Exploring the Cost Effectiveness of a Whole-Genome Sequencing-Based Biomarker for Treatment Selection in Patients with Advanced Lung Cancer Ineligible for Targeted Therapy.

OBJECTIVE: We aimed to perform an early cost-effectiveness analysis of using a whole-genome sequencing-based tumor mutation burden (WGS-TMB), instead of programmed death-ligand 1 (PD-L1), for immunotherapy treatment selection in patients with non-squamous advanced/metastatic non-small cell lung cancer ineligible for targeted therapy, from a Dutch healthcare perspective. METHODS: A decision-model simulating individual patients with metastatic non-small cell lung cancer was used to evaluate diagnostic strategies to select first-line immunotherapy only or the immunotherapy plus chemotherapy combination. Treatment was selected using PD-L1 [A, current practice], WGS-TMB [B], and both PD-L1 and WGS-TMB [C]. Strategies D, E, and F take into account a patient's disease burden, in addition to PD-L1, WGS-TMB, and both PD-L1 and WGS-TMB, respectively. Disease burden was defined as a fast-growing tumor, a high number of metastases, and/or weight loss. A threshold of 10 mutations per mega-base was used to classify patients into TMB-high and TMB-low groups. Outcomes were discounted quality-adjusted life-years (QALYs) and healthcare costs measured from the start of first-line treatment to death. Healthcare costs includes drug acquisition, follow-up costs, and molecular diagnostic tests (i.e., standard diagnostic techniques and/or WGS for strategies involving TMB). Results were reported using the net monetary benefit at a willingness-to-pay threshold of €80,000/QALY. Additional scenario and threshold analyses were performed. RESULTS: Strategy B had the lowest QALYs (1.84) and lowest healthcare costs (€120,800). The highest QALYs and healthcare costs were 2.00 and €140,400 in strategy F. In the base-case analysis, strategy A was cost effective with the highest net monetary benefit (€27,300), followed by strategy B (€26,700). Strategy B was cost effective when the cost of WGS testing was decreased by at least 24% or when immunotherapy results in an additional 0.5 year of life gained or more for TMB high compared with TMB low. Strategies C and F, which combined TMB and PD-L1 had the highest net monetary benefit (≥ €76,900) when the cost of WGS testing, immunotherapy, and chemotherapy acquisition were simultaneously reduced by at least 47%, 39%, and 43%, respectively. Furthermore, strategy C resulted in the highest net monetary benefit (≥ €39,900) in a scenario where patients with both PD-L1 low and TMB low were treated with chemotherapy instead of immunotherapy plus chemotherapy. CONCLUSIONS: The use of WGS-TMB is not cost effective compared to PD-L1 for immunotherapy treatment selection in non-squamous metastatic non-small cell lung cancer in the Netherlands. WGS-TMB could become cost effective provided there is a reduction in the cost of WGS testing or there is an increase in the predictive value of WGS-TMB for immunotherapy effectiveness. Alternatively, a combination strategy of PD-L1 testing with WGS-TMB would be cost effective if used to support the choice to withhold immunotherapy in patients with a low expected benefit of immunotherapy.

Risk factors for unplanned reoperation during the expansion phase in two-stage breast reconstruction in the Dutch Breast Implant Registry.

BACKGROUND: The majority of postmastectomy breast reconstructions (PMBRs) are currently performed in two stages using a tissue expander (TE). However, complications during the expansion phase occur regularly, leading to unplanned reoperations and/or reconstruction failure. This study aimed to identify risk factors for unplanned reoperation after TE placement, assessed the time until unplanned and planned reoperation, and investigated indications for unplanned reoperation. METHODS: Patient and surgery-related characteristics of patients who underwent two-stage PMBR between 2017 and 2021 were collected from the Dutch Breast Implant Registry (DBIR). Unplanned reoperation was defined as TE explantation followed by either no replacement or replacement with the same or a different TE. Co-variate adjusted characteristics associated with unplanned reoperation were determined using backward stepwise selection and multivariable logistic regression analyses. RESULTS: In total, 2529 patients (mean age, 50.2 years) were included. Unplanned reoperation occurred in 19.4 percent of all registered TEs (n=3190). Independent factors associated with unplanned reoperation were BMI≥25 kg/m 2 (adjusted Odds Ratio [aOR]=1.63;99% Confidence Interval [99%CI]=1.20-2.57 for BMI 25-29.9 kg/m2, aOR=2.57;99%CI=1.74-3.78 for BMI≥30 kg/m 2), low institutional volume (aOR=1.51;99%CI=1.06-2.18), no drains (aOR=2.06;99%CI=1.15-3.60), subcutaneous TE placement (aOR=5.71;99%CI=3.59-9.10), and partial pectoralis major muscle coverage (aOR=1.35;99%CI=1.02-1.79). Age<40 years (aOR=0.49;99%CI=0.32-0.74) and delayed PMBR (aOR=0.35;99%CI=0.19-0.60) reduced the risk of unplanned reoperation. Median time until reoperation was 97 days for unplanned and 213 days for planned reoperation. Deep wound infections were most often registered as indication for unplanned reoperation (34.4 percent). CONCLUSION: This study identified several risk factors for unplanned reoperation which may be used to reduce complications in expander-based PMBR.

Development and validation of a decision model for the evaluation of novel lung cancer treatments in the Netherlands.

Recent discoveries in molecular diagnostics and drug treatments have improved the treatment of patients with advanced (inoperable) non-squamous non-small cell lung cancer (NSCLC) from solely platinum-based chemotherapy to more personalized treatment, including targeted therapies and immunotherapies. However, these improvements come at considerable costs, highlighting the need to assess their cost-effectiveness in order to optimize lung cancer care. Traditionally, cost-effectiveness models for the evaluation of new lung cancer treatments were based on the findings of the randomized control trials (RCTs). However, the strict RCT inclusion criteria make RCT patients not representative of patients in the real-world. Patients in RCTs have a better prognosis than patients in a real-world setting. Therefore, in this study, we developed and validated a diagnosis-treatment decision model for patients with advanced (inoperable) non-squamous NSCLC based on real-world data in the Netherlands. The model is a patient-level microsimulation model implemented as discrete event simulation with five health events. Patients are simulated from diagnosis to death, including at most three treatment lines. The base-model (non-personalized strategy) was populated using real-world data of patients treated with platinum-based chemotherapy between 2008 and 2014 in one of six Dutch teaching hospitals. To simulate personalized care, molecular tumor characteristics were incorporated in the model based on the literature. The impact of novel targeted treatments and immunotherapies was included based on published RCTs. To validate the model, we compared survival under a personalized treatment strategy with observed real-world survival. This model can be used for health-care evaluation of personalized treatment for patients with advanced (inoperable) NSCLC in the Netherlands.

Nationwide Outcomes of Octogenarians Following Open or Endovascular Management After Ruptured Abdominal Aortic Aneurysms.

PURPOSE: Octogenarians are known to have less-favorable outcomes following ruptured abdominal aortic aneurysm (rAAA) repair compared with their younger counterparts. Accurate information regarding perioperative outcomes following rAAA-repair is important to evaluate current treatment practice. The aim of this study was to evaluate perioperative outcomes of octogenarians and to identify factors associated with mortality and major complications after open surgical repair (OSR) or endovascular aneurysm repair (EVAR) of a rAAA using nationwide, real-world, contemporary data. METHODS: All patients that underwent EVAR or OSR of an infrarenal or juxtarenal rAAA between January 1, 2013, and December 31, 2018, were prospectively registered in the Dutch Surgical Aneurysm Audit (DSAA) and included in this study. The primary outcome was the comparison of perioperative outcomes of octogenarians versus non-octogenarians, including adjustment for confounders. Secondary outcomes were the identification of factors associated with mortality and major complications in octogenarians. RESULTS: The study included 2879 patients, of which 1146 were treated by EVAR (382 octogenarians, 33%) and 1733 were treated by OSR (410 octogenarians, 24%). Perioperative mortality of octogenarians following EVAR was 37.2% versus 14.8% in non-octogenarians (adjusted OR=2.9, 95% CI=2.8-3.0) and 50.0% versus 29.4% following OSR (adjusted OR=2.2, 95% CI=2.2-2.3). Major complication rates of octogenarians were 55.4% versus 31.8% in non-octogenarians following EVAR (OR=2.7, 95% CI=2.1-3.4), and 68% versus 49% following OSR (OR=2.2, 95% CI=1.8-2.8). Following EVAR, 30.6% of the octogenarians had an uncomplicated perioperative course (UPC) versus 49.5% in non-octogenarians (OR=0.5, 95% CI=0.4-0.6), while following OSR, UPC rates were 20.7% in octogenarians versus 32.6% in non-octogenarians (OR=0.5, 95% CI=0.4-0.7). Cardiac or pulmonary comorbidity and loss of consciousness were associated with mortality and major complications in octogenarians. Interestingly, female octogenarians had lower mortality rates following EVAR than male octogenarians (adjusted OR=0.7, 95% CI=0.6-0.8). CONCLUSION: Based on this nationwide study with real-world registry data, mortality rates of octogenarians following ruptured AAA-repair were high, especially after OSR. However, a substantial proportion of these octogenarians following OSR and EVAR had an uneventful recovery. Known preoperative factors do influence perioperative outcomes and reflect current treatment practice.

Data-driven development of the nationwide hip fracture registry in the Netherlands.

Additional variables for a nationwide hip fracture registry must be carefully chosen to prevent unnecessary registry load. A registry pilot in seven hospitals resulted in recommending polypharmacy, serum hemoglobin at admittance, and questions screening for risk of delirium to be used in case-mix correction and for development of quality indicators. PURPOSE: Clinical registries help improve the quality of care but come at the cost of registration load. Datasets should therefore be as compact as possible; however, variables are usually chosen empirically. This study aims to evaluate potential variables with additional value to improve the nationwide Dutch Hip Fracture Audit (DHFA). METHODS: An expert panel selected eleven new variables for the DHFA, which were tested in a prospective cohort of all hip fracture patients treated in 2018 and 2019 in seven pilot hospitals participating in the DHFA. The association of these eleven variables with complications, mortality, and functional outcomes at 3 months was analyzed using multivariable logistic regression analysis. Based on the results, a proposal for variables to add to the dataset of the DHFA was made. RESULTS: In 4.904 analyzed patients, three tested variables had significant associations (p < 0.01) with outcomes: polypharmacy with complications (aOR 1.34), serum hemoglobin at admittance with complications (aOR 0.63) and mortality (aOR for 30-day mortality 0.78), and a set of questions screening for risk of delirium with complications in general (aOR 1.55), e.g., delirium (aOR 2.98), and decreased functional scores at three months (aOR 1.98). CONCLUSION: This study assesses potential new variables for a hip fracture registry. Based on the results of this study, we recommend polypharmacy, serum hemoglobin at admittance, and questions screening for risk of delirium to be used in case-mix correction and for the development of quality indicators. Incorporating these variables in the DHFA dataset may contribute to better and clinically relevant quality indicators.

Administrative healthcare data as an addition to the Dutch surgical aneurysm audit to evaluate mid-term reinterventions following abdominal aortic aneurysm repair: A pilot study.

BACKGROUND: The Dutch Surgical Aneurysm Audit (DSAA) is a nationwide mandatory quality registry that evaluates the perioperative outcomes of abdominal aortic aneurysms (AAAs). The DSAA includes perioperative outcomes that occur up to 30 days, but various complications following AAA repair occur after this period. Administrative healthcare data yield the possibility to evaluate later occuring outcomes such as reinterventions, without increasing the registration burden. The aim of this study is to assess the feasibility and the potential benefit of administrative healthcare data to evaluate mid-term reinterventions following intact AAA repair. METHOD: All patients that underwent primary endovascular aneurysm repair (EVAR) or open surgical repair (OSR) for an intact infrarenal AAA between January 2017 and December 2018 were selected from the DSAA. Subsequently, these patients were identified in a database containing reimbursement data. Healthcare activity codes that refer to reinterventions following AAA repair were examined to assess reinterventions within 12 and 15 months following EVAR and OSR. RESULTS: We selected 4043 patients from the DSAA, and 2059 (51%) patients could be identified in the administrative healthcare database. Reintervention rates of 10.4% following EVAR and 9.5% following OSR within 12 months (p = 0.719), and 11.5% following EVAR and 10.8% following OSR within 15 months (p = 0.785) were reported. CONCLUSION: Administrative healthcare data as an addition to the DSAA is potentially beneficial to evaluate mid-term reinterventions following intact AAA repair without increasing the registration burden for clinicians. Further validation is necessary before reliable implementation of this tool is warranted.

Development of a data-driven case-mix adjustment model for comparison of hospital performance in hip fracture care.

To compare hospitals' hip fracture patient mortality in a quality of care registry, correction for patient characteristics is needed. This study evaluates in 39,374 patients which characteristics are associated with 30 and 90-day mortality, and showed how using these characteristics in a case mix-model changes hospital comparisons within the Netherlands. PURPOSE: Mortality rates after hip fracture surgery are considerable and may be influenced by patient characteristics. This study aims to evaluate hospital variation regarding patient demographics and disease burden, to develop a case-mix adjustment model to analyse differences in hip fracture patients' mortality to calculate case-mix adjusted hospital-specific mortality rates. METHODS: Data were derived from 64 hospitals participating in the Dutch Hip Fracture Audit (DHFA). Adult hip fracture patients registered in 2017-2019 were included. Variation of case-mix factors between hospitals was analysed, and the association between case-mix factors and mortality at 30 and 90 days was determined through regression models. RESULTS: There were 39,374 patients included. Significant variation in case-mix factors amongst hospitals was found for age ≥ 80 (range 25.8-72.1% p < 0.001), male gender (12.0-52.9% p < 0.001), nursing home residents (42.0-57.9% p < 0.001), pre-fracture mobility aid use (9.9-86.7% p < 0,001), daily living dependency (27.5-96.5% p < 0,001), ASA-class ≥ 3 (25.8-83.3% p < 0.001), dementia (3.6-28.6% p < 0.001), osteoporosis (0.0-57.1% p < 0.001), risk of malnutrition (0.0-29.2% p < 0.001) and fracture types (all p < 0.001). All factors were associated with 30- and 90-day mortality. Eight hospitals showed higher and six showed lower 30-day mortality than expected based on their case-mix. Six hospitals showed higher and seven lower 90-day mortality than expected. The specific outlier hospitals changed when correcting for case-mix factors. CONCLUSIONS: Dutch hospitals show significant case-mix variation regarding hip fracture patients. Case-mix adjustment is a prerequisite when comparing hospitals' 30-day and 90-day hip fracture patients' mortality. Adjusted mortality may serve as a starting point for improving hip fracture care.

Treatment Outcome Trends for Non-Ruptured Abdominal Aortic Aneurysms: A Nationwide Prospective Cohort Study.

OBJECTIVE: The Dutch Surgical Aneurysm Audit (DSAA) initiative was established in 2013 to monitor and improve nationwide outcomes of aortic aneurysm surgery. The objective of this study was to examine whether outcomes of surgery for intact abdominal aortic aneurysms (iAAA) have improved over time. METHODS: Patients who underwent primary repair of an iAAA by standard endovascular (EVAR) or open surgical repair (OSR) between 2014 and 2019 were selected from the DSAA for inclusion. The primary outcome was peri-operative mortality trend per year, stratified by OSR and EVAR. Secondary outcomes were trends per year in major complications, textbook outcome (TbO), and characteristics of treated patients. The trends per year were evaluated and reported in odds ratios per year. RESULTS: In this study, 11 624 patients (74.8%) underwent EVAR and 3 908 patients (25.2%) underwent OSR. For EVAR, after adjustment for confounding factors, there was no improvement in peri-operative mortality (aOR [adjusted odds ratio] 1.06, 95% CI 0.94 - 1.20), while major complications decreased (2014: 10.1%, 2019: 7.0%; aOR 0.91, 95% CI 0.88 - 0.95) and the TbO rate increased (2014: 68.1%, 2019: 80.9%; aOR 1.13, 95% CI 1.10 - 1.16). For OSR, the peri-operative mortality decreased (2014: 6.1%, 2019: 4.6%; aOR 0.89, 95% CI 0.82 - 0.98), as well as major complications (2014: 28.6%, 2019: 23.3%; aOR 0.95, 95% CI 0.91 - 0.99). Furthermore, the proportion of TbO increased (2014: 49.1%, 2019: 58.3%; aOR 1.05, 95% CI 1.01 - 1.10). In both the EVAR and OSR group, the proportion of patients with cardiac comorbidity increased. CONCLUSION: Since the establishment of this nationwide quality improvement initiative (DSAA), all outcomes of iAAA repair following EVAR and OSR have improved, except for peri-operative mortality following EVAR which remained unchanged.

Case-mix adjustment to compare colonoscopy performance between endoscopy centers: a nationwide registry study.

BACKGROUND : Nonmodifiable patient and endoscopy characteristics might influence colonoscopy performance. Differences in these so-called case-mix factors are likely to exist between endoscopy centers. This study aimed to examine the importance of case-mix adjustment when comparing performance between endoscopy centers. METHODS : Prospectively collected data recorded in the Dutch national colonoscopy registry between 2016 and 2019 were retrospectively analyzed. Cecal intubation rate (CIR) and adequate bowel preparation rate (ABPR) were analyzed. Additionally, polyp detection rate (PDR) was studied in screening colonoscopies following a positive fecal immunochemical test (FIT). Variation in case-mix factors between endoscopy centers and expected outcomes for each performance measure were calculated per endoscopy center based on case-mix factors (sex, age, American Society of Anesthesiologist [ASA] score, indication) using multivariable logistic regression. RESULTS: 363 840 colonoscopies were included from 51 endoscopy centers. Mean percentages per endoscopy center were significantly different for age > 65 years, male patients, ASA ≥ III, and diagnostic colonoscopies (all P < 0.001). In the FIT-positive screening population, significant differences were observed between endoscopy centers for age > 65 years, male patients, and ASA ≥ III (all P ≤ 0.001). The expected CIR, ABPR, and PDR ranged from 95.0 % to 96.9 %, from 93.6 % to 96.4 %, and from 76.2 % to 79.1 %, respectively. Age, sex, ASA classification, and indication were significant case-mix factors for CIR and ABPR. In the FIT-positive screening population, age, sex, and ASA classification were significant case-mix factors for PDR. CONCLUSION: Our findings emphasize the importance of considering case-mix adjustment when comparing colonoscopy performance measures between endoscopy centers.

Overall Volume Trends in Esophageal Cancer Surgery Results From the Dutch Upper Gastrointestinal Cancer Audit.

OBJECTIVE: In the pursuit of quality improvement, this study aimed to investigate volume-outcome trends in oncologic esophagectomy in the Netherlands. SUMMARY OF BACKGROUND DATA: Concentration of Dutch esophageal cancer care was dictated by introducing an institutional minimum of 20 resections/yr. METHODS: This nationwide cohort study included all esophagectomy patients registered in the Dutch Upper Gastrointestinal Cancer Audit in 2016-2019 from hospitals currently still performing esophagectomies. Annual esophagectomy hospital volume was assigned to each patient and categorized into quartiles. Multivariable logistic regression investigated short-term surgical outcomes. Restricted cubic splines investigated if volume-outcome relationships eventually plateaued. RESULTS: In 16 hospitals, 3135 esophagectomies were performed. First volume quartile hospitals performed 24-39 resections/yr; second, third, and fourth quartile hospitals performed 40-53, 54-69, and 70-101, respectively. Compared to quartile 1, in quartiles 2 to 4, overall/severe/technical complication, anastomotic leakage, and prolonged hospital/intensive care unit stay rates were significantly lower and textbook outcome and lymph node yield were higher. When raising the cut-off from the first to second quartile, higher-volume centers had less technical complications [Adjusted odds ratio (aOR): 0.82, 95% confidence interval (CI): 0.70-0.96], less anastomotic leakage (aOR: 0.80, 95% CI: 0.66-0.97), more textbook outcome (aOR: 1.25, 95% CI: 1.07-1.46), shorter intensive care unit stay (aOR: 0.80, 95% CI: 0.69-0.93), and higher lymph node yield (aOR: 3.56, 95% CI: 2.68-4.77). For most outcomes the volume-outcome trend plateaued at 50-60 annual resections, but lymph node yield and anastomotic leakage continued to improve. CONCLUSION: Although this study does not reflect on individual hospital quality, there appears to be a volume trend towards better outcomes in high-volume centers. Projects have been initiated to improve national quality of care by reducing hospital variation (irrespective of volume) in outcomes in The Netherlands.

Failure to Cure in Patients Undergoing Surgery for Gastric Cancer: A Nationwide Cohort Study.

BACKGROUND: This study aimed to describe the incidence of failure to cure (a composite outcome measure defined as surgery not meeting its initial aim), and the impact of hospital variation in the administration of neoadjuvant therapy on this outcome measure. METHODS: All patients in the Dutch Upper Gastrointestinal Cancer Audit undergoing curatively intended gastric cancer surgery in 2011-2019 were included. Failure to cure was defined as (1) 'open-close' surgery; (2) irradical surgery (R1/R2); or (3) 30-day/in-hospital mortality. Case-mix-corrected funnel plots, based on multivariable logistic regression analyses, investigated hospital variation. The impact of a hospital's tendency to administer neoadjuvant chemotherapy on the heterogeneity in failure to cure between hospitals was assessed based on median odds ratios and multilevel logistic regression analyses. RESULTS: Some 3862 patients from 28 hospitals were included. Failure to cure was noted in 22.3% (hospital variation: 14.5-34.8%). After case-mix correction, two hospitals had significantly higher-than-expected failure to cure rates, and one hospital had a lower-than-expected rate. The failure to cure rate was significantly higher in hospitals with a low tendency to administer neoadjuvant chemotherapy. Approximately 29% of hospital variation in failure to cure could be attributed to different hospital policies regarding neoadjuvant therapy. CONCLUSIONS: Failure to cure has an incidence of 22% in patients undergoing gastric cancer surgery. Higher failure to cure rates were seen in centers administering less neoadjuvant chemotherapy, which confirms the Dutch guideline recommendation on the administration of neoadjuvant chemotherapy. Failure to cure provides short loop feedback and can be used as a quality indicator in surgical audits.

Response and Adherence to Nilotinib in Daily practice (RAND study): an in-depth observational study of chronic myeloid leukemia patients treated with nilotinib.

INTRODUCTION: This comprehensive observational study aimed to gain insight into adherence to nilotinib and the effect of (non)adherence on exposure (Cmin) and treatment outcomes. METHODS: Chronic myeloid leukemia (CML) patients using nilotinib were followed for 12 months. Adherence was measured by Medication Event Monitoring System (MEMS), pill count, and Medication Adherence Report Scale (MARS-5). Nilotinib Cmin and patient-reported outcomes (i.e., quality of life, side effects, beliefs, satisfaction) were measured at baseline, 3, 6, and 12 months. RESULTS: Sixty-eight patients (57.5 ± 15.0 years, 49% female) participated. Median adherence to nilotinib (MEMS and pill count) was ≥ 99% and adherence < 90% was rare. Self-reported nonadherence (MARS-5) increased in the first year of treatment to a third of patients. In line with the strong beliefs in the necessity of taking nilotinib, forgetting to take a dose was more prevalent than intentionally adjusting/skipping doses. Nilotinib Cmin were generally above the therapeutic target in 95% of patients. Patients reported a variety of side effects, of which fatigue was most frequent. The mean Cmin was higher in patients who reported severe itching and fatigue. The overall 1-year MMR rate ranged from 47 to 71%. CONCLUSION: Substantial nonadherence (< 90%) to nilotinib was rare and nilotinib Cmin were generally above the therapeutic target. Lack of response in our group of patients was not related to nonadherence or inadequate Cmin. Nevertheless, a considerable number of patients experienced difficulties in adhering to the twice daily fasted dosing regimen, emphasizing the importance of continuous support of medication adherence in CML. CLINICAL TRIAL REGISTRATION: NTR3992 (Netherlands Trial Register, www.trialregister.nl ).

Correction to: Medical specialists' basic psychological needs, and motivation for work and lifelong learning: a two-step factor score path analysis.

An amendment to this paper has been published and can be accessed via the original article.

Olanzapine Versus Haloperidol for Treatment of Delirium in Patients with Advanced Cancer: A Phase III Randomized Clinical Trial.

BACKGROUND: Treatment of delirium often includes haloperidol. Second-generation antipsychotics like olanzapine have emerged as an alternative with possibly fewer side effects. The aim of this multicenter, phase III, randomized clinical trial was to compare the efficacy and tolerability of olanzapine with haloperidol for the treatment of delirium in hospitalized patients with advanced cancer. MATERIALS AND METHODS: Eligible adult patients (≥18 years) with advanced cancer and delirium (Delirium Rating Scale-Revised-98 [DRS-R-98] total score ≥17.75) were randomized 1:1 to receive either haloperidol or olanzapine (age-adjusted, titratable doses). Primary endpoint was delirium response rate (DRR), defined as number of patients with DRS-R-98 severity score <15.25 and ≥4.5 points reduction. Secondary endpoints included time to response (TTR), tolerability, and delirium-related distress. RESULTS: Between January 2011 and June 2016, 98 patients were included in the intention-to-treat analysis. DRR was 45% (95% confidence interval [CI], 31-59) for olanzapine and 57% (95% CI, 43-71) for haloperidol (Δ DRR -12%; odds ratio [OR], 0.61; 95% CI, 0.2-1.4; p = .23). Mean TTR was 4.5 days (95% CI, 3.2-5.9 days) for olanzapine and 2.8 days (95% CI, 1.9-3.7 days; p = .18) for haloperidol. Grade ≥3 treatment-related adverse events occurred in 5 patients (10.2%) and 10 patients (20.4%) in the olanzapine and haloperidol arm, respectively. Distress rates were similar in both groups. The study was terminated early because of futility. CONCLUSION: Delirium treatment with olanzapine in hospitalized patients with advanced cancer did not result in improvement of DRR or TTR compared with haloperidol. Clinical trial identification number. NCT01539733. Dutch Trial Register. NTR2559. IMPLICATIONS FOR PRACTICE: Guidelines recommend that pharmacological interventions for delirium treatment in adults with cancer should be limited to patients who have distressing delirium symptoms. It was suggested that atypical antipsychotics, such as olanzapine, outperform haloperidol in efficacy and safety. However, collective data comparing the efficacy and safety of typical versus atypical antipsychotics in patients with cancer are limited. If targeted and judicious use of antipsychotics is considered for the treatment of delirium in patients with advanced cancer, this study demonstrated that there was no statistically significant difference in response to haloperidol or olanzapine. Olanzapine showed an overall better safety profile compared with haloperidol, although this difference was not statistically significant.

Medical specialists' basic psychological needs, and motivation for work and lifelong learning: a two-step factor score path analysis.

BACKGROUND: Continuing professional development and lifelong learning are crucial to secure safe and good quality healthcare. Lack of motivation has been found to be among the most important barriers for participation in lifelong learning. This study was conducted to investigate the relationships between medical specialists' work motivation, lifelong learning motivation, autonomy, competence and relatedness satisfaction. METHODS: Self-Determination Theory was used as a theoretical framework for this study. Data were collected through an online survey, that was sent to all (N = 1591) medical specialists in four Dutch hospitals. The survey measured background characteristics, autonomy, competence, and relatedness satisfaction, autonomous and controlled work motivation, and lifelong learning motivation. Two step factor path analysis with the method of Croon was used to analyze the data from 193 cases. RESULTS: Autonomy need satisfaction was positively associated with autonomous work motivation which in turn was positively associated with lifelong learning motivation. Competence need satisfaction and age were negatively associated with controlled work motivation. Competence need satisfaction was also positively related with lifelong learning motivation. No significant nor any hypothesized associations were found for relatedness. CONCLUSIONS: Our findings, in line with Self-determination Theory literature, show that autonomy and competence need satisfaction are the important factors as they were positively associated with medical specialists' motivation for work and for lifelong learning.

European Survey Study Among Plastic/Breast Surgeons on the Use of and Opinion Toward Autologous Fat Transfer: With Emphasis on Breast Surgery.

Objective. The aim of this study is to examine the experience of European surgeons on autologous fat transfer (AFT) and highlight differences between countries and levels of experience. Background Data. The popularity of AFT causes an increase in sophisticated scientific research and clinical implementation. While results from the former are well-documented, important aspects of the latter are far less recognized. Methods. An international survey study about surgeon background, besides AFT familiarity, technique, and opinion, was distributed among surgeons from 10 European countries. The differences between countries and levels of experience were analyzed using a logistic regression model. Results. The mean respondent age, out of the 358 completed questionnaires, was 46 years. Ninety-seven percent of the respondents were plastic surgeons, who practiced AFT mostly in breast surgery and considered themselves experienced with the technique. The thigh and abdomen were less favored harvest locations by the Belgium and French respondents, respectively, and both the French and Austrian respondents preferred manual aspiration over liposuction in harvesting the fat. Despite minor differences between countries and experience, the intraglandular space was injected in all subgroups. Conclusions. The expanding use of AFT in Europe will lead to more experience and heterogeneity regarding the technique. However, despite an obvious adherence to Coleman's method, deviations thereof become more apparent. An important example of such a deviation is the ongoing practice of intraglandular AFT despite being a contraindication in various European guidelines. These unsafe practices should be avoided until scientific clarification regarding oncological safety is obtained and should therefore be the focus of surgeon education in Europe.

Autologous Fat Transfer After Augmentation and Reconstruction of the Female Breast: An International, Cross-Sectional Photo-Comparison Study Among Different Physician and Laymen Study Groups.

OBJECTIVE: The aim of this study is to compare the cosmetic evaluation of autologous fat transfer (AFT) for various indications between surgeons and different laymen groups. BACKGROUND DATA: Despite the upsurge in AFT scientific/clinical interest, objectifying satisfaction has only recently progressed beyond simple Likert-type/Visual Analog Scales. Furthermore, differences in satisfaction between laymen and surgeons has not been thoroughly studied. METHOD: A photo comparison study between European plastic surgeons and different laymen groups was conducted to investigate agreement on cosmetic evaluation of AFT. Three sets of preoperative/postoperative photographs illustrating patients treated with External Vacuum Expansion (EVE) + AFT for various indications in breast surgery were scored according to the Harris Scale, and the interrater agreement was analyzed using Cohen's κ. RESULTS: The overall agreement between the surgeons and the groups of former augmentation, control group, and deep inferior epigastric artery perforator patients was fair, moderate, and substantial, respectively. Interrater agreements among different laymen groups and surgeons from different countries among themselves was substantial to almost perfect. Finally, we found that laymen are generally more optimistic about postoperative results than surgeons. CONCLUSION: In our study, former augmentation patients showed the lowest agreement with surgeons, in the cosmetic appreciation of EVE + AFT and this group might benefit from a more thorough preoperative consultation regarding expectations when choosing AFT. However, overall laymen tend to be more optimistic about postoperative results and surgeon education in general does not seem influenced by surgeon nationality. The significant differences between surgeons and laymen in the cosmetic evaluation of EVE + AFT justifies further studies that focus on the qualitative aspects of these differences to further balance patients' and surgeons' expectations.

The Association of Readiness for Interprofessional Learning with empathy, motivation and professional identity development in medical students.

BACKGROUND: The Readiness for Interprofessional Learning Scale is among the first scales developed for measurement of attitude towards interprofessional learning (IPL). However, the conceptual framework of the RIPLS still lacks clarity. We investigated the association of the RIPLS with professional identity, empathy and motivation, with the intention of relating RIPLS to other well-known concepts in healthcare education, in an attempt to clarify the concept of readiness. METHODS: Readiness for interprofessional learning, professional identity development, empathy and motivation of students for medical school, were measured in all 6 years of the medical curriculum. The association of professional identity development, empathy and motivation with readiness was analyzed using linear regression. RESULTS: Empathy and motivation significantly explained the variance in RIPLS subscale Teamwork & Collaboration. Gender and belonging to the first study year had a unique positive contribution in explaining the variance of the RIPLS subscales Positive and Negative Professional Identity, whereas motivation had no contribution. More compassionate care, as an affective component of empathy, seemed to diminish readiness for IPL. Professional Identity, measured as affirmation or denial of the identification with a professional group, had no contribution in the explanation of the variance in readiness. CONCLUSIONS: The RIPLS is a suboptimal instrument, which does not clarify the 'what' and 'how' of IPL in a curriculum. This study suggests that students' readiness for IPE may benefit from a combination with the cognitive component of empathy ('Perspective taking') and elements in the curriculum that promote autonomous motivation.

Motivational Profiles and Motivation for Lifelong Learning of Medical Specialists.

INTRODUCTION: Medical specialists face the challenge of maintaining their knowledge and skills and continuing professional development, that is, lifelong learning. Motivation may play an integral role in many of the challenges facing the physician workforce today including maintenance of a high performance. The aim of this study was to determine whether medical specialists show different motivational profiles and if these profiles predict differences in motivation for lifelong learning. METHODS: An online questionnaire was sent to every medical specialist working in five hospitals in the Netherlands. The questionnaire included the validated Multidimensional Work Motivation Scale and the Jefferson Scale of Physician Lifelong Learning together with background questions like age, gender, and type of hospital. Respondents were grouped into different motivational profiles by using a two-step clustering approach. RESULTS: Four motivational profiles were identified: (1) HAMC profile (for High Autonomous and Moderate Controlled motivation), (2) MAMC profile (for Moderate Autonomous and Moderate Controlled motivation), (3) MALC profile (for Moderate Autonomous and Low Controlled motivation), and (4) HALC profile (for High Autonomous and Low Controlled motivation). Most of the female specialists that work in an academic hospital and specialists with a surgical specialty were represented in the HALC profile. DISCUSSION: Four motivational profiles were found among medical specialists, differing in gender, experience and type of specialization. The profiles are based on the combination of autonomous motivation (AM) and controlled motivation (CM) in the specialists. The profiles that have a high score on autonomous motivation have a positive association with lifelong learning.