A novel method to perform morphological measurements on three-dimensional (3D) models of the calcaneus based on computed tomography (CT)-imaging.

Background: While current preoperative and postoperative assessment of the fractured and surgically reconstructed calcaneus relies on computed tomography (CT)-imaging, there are no established methods to quantify calcaneus morphology on CT-images. This study aims to develop a semi-automated method for morphological measurements of the calcaneus on three-dimensional (3D) models derived from CT-imaging. Methods: Using CT data, 3D models were created from healthy, fractured, and surgically reconstructed calcanei. Böhler's angle (BA) and Critical angle of Gissane (CAG) were measured on conventional lateral radiographs and corresponding 3D CT reconstructions using a novel point-based method with semi-automatic landmark placement by three observers. Intraobserver and interobserver reliability scores were calculated using intra-class correlation coefficient (ICC). In addition, consensus among observers was calculated for a maximal allowable discrepancy of 5 and 10 degrees for both methods. Results: Imaging data from 119 feet were obtained (40 healthy, 39 fractured, 40 reconstructed). Semi-automated measurements on 3D models of BA and CAG showed excellent reliability (ICC: 0.87-1.00). The manual measurements on conventional radiographs had a poor-to-excellent reliability (ICC: 0.22-0.96). In addition, the percentage of consensus among observers was much higher for the 3D method when compared to conventional two-dimensional (2D) measurements. Conclusions: The proposed method enables reliable and reproducible quantification of calcaneus morphology in 3D models of healthy, fractured and reconstructed calcanei.

The effect of immunosuppressive therapies on the endothelial host response in critically ill COVID-19 patients.

While several effective therapies for critically ill patients with COVID-19 have been identified in large, well-conducted trials, the mechanisms underlying these therapies have not been investigated in depth. Our aim is to investigate the association between various immunosuppressive therapies (corticosteroids, tocilizumab and anakinra) and the change in endothelial host response over time in critically ill COVID-19 patients. We conducted a pre-specified multicenter post-hoc analysis in a Dutch cohort of COVID-19 patients admitted to the ICU between March 2020 and September 2021 due to hypoxemic respiratory failure. A panel of 18 immune response biomarkers in the complement, coagulation and endothelial function domains were measured using ELISA or Luminex. Biomarkers were measured on day 0-1, day 2-4 and day 6-8 after start of COVID-19 treatment. Patients were categorized into four treatment groups: no immunomodulatory treatment, corticosteroids, anakinra plus corticosteroids, or tocilizumab plus corticosteroids. The association between treatment group and the change in concentrations of biomarkers was estimated with linear mixed-effects models, using no immunomodulatory treatment as reference group. 109 patients with a median age of 62 years [IQR 54-70] of whom 72% (n = 78) was male, were included in this analysis. Both anakinra plus corticosteroids (n = 22) and tocilizumab plus corticosteroids (n = 38) were associated with an increase in angiopoietin-1 compared to no immune modulator (n = 23) (beta of 0.033 [0.002-0.064] and 0.041 [0.013-0.070] per day, respectively). These treatments, as well as corticosteroids alone (n = 26), were further associated with a decrease in the ratio of angiopoietin-2/angiopoietin-1 (beta of 0.071 [0.034-0.107], 0.060 [0.030-0.091] and 0.043 [0.001-0.085] per day, respectively). Anakinra plus corticosteroids and tocilizumab plus corticosteroids were associated with a decrease in concentrations of complement complex 5b-9 compared to no immunomodulatory treatment (0.038 [0.006-0.071] and 0.023 [0.000-0.047], respectively). Currently established treatments for critically ill COVID-19 patients are associated with a change in biomarkers of the angiopoietin and complement pathways, possibly indicating a role for stability of the endothelium. These results increase the understanding of the mechanisms of interventions and are possibly useful for stratification of patients with other inflammatory conditions which may potentially benefit from these treatments.

Seasonal variation of anti-PD-1 outcome in melanoma-Results from a Dutch patient cohort.

Despite the improved survival rates of patients with advanced stage melanoma since the introduction of ICIs, many patients do not have (long-term) benefit from these treatments. There is evidence that the exposome, an accumulation of host-extrinsic factors including environmental influences, could impact ICI response. Recently, a survival benefit was observed in patients with BRAF wild-type melanoma living in Denmark who initiated immunotherapy in summer as compared to winter. As the Netherlands lies in close geographical proximity to Denmark and has comparable seasonal differences, a Dutch validation cohort was established using data from our nationwide melanoma registry. In this study, we did not observe a similar seasonal difference in overall survival and are therefore unable to confirm the Danish findings. Validation of either the Dutch or Danish findings in (combined) patient cohorts from other countries would be necessary to determine whether this host-extrinsic factor influences the response to ICI-treatment.

The impact of geriatric characteristics and comorbidities on distant metastases and other cause mortality in older women with non-metastatic breast cancer treated with primary endocrine therapy.

INTRODUCTION: In recent years, primary surgical treatment of older women with non-metastatic breast cancer has decreased in favor of primary endocrine therapy (PET). PET can be considered in women with a remaining life expectancy of less than five years. The aim of this study was to (1) assess the risk of distant metastases and other cause mortality over ten years in women aged 65 and older with stage I-III breast cancer treated with PET, (2) whether this was associated with geriatric characteristics and comorbidities and to (3) describe the reasons on which the choice for PET was made. METHODS: Women were included from the retrospective FOCUS cohort, which comprises all incident women diagnosed with breast cancer aged 65 or older between January 1997 and December 2004 in the Comprehensive Cancer Center Region West in the Netherlands. We selected women (N = 257) with stage I-III breast cancer and treated with PET from this cohort. Patient characteristics (including comorbidity, polypharmacy, walking, cognitive and sensory impairment), treatment and tumor characteristics were retrospectively extracted from charts. Outcomes were distant metastasis and other cause mortality. Cumulative incidences were calculated using the Cumulative Incidence for Competing Risks method (CICR); and subdistribution hazard ratios (SHR) were tested between groups based on age, geriatric characteristics and comorbidity with the Fine and Gray model. RESULTS: Women treated with PET were on average 84 years old and 41% had one or more geriatric characteristics. Other cause mortality exceeded the cumulative incidence of distant metastasis over ten years (83 versus 5.6%). The risk of dying from another cause further increased in women with geriatric characteristics (SHR 2.06, p < 0.001) or two or more comorbidities (SHR 1.72, p < 0.001). Often the reason for omitting surgery was not recorded (52.9%), but if recorded surgery was omitted mainly at the patient's request (18.7%). DISCUSSION: This study shows that the cumulative incidence of distant metastasis is much lower than other cause mortality in older women with breast cancer treated with PET, especially in the presence of geriatric characteristics or comorbidities. This confirms the importance of assessment of geriatric characteristics to aid counseling of older women.

Pilot implementation of MiLES: a web-based intervention targeted at managers with the aim of enhancing the successful return to work of employees with cancer.

BACKGROUND: MiLES is a web-based intervention targeted at managers with the aim of enhancing the successful return to work (RTW) of employees with cancer. The purpose of this study was to identify barriers to and facilitators of implementing MiLES in organizations, from a manager's perspective. MATERIAL AND METHODS: MiLES was implemented as a pilot in four organizations for six weeks. Sixteen managers were included, of which fourteen were interviewed regarding their perceived barriers to and facilitators of implementation of MiLES in their organization. Interviews were recorded, transcribed verbatim and analyzed with content analysis. RESULTS: The managers experienced barriers to and facilitators of implementation related to: (1) implementation responsibilities, (2) the intervention's content, and (3) organizational characteristics. Regarding implementation responsibilities, management board approval and an organizational infrastructure with distinct described implementation responsibilities were perceived as facilitators. Regarding the intervention's content, its accessibility, user-friendliness and completeness were perceived as facilitators. If the content did not meet the manager's specific needs, this was perceived as a barrier. Regarding organizational characteristics, several intangible (e.g., added value of MiLES within different organizations) and tangible (e.g., integration into absenteeism registration) organizational characteristics were perceived as facilitators. The absence of a quiet place to use MiLES was perceived as barrier. CONCLUSION: Implementation of MiLES in organizations may benefit from an infrastructure within the organization that defines responsibilities regarding intervention delivery to managers of employees with cancer. Such an infrastructure should be aligned to existing organizational structures. As per interviewed managers, MiLES has added value in diverse organizations.

Adults born prematurely prefer a periviability guideline that considers multiple prognostic factors beyond gestational age.

AIM: The aim of the study was to explore the perspectives of adults born prematurely on guidelines for management at extreme premature birth and personalisation at the limit of viability. METHODS: We conducted four 2-h online focus group interviews in the Netherlands. RESULTS: Twenty-three participants born prematurely were included in this study, ranging in age from 19 to 56 years and representing a variety of health outcomes. Participants shared their perspectives on different types of guidelines for managing extremely premature birth. They agreed that a guideline was necessary to prevent arbitrary treatment decisions and to avoid physician bias. All participants favoured a guideline that is based upon multiple prognostic factors beyond gestational age. They emphasised the importance of discretion, regardless of the type of guideline used. Discussions centred mainly on the heterogeneity of value judgements about outcomes after extreme premature birth. Participants defined personalisation as 'not just looking at numbers and statistics'. They associated personalisation mainly with information provision and decision-making. Participants stressed the importance of involving families in decision-making and taking their care needs seriously. CONCLUSION: Adults born prematurely prefer a periviability guideline that considers multiple prognostic factors and allows for discretion.

SARS-CoV-2 incidence in secondary schools; the role of national and school-initiated COVID-19 measures.

INTRODUCTION: Our aim was to gain insight into the effect of COVID-19 measures on SARS-CoV-2 incidence in secondary schools and the association with classroom CO2 concentration and airborne contamination. METHODS: Between October 2020-June 2021, 18 schools weekly reported SARS-CoV-2 incidence and completed surveys on school-initiated COVID-19 measures (e.g. improving hygiene or minimizing contacts). CO2 was measured in occupied classrooms twice, and SARS-CoV-2 air contamination longitudinally using electrostatic dust collectors (EDC) and analyzed using RT-qPCR. National COVID-19 policy measures varied during pre-lockdown, lockdown and post-lockdown periods. During the entire study, schools were recommended to improve ventilation. SARS-CoV-2 incidence rate ratios (IRR) were estimated by Generalized Estimating Equation (GEE) models. RESULTS: During 18 weeks follow-up (range: 10-22) SARS-CoV-2 school-incidence decreased during national lockdown (adjusted IRR: 0.41, 95%CI: 0.21-0.80) and post-lockdown (IRR: 0.60, 0.39-0.93) compared to pre-lockdown. School-initiated COVID-19 measures had no additional effect. Pre-lockdown, IRRs per 10% increase in time CO2 exceeded 400, 550 and 800 ppm above outdoor level respectively, were 1.08 (1.00-1.16), 1.10 (1.02-1.19), and 1.08 (0.95-1.22). Post-lockdown, CO2-concentrations were considerably lower and not associated with SARS-CoV-2 incidence. No SARS-CoV-2 RNA was detected in any of the EDC samples. CONCLUSION: During a period with low SARS-CoV-2 population immunity and increased attention to ventilation, with CO2 levels most of the time below acceptable thresholds, only the national policy during and post-lockdown of reduced class-occupancy, stringent quarantine, and contact testing reduced SARS-CoV-2 incidence in Dutch secondary schools. Widespread SARS-CoV-2 air contamination could not be demonstrated in schools under the prevailing conditions during the study.

Improving person-centered occupational health care for workers with chronic health conditions: a feasibility study.

BACKGROUND: Person-centered care is needed to effectively support workers with chronic health conditions. Person-centered care aims to provide care tailored to an individual person's preferences, needs and values. To achieve this, a more active, supportive, and coaching role of occupational and insurance physicians is required. In previous research, two training programs and an e-learning training with accompanying tools that can be used in the context of person-centered occupational health care were developed to contribute to this changing role. The aim was to investigate the feasibility of the developed training programs and e-learning training to enhance the active, supportive, and coaching role of occupational and insurance physicians needed for person-centered occupational health care. Information about this is important to facilitate implementation of the tools and training into educational structures and occupational health practice. METHODS: A qualitative study was conducted, with N = 29 semi-structured interviews with occupational physicians, insurance physicians, and representatives from occupational educational institutes. The aim was to elicit feasibility factors concerning the implementation, practicality and integration with regard to embedding the training programs and e-learning training in educational structures and the use of the tools and acquired knowledge and skills in occupational health care practice after following the trainings and e-learning training. Deductive analysis was conducted based on pre-selected focus areas for a feasibility study. RESULTS: From an educational perspective, adapting the face-to-face training programs to online versions, good coordination with educational managers and train-the-trainer approaches were mentioned as facilitating factors for successful implementation. Participants underlined the importance of aligning the occupational physicians' and insurance physicians' competences with the educational content and attention for the costs concerning the facilitation of the trainings and e-learning training. From the professional perspective, factors concerning the content of the training and e-learning training, the use of actual cases from practice, as well as follow-up training sessions were reported. Professionals expressed good fit of the acquired skills into their consultation hour in practice. CONCLUSION: The developed training programs, e-learning training and accompanying tools were perceived feasible in terms of implementation, practicality, and integration by occupational physicians, insurance physicians and educational institutes.

Interventions for work participation of unemployed or work-disabled cancer survivors: a systematic review.

Background: Supporting unemployed or work-disabled cancer survivors in their work participation can have extensive individual and societal benefits. We aimed to identify and summarise interventions for work participation of unemployed or work-disabled cancer survivors.Methods: Five databases (Medline, Embase, PsycINFO, CINAHL and Cochrane Library) were systematically searched for quantitative studies on interventions aimed at enhancing work participation of unemployed or work-disabled cancer survivors. Work participation refers to participation in the workforce, fulfilling one's work role. Manual and automatic screening (with ASReview software) were performed on titles and abstracts, followed by manual full-text screening. Data were extracted regarding study, patient and intervention characteristics, and work participation outcomes. Risk of bias (RoB) was assessed using the Cochrane RoB2 and QUIPS tools.Results: We identified 10,771 articles, of which we included two randomised controlled trials (RCTs), of which one feasibility RCT, and three cohort studies. In total, 1862 cancer survivors were included, with predominantly breast cancer. Work participation was mainly measured as time to return to work (RTW) and RTW rate. Interventions included components of coaching (e.g., psychological or rehabilitation), training (e.g., building confidence and managing fatigue) and self-management. Two RCTs with unclear RoB did not show an effect of multicomponent interventions compared to care as usual. One cohort study found a significant effect of a psycho-educational intervention on RTW rates, with moderate RoB. The other two cohort studies, with moderate RoB, reported significant associations between components including job search and placement assistance, and work participation.Discussion: Only few interventions aimed at enhancing work participation of unemployed or work-disabled cancer survivors, have been evaluated. In two cohort studies, promising components for future multicomponent interventions were identified. However, findings suggest that more evidence is necessary on such multicomponent interventions, in which elements explicitly directed at work and including the workplace should be included.

Single-arm trials supporting the approval of anticancer medicinal products in the European Union: contextualization of trial results and observed clinical benefit.

BACKGROUND: Single-arm trials (SATs) can sometimes be used to support marketing authorization of anticancer medicinal products in the European Union. The level and durability of antitumor activity of the product as well as context are important aspects to determine the relevance of trial results. The aim of this study is to provide details on the contextualization of trial results and to evaluate the magnitude of benefit of medicinal products approved based on SATs. MATERIALS AND METHODS: We focused on anticancer medicinal products for solid tumors approved on the basis of SAT results (2012-2021). Data were retrieved from European public assessment reports and/or published literature. The benefit of these medicinal products was evaluated via the European Society for Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS). RESULTS: Eighteen medicinal products were approved based on 21 SATs-few medicinal products were supported by >1 SAT. For the majority of clinical trials, a clinically relevant treatment effect was (pre)specified (71.4%) and most often an accompanying sample size calculation was provided. For 10 studies, each testing a different medicinal product, a justification for the threshold for a clinically relevant treatment effect could be identified. At least 12 out of 18 applications included information to facilitate the contextualization of trial results, including six supportive studies. Of the pivotal SATs analyzed (n = 21), three were assigned an ESMO-MCBS score of 4, which corresponds to 'substantial' benefit. CONCLUSIONS: The clinical relevance of the treatment effects shown by medicinal products for solid tumors tested in SATs is dependent on the effect size and context. To better facilitate regulatory decision making, prespecifying and motivating a clinically relevant effect and aligning the sample size to that effect is important. External controls may facilitate in the contextualization process, but the associated limitations must be addressed.

A workers' health surveillance online training programme for occupational physicians.

BACKGROUND: To support occupational physicians (OPs) in the implementation of workers' health surveillance (WHS), a training programme was developed. AIMS: (i) To evaluate the effects of a WHS training programme for OPs on knowledge, self-efficacy and skills to implement WHS. (ii) To evaluate to what extent a WHS training programme is acceptable and feasible for implementation in practice. METHODS: A single-blinded randomized controlled trial with waiting-list control group was used. The WHS training programme consisted of an e-learning and a 4.5-h online training session. OPs completed a knowledge test (0-8), self-efficacy questionnaires on knowledge and skills (6-60), and vignette assignments (0-16) to measure skills. OPs completed the questionnaires, either before and after the WHS training programme (intervention group), or before the training programme (control group) while receiving the training programme after the waiting period. All OPs completed questionnaires about the training's acceptability, and feasibility for implementation in practice. ANCOVA and Poisson regression analyses were conducted. RESULTS: The self-efficacy score (M = 44.1 versus M = 37.2) (P < 0.001) and skills score (M = 9.6 versus M = 8.3) (P < 0.05) of OPs in the training group (N = 16) were higher than the control group (N = 23). No effect was found on knowledge. Evaluation of acceptability and feasibility showed that 21 (58%) OPs were very satisfied with the training part on initiating WHS, and 29 (85%) would recommend the WHS training programme to colleagues. CONCLUSIONS: This WHS training programme has a positive effect on self-efficacy and skills of OPs to implement WHS, and may be acceptable and feasible to implement in practice.

Individual patient data to allow a more elaborated comparison of trial results with real-world outcomes from first-line immunotherapy in NSCLC.

BACKGROUND: Many studies have compared real-world clinical outcomes of immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC) with reported outcomes data from pivotal trials. However, any differences observed could be only limitedly explored further for causation because of the unavailability of individual patient data (IPD) from trial participants. The present study aims to explore the additional benefit of comparison with IPD. METHODS: This study compares progression free survival (PFS) and overall survival (OS) of metastatic NSCLC patients treated with second line nivolumab in real-world clinical practice (n = 141) with IPD from participants in the Checkmate-057 clinical trial (n = 292). Univariate and multivariate Cox proportional hazards models were used to construct HRs for real-world practice versus clinical trial. RESULTS: Real-world patients were older (64 vs. 61 years), had more often ECOG PS ≥ 2 (5 vs. 0%) and were less often treated with subsequent anti-cancer treatment (28.4 vs. 42.5%) compared to trial patients. The median PFS in real-world patients was longer (3.84 (95%CI: 3.19-5.49) vs 2.30 (2.20-3.50) months) and the OS shorter than in trial participants (8.25 (6.93-13.2) vs. 12.2 (9.90-15.1) months). Adjustment with available patient characteristics, led to a shift in the hazard ratio (HR) for OS, but not for PFS (HRs from 1.13 (0.88-1.44) to 1.07 (0.83-1.38), and from 0.82 (0.66-1.03) to 0.79 (0.63-1.00), respectively). CONCLUSIONS: This study is an example how IPD from both real-world and trial patients can be applied to search for factors that could explain an efficacy-effectiveness gap. Making IPD from clinical trials available to the international research community allows this.

Identification of actions to be taken by managers to facilitate the return to work of cancer survivors: Consensus between managers and cancer survivors.

BACKGROUND: Managers are considered to be main stakeholders in the return to work (RTW) of cancer survivors. However, the perspectives of cancer survivors and managers differ on what managerial actions should be taken during the RTW of cancer survivors. This difference might put effective collaboration and successful RTW at risk. Therefore, this study aims to reach consensus among managers and cancer survivors on the managerial actions to be taken during the four different RTW phases of cancer survivors (i.e., Disclosure, Treatment, RTW plan, Actual RTW). METHODS: The Technique for Research of Information by Animation of a Group of Experts (TRIAGE) was implemented with managers and cancer survivors (hereafter referred to as "experts"). An initial list of 24 actions was derived from a previous study. Firstly, for each action, fifteen experts were asked to indicate individually how important this action is per RTW phase (Likert scale from 1 - "Not important at all" to 6 - "Very important"). Consensus was reached when ≥ 80% (i.e., ≥ twelve experts) of the experts rated that action ≥5. Secondly, for each phase of the RTW process, the 15 actions with the highest percentage were discussed with eight experts during the collective consultation, except for the actions that already reached consensus. After discussion, the experts voted whether each action was important ("yes" / "no") and consensus required ≥ 87.5% (i.e., ≥ seven experts) of the experts to consider an action as important. RESULTS: Twenty-five managerial actions were finally retained for at least one of the RTW phases, e.g., Disclosure: "respect privacy" and "radiate a positive attitude", Treatment: "show appreciation" and "allow sufficient sick leave", RTW Plan: "tailor" and "communicate", and Actual RTW: "support practically" and "balance interest". CONCLUSION: Cancer survivors and managers reached consensus on the importance of 25 managerial actions, distributed into each phase of the RTW process. These actions should be considered an interplay of managerial actions by different stakeholders on the part of the employer (e.g., direct supervisor, HR-manager), and should be a responsibility that is shared by these stakeholders. The collective implementation of these actions within the company will help cancer survivors feel fully supported.

Under careful construction: combining findings, arguments, and values into robust health care coverage decisions.

BACKGROUND: Health care coverage decisions deal with health care technology provision or reimbursement at a national level. The coverage decision report, i.e., the publicly available document giving reasons for the decision, may contain various elements: quantitative calculations like cost and clinical effectiveness analyses and formalised and non-formalised qualitative considerations. We know little about the process of combining these heterogeneous elements into robust decisions. METHODS: This study describes a model for combining different elements in coverage decisions. We build on two qualitative cases of coverage appraisals at the Dutch National Health Care Institute, for which we analysed observations at committee meetings (n = 2, with field notes taken) and the corresponding audio files (n = 3), interviews with appraisal committee members (n = 10 in seven interviews) and with Institute employees (n = 5 in three interviews), and relevant documents (n = 4). RESULTS: We conceptualise decisions as combinations of elements, specifically (quantitative) findings and (qualitative) arguments and values. Our model contains three steps: 1) identifying elements; 2) designing the combinations of elements, which entails articulating links, broadening the scope of designed combinations, and black-boxing links; and 3) testing these combinations and choosing one as the final decision. CONCLUSIONS: Based on the proposed model, we suggest actively identifying a wider variety of elements and stepping up in terms of engaging patients and the public, including facilitating appeals. Future research could explore how different actors perceive the robustness of decisions and how this relates to their perceived legitimacy.

Workers' health surveillance targeting mental health: evaluation of a training.

BACKGROUND: Mental health complaints occur frequently among healthcare workers. A workers' health surveillance mental health module (WHS-MH) was found to be effective in improving work functioning of nurses, although not implemented regularly. Therefore, training for occupational physicians and nurses to facilitate the implementation of WHS-MH was developed and evaluated. AIMS: This study was aimed to evaluate the effect of training on knowledge, self-efficacy and motivation to implement WHS-MH, and to evaluate participants' satisfaction with the training. METHODS: Three-hour training was held among 49 occupational physicians and nurses in the Netherlands. Effect on knowledge, self-efficacy and motivation was assessed using knowledge tests and questionnaires before and immediately after the training. Satisfaction with the training was measured using questionnaires after the training. RESULTS: A mean knowledge test score of 5.3 (SD = 1.6) was found before training, which did not significantly increase after training (M = 5.6, SD = 1.8). In total, 43% agreed or strongly agreed to have sufficient skills to implement WHS-MH, which significantly increased to 78% after the training. Furthermore, 87% agreed or strongly agreed to be motivated to initiate WHS, which significantly increased to 94% after the training. The majority of participants were satisfied with the training. CONCLUSIONS: Training may enhance the implementation of the WHS-MH through increasing self-efficacy and motivation. However, no effect on level of knowledge to implement WHS-MH was found.

Atrial fibrillation: trends in prevalence and antithrombotic prescriptions in the community.

INTRODUCTION: In the past decade, the atrial fibrillation (AF) landscape, including the treatment modalities, has drastically changed. This raises the question how AF prevalence and choices in antithrombotic therapy prescription have developed in the community over time. METHODS: Routine care data from the Julius General Practitioners' Network (JGPN) were used to calculate the yearly prevalence of AF and to quantify the percentage of all patients who were prescribed a platelet inhibitor, vitamin K antagonist (VKA), non-VKA oral anticoagulant (NOAC) or no antithrombotic medication. To explore whether certain patient characteristics are associated with selective prescription of oral anticoagulants (OAC), we applied logistic regression analyses. RESULTS: From 2008 through 2017, the JGPN database included 7459 unique AF patients. During this period, the prevalence of AF increased from 0.4% to 1.4%. The percentage of patients prescribed a VKA declined from 47% to 41%, whereas the percentage of patients prescribed a NOAC rose from 0% to 20%. In patients with new-onset AF, older age, heart failure, diabetes mellitus, vascular disease and dementia were independently associated with a higher likelihood of VKA rather than NOAC prescription. In 2017, 25% of all patients with AF and a CHA2DS2-VASc score ≥ 2 were not prescribed OAC therapy (i.e. 8% with platelet inhibitor monotherapy and 17% without any antithrombotic therapy). CONCLUSION: Between 2008 and 2017, AF prevalence in the community more than tripled. Prescription patterns showed possible 'channelling' of VKAs over NOACs in frailer, elderly patients, whereas still about one in every four AF patients with a CHA2DS2-VASc score ≥ 2 was not prescribed any prophylactic OAC therapy.

Dignity-conserving palliative care in a diverse population: A qualitative study of physicians' perspective.

BACKGROUND: Preserving personal dignity is an important aim of palliative care. Little is known about how physicians perceive and preserve dignity of patients from non-western migration backgrounds. Insight in this is important given the increased demand for culturally sensitive palliative care. AIM: To gain insight in how Dutch physicians perceive and preserve dignity in the last phase of life for patients from non-western migration backgrounds. DESIGN: Qualitative thematic analysis of semi-structured interviews. PARTICIPANTS: Fifteen physicians experienced in palliative care. RESULTS: Physicians experienced dilemmas in preserving dignity of non-western patients in three situations: (a) relief of suffering in the terminal phase, (b) termination of interventions and treatment, and (c) disclosure of diagnosis. Physicians wanted to grant the needs of patients in the last phase of their lives, which was central to physicians' view on dignity, but dilemmas arose when this conflicted with physicians' other personal and professional values. To make the dilemmas manageable, physicians assessed whether needs of patients were authentic, but due to linguistic, cultural, and communication barriers, this was difficult with non-western patients. To find a way out of the dilemmas, physicians had three strategies: accept and go along with patient's wishes, convince or overrule the patient or family, or seek solutions that were acceptable for all. CONCLUSIONS: Physicians encounter dilemmas providing palliative care for people from non-western backgrounds. Future physicians can be trained in connective strategies and seeking middle grounds to optimally preserve patients' dignity while being in concordance with their personal and professional values.

Palbociclib dose reductions and the effect on clinical outcomes in patients with advanced breast cancer.

BACKGROUND: This study aimed to provide insights into the real-world use of palbociclib, dose reductions, and drug effectiveness in (older) patients with advanced breast cancer (BC). PATIENTS AND METHODS: Patients with advanced BC treated with palbociclib from 2017 to 2020 were included. The Kaplan-Meier method was used to calculate time to next treatment (TTNT) and overall survival (OS) for patients with or without dose reductions. These clinical outcomes were also compared in subgroup analyses for older patients (≥70 years) and younger patients (<70 years) and for patients discontinuing palbociclib early (<4 administrations). RESULTS: A total of 598 patients with advanced BC were included, with a median age of 64 years. Palbociclib dose reductions occurred in 33% of all patients. Early discontinuation of palbociclib without dose reductions occurred in 23% of the patients. Patients who required a palbociclib dose reduction were older (median age 67 years vs. 63 years). Patients with dose reductions had a significantly higher TTNT of 16.9 vs. 11.4 months (p < 0.001) and median OS of 29.7 vs. 21.9 months (p = 0.003) compared to patients without dose reductions. The TTNT in older patients was significantly longer (16.9 vs. 11.6 months, p = 0.013) than younger patients, but OS was similar (20.7 vs. 26.7 months, p = 0.051). CONCLUSION: Palbociclib dose reductions occurred in real-world practice similarly to the PALOMA-3 trial. Patients with dose reductions had no poorer outcomes compared to patients not requiring a dose reduction. Older patients treated with palbociclib had more frequent dose reductions, but this did not appear to affect OS.