QALYs were analyzed. The QALY scores were estimated from the EuroQol-5D-5L (EQ5D-5L) questionnaire responses., Results: From the perspective of the PHS, the cost per patient was 53.04% lower in the TD group (p < 0.001). Hospital visits decreased by 72.43% in the TD group (p < 0.001). From the patients' perspective, TD reduced costs per patient by 77.59% (p < 0.001). The cost per QALY was 63.34% higher in the F-F/D group (p < 0.001). The TD group's total costs were 56.34% lower (p < 0.001). Furthermore, patients in the TD group gained 0.05 QALYs more than those in the F-F/D group (p = 0.004)., Conclusions: This study shows that TD units in PC represent a significant cost-effective alternative to conventional hospital follow-up. To enhance TD in PC, it is important to introduce remote consultation platforms incorporating artificial intelligence for prediagnosis. This will enable general practitioners and nurses to make more accurate initial assessments. It is also crucial to provide thorough training to healthcare personnel using these technologies to ensure more efficient and personalized care. Public health nurses will benefit from gaining new skills in managing digital tools, which will help in the early identification of dermatological diseases and reduce unnecessary referrals to specialists. This will optimize resources and improve response times for patients., (© 2024 Wiley Periodicals LLC.)

Background: A large number of individuals suffer from post-COVID-19 condition (PCC), characterised by persistent symptoms following a SARS-CoV-2 infection with an impact on daily personal and professional activities. This study aims at examining which (health) care services are used by PCC patients in the German federal state of Lower Saxony, and how these patients manage their condition. The perspectives of patients, informal caregivers and general practitioners (GPs) will be considered., Methods: The study will employ a mixed methods design. Patients' perspective will be evaluated through an online survey of: (1) 21,000 adult individuals with a PCC diagnosis (ICD10 U09.9!) in their statutory health insurance claims data in 2022 ("AOK survey") and (2) a self-selected sample of adult individuals with a proven SARS-CoV-2 infection in 2023 and persistent symptoms ("public survey"). Additional data sources will be claims data (n = 27,275) and 25-30 semi-structured interviews. Informal caregivers' perspective will be collected through an online survey and semi-structured interviews. GPs' perspective will be evaluated through four focus groups involving six to eight participants each and an online survey of all registered and practicing GPs in Lower Saxony (approximately 5,000). All survey data will be descriptively analysed. In addition, correlation analyses and multivariable regression analyses will be conducted, for example on factors influencing affected individuals' use of medical services. Interview and focus group data will be subjected to qualitative content analysis. A health economic analysis will be used to determine the costs of PCC to health care payers, patients and society. The project will conclude with an expert workshop to discuss the results and derive recommendations., Discussion: The results of the study will provide a multidimensional description of the (health) care situation and needs of patients with PCC, and derive recommendations for improving health care., Trial Registration: The VePoKaP study is registered at the German Clinical Trials Register (DRKS00032846)., Competing Interests: CH-L has received a lecture honorarium from Novartis and royalties from Hogrefe Publish-ers for the German version of the Hospital Anxiety and Depression Scale. His research is supported by grants from the German Ministry of Education and Research, the German Re-search Foundation and the European Commission. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors declare that they have no competing interests., (Copyright: © 2024 Brinkmann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Stigma of mental health conditions hinders recovery and well-being. The Honest, Open, Proud (HOP) program shows promise in reducing stigma but there is uncertainty about the feasibility of a randomized trial to evaluate a peer-delivered, individual adaptation of HOP for psychosis (Let's Talk)., Methods: A multi-site, Prospective Randomized Open Blinded Evaluation (PROBE) design, feasibility randomised controlled trial (RCT) comparing the peer-delivered intervention (Let's Talk) to treatment as usual (TAU). Follow-up was 2.5 and 6 months. Randomization was via a web-based system, with permuted blocks of random size. Up to 10 sessions of the intervention over 10 weeks were offered. The primary outcome was feasibility data (recruitment, retention, intervention attendance). Primary outcomes were analyzed by intention to treat. Safety outcomes were reported by as treated status. The study was prospectively registered: https://doi.org/10.1186/ISRCTN17197043., Results: 149 patients were referred to the study and 70 were recruited. 35 were randomly assigned to intervention + TAU and 35 to TAU. Recruitment was 93% of the target sample size. Retention rate was high (81% at 2.5 months primary endpoint), and intervention attendance rate was high (83%). 21% of 33 patients in Let's talk + TAU had an adverse event and 16% of 37 patients in TAU. One serious adverse event (pre-randomization) was partially related and expected., Conclusions: This is the first trial to show that it is feasible and safe to conduct a RCT of HOP adapted for people with psychosis and individual delivery. An adequately powered trial is required to provide robust evidence.

Objectives: There is limited evidence regarding the impact of lipid-lowering drugs (LLDs) on the socioeconomic gradient in a longitudinal perspective. The study investigates the longitudinal socioeconomic gradient in total cholesterol levels and whether this is affected by the use of LLDs., Design: Population-based cohort study., Setting: Sample from adult inhabitants of Tromsø municipality, Norway, who participated in the Tromsø Study (1994-2016)., Participants: 17 550 participants of the population-based Tromsø Study in 1994-1995 who were non-users of LLD, aged 25-78 years at baseline and who attended one or more of three subsequent surveys in 2001, 2007-2008 and 2015-2016 were included in the study., Outcome Measure: Socioeconomic gradient in total cholesterol levels was compared among participants treated and not treated with LLDs during the observation period., Results: The total cholesterol levels across all educational groups increased from 1994-1995 to 2015-2016 among untreated women (+0.33 mmol/L to +0.48 mmol/L), except for those with primary education (-0.12 mmol/L). Total cholesterol levels decreased among untreated men (-0.40 mmol/L to -0.06 mmol/L, from lowest education to highest education), treated women (-1.88 mmol/L to -1.35 mmol/L) and men (-2.21 mmol/L to -1.84 mmol/L) across all educational groups. At baseline, we observed a significant inverse association between education and total cholesterol levels among non-users of LLDs. There was no clear educational gradient in total cholesterol levels among users of LLDs., Conclusions: Users of LLDs experienced a more substantial decrease in total cholesterol levels over time compared with non-users. The educational gradient in total cholesterol levels observed among non-users of LLD was not apparent among users., 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 Group.)

Health equity matters, but there is no universally accepted definition of this or associated terms, such as inequities, inequalities, and disparities. Given the flexibility of these terms, investigating how policymakers understand them is important to observe priorities and perhaps course correct. Accordingly, this study analyzed the perceptions high-level policymakers within the WHO African Region. An online survey was distributed to attendees of the WHO's Fifth Health Sector Directors' Policy and Planning Meeting for the WHO African Region by email. After responses were collected, both inductive and deductive coding were applied. Inductive coding was undertaken to glean central concepts from free-form responses on understandings of health equity and deductive coding was used to assess alignment with four theories of distributive justice using a coding framework. In analyzing central concepts, three became apparent: access to health services and/or health care, financial protection, and recognizing subgroups. And when we investigated alignment with theory, most respondents' understandings of health equity aligned with Rawls' 'Theory of Justice' (95%). Of these responses, 70% were exclusively aligned with Rawls' 'Theory of Justice' and 30% aligned also with another theory (this 30% was split 55% utilitarianism and 45% Sen's Capabilities Approach). Respondent understandings of health equity showed limited alignment with other theories of distributive justice, which were: utilitarianism (n = 7/39; 17.95%), Sen's Capabilities Approach (n = 5/39; 12.82%), and libertarianism (n = 2/39; 5.13%). Our study demonstrates that alignment with certain theories is tied to specific themes (i.e., theoretical underpinnings may guide policymakers to favour certain policy approaches). For instance, a utilitarian-minded policymaker may be focused on a widespread vaccination campaign, whereas a Rawlsian-aligned policymaker may focus on a targeted approach to reach communities that have lower vaccination rates, and a Senian-aligned policymaker may focus on health literacy programs targeted at addressing vaccine-hesitant individuals within communities with lower vaccination rates. These findings can guide high-level policymakers and international organizations to optimize decision-making by clarifying ethical alternatives., Competing Interests: Declarations. Ethics approval and consent to participate: Harvard University’s institutional research board provided ethics exemption for this study (protocol number: IRB21-1176) and informed consent was received from all respondents. This study was performed in accordance with relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: MA reports short-term instances of consulting for the World Health Organization and membership with the World Health Organization Collaborating Centre for Knowledge Translation and Health Technology Assessment in Health Equity. The remaining authors declare that they have no competing interests., (© 2024. The Author(s).)

To address the challenges posed by influenza, its associated complications, and economic burden, the World Health Organization recommends a vaccination rate exceeding 75 % for populations at elevated risk of severe diseases. Presently, vaccination rates in Germany severely lag behind. To augment these rates, pilot projects have been initiated, allowing community pharmacists to administer vaccines. This study aimed to investigate the the acceptability of pharmacy-led influenza vaccinations among clients and pharmacists, clients' motivations to get vaccinated in community pharmacies, and the rate of adverse events during this process. Data were obtained through anonymous questionnaires from influenza vaccination pilot projects in various German regions between 2020 and 2023. The questionnaire consisted of two sections: one for the vaccinating pharmacist to record and document the vaccination process and one for the recipient, focusing on their experiences and views. In total 11,571 responses were evaluated. Notably, 44 % of participants mentioned they would not have sought vaccination outside a pharmacy setting. This percentage was higher (65 %) in those receiving their first influenza vaccination. Vaccinees reported high levels of satisfaction with the supplied information (88.5 %) and vaccination procedure (93.8 %). Furthermore, clients declared a high willingness to repeat the vaccination (93.9 %) and the possibility of receiving other vaccinations in pharmacies (79.7 %). Among all surveyees, only nine reported adverse reactions post pharmacy-administered vaccination, with none necessitating emergency intervention. Pharmacy-led influenza vaccinations were identified as safe, well-received by vaccinees and effective in increasing vaccination acceptability with the potential to enhance vaccination rates across diverse demographics in Germany., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Immune-related adverse events (irAE) pose challenges to the use of immune checkpoint inhibitors (ICI). While risk factors for irAE are emerging, most studies are small, retrospective analyses that seldom report on diverse cancers or rare irAE. This paper reports a systematic review that summarises literature on irAE risk factors across cancers and proposes a categorisation approach., Method: A systematic search was conducted in Medline OVID, Embase and Web of Science databases following PRISMA guidelines (CRD42022310127). Original research published in peer-reviewed journals between January 2017-Decmeber 2021 were selected. Eligible studies included patients with any cancer and evaluated any potential risk factor for any grade/type of irAE. Study design, sample size, and method for analysing association between irAE and risk factors were compared., Results: A total of 293 eligible studies containing 305,879 patients receiving ICI reported irAE in 58,291 patients (19.1 %). There were 221 retrospective, 55 prospective studies, and 17 systematic reviews/meta-analyses. Eighteen studies evaluated the predictive validity of models. Proposed risk factors were grouped based on common themes and underlying aetiology: 1) patient, 2) laboratory, 3) medical history, 4) cancer-related, 5) clinical score, 6) medications, and 7) imaging features. Opposing associations were reported between advancing age and irAE risk., Conclusion: This systematic review provides a comprehensive overview of evidence on irAE risk factors across a large patient population. Studies were heterogeneous resulting from variations in design, sample size and analysis method, and lack generalisability due to statistically underpowered evidence. We propose an approach to categorise potential irAE risk factors to support ongoing collaborative research., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Lower-than-expected recruitment continues to be one of the major causes of trial delays, and trials to improve mental health are no exception. Indeed, recruitment challenges in trials of vulnerable populations, such as those living with mental health illness, can even be exacerbated. To address this, researchers are turning to digital and online recruitment strategies, e.g. web-based approaches and multi-media in order to (1) increase recruitment efficiency (recruit to target and on time) and (2) improve diversity in mental health clinical trials to be more inclusive and reduce health inequity. There is, however, inconclusive evidence on the success of digital and online recruitment strategies in mental health clinical trials. The RE-MIND study comprised a scoping review to assess the impact of using such recruitment strategies in mental health clinical trials to inform a more systematic scoping review., Methods: A cohort of 191 recently published RCTs and randomised feasibility studies were identified from the NIHR Journals Library and top two mental health journals (based on citation metrics), Lancet Psychiatry and JAMA Psychiatry. Population characteristics including gender, ethnicity and age were summarised for inclusivity using descriptive statistics, and recruitment strategies were compared to examine differences in their success in recruiting to target., Results: After screening, 97 articles were included for review. The review findings showed no evidence that offline or mixed strategies were superior for achieving recruitment targets in mental health trials. However, there was a suggestion that trials using a mixed recruitment strategy improved inclusivity and tended to recruit closer to the target., Conclusions: The key finding was that consideration should be given to a mixed methods approach to recruitment not only to enable wider and more diverse participation in mental health trials but also to realize greater efficiency., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval was not required as this study was a scoping review of peer-reviewed journal articles. Consent for publication: N/A. Competing interests: None declared., (© 2024. The Author(s).)

It is well known that healthcare resource constraints influence the capacity to deliver care, affecting both the costs and outcomes of medical interventions. If these constraints are not adequately accounted for in economic evaluations, there may be a lack of understanding regarding the full impact of implementing health technologies, leading to decisions being made with suboptimal information. This paper offers an overview of the types of healthcare resource constraints and their potential effects, and introduces a framework grounded in operations research and health economics principles, outlining the methodological considerations for incorporating resource constraints into economic evaluations. Drawing from a literature review and advisory group feedback, three categories of resource constraints were identified: single-use resource constraints, reusable resource constraints and patient throughput constraints. The proposed framework outlines a comprehensive set of steps necessary for effectively incorporating constraints into health economic evaluations and details specific approaches and methodological considerations for each stage to ensure a more accurate and realistic assessment of health interventions. This paper also aims to raise awareness among payers and decision-makers with regards to the limitations of technology evaluations in a resource-constrained health system. Specifically, it suggests that health technology assessment agencies ought to offer guidance on incorporating constraints into the submissions they receive. Moreover, it advocates for a more comprehensive economic evaluation in economic assessments to fully capture an intervention's value., Competing Interests: Declarations. Conflict of Interest: Henrique Duarte and Roelien Postema are full-time employees of Putnam Associates. Gerardo Machnicki is a full-time employee of F. Hoffmann-La Roche, Ltd. Praveen Thokala is the director of PT Health Economics Ltd and has been paid consultancy fees by Putnam/PHMR Ltd to advise on this study. He has also performed paid consultancy in the past with IQVIA, RTI-HS, Roche, Pfizer, Daiichi Sankyo, Exact Sciences, Abbvie, Novo Nordisk and Novartis. Stuart Wright is supported by a Wellcome Trust Early Career Award (226922/Z/23/Z). Don Husereau has received fees from F. Hoffmann-La Roche AG for unrelated projects. Isabelle Durand-Zaleski reports fees for speaking engagements and advisory board participation from BMS, Janssen, MSD, NovoNordisk and Hoffmann-La Roche AG for unrelated projects. Peter Lindgren reports institutional grants from AstraZeneca, Biogen, Jansen, MSD and Novartis and fees for speaking engagements and advisory board participation from Astellas, AstraZeneca, Biomarin, Daiichi Sankyo, Jansen, MSD, NovoNordisk, SOBI, Takeda and Vertex. Lou Garrison has received consulting and speaking fees unrelated to this project from Pfizer, Novartis Gene Therapy, Roche, Merck, J&J and BioMarin. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication (From Patients/Participants): Not applicable., (© 2024. The Author(s).)

Introduction: Nutrition trials are important for informing dietary and clinical guidelines. Central to the success of these trials is participant adherence to dietary behaviors. However, trials commonly experience poor adherence. This study seeks to understand if and how researchers consider supporting participant adherence to dietary behaviors and their relationship to using behavior change science when designing trials., Methods: A mapping exercise was undertaken to create matrices that describe the landscape of current nutrition trials. A total of 12 researchers participated in semi-structured, one-on-one interviews. Transcripts were analyzed using (i) the theoretical domains framework (TDF) to identify themes in current practice and beliefs, and (ii) the capability, opportunity, motivation, and behavior model to identify barriers and enablers to using behavior change science in the design of nutrition trials., Results: Twenty-two belief statements were identified across all 14 TDF domains and were conceptualized as 5 key themes with respect to designing nutrition trials to improve participant adherence: (i) what was done, (ii) how it was done, (iii) why it was done, (iv) adherence challenges, and (v) conflicting beliefs. Regarding using behavior change science when designing trials, some researchers felt this would be beneficial but lacked the knowledge and skills to do so, while others were skeptical of its value over the current experience-based practice., Discussion: Researchers are motivated to encourage participant adherence to dietary behaviors, and, consciously and subconsciously, implement a range of strategies through non-systematic methods in their trials. Future publications would benefit from the explicit documentation of levels of adherence to dietary behaviors and strategies implemented to improve adherence., Competing Interests: 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 Worthington, Coffey, Gillies, Roy and Braakhuis.)

Introduction: The clinical landscape for the treatment of patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) is rapidly evolving. As part of the FOUNTAIN platform (NCT05526157; EUPAS48148), we described and compared cohorts of adult patients with CKD and T2D initiating a sodium-glucose cotransporter 2 inhibitor (SGLT2i) before the launch of finerenone in Europe, Japan, and the United States (US)., Methods: This was a multinational, multi-cohort study of patients with T2D in five data sources: the Danish National Health Registers (DNHR) (Denmark), PHARMO Data Network (The Netherlands), Valencia Health System Integrated Database (VID) (Spain), Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex) (Japan), and Optum's de-identified Clinformatics ® Data Mart Database (CDM) (US). Eligible patients had CKD (based on either diagnosis codes, eGFR values, and/or urine ACR) and initiated an SGLT2i between 2012 and 2021. Baseline demographic, lifestyle, and clinical characteristics were analyzed, and drug utilization patterns were described., Results: The final cohorts included 21,739 patients in DNHR, 381 in PHARMO, 31,785 in VID, 1157 in J-CKD-DB-Ex, and 56,219 in CDM. Across data sources, approximately 41-70% had CKD stage 1 or 2 at baseline; severe CKD (stage 4) was uncommon (1.6-6.7%). The median duration of SGLT2i therapy ranged from 7.5 months in PHARMO to 17.0 months in VID. At least 50% of patients were currently receiving SGLT2i treatment at 1 year after initiation., Conclusions: At a 1-year follow-up, at least half of the patients with CKD and T2D were receiving SGLT2i treatment across the data sources. In patients initiating SGLT2i, treatment options for T2D and CKD were heterogeneous and dynamic within and among data sources., Competing Interests: Declarations. Conflict of Interest: Alfredo E. Farjat, Fangfang Liu, Suguru Okami, Satoshi Yamashita, and Nikolaus G. Oberprieler are employees of Bayer, which funded this study. Alain Gay was an employee of Bayer when this research was conducted and is now an employee of Clario, Philadelphia, PA, USA. David Vizcaya was an employee of Bayer when this research was conducted and is now an employee of Alexion Pharma S.L., Barcelona, Spain. Catherine B. Johannes, Ryan Ziemiecki, Manel Pladevall-Vila, and J. Bradley Layton are employees of RTI Health Solutions, which received research funding for this study from Bayer. Brenda N. Baak, Jetty A. Overbeek, Fernie J.A. Penning-van Beest, and Ron M.C. Herings are employees of the PHARMO Institute for Drug Outcomes Research. This independent research institute performs financially supported studies for government and related healthcare authorities and several pharmaceutical companies. Craig I. Coleman has received grant funding and consulting fees from Bayer AG and AstraZeneca Pharmaceuticals. Csaba P. Kovesdy received consulting fees from Abbott, Akebia, Astra Zeneca, Bayer, Boehringer Ingelheim, Cara Therapeutics, CSL Behring, CSL Vifor, GSK, Pharmacosmos, ProKidney, Renibus and Takeda. Yuichiro Yano reports consultancy for Bayer. Naoki Kashihara reports research grants from Daiichi Sankyo, AstraZeneca, and Bayer. Natalie Ebert receives honoraria from Bayer AG. Reimar W. Thomsen, Ina Trolle Andersen, Christian Fynbo Christiansen, and Frederik Pagh Bredahl Kristensen are employees of Aarhus University, which receives institutional research funding from public and private entities, including regulators, pharmaceutical companies, and contract research organizations. This includes the present study. Reimar W. Thomsen has given presentations and lectures on medical research (both with and without financial compensation) for pharmaceutical companies, including AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi. Aníbal García-Sempere, Clara Rodríguez Bernal, Celia Robles Cabaniñas, and Isabel Hurtado are employed by FISABIO, a research body in Spain affiliated with the Health Department of the Valencia Government, which receives public and private funding to conduct biomedical research, including the present study. Ethical Approval: This study used de-identified data from electronic health records. Ethics committee review was waived for DNHR and PHARMO. The study protocol was reviewed and approved by the Comité Ético de Investigación con Medicamentos del Hospital Clínico Universitario de Valencia for VID (2022/164). This study protocol was reviewed and approved by the ethics committee of the Shiga University of Medical Science for J-CKD-DB-Ex (R2022-143). CDM data are de‐identified and are compliant with the Health Insurance Portability and Accountability Act of 1996. This study was deemed to not constitute research involving human subjects according to 45 Code of Federal Regulations 46.102(f) and was deemed exempt from board oversight. The institutional review board of RTI International deemed the study exempt from full review. This study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments. Patient consent for participation and patient consent for publication are not applicable., (© 2024. The Author(s).)

Competing Interests: There is no conflict of interest to declare related to this communication.

Background: Demographic changes are leading to a rise in the demand for care services, with nursing homes (NHs) playing an increasingly important role in end-of-life care. Evidence suggests that NH residents at the end of life significantly benefit from hospice and palliative care and the implementation of advance care planning (ACP). In 2018, Germany passed a law to promote the implementation of ACP in NHs and to enable the refinancing of ACP services by the statutory health insurance funds. The present study aimed at assessing current hospice and palliative care structures, examining the implementation of ACP and identifying barriers to obtain approval for billing for ACP services under this specific legislative (§ 132 g SGB V)., Methods: As a part of the "Gut-Leben" project, the present study administered a cross-sectional quantitative survey in 2023 to evaluate hospice and palliative care structures, the implementation of ACP, and barriers to ACP approval in German NHs. A questionnaire was distributed to a random sample of N = 1,369 NH managers. Responses were analyzed using descriptive statistical methods., Results: N = 330 NH managers responded to the questionnaire (24.1% response). The majority described the end-of-life care structures in their region as rather good (77.7; n = 256), and very strong collaboration was reported with general practitioners (54.7%), physiotherapists (42.9%), and palliative care physicians (38.6%). Awareness of the legislative for ACP was reported by n = 201 NHs (64.4%), and 100 (50.3%) of these NHs had already obtained approval. The primary barriers to approval identified by 68 NHs included a lack of available staff (48.5%; n = 33) and a small facility size (27.9%; n = 19)., Conclusions: Although half of the NHs have implemented ACP, there is still a need to enhance awareness of the ACP legislative. These efforts should aim to reduce the existing barriers to approval, which could be achieved, for instance, by fostering collaboration between NHs or by cooperating with external ACP service providers., Competing Interests: Declarations. Ethics approval and consent to participate: The present study received a waiver from the local medical ethics committee of the Carl von Ossietzky Universität of Oldenburg (no. 2022–154). Since data was collected anonymously, consent to participate was not required. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background & Aim: Understanding local vulnerability to heat and cold is crucial for public health planning, yet few studies have provided a nationwide analysis of temperature-related mortality across diverse communities. This study analyses the association between ambient air temperature and non-accidental mortality across mainland Norway, using a constrained hierarchical clustering algorithm to group municipalities with similar geographic, environmental, socioeconomic, and demographic patterns., Methods: This study analysed the association between ambient air temperature and non-accidental mortality across 356 Norwegian municipalities, using daily data from 1996 to 2018. We applied a case time series design with distributed lag non-linear models. A downscaling procedure assessed the effect of 21 vulnerability factors on temperature-related mortality risks, using Principal Components Analysis to explore heterogeneity across clusters., Findings: Cold temperatures contributed to an estimated 3879 deaths per year (95% CI 3718-4130), while heat was associated with 44 deaths annually (95%CI: 29-58). The highest heat-related mortality risk occurred in the South-East, and the highest cold-related risk in the Central-East. Greater heat-related mortality correlated with medium-to sparsely-populated areas, while higher education levels were linked to reduced vulnerability to both heat and cold., Interpretation: By providing the first comprehensive assessment of temperature-related excess mortality and associated risk factors in Norway, our findings underscore the need for targeted, equitable health policies that integrate environmental and socioeconomic factors. These insights are essential to guide climate adaptation strategies, prioritising vulnerable rural communities and socioeconomically disadvantaged groups to mitigate future climate-related health impacts., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Splanchnic vein thrombosis (SpVT) occurs in 17%-23 % of acute pancreatitis cases. Serious sequelae include hepatic and bowel ischaemia. However, management with therapeutic anticoagulation remains controversial due to potential bleeding risk. We aim to determine the level of consensus on prognosis, diagnosis, management, and outcomes of SpVT through a DELPHI process., Methods: Using purposive, non-probability sampling and DELPHI methodology, 173 clinicians with experience of SpVT in acute pancreatitis were approached. From April 2022 to April 2023, a three-round DELPHI process was implemented to completion. A total of 88 statements were posed for ranking via a four-point Likert scale., Results: The mean acute pancreatitis caseload per respondent per year was 68·0, 72·6 and 73·0 for DELPHI rounds 1,2 and 3 respectively. For SpVT anatomical location, there was strong consensus favouring anticoagulation for portal vein (89·1 %) and SMV thrombosis (90·9 %), and no consensus to treat splenic vein thrombosis (47·3 %). 74·1 % rejected radiological resolution as a definitive anticoagulation endpoint. Majority consensus favoured death, bleeding risk, bowel or liver ischaemia, hospital admission length and ITU admission as significant outcomes for experimental research design., Conclusion: There was significant consensus for anticoagulation treatment of SpVT of the portal and superior mesenteric veins, especially with complete occlusion by thrombosis. Randomised controlled trials are required to grade management recommendations., Competing Interests: Conflict on interest None declared., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Objective: Whether radical prostate cancer treatment affects long-term physical performance and physical activity in older men is not known. We aimed to compare physical performance and self-reported physical activity between relapse-free older prostate cancer survivors and population-based controls., Methods: A single-centre, cross-sectional study including 109 men aged ≥70 yr receiving robotic-assisted radical prostatectomy (61.5%) or external beam radiotherapy (38.5%) between 2014 and 2018 was conducted. Population-based matched (age, gender, and education) controls ( n  = 327) were drawn from the Trøndelag Health Study. The primary (the Short Physical Performance Battery [SPPB] summary score) and secondary (gait speed, grip strength, one-legged balance, and the self-reported Physical Activity Index) outcomes were compared between survivors and controls by adjusted linear mixed models., Key Findings and Limitations: The SPPB score, gait speed, and Physical Activity Index did not differ between survivors (mean age 78.3 yr, mean time since treatment 52.9 mo) and controls (mean age 78.2 yr). Survivors had slightly poorer grip strength (regression coefficient [RC] -5.81, p  < 0.001, 95% confidence interval [CI] -7.46; -4.17) and one-legged balance (RC -4.36, p  < 0.001, 95% CI -6.72; -2.00; adjusted models), but the clinical significance is uncertain. Small sample size and potential selection of the fittest survivors are limitations that may reduce the generalisability of our findings., Conclusions and Clinical Implications: 3 to 8 yr after radical prostate cancer treatment, older men's overall physical performance and physical activity level were comparable with those of matched controls. This suggests that the treatment had little impact on functional status., Patient Summary: In this study, we investigated physical function in older men several years after they had undergone curatively intended treatment for prostate cancer in comparison with men in a general population of the same age and education. We found that physical function was similar, except slightly poorer grip strength and balance on one leg in men treated for prostate cancer. We conclude that the overall physical function was comparable with that of the general population and believe that this indicates that prostate cancer treatment was well tolerated despite older age., (© 2024 The Author(s).)

Satisfaction with services among service users is an important aspect of quality in mental health care. This prospective study investigated associations between service and treatment factors at baseline and satisfaction with services at 18-month follow-up among service users with psychosis in specialist mental health services. Data were collected from 119 service users with psychosis and their clinicians from 26 clinical sites across Norway at baseline and after 18 months. Satisfaction with services was measured using the Client Satisfaction Questionnaire-8 (CSQ-8). Linear mixed models with random intercepts for units were estimated to test the association between service- and treatment-related predictors and the CSQ-8. Participating in the Individual Placement and Support program or other interventions to promote work or study, receiving well-coordinated services, and receiving helpful assistance from a general practitioner at baseline were positively associated with satisfaction with services at 18-month follow-up. The present results suggest that receiving integrated and well-coordinated services and targeting the goal of facilitating employment and study opportunities is important for satisfaction with services among service users with psychosis., Competing Interests: Declarations. Competing Interest: The authors declare that they have no competing interest., (© 2024. The Author(s).)

Many patients with chronic thromboembolic pulmonary disease (CTEPD) suffer from exertional dyspnea. It is unclear if CTEPD is associated with exercise pulmonary hypertension (ePH). This cross-sectional study aimed to determine the occurrence of ePH in patients with CTEPD and to identify the haemodynamic changes during exercise. We recruited 36 patients with persistent dyspnoea and residual perfusion defects by ventilation/perfusion scintigraphy from a large cohort of patients with previous pulmonary embolism. All patients underwent exercise right heart catheterization before being classified into the following groups: (1) CTEPD without ePH; comprising patients with normal mean pulmonary artery pressure (mPAP) of ≤20 mmHg, but with mPAP/cardiac output (CO) slope of ≤3 mmHg/L/min, (2) CTEPD with ePH (CTEPD-ePH); those with CTEPD with an mPAP/CO slope of >3 mmHg/L/min, (3) chronic thromboembolic pulmonary hypertension (CTEPH); those with mPAP >20 mmHg, pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg and pulmonary vascular resistance >2 WU. The postcapillary contribution during exercise was considered present if the PAWP/CO slope of >2 mmHg/L/min. CTEPD without resting pulmonary hypertension (PH) was present in 29 (81%) of the 36 patients, of whom six (21%) had ePH, while five (14%) had CTEPH. Two patients had unclassified PH. Two (33%) of the six patients with CTEPD-ePH had a PAWP/CO slope of >2 mmHg/L/min, compared with two (40%) of the five of those with CTEPH. In conclusion, about 20% of patients with CTEPD and exertional dyspnoea had ePH. Exercise right heart catheterization revealed a notable proportion of patients with postcapillary contribution., Competing Interests: K. Stavem reports consulting fees from MSD and Union Chimique Belge (UCB) unrelated to this study. W. G. reports fees for participation in an advisory board from Amgen, Novartis, Pfizer, Principia Biopharma Inc.—a Sanofi Company, Sanofi, SOBI, Grifols, UCB, Argenx, Cellphire, Alpine, Kedrion and HiBio; lecture honoraria from Amgen, Novartis, Pfizer, Bristol Myers Squibb, SOBI, Grifols, Sanofi and Bayer; and research grants from Bayer, BMS/Pfizer, and UCB. The remaining authors declare no conflict of interest., (© 2024 The Author(s). Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background: This systematic review evaluates the effect of audit and feedback (A&F) interventions targeting antibiotic prescribing in primary care and examines factors that may explain the variation in effectiveness., Methods: Randomized controlled trials (RCTs) involving A&F interventions targeting antibiotic prescribing in primary care were included in the systematic review. Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and ClinicalTrials.gov were searched up to May 2024. Trial, participant, and intervention characteristics were extracted independently by two researchers. Random effects meta-analyses of trials that compared interventions with and without A&F were conducted for four outcomes: 1) total antibiotic prescribing volume; 2) unnecessary antibiotic initiation; 3) excessive prescription duration, and 4) broad-spectrum antibiotic selection. A stratified analysis was also performed based on study characteristics and A&F intervention design features for total antibiotic volume., Results: A total of 56 RCTs fit the eligibility criteria and were included in the meta-analysis. A&F was associated with an 11% relative reduction in antibiotic prescribing volume (N=21 studies, rate ratio [RR]=0.89; 95% confidence interval [CI] 0.84, 0.95; I2=97); 23% relative reduction in unnecessary antibiotic initiation (N=16 studies, RR=0.77; 95%CI 0.68, 0.87; I2=72); 13% relative reduction in prolonged duration of antibiotic course (N=4 studies, RR=0.87 95%CI 0.81, 0.94; I2=86); and 17% relative reduction in broad-spectrum antibiotic selection (N=17 studies, RR=0.83 95%CI 0.75, 0.93; I2=96)., Discussion: A&F interventions reduce antibiotic prescribing in primary care. However, heterogeneity was substantial, outcome definitions were not standardized across the trials, and intervention fidelity was not consistently assessed., Funding: Canadian Institutes of Health Research FRN 173704., Registration: Prospero (CRD42022298297)., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: Considering that the remission rate for major depressive disorder (MDD) in elderly patients is below 50%, there is a compelling requirement for an enhanced comprehension of the underlying mechanisms. Chronic low-grade inflammation has been posited as one potential contributor to treatment-resistant MDD in the elderly. Accordingly, the objective of our study was to explore the longitudinal trends of systemic immune markers in elderly inpatients referred to electroconvulsive therapy due to an episode of treatment resistant unipolar MDD., Methods: The study encompassed 64 elderly inpatients with unipolar MDD that had failed to respond to therapy in primary health care, and 18 non-depressed controls. Blood samples were collected at pre-treatment, mid-treatment, post-treatment and 12 weeks follow-up. We assessed 27 immune markers via multiplex assays. Depressive symptoms were evaluated using the Hamilton Rating Scale of Depression at these timepoints. For controls, the immune markers and depressive symptoms, were measured at baseline and eight weeks follow-up using identical methods., Results: At follow-up, patients showed higher concentrations of 23 immune markers compared to controls, although the concentration of 19 immune markers decreased significantly from pre-treatment to follow-up. No differences in immune marker concentrations between treatment responders and non-responders were observed pre- and post-treatment in the patient group., Conclusion: Our findings suggest that a pro-inflammatory trait persists in elderly after an episode of treatment resistant unipolar MDD. Thus, our study supports that chronic low-grade inflammation may characterise elderly with treatment-resistant unipolar MDD.

Household income and caregiver mental health are important drivers of children's health and development. The COVID-19 pandemic created huge economic and mental health disruptions. This study examines financial hardship and its relationship with caregiver and child mental health using Australia's only representative data spanning three years of the pandemic. Analysis of the repeated, cross-sectional National Child Health Poll included 12,408 caregivers and 20,339 children over six waves (June 2020-April 2023). Caregivers reported their income (dichotomised into low versus not) and deprivation (missing one or more of eight essential items, versus not) and mental health for themselves (Kessler-6, poor versus not) and each child (Self-Rated Mental Health, poor/fair versus good/very good/excellent). Binary logistic models were fitted to predict marginal probabilities of mental health measures by low income and deprivation, over time. Results show that while low income decreased from 41% to 34% over the study period, deprivation increased from 30% to 35%. Poor mental health peaked with stay-at-home orders in 2021 before recovering. Caregivers experiencing low income or deprivation had higher rates of poor mental health throughout the study and slower recovery compared to those without financial hardship. Children in families experiencing financial hardship had slightly higher proportions of poor/fair mental health in 2021-2022, but they were mostly equivalent in June 2020 and April 2023 (range 6-8%). Addressing financial hardship may offer an avenue for improving caregiver mental health. This has implications for post-pandemic recovery and addressing contemporary issues of increasing cost of living and limited mental health supports and services.

Background: There is evidence of rapidly growing resistance to antibiotics across Africa. We aimed to establish whether blood culture and sensitivity (BCS) testing is a feasible component of the response to antimicrobial resistance (AMR) in large Kenyan hospitals., Methods: We used a qualitative study design and conducted key informant interviews (KIIs) using iteratively developed, semi-structured interviews with purposively sampled health-care workers (HCWs) within a network of facilities in Kenya called the Clinical Information Network. Only hospital laboratories that either reported fewer than 50 BCS tests in the previous 6 months or had not recorded use of BCS tests for the past 6 months were included in this study. This selection was further limited by considerations of timing, logistics, and data saturation. Our purposive selection of interviewees was guided by the level of expertise, profession, the number of key informants per hospital, and existing relations with the hospital staff. Each interview took an average of 45 min. Our thematic analysis used inductive coding to identify key themes, and we used causal loop diagrams (CLDs) to explain interactions between themes. The CLDs illustrate how health system issues relate to each other and influence the use of BCS testing in these study settings., Findings: We conducted 72 KIIs across eight tertiary-level Kenyan hospitals between Oct 27 and Dec 2, 2021. Of the 72 HCWs interviewed, 33 (46%) were women and 39 (54%) were men. The participants consisted of 24 clinicians, 26 laboratory staff, and 22 pharmacists with a median age of 36 years (IQR 31-40). We found that the main issues that led to insufficient use of BCS testing in these hospitals related to demand and supply. A host of issues influence clinician demand for BCS testing, including: the use and uptake of BCS, normalisation of clinical diagnosis, unaffordability of the BCS test, turnaround time of the BCS test, preferential use of alternative biochemistry and haematology tests by clinicians, diagnosis by malaria confirmation, and negative results discouraging clinicians from ordering this test. Similarly, health system logistics or supply issues, including laboratory capacity, support and goodwill from hospital management, and scarcity of refresher training opportunities, hinder the availability and sustenance of BCS testing. The CLDs show that these multiple factors can create mutually reinforcing feedback loops that undermine efforts to provide BCS testing in hospitals., Interpretation: The findings suggest that sustainable and routine provision of BCS testing would require many issues to be targeted simultaneously and continuously at the health system level, which is unlikely to be feasible in the short term for Kenyan hospitals. Therefore, in these settings, alternatives to routine BCS testing-such as the adoption of a targeted or vertical approach and the use of survey-informed antimicrobial stewardship to inform local treatment guidelines-should be considered for the control of AMR., Funding: Wellcome Trust., Competing Interests: Declaration of interests SA, JM, and ME received a grant from the Wellcome Trust (London, UK). The funding from the grant supported this work. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Importance: This diagnostic study describes the merger of domain knowledge (Kramer principle of dermal advancement of icterus) with current machine learning (ML) techniques to create a novel tool for screening of neonatal jaundice (NNJ), which affects 60% of term and 80% of preterm infants., Objective: This study aimed to develop and validate a smartphone-based ML app to predict bilirubin (SpB) levels in multiethnic neonates using skin color analysis., Design, Setting, and Participants: This diagnostic study was conducted between June 2022 and June 2024 at a tertiary hospital and 4 primary-care clinics in Singapore with a consecutive sample of neonates born at 35 or more weeks' gestation and within 21 days of birth., Exposure: The smartphone-based ML app captured skin images via the central aperture of a standardized color calibration sticker card from multiple regions of interest arranged in a cephalocaudal fashion, following the Kramer principle of dermal advancement of icterus. The ML model underwent iterative development and k-folds cross-validation, with performance assessed based on root mean squared error, Pearson correlation, and agreement with total serum bilirubin (TSB). The final ML model underwent temporal validation., Main Outcomes and Measures: Linear correlation and statistical agreement between paired SpB and TSB; sensitivity and specificity for detection of TSB equal to or greater than 17mg/dL with SpB equal to or greater than 13 mg/dL were assessed., Results: The smartphone-based ML app was validated on 546 neonates (median [IQR] gestational age, 38.0 [35.0-41.0] weeks; 286 [52.4%] male; 315 [57.7%] Chinese, 35 [6.4%] Indian, 169 [31.0%] Malay, and 27 [4.9%] other ethnicities). Iterative development and cross-validation was performed on 352 neonates. The final ML model (ensembled gradient boosted trees) incorporated yellowness indicators from the forehead, sternum, and abdomen. Temporal validation on 194 neonates yielded a Pearson r of 0.84 (95% CI, 0.79-0.88; P < .001), 82% of data pairs within clinically acceptable limits of 3 mg/dL, sensitivity of 100%, specificity of 70%, positive predictive value of 10%, negative predictive value of 100%, positive likelihood ratio of 3.3, negative likelihood ratio of 0, and area under the receiver operating characteristic curve of 0.89 (95% CI, 0.82-0.96)., Conclusions and Relevance: In this diagnostic study of a new smartphone-based ML app, there was good correlation and statistical agreement with TSB with sensitivity of 100%. The screening tool has the potential to be an NNJ screening tool, with treatment decisions based on TSB (reference standard). Further prospective studies are needed to establish the generalizability and cost-effectiveness of the screening tool in the clinical setting.

Objective: The objective was to identify a prioritized list of research themes and key data points (baseline data and research outcomes) for future studies regarding child and adolescent emergency department (ED) mental health presentations., Methods: A prospective survey-based Delphi process was undertaken in Australia within the Pediatric Research in Emergency Departments International Collaborative (PREDICT) network. Hospital-based and community-based clinicians, researchers, police, ambulance paramedics, pediatric patients, and their carers were recruited to generate research themes and key data points for future pediatric ED mental health research. Responses were collated and analyzed by a steering group consisting of pediatric mental health, medical, and research/academic experts. Participants then prioritized the items through three survey rounds using a 9-point Likert-type scale to generate a final prioritized list., Results: 184 participants (36 patients/carers and 148 clinicians/researchers) were recruited and generated 267 items for initial prioritization; 23 completed all survey rounds. The surveys identified a consensus of 71 items: 35 research themes and 36 key data points (11 baseline data points and 25 research outcomes) for future research. The top-rated research themes included patient/staff safety within the ED, the efficacy of dedicated mental health spaces, and the importance of patient follow-up. Important baseline data points included risk factors for mental health presentations and history of child abuse and/or family violence. Top-rated research outcomes included the occurrence of severe behavioral disturbance in the ED, the use of parenteral sedation, and ED re-presentation and/or suicide attempt postdischarge., Conclusions: The Delphi process identified a prioritized list of research themes and key data points that will inform future research on child and adolescent mental health-related ED presentations., (© 2024 The Author(s). Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Objective: Social prescribing models are expanding worldwide to serve multiple goals, such as attending to social conditions that affect people's health, supporting patients with mental health issues or other long-term conditions, facilitating community building and reducing demands on the health care system. Implicitly, many social prescribing services seek to promote health, prevent morbidity or deterioration of disease. Given that the scientific literature currently does not systematically describe these services as preventive service models, we propose a framework to explicitly conceptualize social prescribing from a prevention perspective., Methods: Based on concepts from prevention science (e.g., classifications of prevention approaches), and a comparison of social prescribing models in different countries, we compiled a framework allowing to conceptualize, plan and evaluate social prescribing from a prevention perspective. Examples of social prescribing models were identified using systematic reviews and focused key-word-searches., Results: Our framework outlines a systematic process for explicitly designing social prescribing models for prevention purposes. It consists of the following steps: defining target populations (e.g., young people with mild mental health issues), formulating intended outcomes (e.g., improved social participation), determining a prevention approach (e.g., universal or indicated prevention), deciding on the implementation setting (e.g., primary or specialized care) and selecting services for prescription (e.g., physical activity outdoors)., Conclusion: The framework advances the field by guiding the conceptualization, development and evaluation of social prescribing services. It contributes to widening possible settings for social prescribing and considers potential adverse consequences. Thereby the framework opens up new avenues for social prescribing as preventive service model., 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 article. The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for [YPMED] and was not involved in the editorial review or the decision to publish this article., (Copyright © 2024. Published by Elsevier Inc.)

Expressions of concern (EoC) can reduce the adverse effects of unreliable publications by alerting readers to concerns about publication integrity while assessment is undertaken. We investigated the use of EoC for 463 publications by two research groups for which we notified concerns about publication integrity to 142 journals and 44 publishers between March 2013 and February 2020. By December 2021, 95 papers had had an EoC, and 83 were retracted without an EoC. Median times from notification of concerns to EoC (10.4mo) or retraction without EoC (13.1mo) were similar. Among the 95 EoCs, 29 (30.5%) were followed by retraction after a median of 5.4mo, none was lifted, and 66 (69.5%) remained in place after a median of 18.1mo. Publishers with >10 notified publications issued EoCs for 0-81.8% of papers: for several publishers the proportions of notified papers for which EoCs were issued varied considerably between the 2 research groups. EoCs were issued for >30% of notified publications of randomized clinical trials and letters to the editor, and <20% of other types of research. These results demonstrate inconsistent application of EoCs between and within publishers, and prolonged times to issue and resolve EoCs.

Introduction: The pragmatic explanatory continuum indicator summary (PRECIS) tool, initially published in 2009 and revised in 2015, was created to assist trialists to align their design choices with the intended purpose of their randomised controlled trial (RCT): either to guide real-world decisions between alternative interventions (pragmatic) or to test hypotheses about intervention mechanisms by minimising sources of variation (explanatory). There have been many comments, suggestions, and criticisms of PRECIS-2. This summary will be used to facilitate the development of to the next revision, which is PRECIS-3., Methods: We used Web of Science to identify all publication types citing PRECIS-2, published between May 2015 and July 2023. Citations were eligible if they contained 'substantive' suggestions, comments, or criticism of the PRECIS-2 tool. We defined 'substantive' as comments explicitly referencing at least one PRECIS-2 domain or a concept directly linked to an existing or newly proposed domain. Two reviewers independently extracted comments, suggestions, and criticisms, noting their implications for the update. These were discussed among authors to achieve consensus on the interpretation of each comment and its implications for PRECIS-3., Results: The search yielded 885 publications, and after full-text review, 89 articles met the inclusion criteria. Comments pertained to new domains, changes in existing domains, or were relevant across several or all domains. Proposed new domains included assessment of the comparator arm and a domain to describe blinding. There were concerns about scoring eligibility and recruitment domains for cluster trials. Suggested areas for improvement across domains included the need for more scoring guidance for explanatory design choices., Discussion: Published comments recognise PRECIS-2's success in aiding trialists with pragmatic or explanatory design choices. Enhancing its implementation and widespread use will involve adding new domains, refining domain definitions, and addressing overall tool issues. This citation review offers valuable user feedback, pivotal for shaping the upcoming version of the PRECIS tool, PRECIS-3., Competing Interests: Declaration of competing interest All authors declare no conflict of interest. Dr Kirsty Loudon developed the PRECIS-2 tool as part of a DPhil., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate pelvic floor dysfunction (PFD; urinary incontinence (UI), faecal incontinence (FI) and prolapse) ≥20 years after childbirth and their association with delivery mode history and demographic characteristics., Design: Cohort study with long-term follow-up., Setting: Maternity units in Aberdeen and Birmingham (UK) and Dunedin (NZ)., Population: Women giving birth in 1993/1994., Methods: Postal questionnaires at 20 (New Zealand) or 26 (United Kingdom) years after index birth (n = 6195). Regression analyses investigated associations between risk factors and UI, FI and prolapse symptoms., Main Outcome Measures: Prevalence of self-reported UI, FI, 'something coming down' from or in the vagina (SCD), and the Pelvic Organ Prolapse-Symptom Score, and relationships with delivery method., Results: Thirty-seven per cent (n = 2270) responded at 20/26 years, of whom 61% reported UI (59% of whom reported more severe UI), 22% FI and 17% prolapse symptoms. Having only caesarean section (CS) was associated with a significantly lower risk of UI (OR 0.63, 95% CI 0.46-0.85), FI (OR 0.63, 95% CI 0.42-0.96) and SCD (OR 0.44, 95% CI 0.27-0.74) compared to only spontaneous vaginal deliveries (SVDs). Having any forceps delivery was associated with reporting FI compared to only SVDs (OR 1.29, 95% CI 1.00-1.66), but there was no association for UI (OR 0.95, 95% CI 0.76-1.19) or SCD (OR 1.05, 95% CI 0.80-1.38). Higher current BMI was associated with all PFD outcomes., Conclusions: Prevalence of PFD continues to increase up to 26 years following index birth, and differences were observed according to delivery mode history. Exclusive CS was associated with less risk of UI, FI and any prolapse symptoms., (© 2024 The Author(s). BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: In Norway, municipal acute wards (MAWs) were implemented as alternatives to hospitalisation. Evaluations of the quality of MAW services are lacking. The primary objective of this study was to compare patient experiences after admission to a MAW versus to a hospital. The secondary objective was to compare 'readmissions', 'length of stay', 'self-assessed health-related quality of life' as measured by the EuroQol 5 items 5 level (EQ-5D-5L) index, and 'health status' measured by the RAND-12, in patients admitted to a MAW versus a hospital., Methods: A multicentre randomised controlled trial (RCT), randomising patients to either MAW or hospital., Results: In total, 164 patients were enrolled in the study; 115 were randomised to MAW and 49 to hospital. There were no significant differences between the MAW and hospital groups regarding patient experience, which was rated positively in both groups. Patients in the MAW group reported significantly better physical health status as measured by the RAND-12 four to six weeks after admittance than those randomised to hospital (physical component summary score, 31.7 versus 27.1, p  = 0.04). The change in EQ-5D index score from baseline to four to six weeks after admittance was significantly greater among patients randomised to MAWs versus hospitals (0.20 versus 0.02, p  = 0.03). There were no other significant differences between the MAW and hospital groups., Conclusions: In this study, patient experiences and readmissions were similar, whether patients were admitted to a MAW or a hospital. The significant differences in health status and quality of life favouring the MAWs suggest that these healthcare services may be better for elderly patients. However, unfortunately we did not reach the planned sample size due to challenges in the data collection posed by the Covid-19 pandemic.

Background and Objectives: Conducting high-quality randomized clinical trials (RCTs) is challenging and resource intensive. Funders and academic investigators depend on limited financial resources and, therefore, need empirical data for optimal budget planning. However, current literature lacks detailed empirical data on resource use and costs of investigator-sponsored RCTs. The aim of this study is to systematically collect cost data from investigator-sponsored RCTs from Switzerland, Germany, and the United Kingdom (UK)., Methods: Principal investigators were asked to share their RCT cost and resource use data and enter it into an online case report form. We assessed cost patterns, cost drivers, and specific cost items, examined costs by study phase (planning-, conduct-, and finalization phase), compared planned with actual RCT costs, and explored differences in cost patterns across countries, medical fields, and intervention types., Results: We included 93 RCTs which were initiated in Switzerland (n = 53; including eight conducted in low- and lower middle-income countries), Germany (n = 22), and the UK (n = 18). The median total trial cost in our RCT sample was $645,824 [interquartile range (IQR), $269,846-$1,577,924]. The median proportion of the total costs spent for planning phase was 27.5% [IQR, 20.6%-39.7%], for conduct phase 57.3% [IQR, 44.4%-66.3%], and for finalization phase 12.7% [IQR, 8.5%-19.3%] with little variation across countries. The items that contributed most to the total costs were protocol writing (7.2%; IQR 3.8%-10.6%), data management (5.0%; IQR 2.2%-8.1%) and follow-up (4.5%; IQR 2.3%-8.4%). Of the 66 RCTs with an available original budget, 46 (69.7%) exceeded the budget by over 50%. Use of routinely collected data to assess primary outcomes was independently associated with lower per patient- and lower total trial costs., Conclusion: Over a quarter of total trial costs were incurred in the planning phase, which is typically not fully funded. Two-thirds of RCTs exceeded their budget by more than 50%. Investigators and funders should consider empirical cost data to improve budgeting and funding practices., Competing Interests: Declaration of competing interest B.S. and M.B. report an unrestricted grant from Moderna for a study outside of the submitted work. There are no competing interests for any other author., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

PACIFIC-PGx evaluated the feasibility of implementing pharmacogenetics (PGx) screening in Australia and the impact of DPYD/UGT1A1 genotype-guided dosing on severe fluoropyrimidine (FP) and irinotecan-related toxicities and hospitalizations, compared to historical controls. This prospective single arm trial enrolled patients starting FP/irinotecan for any cancer between 7 January 2021 and 25 February 2022 from four Australian hospitals (one metropolitan, three regional). During the accrual period, 462/487 (95%) consecutive patients screened for eligibility for DPYD and 50/109 (46%) for UGT1A1 were enrolled and genotyped (feasibility analysis), with 276/462 (60%) for DPYD and 30/50 (60%) for UGT1A1 received FP/irinotecan (safety analysis). DPYD genotyping identified 96% (n = 443/462) Wild-Type, 4% (n = 19/462) Intermediate Metabolizers (50% dose reduction), and 0% Poor Metabolizers. UGT1A1 genotyping identified 52% (n = 26/50) Wild-Type, 40% (n = 20/50) heterozygous, and 8% (n = 4/50) homozygous (30% dose reduction). Key demographics for the FP/irinotecan safety cohorts included: age range 23-89/34-74 years, male 56%/73%, Caucasian 83%/73%, lower gastrointestinal cancer 50%/57%. Genotype results were reported prior to cycle-1 (96%), average 5-7 days from sample collection. PGx-dosing for DPYD variant allele carriers reduced high-grade toxicities compared to historic controls (7% vs. 39%; OR = 0.11, 95% CI 0.01-0.97, p = 0.024). High-grade toxicities among Wild-Type were similar (14% vs. 14%; OR = 0.99, 95% CI 0.64-1.54, p = 0.490). PGx-dosing reduced FP-related hospitalizations (-22%) and deaths (-3.7%) compared to controls. There were no high-grade toxicities or hospitalizations for UGT1A1*28 homozygotes. PGx screening and prescribing were feasible in routine oncology care and improved patient outcomes. Findings may inform expanded PGx programs within cancer and other disease settings., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objectives: This study aimed to evaluate the cost-effectiveness of an extended-role general practitioner symptoms clinic (SC), added to usual care (UC) for patients with multiple persistent physical symptoms (sometimes known as medically unexplained symptoms)., Methods: This was a 52-week within-trial cost-utility analysis of a pragmatic multicenter randomized controlled trial comparing SC + UC (n = 178) with UC alone (n = 176), conducted from the primary perspective of the UK National Health Service and personal and social services (PSS). Base-case quality-adjusted life-years (QALYs) were measured using EQ-5D-5L. Missing data were imputed using multiple imputation. Cost-effectiveness results were presented as incremental cost-effectiveness ratios and incremental net monetary benefits. Uncertainty was explored using cost-effectiveness acceptability curves (using 1000 nonparametric bootstrapped samples) and sensitivity analysis (including societal costs, using SF-6D and ICECAP-A capability measure for adults outcomes to estimate QALYs and years of full capability, respectively, varying intervention costs, missing data mechanism assumptions)., Results: Multiple imputation analysis showed that compared with UC alone, SC + UC was more expensive (adjusted mean cost difference: 704; 95% CI £605-£807) and more effective (adjusted mean QALY difference: 0.0447; 95% CI 0.0067-0.0826), yielding an incremental cost-effectiveness ratio of £15 765/QALY, incremental net monetary benefit of £189.22 (95% CI -£573.62 to £948.28) and a 69% probability of the SC + UC intervention arm being cost-effective at a threshold of £20 000 per QALY. Results were robust to most sensitivity analyses but sensitive to missing data assumptions (2 of the 8 scenarios investigated), SF-6D, and ICECAP&#95;A capability measure for adults quality-of-life outcomes., Conclusions: A symptoms clinic is likely to be a potentially cost-effective treatment for patients with persistent physical symptoms., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

To estimate occurrence of non-communicable diseases (NCDs) over the life-course in the Norwegian population, national health registries are a vital source of information since they fully represent the entire non-institutionalised population. However, as they are mainly established for administrative purposes, more knowledge about how NCDs are recorded in the registries is needed. To establish this, we begin by counting the number of individuals registered annually with one or more NCDs in any of the registries. The study population includes all inhabitants who lived in Norway from 2004 to 2020 ( N ~6.4m). The NCD outcomes are diabetes, cardiovascular diseases, chronic obstructive lung diseases, cancer and mental disorders/substance use disorders. Further, we included hip fractures in our NCD concept. The data sources used to identify individuals with NCDs, including detailed information on diagnoses in primary and secondary health care and dispensings of prescription drugs, are the Cancer Registry of Norway, The Norwegian Patient Registry, The Norwegian Control and Payment of Health Reimbursement database, and The Norwegian Prescription Database. The number of individuals registered annually with an NCD diagnosis and/or a dispensed NCD drug increased over the study period. Changes over time may reflect changes in disease incidence and prevalence, but also changes in disease-specific guidelines, reimbursement schemes and access to and use of health services. Data from more than one health registry to identify individuals with NCDs are needed since the registries reflect different levels of health care services and therefore may reflect disease severity., Competing Interests: Data sharing statementThe authors are not permitted to share data within this research project with others. However, interested readers can apply to the Norwegian Health Data Authority and Statistics Norway to obtain access to registry data. At the end of the project period, we will publish our Data Management Plan, describing how we handled our research data throughout the project. Declaration of conflicting interestsThe authors have no conflicts of interest to declare.

Purpose: Chemotherapy in combination with trastuzumab is the standard neoadjuvant and adjuvant therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). Assessing the regimens administered to patients with HER2-positive BC in the real world is lacking. We evaluated neoadjuvant and adjuvant regimen patterns among HER2-positive BC patients (2007 to 2021) identified in a health insurance claims database., Methods: Female BC patients ≥ 18 years who received chemotherapy, surgery, and trastuzumab were chosen from Optum's de-identified Clinformatics® Data Mart database. Summary statistics, Joinpoint models, Kaplan-Meier survival curves, and Cox regression models were used to analyze the data., Results: We identified 6474 patients (median age 60 years), 71.7% were White, 10.9% were Black, 8.6% were Hispanic, 4.1% were Asian, and 4.7% had unknown race/ethnicity. About 33.8% received neoadjuvant therapy and neoadjuvant therapy use increased with an annual percent change of 10.24% (P < .001). The three most common regimens were adjuvant docetaxel, carboplatin, and trastuzumab (TCH; 29.0%); adjuvant paclitaxel and trastuzumab (17.7%); and neoadjuvant TCH with pertuzumab followed by adjuvant trastuzumab (17.7%). The 5-year overall survival (OS) was 96% (95% CI, 95-96%). Patients had an increased risk of death if they were ≥ 59 years at diagnosis, had a health maintenance organization or other insurance plan, had dual Medicare/Medicaid eligibility, had a mastectomy, did not receive 18 cycles of trastuzumab, or received regimens not recommended by the National Comprehensive Cancer Network., Conclusion: Treatment regimen patterns for HER2-positive BC evolved in correspondence with the U.S. Food and Drug Administration's approval of new drugs for this cancer and National Comprehensive Cancer Network treatment guidelines., Competing Interests: Declarations. Conflict of interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Collagenase Clostridium histolyticum (CCH) and percutaneous needle fasciotomy (PNF) are 2 treatment options for Dupuytren disease. The purpose of this study was to compare these 2 methods in terms of clinical and patient-reported outcomes., Methods: Eighty patients (median age, 72 years; 83% male) with a single-digit primary metacarpophalangeal (MCP) joint contracture of ≥30° were randomized to either CCH or PNF and followed for 5 years. The primary outcome was the difference in flexion-contracture reduction at the MCP joint from baseline to 2 years, with additional analysis examining the effect of the primary endpoint variable up to 5 years. Secondary outcomes included complications, grip strength, scores on the visual analogue scale (VAS) for pain, the shortened version of the Disabilities of the Arm, Shoulder and Hand, the brief Michigan Hand Questionnaire, Unité Rhumatologique des Affections de la Main, and a VAS for treatment satisfaction as well as recurrence and retreatments., Results: The mean MCP joint contracture was 48° at baseline and 2° at 5 years in the CCH group, and 50° at baseline and 7° at 5 years in the PNF group. The reduction in MCP contracture at 2 years was larger in the CCH group than in the PNF group, with a mean difference between the groups of 12° (95% confidence interval [CI], 1.5° to 22.3°; p = 0.026). At 5 years, this mean difference was reduced to 6° (-1.5° to 12.8°; p = 0.1). There was no difference between the groups in any patient-reported outcome scores or grip strength beyond 4 weeks, with the exception of the brief Michigan Hand Questionnaire at 5 years. Ten (25%) of the patients in the PNF group compared with no patient in the CCH group had recurrence (contracture of ≥30°) at the MCP joint at 2 years. At 5 years, 17 (42.5%) of 40 patients in the PNF group had been retreated compared with 4 (10%) of 40 in the CCH group (p < 0.001). The CCH group experienced more transient complications (stiffness and hematoma) during the first week and were more satisfied (VAS satisfaction) from 1 year to the 5-year follow-up., Conclusions: The main finding of this study is that CCH and PNF were equally effective in reducing MCP flexion contracture, but the correction of contracture lasted longer in the CCH group., Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The study received funding from The Sophies Minde Foundation and Akershus University Hospital strategic research fund. The Article Processing Charge for open access publication was funded by Akershus University Hospital and the University of Oslo. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSOA/A712)., (Copyright © 2024 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)