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Objectives: Rheumatoid arthritis (RA) has a considerable disease burden with life-long physical limitations, reduced work productivity and high societal costs. Trials on arthralgia at-risk for RA are therefore conducted, aiming to intercept evolving RA and reduce the disease burden. A 1-year course of methotrexate in patients with clinically suspect arthralgia (CSA) caused sustained improvements in subclinical joint inflammation and physical impairments. Since the cost-effectiveness of treatment in CSA has never been investigated, we investigated whether methotrexate is cost-effective., Methods: Cost-effectiveness was assessed using the TREAT EARLIER trial. 236 patients with CSA with subclinical joint inflammation were randomised to 1-year treatment with methotrexate, or placebo, and followed for 2 years. Cost-effectiveness was analysed by computing costs and effects. For costs, both a societal perspective (healthcare-productivity and work-productivity costs) and a healthcare perspective (healthcare costs only) were used. For effects, quality adjusted life years (QALYs) were used., Results: Treatment increased QALYs by 0.041 (95% CI -0.050 to 0.091), and reduced costs with €-4809 (95% CI -12 382 to 2726) over the course of 2 years using a societal perspective, with a probability of 88.1% that treatment was cost-effective. From a healthcare perspective, the cost-difference between treatment and placebo was estimated at €-418 (95% CI -1198 to 225)., Conclusion: A fixed treatment course in individuals with arthralgia at-risk for RA and MRI-detected subclinical joint inflammation resulted in better work productivity, lower healthcare costs and improved quality of life over the course of 2 years; with the largest gain in productivity costs. This is the first evidence that methotrexate treatment aiming at secondary prevention in arthralgia at-risk for RA is cost-effective., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Background: Whole genome sequencing (WGS) has transformative potential for blood cancer management, but reimbursement is hindered by uncertain benefits relative to added costs. This study employed scenario planning and multi-criteria decision analysis (MCDA) to evaluate stakeholders' preferences for alternative reimbursement pathways, informing future health technology assessment (HTA) submission of WGS in blood cancer., Methods: Key factors influencing WGS reimbursement in blood cancers were identified through a literature search. Hypothetical scenarios describing various evidential characteristics of WGS for HTA were developed using the morphological approach. An online survey, incorporating MCDA weights, was designed to gather stakeholder preferences (consumers/patients, clinicians/health professionals, industry representatives, health economists, and HTA committee members) for these scenarios. The survey assessed participants' approval of WGS reimbursement for each scenario, and scenario preferences were determined using the geometric mean method, applying an algorithm to improve reliability and precision by addressing inconsistent responses., Results: Nineteen participants provided complete survey responses, primarily clinicians or health professionals (n = 6; 32 %), consumers/patients and industry representatives (both at n = 5; 26 %). "Clinical impact of WGS results on patient care" was the most critical criterion (criteria weight of 0.25), followed by "diagnostic accuracy of WGS" (0.21), "cost-effectiveness of WGS" (0.19), "availability of reimbursed treatment after WGS" (0.16), and "eligibility criteria for reimbursed treatment based on actionable WGS results" and "cost comparison of WGS" (both at 0.09). Participants preferred a scenario with substantial clinical evidence, high access to reimbursed targeted treatment, cost-effectiveness below $50,000 per quality-adjusted life year (QALY) gained, and affordability relative to standard molecular tests. Reimbursement was initially opposed until criteria such as equal cost to standard tests and better treatment accessibility were met., Conclusion: Payers commonly emphasize acceptable cost-effectiveness, but strong clinical evidence for many variants and comparable costs to standard tests are likely to drive positive reimbursement decisions for WGS., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. M.V. received funding support from Illumina, a supplier of the NovaSeq 6000 that was considered in this study. At the time of publication, K.D. was an employee of Healthcare Consultancy Group, but did not contribute to this research as such and Healthcare Consultancy Group was in no way involved in this research or publication. The other authors declare no competing financial interests, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Whole genome and whole transcriptome sequencing (WGTS) can accurately distinguish B-cell acute lymphoblastic leukemia (B-ALL) genomic subtypes. However, whether this is economically viable remains unclear. This study compared the direct costs and molecular subtype classification yield using different testing strategies for WGTS in adolescent and young adult/adult patients with B-ALL. These approaches were: (1) combined BCR::ABL1 by fluorescence in situ hybridization (FISH) + WGTS for all patients; and (2) sequential BCR::ABL1 FISH + WGTS contingent on initial BCR::ABL1 FISH test outcome. The cost of routine diagnostic testing was estimated using Medicare or hospital fees, and the additional cost of WGTS was evaluated from the health care provider perspective using time-driven activity-based costing with resource identification elicited from experts. Molecular subtype classification yield data were derived from literature sources. Parameter uncertainty was assessed through deterministic sensitivity analysis; additional scenario analyses were performed. The total per patient cost of WGTS was $4319 (all costs reported in US dollars); consumables accounted for 74% of the overall cost, primarily driven by sequencing-related consumables. The incremental cost per additional patient categorized into molecular subtype was $8498 for combined BCR::ABL1 FISH + WGTS for all patients and $5656 for initial BCR::ABL1 FISH + WGTS for select patients compared with routine diagnostic testing. A reduction in the consumable costs of WGTS or an increase in the yield of molecular subtype classification is favorable., Competing Interests: Disclosure Statement M.V. received funding support from Illumina, a supplier of the NovaSeq 6000 that was considered in this study. At the time of publication, K.D. was an employee of Healthcare Consultancy Group, but did not contribute to this research as such and Healthcare Consultancy Group was in no way involved in this research or publication., (Copyright © 2024 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

BackgroundVaccine uptake differs between social groups. Mobile vaccination units (MV-units) were deployed in the Netherlands by municipal health services in neighbourhoods with low uptake of COVID-19 vaccines.AimWe aimed to evaluate the impact of MV-units on vaccine uptake in neighbourhoods with low vaccine uptake.MethodsWe used the Dutch national-level registry of COVID-19 vaccinations (CIMS) and MV-unit deployment registrations containing observations in 253 neighbourhoods where MV-units were deployed and 890 contiguous neighbourhoods (total observations: 88,543 neighbourhood-days). A negative binomial regression with neighbourhood-specific temporal effects using splines was used to study the effect.ResultsDuring deployment, the increase in daily vaccination rate in targeted neighbourhoods ranged from a factor 2.0 (95% confidence interval (CI): 1.8-2.2) in urbanised neighbourhoods to 14.5 (95% CI: 11.6-18.0) in rural neighbourhoods. The effects were larger in neighbourhoods with more voters for the Dutch conservative Reformed Christian party but smaller in neighbourhoods with a higher proportion of people with non-western migration backgrounds. The absolute increase in uptake over the complete intervention period ranged from 0.22 percentage points (95% CI: 0.18-0.26) in the most urbanised neighbourhoods to 0.33 percentage point (95% CI: 0.28-0.37) in rural neighbourhoods.ConclusionDeployment of MV-units increased daily vaccination rate, particularly in rural neighbourhoods, with longer travel distance to permanent vaccination locations. This public health intervention shows promise to reduce geographic and social health inequalities, but more proactive and long-term deployment is required to identify its potential to substantially contribute to overall vaccination rates at country level.

Background and Objectives: Studying malpractice claims is important to improve quality of health care and patient safety and to educate the individual healthcare providers. The objective of this study was to describe characteristics of neurosurgical claims in the Netherlands., Methods: A nationwide retrospective observational study of neurosurgery-related claims closed by Centramed and MediRisk, 2 major insurance companies in the Netherlands, was performed. Relevant data, including type of neurosurgical pathology, theme and category of the claim, type and severity of injury, outcome, and financial burden, were extracted from anonymized claim files. The estimated annual risk was used to determine the risk for claims by adjusting for the number of annually practicing neurosurgeons in the Netherlands., Results: A total of 388 claims against neurosurgeons were closed between 2007 and 2021. Liability was denied in a slight majority of claims (n = 230; 59%). The total burden during this period was €6 165 000 (amount paid out to patients: €5 497 000). The estimated annual risk per Dutch neurosurgeon for a claim was 15.5%, meaning 1 claim per 6.5 years. The case-level analysis of 238 available anonymized claims revealed that most claims were related to spinal pathology (81.5%), followed by cranial pathology (10.9%) and peripheral nerve (7.6%). The motivations for filing claims were mostly related to alleged surgical (56.3%) or diagnostic errors (22.3%). Most of these claims were denied (151/238; 63.4%), and fewer were settled (42/238; 17.6%), sustained (31/238; 13.0%), or closed without final decision (14/238; 5.9%)., Conclusion: Neurosurgery-related malpractice claims primarily involved spinal pathology and were mostly related to alleged treatment errors. Most claims did not result in compensation because there seemed to be no liability or culpable injury. However, the annual risk for a claim for Dutch neurosurgeons is considerable., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

Objective: Early diagnosis and treatment-start is key for rheumatoid arthritis (RA), but the economic effect of an early versus a later diagnosis has never been investigated. We aimed to investigate whether early diagnosis of RA is associated with lower treatment-related costs compared with later diagnosis., Methods: Patients with RA consecutively included in the Leiden Early Arthritis Clinic between 2011 and 2017 were studied (n=431). Symptom duration was defined as the time between symptom onset and first presentation at the outpatient clinic; early treatment start was defined as symptom duration <12 weeks. Information on disease-modifying anti-rheumatic drug use per patient over 5 years was obtained from prescription data from patient records. Prices were used from 2022 and 2012 (proxy of time of prescription) to study the impact of changes in drug costs. Autoantibody-positive and autoantibody-negative RA were studied separately because differences in disease severity may influence costs., Results: Within autoantibody-negative RA, costs were 316% higher in the late compared with the early group (β=4.16 (95% CI 1.57 to 11.1); €4856 vs €1159). When using 2012 prices, results were similar. For autoantibody-positive RA, costs were 19% higher in the late group (€9418 vs €7934, β=1.19, 0.57 to 2.47). This effect was present but smaller when using 2012 prices. Within patients with autoantibody-positive RA using biologicals, late treatment start was associated with 46% higher costs (β=1.46 (0.91 to 2.33)); higher costs were also seen when using 2012 prices., Conclusion: When RA is detected within 12 weeks after symptom onset, treatment-related costs were lower in both autoantibody-negative and autoantibody-positive RA. This study is the first to report how early diagnosis and treatment start impact treatment-related costs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objectives: Effective healthcare planning, resource allocation, and budgeting require accurate predictions of the number of patients needing treatment at specific cancer stages and treatment lines. The Predicting the Population Health Economic Impact of Current and New Cancer Treatments (PRIMCAT) for Colorectal Cancer (CRC) simulation model (PRIMCAT-CRC) was developed to meet this requirement for all CRC stages and relevant molecular profiles in Australia., Methods: Real-world data were used to estimate treatment utilization and time-to-event distributions. This populated a discrete-event simulation, projecting the number of patients receiving treatment across all disease stages and treatment lines for CRC and forecasting the number of patients likely to utilize future treatments. Illustrative analyses were undertaken, estimating treatments across disease stages and treatment lines over a 5-year period (2022-2026). We demonstrated the model's applicability through a case study introducing pembrolizumab as a first-line treatment for mismatch-repair-deficient stage IV., Results: Clinical registry data from 7163 patients informed the model. The model forecasts 15 738 incident and 2821 prevalent cases requiring treatment in 2022, rising to 15 921 and 2871, respectively, by 2026. Projections show that over 2022 to 2026, there will be a total of 116 752 treatments initiated, with 43% intended for stage IV disease. The introduction of pembrolizumab is projected for 706 patients annually, totaling 3530 individuals starting treatment with pembrolizumab over the forecasted period, without significantly altering downstream utilization of subsequent treatments., Conclusions: PRIMCAT-CRC is a versatile tool that can be used to estimate the eligible patient populations for novel cancer therapies, thereby reducing uncertainty for policymakers in decisions to publicly reimburse new treatments., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material., (Copyright © 2024. Published by Elsevier Inc.)

Background: Efforts to mitigate unwarranted variation in the quality of care require insight into the 'level' (eg, patient, physician, ward, hospital) at which observed variation exists. This systematic literature review aims to synthesise the results of studies that quantify the extent to which hospitals contribute to variation in quality indicator scores., Methods: Embase, Medline, Web of Science, Cochrane and Google Scholar were systematically searched from 2010 to November 2023. We included studies that reported a measure of between-hospital variation in quality indicator scores relative to total variation, typically expressed as a variance partition coefficient (VPC). The results were analysed by disease category and quality indicator type., Results: In total, 8373 studies were reviewed, of which 44 met the inclusion criteria. Casemix adjusted variation was studied for multiple disease categories using 144 indicators, divided over 5 types: intermediate clinical outcomes (n=81), final clinical outcomes (n=35), processes (n=10), patient-reported experiences (n=15) and patient-reported outcomes (n=3). In addition to an analysis of between-hospital variation, eight studies also reported physician-level variation (n=54 estimates). In general, variation that could be attributed to hospitals was limited (median VPC=3%, IQR=1%-9%). Between-hospital variation was highest for process indicators (17.4%, 10.8%-33.5%) and lowest for final clinical outcomes (1.4%, 0.6%-4.2%) and patient-reported outcomes (1.0%, 0.9%-1.5%). No clear pattern could be identified in the degree of between-hospital variation by disease category. Furthermore, the studies exhibited limited attention to the reliability of observed differences in indicator scores., Conclusion: Hospital-level variation in quality indicator scores is generally small relative to residual variation. However, meaningful variation between hospitals does exist for multiple indicators, especially for care processes which can be directly influenced by hospital policy. Quality improvement strategies are likely to generate more impact if preceded by level-specific and indicator-specific analyses of variation, and when absolute variation is also considered., Prospero Registration Number: CRD42022315850., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Current choice models in healthcare (and beyond) can provide suboptimal predictions of healthcare users' decisions. One reason for such inaccuracy is that standard microeconomic theory assumes that decisions of healthcare users are made in a social vacuum. Healthcare choices, however, can in fact be (entirely) socially determined. To achieve more accurate choice predictions within healthcare and therefore better policy decisions, the social influences that affect healthcare user decision-making need to be identified and explicitly integrated into choice models. The purpose of this study is to develop a socially interdependent choice framework of healthcare user decision-making., Design: A mixed-methods approach will be used. A systematic literature review will be conducted that identifies the social influences on healthcare user decision-making. Based on the outcomes of a systematic literature review, an interview guide will be developed that assesses which, and how, social influences affect healthcare user decision-making in four different medical fields. This guide will be used during two exploratory focus groups to assess the engagement of participants and clarity of questions and probes. The refined interview guide will be used to conduct the semistructured interviews with healthcare professionals and users. These interviews will explore in detail which, and how, social influences affect healthcare user decision-making. Focus group and interview transcripts will be analysed iteratively using a constant comparative approach based on a mix of inductive and deductive coding. Based on the outcomes, a social influence independent choice framework for healthcare user decision-making will be drafted. Finally, the Delphi technique will be employed to achieve consensus about the final version of this choice framework., Ethics and Dissemination: This study was approved by the Erasmus School of Health Policy and Management Research Ethics Review Committee (ESHPM, Rotterdam, The Netherlands; reference ETH2122-0666)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Since there is no diet that is perfect for everyone, personalized nutrition approaches are gaining popularity to achieve goals such as the prevention of obesity-related diseases. However, appropriate choices about funding and encouraging personalized nutrition approaches should be based on sufficient evidence of their effectiveness and cost-effectiveness. In this study, we assessed whether a newly developed personalized plan (PP) could be cost-effective relative to a non-personalized plan in Denmark., Methods: Results of a 10-week randomized controlled trial were combined with a validated obesity economic model to estimate lifetime cost-effectiveness. In the trial, the intervention group (PP) received personalized home-delivered meals based on metabolic biomarkers and personalized behavioral change messages. In the control group these meals and messages were not personalized. Effects were measured in body mass index (BMI) and quality of life (EQ-5D-5L). Costs [euros (€), 2020] were considered from a societal perspective. Lifetime cost-effectiveness was assessed using a multi-state Markov model. Univariate, probabilistic sensitivity, and scenario analyses were performed., Results: In the trial, no significant differences were found in the effectiveness of PP compared with control, but wide confidence intervals (CIs) were seen [e.g., BMI (-0.07, 95% CI -0.51, 0.38)]. Lifetime estimates showed that PP increased costs (€520,102 versus €518,366, difference: €1736) and quality-adjusted life years (QALYs) (15.117 versus 15.106, difference: 0.011); the incremental cost-utility ratio (ICUR) was therefore high (€158,798 to gain one QALY). However, a 20% decrease in intervention costs would reduce the ICUR (€23,668 per QALY gained) below an unofficial gross domestic product (GDP)-based willingness-to-pay threshold (€47,817 per QALY gained)., Conclusion: On the basis of the willingness-to-pay threshold and the non-significant differences in short-term effectiveness, PP may not be cost-effective. However, scaling up the intervention would reduce the intervention costs. Future studies should be larger and/or longer to reduce uncertainty about short-term effectiveness., Trial Registration Number: ClinicalTrials.gov registry (NCT04590989)., (© 2023. The Author(s).)

Background: Patients treated with immune checkpoint inhibitors (ICI) are at risk of adverse events (AEs) even though not all patients will benefit. Serum tumor markers (STMs) are known to reflect tumor activity and might therefore be useful to predict response, guide treatment decisions and thereby prevent AEs., Objective: This study aims to compare a range of prediction methods to predict non-response using multiple sequentially measured STMs., Methods: Nine prediction models were compared to predict treatment non-response at 6-months (n = 412) using bi-weekly CYFRA, CEA, CA-125, NSE, and SCC measurements determined in the first 6-weeks of therapy. All methods were applied to six different biomarker combinations including two to five STMs. Model performance was assessed based on sensitivity, while model training aimed at 95% specificity to ensure a low false-positive rate., Results: In the validation cohort, boosting provided the highest sensitivity at a fixed specificity across most STM combinations (12.9% -59.4%). Boosting applied to CYFRA and CEA achieved the highest sensitivity on the validation data while maintaining a specificity >95%., Conclusions: Non-response in NSCLC patients treated with ICIs can be predicted with a specificity >95% by combining multiple sequentially measured STMs in a prediction model. Clinical use is subject to further external validation.

Background: Clinical indications for ibrutinib reimbursement in Australia should consider the inclusion of patients with chronic lymphocytic leukemia (CLL) harboring prognostically unfavorable TP53/IGHV genomic aberrations. This study assessed the cost effectiveness of five first-line treatment strategies in CLL for young (aged ≤ 65 years), fit patients without significant comorbidities: (1) no testing (fludarabine, cyclophosphamide and rituximab [FCR] for all), (2) test for del(17p) only, (3) test for TP53 gene mutation status, (4) test for TP53 and IGHV gene mutation status and (5) no testing (ibrutinib for all)., Method: A decision analytic model (decision tree and partitioned survival model) was developed from the Australian healthcare system perspective with a lifetime horizon. Comparative treatment effects were estimated from indirect treatment comparisons and survival analysis using several studies. Costs, utility and adverse events were derived from public literature sources. Deterministic and probabilistic sensitivity analyses explored the impact of modeling uncertainties on outcomes., Results: Strategy 1 was associated with 5.69 quality-adjusted life-years (QALYs) and cost 458,836 Australian dollars (AUD). All other strategies had greater effectiveness but were more expensive than Strategy 1. At the willingness-to-pay (WTP) threshold of 100,000 AUD per QALY gained, Strategy 1 was most cost effective with an estimated probability of 68.8%. Strategy 4 was cost effective between thresholds 155,000-432,300 AUD per QALY gained, and Strategy 5 >432,300 AUD per QALY gained., Conclusion: Population targeting using mutation testing for TP53 and IGHV when performed with del(17p) testing specifically in the context of frontline ibrutinib choice does not make a cost-ineffective treatment into a cost-effective treatment., (© 2023. The Author(s).)

Objectives: Increasing the price of tobacco is one of the most effective measures to reduce the prevalence of smoking. In the Netherlands, the excise tax on tobacco increased by €1.14 in 2020, raising the price of a standard package of cigarettes to €8.00. This study investigates how young adults intend to change their smoking behaviour in the case of hypothetical price increases of a pack of cigarettes, and which background characteristics are associated with intended behaviour change., Design: A cross-sectional online survey was carried out between September and November 2020. Smokers indicated how they would react to several hypothetical increases in price. Four behavioural options were investigated: smoking less, quitting smoking, switching to another/cheaper product and buying cheaper cigarettes cross-border., Participants: Data were obtained from 776 Dutch smokers between 15 and 25 years., Results: At a hypothetical price of €10 per package, most respondents reported an intention to smoke less (67%), followed by switching to another/cheaper product (61%), quitting smoking (49%) and shopping for cigarettes cross-border (47%). Prior quit attempts, agreeing with the increase in excise tax and the intention to quit smoking in the future increased the odds of changing behaviour. Higher self-efficacy decreased the odds of behavioural change., Conclusion: Many young adults intend to change their smoking behaviour in the event of increased prices. Although intended behaviour can deviate significantly from actual behaviour, an increase in excise tax may result in a significant amount of quit attempts and reduced smoking among young adults., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Horizon scanning (HS) is the systematic identification of emerging therapies to inform policy and decision-makers. We developed an agile and tailored HS methodology that combined multi-criteria decision analysis weighting and Delphi rounds. As secondary objectives, we aimed to identify new medicines in melanoma, non-small cell lung cancer and colorectal cancer most likely to impact the Australian government's pharmaceutical budget by 2025 and to compare clinician and consumer priorities in cancer medicine reimbursement., Method: Three cancer-specific clinician panels (total n = 27) and a consumer panel (n = 7) were formed. Six prioritisation criteria were developed with consumer input. Criteria weightings were elicited using the Analytic Hierarchy Process (AHP). Candidate medicines were identified and filtered from a primary database and validated against secondary and tertiary sources. Clinician panels participated in a three-round Delphi survey to identify and score the top five medicines in each cancer type., Results: The AHP and Delphi process was completed in eight weeks. Prioritisation criteria focused on toxicity, quality of life (QoL), cost savings, strength of evidence, survival, and unmet need. In both curative and non-curative settings, consumers prioritised toxicity and QoL over survival gains, whereas clinicians prioritised survival. HS results project the ongoing prevalence of high-cost medicines. Since completion in October 2021, the HS has identified 70 % of relevant medicines submitted for Pharmaceutical Benefit Advisory Committee assessment and 60% of the medicines that received a positive recommendation., Conclusion: Tested in the Australian context, our method appears to be an efficient and flexible approach to HS that can be tailored to address specific disease types by using elicited weights to prioritise according to incremental value from both a consumer and clinical perspective., Policy Summary: Since HS is of global interest, our example provides a reproducible blueprint for adaptation to other healthcare settings that integrates consumer input and priorities., Competing Interests: Declaration of Competing Interest MA has received financial support to attend conferences and meetings by AstraZeneca and serves on the advisory board for Pfizer and Bristol Myers Squibb. PAA has/had a consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Canofi, Idera, Sandoz, Immunocore, 4SC, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen, iTeos, Medicenna, Bio-Al Health, ValoTX, Replimmune. He has received research funding grants from Bristol Myers Squibb, Roche-Genentech, Pfizer, Sanofi. He has received travel support from Pfizer. SA has served uncompensated on the boards of Health Issues Centre, Australia, Victorian Agency for Health Information, and Safer Care Victoria. MPB has received honoraria from BNS Australia, USD Oncology, and Novartis. He holds an advisory role for Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, and Cartherics for which his institution receives reimbursements. His institution has also received reimbursement for research support from Bristol Myers Squibb, Merck Sharp & Dohme, Pharmaust, Zucero Therapeutics, and CStone Pharmaceuticals. MB has received compensation and research support as an advisor and consultant to Pierre Fabre, MSD, GSK, Servier, and AstraZeneca. MI is on the advisory boards of Pfizer, Roche, Takeda, BeiGene, Amgen, Merck, and MSD and has received honoraria from Pfizer, Roche, Takeda, Novartis, as well as research funding from Pfizer. TJ reports consulting fees from AstraZeneca and MSD, and advisory boards and committees for AstraZeneca, Amgen, Bristol Myers Squibb, Merck & Co., MSD, Gilead, Puma, Pfizer Inc., Roche AG, Specialised Therapeutics, and Takeda Pharmaceutical, outside the submitted work. SK reports honoraria to institution from Astra Zeneca, Roche, Pfizer, Bristol Myers Squibb, MSD and Takeda; consulting fees from AstraZeneca, Pfizer, MSD, Novartis, Roche, Takeda, Amgen; and research funding to institution from Astra Zeneca. MK reports institutional grants from Nordic Farma, Merck-Serono, Pierre Fabre, Servier, Bayer, Bristol Myers Squibb, Merck, and Roche; and consulting fees and honoraria paid to institution from Pierre Fabre and Servier. BTL has served as an uncompensated advisor and consultant to Amgen, AstraZeneca, Boehringer Ingelheim, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, and Lilly. He has received research grants to his institution from Amgen, AstraZeneca, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, Hengrui USA, and Lilly. He has received academic travel support from Amgen, Jiangsu Hengrui Medicine and MORE Health. He is an inventor on two institutional patents at MSK (US62/685,057, US62/514,661) and has intellectual property rights as a book author at Karger Publishers and Shanghai Jiao Tong University Press. BTL is supported by the Memorial Sloan Kettering Cancer Centre Support Grant P30 CA008748 and Research Project Grant R01CA249666 from the National Institutes of Health. GVL is consultant advisor for Agenus, Amgen, Array Biopharma, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Evaxion, Hexal AG (Sandoz Company), Highlight Therapeutics S.L., Innovent Biologics USA, Merck Sharpe & Dohme, Novartis, OncoSec, PHMR Ltd, Pierre Fabre, Provectus, Qbiotics, Regeneron. JML receives research support from Ipsen Pharmaceuticals, Novartis and Amgen, and reports consulting fees and/or honoraria from Amgen, Ipsen, Taiho, Novartis, SAGA Diagnostics and Natera. BM is on the advisory boards of Amgen, MSD, Bristol Myers Squibb, Beigene and AstraZeneca. GAM has received research support from Bristol Myers Squibb and as Principal Investigator his institution has received reimbursement of trial costs from Roche-Genentech. TMM reports consulting fees and participation on advisory boards for Bristol Myers Squibb, MSD, Merck, AstraZeneca, Novartis, GSK, Eisai, and honoraria from AstraZeneca. TMM has received support to attend meetings from Bristol Myers Squibb and AstraZeneca. LN has received institutional consulting fees from Bristol Myers Squibb, Pfizer, and Merck Sharp & Dohme, and reports support to attend a research meeting from AstraZeneca. NP has served on advisory boards or received personal honoraria from Boehringer Ingelheim, MSD, Merck, Bristol-Myers Squib, Astra Zeneca, Takeda, Pfizer, Roche, Novartis, Ipsen and Bayer and has received research funding to his institution from Bayer, Pfizer and Roche. TMP has received research support from Roche and Pfizer, and holds a consulting or advisory role for Merck, Bristol Myers Squibb, Novartis, Sanofi/Regeneron, and Pfizer. SP is compensated consultant to Amgen, AstraZeneca, Bayer, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, EQRx, GSK, Guardant Health, Incyte, Janssen, Lilly, Merck Serono, MSD, Novartis, Roche, Takeda, Pfizer, Seattle Genetics, Turning Point Therapeutics, declares expert testimony to Roche and Merck Serono, and travel support from Janssen and Roche.BJS is on the Advisory Boards/Honoraria for Pfizer, Novartis, Roche, AstraZeneca, Merck, Bristol Myers Squibb, Eli Lilly, Amgen, BeiGene, Janssen, Takeda. JAS has received support for conference attendance from MSD (virtual registration ASCO). JT has received consulting fees or honoraria from Haystack Oncology, Servier, Pierre Fabre, MSD, Merck Serono, Amgen, Novartis, Seres and AstraZeneca. JT is on the advisory boards of Beigene, Daiichi Sankyo, Gilead, Illumina, Novartis, BMS, and MSD. WX has received research support from Merck, honoraria from MSD, Merck and AstraZeneca, and support for attending meetings from MSD (virtual registration ASCO) and Eli Lilly (virtual registration SABCS). WX is on the advisory boards of MSD, Merck and Novartis, and holds unpaid positions as Chair of the Melanoma and Skin Cancer trials group and Australasian Merkel Cell Carcinoma interest group.DY has received institutional payments for his role on advisory boards for AstraZeneca, Servier, Specialised Therapeutics, MSD and BayerJZ serves in an advisory/consultancy role for Merck Sharp & Dohme, Specialised Therapeutics, CEND, Deciphera, Revolution Medicine, FivePHusion, Genorbio, 1Global, Novotech, Alloplex Biotherapeutics, NOUS Consulting, and Oncology Republic; owns stock in Biomarin, Ophthea, Amarin, Concert Pharmaceuticals, Frequency Therapeutics, Gilead, Madrigal Pharmaceuticals, UniQure, Zogenix, Orphazyme, Moderna Therapeutics, TWST, Novavax, and Teladoc; has received honoraria from Gilead Sciences, MSD Oncology, and Viatris; and his institution has received research funding from Bristol-Myers Squibb, AstraZeneca, Pfizer, IQvia, Mylan, Ipsen, Eisai, Medtronic, MSD Oncology and Servier; and has received travel, accommodations, expenses from ICON Group, MSD Oncology, and PRAXIS., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To assess the relationship between childhood immunization and mortality risks for nonvaccine-preventable diseases (competing mortality risks, or CMR) in Kenya., Study Design: A combination of the Global Burden of Disease and Demographic Health Survey data was used to measure basic vaccination status, CMR, and control variables for each child in the Demographic Health Survey data. A longitudinal analysis was performed. This uses within-mother variation between children to compare the vaccine decisions for different children, who are exposed to different mortality risks. The analysis also distinguishes between overall and disease-specific risks., Results: The study included 15 881 children born between 2009 and 2013, who were at least 12 months old at the time of interview and not part of a twin birth. Mean basic vaccination rates ranged from 27.1% to 90.2% and mean CMR from 13.00 to 738.32 deaths per 100 000 across different counties. A one-unit increase in mortality risk from diarrhea, the most prevalent disease among children in Kenya, is associated with a 1.1 percentage point decline in basic vaccination status. In contrast, mortality risks for other diseases and HIV increase the likelihood of vaccination. The effect of CMR was found to be stronger for children with higher birth orders., Conclusions: A significant negative correlation between severe CMR and vaccination status was found, which has important implications for immunization policies, particularly in Kenya. Interventions aimed at reducing the most severe CMR, such as diarrhea, and targeted toward multiparous mothers may improve childhood immunization coverage., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Although validated patient-reported outcome (PRO) measurements can categorize patients with inflammatory bowel disease (IBD) into clinical remission or active disease, patients may have different definitions of remission. The purpose of this study was to compare patient-defined remission to remission based on PRO measures and physician global assessment (PGA) and to understand the clinical and demographic factors associated with disagreements., Methods: We retrospectively analyzed 3257 de-identified surveys from 2004 IBD patients who consented to participate in the Crohn's and Colitis Foundation's IBD Qorus Learning Health System between September 2019 and February 2021. We used logistic regression models with generalized estimating equations to analyze the clinical and demographic factors (eg, age, disease duration, health confidence) associated with discordance between patient-defined remission (yes/no) and PRO-defined remission for ulcerative colitis (UC; PRO2: stool frequency, rectal bleeding) and Crohn's disease (CD; PRO-3: average number of liquid stools, abdominal pain, well-being)., Results: Among patients with UC, overall concordance was 79% between patient self-report and PRO2-defined remission and 49% between patient self-report and PGA-defined remission. Among patients with CD, overall concordance was 69% between patient self-report and PRO3-defined remission and 54% between patient self-report and PGA-defined remission. Patients in PRO-defined remission were more likely to report active disease if they had IBD <5 years and low health confidence. Patients with PRO-defined active disease were more likely to report remission if they were not using prednisone and had high health confidence., Conclusion: Discordance exists between how remission is defined by patients, PRO measures, and PGA., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Whereas in the treatment of rheumatoid arthritis much evidence exists on the effects of current pharmacologic treatment on clinical outcomes, little is known about the effects on patient-reported outcomes. This systematic review aims to evaluate the effects of disease-modifying antirheumatic drugs (DMARDs) on the patient-relevant domains of pain, fatigue, activity limitation, overall emotional and physical health impact, and work/school/housework ability and productivity., Methods: A literature search was conducted to identify randomized controlled trials wherein registered DMARDs were compared with placebo or methotrexate and reported the effects on patient-reported outcomes included in the International Consortium of Health Outcomes Measurement standard set for inflammatory arthritis. Random effects meta-analyses using the standardized mean differences of change scores as the effect measure were performed for the domains of pain, fatigue, and activity limitation, comparing DMARDs with placebo and methotrexate. The other 2 domains were presented narratively., Results: Across the 5 domains, 69 records belonging to 52 studies were identified. All meta-analyses showed a decrease of burden when DMARDs were compared with placebo (standardized mean differences [95% confidence interval] in pain -0.80 [-0.99, -0.61], fatigue -0.48 [-0.64, -0.32], and activity limitation -0.56 [- 0.63, -0.49]) and when compared with methotrexate (-0.55 [-0.70, -0.41), -0.44 [-0.55, -0.33], and - 0.37 [-0.44, -0.30], respectively)., Conclusion: DMARDs decrease the burden in all the domains that are relevant to patients. Effect sizes may be influenced by DMARD type. Therefore, in the decision for rheumatoid arthritis treatment, patient-reported outcomes should be taken into account., (© 2022 American College of Rheumatology.)

NTRK gene fusions are rare somatic mutations found across cancer types with promising targeted therapies emerging. Healthcare systems face significant challenges in integrating these treatments, with uncertainty in prevalence and optimal testing methods to identify eligible patients. We performed a systematic review of NTRK fusion prevalence to inform efficient diagnostic screening and scale of therapeutic uptake. We searched Medline, Embase and Cochrane databases on 31/03/2021. Inclusion criteria were studies reporting fusion rates in solid tumours, English language, post-2010 publication and minimum sample size. Critical appraisal was performed using a custom 11-item checklist. Rates were collated by cancer type and pooled if additional synthesis criteria were met. 160 studies were included, with estimates for 15 pan-cancer and 429 specific cancer types (63 paediatric). Adult pan-cancer estimates ranged 0.03-0.70%, with higher rates found in RNA-based assays. In common cancers, rates were consistently below 0.5%. Rare morphological subtypes, colorectal microsatellite instability, and driver mutation exclusion cancers had higher rates. Only 35.6% of extracted estimates used appropriate methods and sample size to identify NTRK fusions. NTRK fusion-positive cancers are rare and widely distributed across solid tumours. Small-scale, heterogeneous data confound prevalence prediction. Further large-scale, standardised genomic data are needed to characterise NTRK fusion epidemiology., (© 2023. The Author(s).)

Introduction: Integrated care can create several advantages, such as better quality of care and better outcomes. These advantages apply especially to clients with multiple problems (CWMPs) who have multiple, interconnected needs that span health and social issues and require different health care (e.g., mental health care or addiction care), social care (e.g., social benefits) and welfare services at the same time. Integrated care is most often studied as a phenomenon taking place at the system, organizational, professional and clinical levels. Therefore, in many studies, clients seem to be implicitly conceptualized as passive recipients of care. Less research has been conducted on how clients and (in)formal caretakers coproduce integrated care., Methods: We performed a longitudinal study to investigate how CWPMs and (in)formal caretakers coproduce integrated care. Data were collected among CWMPs and their (in)formal caretakers in Rotterdam, the Netherlands. CWMPs' care trajectories were followed for 1-1.5 years. CWMPs were interviewed three times at an interval of 6 months (T0, T1, T2). Informal caretakers were interviewed three times (T0, T1, T2), and formal caretakers of 16 clients were interviewed twice (T1, T2). Data in the municipal record systems about participating CWMPs were also included., Results: Our study shows that the CWMPs' multidimensional needs, which should function as the organizing principle of integrated care, are rarely completely assessed at the start (first 6 weeks) of CWMPs' care trajectories. Important drivers behind this shortcoming are the urgent problems CWMPs enter the support trajectory with, their lack of trust in 'the government' and the complexity of their situations. We subsequently found two distinct types of cases. The highest level of integrated care is achieved when formal caretakers initiate an iterative process in which the CWMP's multidimensional needs are constantly further mapped out and interventions are attuned to this new information., Conclusions: Our study indicates that integrated care is the joint product of formal caretakers and CWMPs. Integrated care however does not come naturally when CWMPs are 'put at the center'. Professionals need to play a leading role in engaging CWMPs to coproduce integrated care., Patient Contribution: CWMPs and their (in)formal caretakers participated in this study via interviews and contributed with their experiences of the process., (© 2022 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Background: Unprofessional behaviour undermines organizational trust and negatively affects patient safety, the clinical learning environment, and clinician well-being. Improving professionalism in healthcare organizations requires insight into the frequency, types, sources, and targets of unprofessional behaviour in order to refine organizational programs and strategies to prevent and address unprofessional behaviours., Objective: To investigate the types and frequency of perceived unprofessional behaviours among health care professionals and to identify the sources and targets of these behaviours., Methods: Data was collected from 2017-2019 based on a convenience sample survey administered to all participants at the start of a mandatory professionalism course for health care professionals including attending physicians, residents and advanced practice providers (APPs) working at one academic hospital in the United States., Results: Out of the 388 participants in this study, 63% experienced unprofessional behaviour at least once a month, including failing to respond to calls/pages/requests (44.3%), exclusion from decision-making (43.0%) and blaming behaviour (39.9%). Other monthly experienced subtypes ranged from 31.7% for dismissive behaviour to 4.6% for sexual harassment. Residents were more than twice as likely (OR 2.25, p<0.001)) the targets of unprofessional behaviour compared to attending physicians. Female respondents experienced more discriminating behaviours (OR 2.52, p<0.01). Nurses were identified as the most common source of unprofessional behaviours (28.1%), followed by residents from other departments (21%)., Conclusions: Unprofessional behaviour was experienced frequently by all groups, mostly inflicted on these groups by those outside of the own discipline or department. Residents were most frequently identified to be the target and nurses the source of the behaviours. This study highlights that unprofessional behaviour is varied, both regarding types of behaviours as well as targets and sources of such behaviours. This data is instrumental in developing training and remediation initiatives attuned to specific professional roles and specific types of professionalism lapses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Dabekaussen 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.)

Societies face the challenge of providing appropriate arrangements for individuals who need living support due to their mental disorders. We estimate the effects of eligibility to the Dutch supported housing program (Beschermd Wonen), which offers a structured living environment in the community as an intermediate alternative to independent housing and inpatient care. For this, we use exogenous variation in eligibility based on conditionally random assignment of applications to assessors, and the universe of applications to supported housing in the Netherlands, linked to rich administrative data. Supported housing eligibility increases the probability of moving into supported housing and decreases the use of home care, resulting in higher total care expenditures. This increase is primarily due to the costs of supported housing, but potentially also higher consumption of curative mental health care. Supported housing eligibility reduces the total personal income and income from work. Findings do also suggest lower participation in the labor market by the individuals granted eligibility, but the labor participation of their parents increases in the long-run. Our study highlights the trade-offs of access to supported housing for those at the margin of eligibility, informing the design of long-term mental health care systems around the world., (© 2022 The Authors. Health Economics published by John Wiley & Sons Ltd.)

Dutch policy stipulates that people with dementia should remain at home for as long as possible. If they need care, they must preferably appeal to family, friends and neighbours. Professional help and nursing homes are deemed last resorts. Therefore, case managers must coproduce their public services increasingly in healthcare triads with both people with dementia (PWDs) and their informal caregivers. Case managers are professionals who provide and coordinate care and support for PWDs and their informal caregivers during the entire trajectory from (suspected) diagnosis until institutionalisation. The literature on coproduction has focused on the bilateral interactions between service providers and users rather than the multilateral collaborative relationships through which many public services are currently delivered, as is the case in dementia care. Little is known about how frontline workers, case managers in this study, handle conflicts in these healthcare triads. Our study addresses this gap in the coproduction literature and explores the action strategies case managers use to handle conflicts. We interviewed 19 Dutch case managers and observed 10 of their home visits between January and May 2017. We focused on the end stage of dementia at home, just before admission to a nursing home, as we assumed that most conflicts occur in that phase. The findings reveal that the case managers use a variety of action strategies to resolve and intervene in these conflicts. Their initial strategies are in line with the ideals underlying coproduction; however, their successive strategies abandon those ideals and are more focused on production or result from their own lack of power. We also found that current reforms create new dilemmas for case managers. Future research should focus on the boundaries of coproducing public services in triadic relationships and the effects of current welfare reforms aimed at coproducing public services in healthcare triads., (© 2021 The Authors. Health and Social Care in the Community published by John Wiley & Sons Ltd.)

Background: A just culture is regarded as vital for learning from errors and fostering patient safety. Key to a just culture after incidents is a focus on learning rather than blaming. Existing research on just culture is mostly theoretical in nature., Aim: This study aims to explore requirements and challenges for fostering a just culture within healthcare organizations., Methods: We examined initiatives to foster the development of a just culture in five healthcare organizations in the Netherlands. Data were collected through interviews with stakeholders and observations of project group meetings in the organizations., Results: According to healthcare professionals, open communication is particularly important, paying attention to different perspectives on an incident. A challenge related to open communication is how to address individual responsibility and accountability. Next, room for emotions is regarded as crucial. Emotions are related to the direct consequences of incidents, but also to the response of the outside world, including the media and the health inspectorate., Conclusions: A challenge in relation to emotions is how to combine attention for emotions with focusing on facts, both within and outside the organization. Finally, healthcare professionals attach importance to commitment and exemplary behavior of management. A challenge as a manager here is how to keep distance while also showing commitment. Another challenge is how to combine openness with privacy of the parties involved, and how to deal with less nuanced views in other layers of the organization and in the outside world. Organizing reflection on the experienced tensions may help to find the right balance., (© 2022. The Author(s).)

Objective: To explore worry and decision-making processes used by faecal immunochemical test (FIT)-positive participants in the Dutch national screening programme for colorectal cancer., Methods: A mixed-methods study consisting of 22 semi-structured interviews in FIT-positive participants who underwent the recommended colonoscopy within 4-6 months after the FIT result, followed by a widespread questionnaire in a larger target population (N = 1495)., Results: In the interviews, we recognised two different decision-making processes. The first is an affective heuristic decision process where the decision to participate is made instantly and is paired with high-risk perception, worry and (severe) emotional turmoil. The second is a more time-consuming analytical decision process in which participants describe discussing options with others. In the questionnaire, high levels of cancer worry (CWS > 9) were reported by 34% of respondents. Decisional difficulties were reported by 15% of respondents, and 34% of respondents reported discussing the positive FIT result with their GP. Individuals with high levels of cancer worry contacted their GP less often than those with low levels., Conclusions: The Dutch two-step screening programme may result in high levels of cancer worry in a non-cancer population. More research is needed to monitor worry and its role in decision-making in cancer screening, as well as ways to facilitate decision-making for participants., (© 2021 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.)

Background: Patients with metastatic castration resistant prostate cancer (mCRPC) are at risk of symptomatic skeletal events (SSE). Bone health agents (BHA, ie bisphosphonates and denosumab) and new life-prolonging drugs (LPDs) can delay SSEs. The aim of this study is to investigate the use of BHAs in relation to SSEs in treated real-world mCRPC population., Patients and Methods: We included patients from the CAPRI registry who were treated with at least one LPD and diagnosed with bone metastases prior to the start of first LPD (LPD1). Outcomes were SSEs (external beam radiation therapy (EBRT) to the bone, orthopedic surgery, pathologic fracture or spinal cord compression) and SSE-free survival (SSE-FS) since LPD1., Results: One-thousand nine hundred and twenty-three patients were included with a median follow-up from LPD1 of 16.7 months. Fifty-two percent (n = 996) started BHA prior or within 4 weeks after the start of LPD1 (early BHA). In total, 41% experienced at least one SSE. SSE incidence rate was 0.29 per patient year for patients without BHA and 0.27 for patients with early BHA. Median SSE-FS from LPD1 was 12.9 months. SSE-FS was longer in patients who started BHA early versus patients without BHA (13.2 vs. 11.0 months, P = .001)., Conclusion: In a real-world population we observed an undertreatment with BHAs, although patients with early BHA use had lower incidence rates of SSEs and longer SSE-FS. This finding was irrespective of type of SSE and presence of risk factors. In addition to LPD treatment, timely initiation of BHAs is recommended in bone metastatic CRPC-patients with both pain and/or opioid use and prior SSE., (Copyright © 2021. Published by Elsevier Inc.)

Objective: The goal of this review was to assess the relationships among aims, designs, and outcomes of integrated inpatient medical and psychiatric care units (IMPUs) and gather the evidence base on the effectiveness of these units., Methods: Using online searches of Embase, Medline, Web of Science, PsycINFO, Scopus, CINAHL, Cochrane, and Google Scholar, the authors identified and reviewed literature describing the aims and outcomes of specific IMPU designs., Results: The search yielded 55 studies, in which the authors identified 39 IMPUs that focused on patients with mood, psychotic, somatic symptom, substance use, organic, and personality disorders and a broad array of medical diagnoses. Most units were psychiatric-medical units and had medium medical and psychiatric acuity capabilities. The studies reviewed provided little information on the cost-effectiveness of various IMPU designs. Although some comparative studies indicated reductions in hospital length of stay (LOS), these studies were generally of low quality and rarely reported other intended outcomes., Conclusions: IMPUs may help shorten LOS. IMPUs should focus care on patients with complex conditions and high acuity to maximize health system value. Implementing compulsory admission facilities; qualified psychiatric, medical, and nursing staff involvement; and cross-disciplinary training may improve IMPUs' capacity to treat high-acuity patients. Future research should relate IMPU designs to intended outcomes.

Background: Intensive end-of-life care (i.e., the overuse of treatments and hospital resources in the last months of life), is undesirable since it has a minimal clinical benefit with a substantial financial burden. The aim was to investigate the care in the last three months of life (end-of-life [EOL]) in castration-resistant prostate cancer (CRPC). Methods: Castration-resistant prostate cancer registry (CAPRI) is an investigator-initiated, observational multicenter cohort study in 20 hospitals retrospectively including patients diagnosed with CRPC between 2010 and 2016. High-intensity care was defined as the initiation of life-prolonging drugs (LPDs) in the last month, continuation of LPD in last 14 days, >1 admission, admission duration ≥14 days, and/or intensive care admission in last three months of life. Descriptive and binary logistic regression analyses were performed. Results: High-intensity care was experienced by 41% of 2429 patients in the EOL period. Multivariable analysis showed that age (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.97-0.99), performance status (OR 0.57, 95% CI 0.33-0.97), time from CRPC to EOL (OR 0.98, 95% CI 0.97-0.98), referral to a medical oncologist (OR 1.99, 95% CI 1.55-2.55), prior LPD treatment (>1 line OR 1.72, 95% CI 1.31-2.28), and opioid use (OR 1.45, 95% CI 1.08-1.95) were significantly associated with high-intensity care. Conclusions: High-intensity care in EOL is not easily justifiable due to high economic cost and little effect on life span, but further research is awaited to give insight in the effect on patients' and their caregivers' quality of life.

Background: Anxiety disorders are highly prevalent and cause substantial economic burden. Blended cognitive-behavioural therapy (bCBT), which integrates Internet-based CBT and face-to-face CBT (ftfCBT), is an attractive and potentially cost-saving treatment alternative to conventional CBT for patients with anxiety disorders in specialised mental health care. However, little is known about the effectiveness of bCBT in routine care. We examined the acceptability, effectiveness and cost-effectiveness of bCBT versus ftfCBT in outpatient specialised care to patients with panic disorder, social anxiety disorder and generalised anxiety disorder., Methods and Findings: Patients with anxiety disorders were randomised to bCBT (n = 52) or ftfCBT (n = 62). Acceptability of bCBT and ftfCBT were evaluated by assessing treatment preference, adherence, satisfaction and therapeutic alliance. Costs and effects were assessed at post-treatment and one-year follow-up. Primary outcome measure was the Beck Anxiety Inventory (BAI). Secondary outcomes were depressive symptoms, general psychopathology, work and social adjustment, quality of life and mastery. Incremental cost-effectiveness ratios (ICERs) were computed from societal and healthcare perspectives by calculating the incremental costs per incremental quality-adjusted life year (QALY). No significant differences between bCBT and ftfCBT were found on acceptability or effectiveness measures at post-treatment (Cohen's d between-group effect size on BAI = 0.15, 95% CI -0.30 to 0.60) or at one-year follow-up (d = -0.38, 95% CI -0.84 to 0.09). The modelled point estimates of societal costs (bCBT €10945, ftfCBT €10937) were higher and modelled point estimates of direct medical costs (bCBT €3748, ftfCBT €3841) were lower in bCBT. The acceptability curves showed that bCBT was expected to be a cost-effective intervention. Results should be carefully interpreted due to the small sample size., Conclusions: bCBT appears an acceptable, clinically effective and potentially cost-saving alternative option for treating patients with anxiety disorders. Trials with larger samples are needed to further investigate cost-effectiveness., Trial Registration: Netherlands Trial Register: NTR4912., Competing Interests: The authors have declared that no competing interests exist.

Currently, many policymakers try to encourage client involvement during the public service delivery process and make it a co-production. Clients are encouraged to act as active agents and embrace an integrated approach to address their problems to empower them. However, different studies have raised questions regarding to what extent these ambitions are appropriate for clients with vulnerabilities, such as clients with multiple problems. Aiming to further explore this issue, we studied the expectations of clients with multiple problems concerning the co-production of public services. We interviewed 46 clients with multiple problems at the start of their support trajectory. All 46 participants lived in five districts in Rotterdam, the Netherlands, and were recruited via community-based primary care teams. Our study indicates that co-production ambitions might not resonate with clients with multiple problems. The study shows that these clients' expectations are driven by their feelings of being overwhelmed and stressed out by their situation, feelings of being a victim of circumstances, bad experiences with public services in the past, their evaluation of what counts as a problem and the envisioned solutions. These clients expect public service providers to take over, fix their main problem(s) and not interfere with other aspects of their lives (not an integrated approach). Although participants seek a 'normal' life with, e.g., a house, work, partner, children, holidays, a pet, and no stress (a white picket fence life) as ideal, they do not feel that this is attainable for them. More insight into the rationale behind these expectations could help to bridge the gap between policymakers' ambitions and clients' expectations., (© 2021 The Authors. Health and Social Care in the Community published by John Wiley & Sons Ltd.)

Importance: The association between household income and perinatal health outcomes has been understudied. Examining disparities in perinatal mortality within strata of gestational age and before and after adjusting for birth weight centile can reveal how the income gradient is associated with gestational age, birth weight, and perinatal mortality., Objectives: To investigate the association between household income and perinatal mortality, separately by gestational age strata and time of death, and the potential role of birth weight centile in mediating this association., Design, Setting, and Participants: This cross-sectional study used individually linked data of all registered births in the Netherlands with household-level income tax records. Singletons born between January 1, 2004, and December 31, 2016, at 24 weeks to 41 weeks 6 days of gestation with complete information on birth outcomes and maternal characteristics were studied. Data analysis was performed from March 1, 2018, to August 30, 2021., Exposures: Household income rank (adjusted for household size)., Main Outcomes and Measures: Perinatal mortality, stillbirth (at ≥24 weeks of gestation), and early neonatal mortality (at ≤7 days after birth). Disparities were expressed as bottom-to-top ratios of projected mortality among newborns with the poorest 1% of households vs those with the richest 1% of households. Generalized additive models stratified by gestational age categories, adjusted for potential confounding by maternal age at birth, maternal ethnicity, parity, sex, and year of birth, were used. Birth weight centile was included as a potential mediator., Results: Among 2 036 431 singletons in this study (1 043 999 [51.3%] males; 1 496 579 [73.5%] with mother of Dutch ethnicity), 121 010 (5.9%) were born before 37 weeks of gestation, and 8720 (4.3 deaths per 1000) died during the perinatal period. Higher household income was positively associated with higher rates of perinatal survival, with an unadjusted bottom-to-top ratio of 2.18 (95% CI, 1.87-2.56). The bottom-to-top ratio decreased to 1.30 (95% CI, 1.22-1.39) after adjustment for potential confounding factors and inclusion of birth weight centile as a possible mediator. The fully adjusted ratios were lower for stillbirths (1.27; 95% CI, 1.20-1.36) than for early neonatal deaths (1.35; 95% CI, 1.14-1.66). Inequalities in perinatal mortality were found for newborns at greater than 26 weeks of gestation but not between 24 and 26 weeks of gestation (fully adjusted bottom-to-top ratio, 0.89; 95% CI, 0.77-1.04)., Conclusions and Relevance: The results of this large nationally representative cross-sectional study suggest that a large part of the increased risk of perinatal mortality among low-income women is mediated via a lower birth weight centile. The absence of disparities at very low gestational ages suggests that income-related risk factors for perinatal mortality are less prominent at very low gestational ages. Further research should aim to understand which factors associated with preterm birth and lower birth weight can reduce inequalities in perinatal mortality.

Background: In 2004 docetaxel was the first life-prolonging drug (LPD) registered for metastatic castration-resistant prostate cancer (mCRPC) patients. Between 2011 and 2014 new LPDs for mCRPC (cabazitaxel, abiraterone, enzalutamide, and radium-223) were introduced in the Netherlands. The objective of this study is to assess the impact of the introduction of new LPDs on treatment patterns and overall survival (OS) over time., Patients and Methods: CRPC patients diagnosed in the years 2010-2016 in the observational, retrospective CAPRI registry (20 hospitals) were included and followed up to 2018. Two subgroups were analyzed: treatment-naïve patients (subgroup 1, n = 3600) and post-docetaxel patients (subgroup 2, n = 1355)., Results: In both subgroups, the use of any LPD increased: from 57% (2010-2011) to 69% (2014-2015) in subgroup 1 and from 65% (2011-2012) to 79% (2015-2016) in subgroup 2. Chemotherapy as first mCRPC-treatment (i.e., docetaxel) and first post-docetaxel treatment (i.e., cabazitaxel or docetaxel rechallenge) decreased (46-29% and 20-9% in subgroup 1 and 2, respectively), while the use of androgen-receptor targeting treatments (ART) increased from 11% to 39% and 46% to 64% in subgroup 1 and 2, respectively. In subgroup 1, median OS (mOS) from diagnosis CRPC increased from 28.5 months to 31.0 months (p = 0.196). In subgroup 2, mOS from progression on docetaxel increased from 7.9 months to 12.5 months (p < 0.001). After multiple imputations of missing values, in multivariable cox-regression analysis with known prognostic parameters, the treatment period was independent significant for OS in subgroup 1 (2014-2015 vs. 2010-2011 with HR 0.749, p < 0.001) and subgroup 2 (2015-2016 vs. 2011-2012 with HR 0.811, p = 0.037)., Conclusion: Since 2010, a larger proportion of mCRPC patients was treated with LPDs, which was related to an increased mOS., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: To compare patient-reported outcome (PRO) domains between three arthritis phenotypes [undifferentiated arthritis (UA), autoantibody-negative RA (RA-) and autoantibody-positive RA (RA+)] at diagnosis, after 2 years and over time., Methods: All UA (n = 130), RA- (n = 176) and RA+ (n = 331) patients from the tREACH trial, a stratified single-blinded trial with a treat-to-target approach, were used. PRO comparisons between phenotypes at baseline and after 2 years were performed with analysis of variance, while a linear mixed model compared them over time. Effect sizes were weighted against the minimal clinically important differences (MCIDs) for each PRO., Results: RA- patients had a higher disease burden compared with RA+ and UA. At baseline and after 2 years, RA- patients had more functional impairment and a poorer Physical Component Summary (PCS) compared with the other phenotypes, while they only scored worse for general health and morning stiffness duration at baseline. The MCIDs were exceeded at baseline, except for functional ability between RA+ and UA, while after 2 years only the MCID of the PCS was exceeded by RA- compared with UA and RA. After 2 years the PROs of all phenotypes improved, but PROs measuring functioning were still worse compared with the general population, even when patients had low disease activity., Conclusion: RA- patients had the highest disease burden of all phenotypes. Although most patients have low disease activity after treatment, all clinical phenotypes still have a similar significant impact on patients' lives, which is mainly physical. Therefore it is important to assess and address PROs in daily practice because of persistent disease burden despite low disease activity., Trial Registration: ISRCTN26791028., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Cross resistance between androgen-receptor targeting therapies (ARTs) (abiraterone acetate plus prednisone [ABI+P] or enzalutamide [ENZ]) for treatment of metastatic castration-resistant prostate cancer (mCRPC) may affect responses to second ART (ART2)., Objective: To establish treatment duration and prostate-specific antigen (PSA) response of ART2 in real-world mCRPC patients treated with or without other life-prolonging drugs (LPDs; ie, docetaxel, cabazitaxel, or radium-223) between ART1 and ART2., Design, Setting, and Participants: Castration-resistant prostate cancer patients, diagnosed between 2010 and 2016 were retrospectively registered in Castration-resistant Prostate Cancer Registry (CAPRI). Patients treated with both ARTs were clustered into two subgroups: ART1>ART2 or ART1>LPD>ART2., Outcome Measurements and Statistical Analysis: Outcomes were ≥50% PSA response and treatment duration of ART2. Descriptive statistics and binary logistic regression after multiple imputations were performed., Results and Limitations: A total of 273 patients were included with a median follow-up of 8.4 mo from ART2. Patients with ART1>ART2 were older and had favourable prognostic characteristics at ART2 baseline compared with patients with ART1>LPD>ART2. No differences between ART1>ART2 and ART1>LPD>ART2 were found in PSA response and treatment duration. Multivariate analysis suggested that PSA response of ART2 was less likely in patients with visceral metastases (odds ratio [OR] 0.143, p=0.04) and more likely in patients with a relatively longer duration of androgen-deprivation treatment (OR 1.028, p=0.01) and with ABI + P before ENZ (OR 3.192, p=0.02). A major limitation of this study was missing data, a common problem in retrospective observational research., Conclusions: The effect of ART2 seems to be low, with a low PSA response rate and a short treatment duration irrespective of interposed chemotherapy or radium-223, especially in patients with short time on castration, visceral disease, and ENZ before ABI+P., Patient Summary: We observed no differences in outcomes of patients treated with sequential abiraterone acetate plus prednisone (ABI+P) and enzalutamide (ENZ) with or without interposed chemotherapy or radium-223. In general, outcomes were lower than those in randomised trials, questioning the additional effect of second treatment with ABI+P or ENZ in daily practice., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

In this article, the author comments on the research publication 'Estimating the lifetime risk of dementia using nationwide individually linked cause-of-death and health register data'. By combining 7 Dutch registries on causes of death and the use of health care, the lifetime risk of dementia was calculated at 29.4% (women) and 18.3% (men). In 2017, 62% of the deaths either by dementia (15,950 persons) or with dementia (19,560 persons) occurred in nursing homes. Discussing the difficulties of adequate and linkable registrations, the author concludes that the lifetime risk of dementia is probably underestimated with an additional 3 to 5 percentage points. The author also suggests improvements for the registration of dementia (for instance by one integrated client record during the whole 'dementia journey') and for daily practice in dementia care, like better diagnostics, focus on quality of life, psycho-social interventions, advanced care planning, and comprehensive prevention programs.

Background: Evidence concerning third-line life-prolonging drugs (LPDs) in the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients is incomplete., Objective: To evaluate third-line LPD outcomes in a real-world cohort of mCRPC patients, identify variables associated with overall survival (OS), and establish a prognostic model., Design, Setting, and Participants: Patients with mCRPC who were progressive on second-line LPD before July 1, 2017 were retrospectively identified from the Dutch Castration-resistant Prostate Cancer Registry (CAPRI) and followed until December 31, 2017., Outcome Measurements and Statistical Analysis: Association of potential risk factors with OS was tested by Cox proportional hazard models after multiple imputation of missing baseline characteristics. A predictive score was computed from the regression coefficient and used to classify patients into risk groups., Results and Limitations: Of 1011 mCRPC patients progressive on second-line LPD, 602 (60%) received third-line LPD. Patients receiving third-line LPD had a more favorable prognostic profile at baseline and longer median OS than patients with best supportive care (10.4 vs 2.4 mo, p < 0.001). Eastern Cooperative Oncology Group performance status 1 and ≥2 (hazard ratio [HR] 1.51, p < 0.007 and HR 3.08, p < 0.001, respectively), opioid use (HR 1.55, p = 0.019), visceral metastases (HR 2.09, p < 0.001), hemoglobin <7 mmol/l (HR 1.44, p < 0.002), prostate-specific antigen ≥130 μg/l (HR 1.48, p = 0.001), alkaline phosphatase ≥170 U/l (HR 1.52, p < 0.001), and lactate dehydrogenase ≥250 U/l (HR 1.44; p = 0.015) were associated with shorter survival. Harrell's C-index was 0.74. The median OS values for low-, low-intermediate-, high-intermediate-, and high-risk groups were 14, 7.7, 4.7, and 1.8 mo, respectively. Limitations include the retrospective design., Conclusions: We developed a prognostic model and identified a subgroup of patients in whom third-line LPD treatment has no meaningful benefit. Our results need to be confirmed by prospective clinical trials., Patient Summary: We reported outcomes from third-line life-prolonging drugs in metastatic prostate cancer patients and developed a prognostic model that could be used to guide treatment decisions., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: While the uptake of value-based health care (VBHC) is remarkable, uncertainty prevails regarding the most important actions and practices in establishing a value-based healthcare system. In this paper, we generate expert consensus on the most important aspects of VBHC., Design: The Delphi technique was used to reach consensus on the most important practices in moving towards a value-based healthcare system., Setting and Participants: A Dutch expert panel consisting of nine members participated in a two-round survey., Primary and Secondary Outcome Measures: We developed 39 initial items based on the pioneering literature on VBHC and recent health policies in the Netherlands. Experts rated the importance of each item on a 4-point Likert scale. Experts could change items or add new ones as they saw fit. We retained items that were rated (very) important by ≥80% of the panel., Results: After two survey rounds, 32 items (72%) were included through expert consensus. Experts unanimously agree on the importance of shared decision-making, with this item uniquely obtaining the maximum score. Experts also reached consensus on the importance of outcome measurements, a focus on medical conditions, and full cycles of care. No consensus was reached on the importance of benchmarking., Conclusion: This paper provides new insight into the most important actions and practices for establishing a value-based healthcare system in the Netherlands. Interestingly, several of our findings contrast with the pioneering literature on VBHC. This raises the question whether VBHC's widespread international uptake indicates its actual implementation, or rather that the original concept primarily serves as an inspiring idea., Competing Interests: Competing interests: The fourth author, DD, is professor at the Erasmus University Rotterdam while also employed at Zorginstituut Nederland (National Health Care Institute), which partially funds this research., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)