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.publishersversionepub_ahead_of_prin

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.</p

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

The associations of thiopurines with male fertility and paternally exposed offspring: a systematic review and meta-analysis

BACKGROUND: Thiopurines are widely used immunosuppressive agents. In high dosages, they inhibit the purine synthesis and are considered to be possibly harmful to spermatogenesis, and subsequently to men's fertility and their offspring. However, the clear association between thiopurine exposure and male fertility and reproduction safety, if any, is still poorly understood. OBJECTIVE AND RATIONALE: The aim of this review was to systematically summarize and meta-analyse the available data, derived from animal and human studies, regarding the influence of thiopurine exposure on fertility and conception safety in men and their offspring. SEARCH METHODS: A systematic literature search of the MEDLINE and EMBASE databases was performed using a combination of relevant terms related to 'thiopurines', 'fertility', 'conception', 'reproduction', 'semen quality' and 'birth outcome', combined with 'male', 'men', 'father' and 'paternal'. The search was not restricted exclusively to human subjects, neither to a type of disease or condition, to gather all available studies with regards to this topic. All published articles on thiopurines and male fertility, written in English and published until May 2017, were screened for eligibility. The GRADE guidelines were used to assess the quality of evidence of the included articles. OUTCOMES: A total of 28 studies (including 14 observational studies in humans) were included in this review and six of these were included in the meta-analysis. In various rodents, thiopurines adversely affected the germ cells (in administered doses of 2 to 20 times the human equivalent dose). In human studies, thiopurine therapy was not evidently associated with impaired testicular function or semen quality in 83 men with a variety of underlying diseases. In total, 53 out of 975 offspring with congenital anomalies (5.4%, the background prevalence is 3%), possibly as a result of paternal thiopurine exposure, were described in all studies together. The risk of congenital anomalies was not significantly increased when compared with offspring without paternal thiopurine exposure (4.7%) (pooled odds ratio 1.32, 95% confidence interval 0.75, 2.34). WIDER IMPLICATIONS: Thiopurines have spermatotoxic effects in rodents. In humans, overall data are limited and derived from underpowered studies, and therefore not conclusive with regards to the possible effects of thiopurines on spermatogenesis or paternally exposed offspring. Larger, epidemiological trials evaluating the safety of thiopurines to men's fertility and their offspring are mandatory to adequately counsel thiopurine treated men who wish to conceive

An international study on teachers' conceptions of learning and teaching and corresponding teacher profiles

Introduction: Teachers’ conceptions of learning and teaching (COLT) affect their teaching behaviour. The 18 item COLT instrument has been developed in the Netherlands and comprises three scales, ‘teacher centredness’, ‘appreciation of active learning’ and ‘orientation to professional practice’. Previously we found five teacher profiles. The aim of this study was to find out if the COLT instrument can be used in an international setting. Methods: Data were collected with the web-based COLT. Cronbach’s alphas of the three COLT scales were calculated. Subsequently a cluster analysis was conducted to identify different teacher profiles, followed by a split half validation procedure. Results: Respondents (n = 708) worked in 28 countries. Cronbach’s alphas were 0.67, 0.54, and 0.66. A six-cluster solution fitted best, based on meaning and explained variance. The sixth teacher profile scored high on ‘teacher centredness’, average on ‘appreciation of active learning’ and low on ‘orientation to professional practice’. The split half validation resulted in a Cohen’s kappa of 0.744. Discussion: Cronbach’s alphas indicated acceptable reliablities for all three subscales. The new, sixth profile was labelled ‘neo-transmitter’. Conclusion: We found evidence supporting the validity of the use of COLT in an international context and identified a new, sixth teacher profile

Stool DNA testing to screen for colorectal cancer in the Medicare population: a cost-effectiveness analysis

BACKGROUND: The Centers for Medicare & Medicaid Services considered whether to reimburse stool DNA testing for colorectal cancer screening among Medicare enrollees. OBJECTIVE: To evaluate the conditions under which stool DNA testing could be cost-effective compared with the colorectal cancer screening tests currently reimbursed by the Centers for Medicare & Medicaid Services. DESIGN: Comparative microsimulation modeling study using 2 independently developed models. DATA SOURCES: Derived from literature. TARGET POPULATION: A cohort of persons aged 65 years. A sensitivity analysis was also conducted, in which a cohort of persons aged 50 years was studied. TIME HORIZON: Lifetime. PERSPECTIVE: Third-party payer. INTERVENTION: Stool DNA test every 3 or 5 years in comparison with currently recommended colorectal cancer screening strategies. OUTCOME MEASURES: Life expectancy, lifetime costs, incremental cost-effectiveness ratios, and threshold costs. RESULTS OF BASE-CASE ANALYSIS: Assuming a cost of $350 per test, strategies of stool DNA testing every 3 or 5 years yielded fewer life-years and higher costs than the currently recommended colorectal cancer screening strategies. Screening with the stool DNA test would be cost-effective at a per-test cost of$40 to $60 for stool DNA testing every 3 years, depending on the simulation model used. There were no levels of sensitivity and specificity for which stool DNA testing would be cost-effective at its current cost of$350 per test. Stool DNA testing every 3 years would be cost-effective at a cost of $350 per test if the relative adherence to stool DNA testing were at least 50% better than that with other screening tests. RESULTS OF SENSITIVITY ANALYSIS: None of the results changed substantially when a cohort of persons aged 50 years was considered. LIMITATION: No pathways other than the traditional adenoma-carcinoma sequence were modeled. CONCLUSION: Stool DNA testing could be a cost-effective alternative for colorectal cancer screening if the cost of the test substantially decreased or if its availability would entice a large fraction of otherwise unscreened persons to receive screening

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