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Summary: The aim of this study was to determine the total medical costs for treating displaced femoral neck fractures with hemi- or total hip arthroplasty in fit elderly patients. The mean total costs per patient at 2 years of follow-up were €26,399. These results contribute to cost awareness. Introduction: The absolute number of hip fractures is rising and increases the already significant burden on society. The aim of this study was to determine the mean total medical costs per patient for treating displaced femoral neck fractures with hemi- or total hip arthroplasty in fit elderly patients. Methods: The population was the Dutch sample of an international randomized controlled trial consisting of femoral neck fracture patients treated with hemi- or total hip arthroplasty. Patient data and health care utilization were prospectively collected during a total follow-up period of 2 years. Costs were separated into costs for hospital care during primary stay, hospital costs for clinical follow-up, and costs generated outside the hospital during rehabilitation. Multiple imputations were used to account for missing data. Results: Data of 141 participants (mean age 81 years) were included in the analysis. The 2-year mortality rate was 19 %. The mean total cost per patient after 10 weeks of follow-up was €15,216. After 1 and 2 years of follow-up the mean total costs were €23,869 and €26,399, respectively. Rehabilitation was the main cost determinant, and accounted for 46 % of total costs. Primary hospital admission days accounted for 22 % of the total costs, index surgery for 11 %, and physical therapy for 7 %. Conclusions: The main cost determinants for hemi- or total hip arthroplasty after treatment of displaced femoral neck fractures (€26,399 per patient until 2 years) were rehabilitation and nursing homes. Most of the costs were made in the first year. Reducing costs after hip fracture surgery should focus on improving the duration and efficiency of the rehabilitation phase. [ABSTRACT FROM AUTHOR]

Suboptimal guideline adherence in chronic myeloid leukemia (CML) care is associated with worse treatment outcomes. Current study focused on adherence to seven quality indicators (QIs) based on the European Leukemia Network guideline (one diagnostic, one therapeutic, and five monitoring indicators). Data were obtained from population-based registries in the Netherlands of 405 newly diagnosed chronic phase CML patients between January 2008 and April 2013. Compliance rates regarding diagnostic and therapeutic indicator were 83% and 78%, respectively. Monitoring indicators rates were lower: 21-27% for indicators concerning the first year and 58% and 62% for the second and third year, respectively. Noncompliance occurred mostly due to non-timely monitoring. Twenty cases did not comply with any indicator, 6% complied with all indicators. After adjustment for age, overall survival rates did not differ significantly between the groups. Adherence to guideline-based QIs was suboptimal. This demonstrates the evidence-practice gap, shows room for improvement and underscores the need for real-world data.

Background: There has been a cultural shift toward patient engagement in health, with a growing demand from patients to access their results., Objective: The Lymphoma Intervention (LIVE) trial is conducted to examine the impact of return of individual patient-reported outcome (PRO) results and a web-based self-management intervention on psychological distress, self-management, satisfaction with information, and health care use in a population-based setting., Methods: Return of PRO results included comparison with age- and sex-matched peers and was built into the Patient-Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship registry. The self-management intervention is an adaptation of a fully automated evidence-based intervention for breast cancer survivors. Patients with lymphoma who completed the web-based questionnaire were equally randomized to care as usual, return of PRO results, and return of PRO results plus self-management intervention. Patients completed questionnaires 9 to 18 months after diagnosis (T0; n=227), 4 months (T1; n=190), 12 months (T2; n=170), and 24 months (T3; n=98)., Results: Of all invited patients, 51.1% (456/892) responded and web-based participants (n=227) were randomly assigned to care as usual (n=76), return of PRO results (n=74), or return of PRO results and access to Living with lymphoma (n=77). Return of PRO results was viewed by 76.7% (115/150) of those with access. No statistically significant differences were observed for psychological distress, self-management, satisfaction with information provision, and health care use between patients who received PRO results and those who did not (P>.05). Use of the self-management intervention was low (2/76, 3%), and an effect could therefore not be determined., Conclusions: Return of individual PRO results seems to meet patients' wishes but had no beneficial effects on patient outcome. No negative effects were found when individual PRO results were disclosed, and the return of individual PRO results can therefore be safely implemented in daily clinical practice., Trial Registration: Netherlands Trial Register NTR5953; https://www.trialregister.nl/trial/5790., International Registered Report Identifier (irrid): RR2-10.1186/s13063-017-1943-2., (©Simone Oerlemans, Lindy Paulina Johanna Arts, Jacobien M Kieffer, Judith Prins, Mels Hoogendoorn, Marjolein van der Poel, Ad Koster, Chantal Lensen, Wendy Bernadina Catharina Stevens, Djamila Issa, Johannes F M Pruijt, Margriet Oosterveld, René van der Griend, Marten Nijziel, Lidwine Tick, Eduardus F M Posthuma, Lonneke V van de Poll-Franse. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 14.12.2021.)

Background: Ineffective hematopoiesis in patients with myelodysplastic syndromes (MDS) often results in transfusion dependence. The burden of frequent transfusions in the real-world MDS population is largely unknown., Study Design and Methods: An observational, retrospective, population-based study, using the HemoBase registry, was performed including all patients diagnosed with MDS between 2005 and 2017 in Friesland, a province in the Netherlands with approximately 650,000 inhabitants. Detailed clinical information was collected from the electronic health records. Transfusion burden was classified according to the International Working Group 2018 criteria: not transfusion dependent, low (LTB), or high transfusion burden (HTB). Univariate and multivariable regression analyses were performed., Results: Of 292 patients, 136 (46.6%) had a HTB of ≥8 units/16 weeks and 17 (5.8%) had a LTB of 3-7 units/16 weeks. This was present in all types of MDS patients, but patients aged 75-84 years (odds ratio [OR] 4.02, 95% confidence interval [CI]: 1.84-8.82), high-risk MDS patients (OR 2.88, 95% CI: 1.08-7.68) and MDS-EB-2 patients (OR 7.07, 95% CI: 2.17-22.90) were particularly at risk for a HTB., Discussion: This study provides a reliable estimate of the transfusion burden in real-world MDS patients, with almost half of the patients having a HTB. A HTB was observed in all MDS subtypes and both low- and high-risk MDS. Therefore, we conclude that the entire MDS population might benefit from novel agents that reduce the transfusion need and that might have beneficial effects on patient outcomes and healthcare utilization outcomes., (© 2021 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: The Coronavirus disease 2019 (COVID-19) pandemic has underlined the urgent need for reliable, multicenter, and full-admission intensive care data to advance our understanding of the course of the disease and investigate potential treatment strategies. In this study, we present the Dutch Data Warehouse (DDW), the first multicenter electronic health record (EHR) database with full-admission data from critically ill COVID-19 patients., Methods: A nation-wide data sharing collaboration was launched at the beginning of the pandemic in March 2020. All hospitals in the Netherlands were asked to participate and share pseudonymized EHR data from adult critically ill COVID-19 patients. Data included patient demographics, clinical observations, administered medication, laboratory determinations, and data from vital sign monitors and life support devices. Data sharing agreements were signed with participating hospitals before any data transfers took place. Data were extracted from the local EHRs with prespecified queries and combined into a staging dataset through an extract-transform-load (ETL) pipeline. In the consecutive processing pipeline, data were mapped to a common concept vocabulary and enriched with derived concepts. Data validation was a continuous process throughout the project. All participating hospitals have access to the DDW. Within legal and ethical boundaries, data are available to clinicians and researchers., Results: Out of the 81 intensive care units in the Netherlands, 66 participated in the collaboration, 47 have signed the data sharing agreement, and 35 have shared their data. Data from 25 hospitals have passed through the ETL and processing pipeline. Currently, 3464 patients are included in the DDW, both from wave 1 and wave 2 in the Netherlands. More than 200 million clinical data points are available. Overall ICU mortality was 24.4%. Respiratory and hemodynamic parameters were most frequently measured throughout a patient's stay. For each patient, all administered medication and their daily fluid balance were available. Missing data are reported for each descriptive., Conclusions: In this study, we show that EHR data from critically ill COVID-19 patients may be lawfully collected and can be combined into a data warehouse. These initiatives are indispensable to advance medical data science in the field of intensive care medicine., (© 2021. The Author(s).)

Objectives: Chronic obstructive pulmonary disease (COPD) guidelines advocate treatment with combinations of long-acting bronchodilators for patients with COPD who have persistent symptoms or continue to have exacerbations while using a single bronchodilator. This study assessed the cost-utility of the fixed dose combination of the bronchodilators tiotropium and olodaterol versus two comparators, tiotropium monotherapy and long-acting β2 agonist/inhaled corticosteroid (LABA/ICS) combinations, in three European countries: Finland, Sweden and the Netherlands., Methods: A previously published COPD patient-level discrete event simulation model was updated with most recent evidence to estimate lifetime quality-adjusted life years (QALYs) and costs for COPD patients receiving either tiotropium/olodaterol, tiotropium monotherapy or LABA/ICS. Treatment efficacy covered impact on trough forced expiratory volume in 1 s (FEV 1 ), total and severe exacerbations and pneumonias. The unit costs of medication, maintenance treatment, exacerbations and pneumonias were obtained for each country. The country-specific analyses adhered to the Finnish, Swedish and Dutch pharmacoeconomic guidelines, respectively., Results: Treatment with tiotropium/olodaterol gained QALYs ranging from 0.09 (Finland and Sweden) to 0.11 (the Netherlands) versus tiotropium and 0.23 (Finland and Sweden) to 0.28 (the Netherlands) versus LABA/ICS. The Finnish payer's incremental cost-effectiveness ratio (ICER) of tiotropium/olodaterol was €11 000/QALY versus tiotropium and dominant versus LABA/ICS. The Swedish ICERs were €6200/QALY and dominant, respectively (societal perspective). The Dutch ICERs were €14 400 and €9200, respectively (societal perspective). The probability that tiotropium/olodaterol was cost-effective compared with tiotropium at the country-specific (unofficial) threshold values for the maximum willingness to pay for a QALY was 84% for Finland, 98% for Sweden and 99% for the Netherlands. Compared with LABA/ICS, this probability was 100% for all three countries., Conclusions: Based on the simulations, tiotropium/olodaterol is a cost-effective treatment option versus tiotropium or LABA/ICS in all three countries. In both Finland and Sweden, tiotropium/olodaterol is more effective and cost saving (ie, dominant) in comparison with LABA/ICS., Competing Interests: Competing interests: MH reports grants from Boehringer Ingelheim, during the conduct of the study. SS is an employee of Boehringer Ingelheim. JC is an employee of Boehringer Ingelheim. ES is a partner, employee and CEO of ESiOR Oy, Kuopio, Finland. ESiOR Oy carries out studies, statistical analysis, consultancy, education, reporting and health economic evaluations for several pharmaceutical (including companies producing and marketing treatments for chronic obstructive pulmonary disease), food industry, diagnostics and device companies, hospitals, consultancies, projects and academic institutions. EP reports grants from Institute for Medical Technology Assessment, Erasmus University Rotterdam, during the conduct of the study; personal fees and other from Quantify Research AB, outside the submitted work. MR-vM reports grants from Boehringer Ingelheim during the conduct of the study., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Early recognition of individuals with increased risk of sudden cardiac arrest (SCA) remains challenging. SCA research so far has used data from cardiologist care, but missed most SCA victims, since they were only in general practitioner (GP) care prior to SCA. Studying individuals with type 2 diabetes (T2D) in GP care may help solve this problem, as they have increased risk for SCA, and rich clinical datasets, since they regularly visit their GP for check-up measurements. This information can be further enriched with extensive genetic and metabolic information., Aim: To describe the study protocol of the REcognition of Sudden Cardiac arrest vUlnErability in Diabetes (RESCUED) project, which aims at identifying clinical, genetic and metabolic factors contributing to SCA risk in individuals with T2D, and to develop a prognostic model for the risk of SCA., Methods: The RESCUED project combines data from dedicated SCA and T2D cohorts, and GP data, from the same region in the Netherlands. Clinical data, genetic data (common and rare variant analysis) and metabolic data (metabolomics) will be analysed (using classical analysis techniques and machine learning methods) and combined into a prognostic model for risk of SCA., Conclusion: The RESCUED project is designed to increase our ability at early recognition of elevated SCA risk through an innovative strategy of focusing on GP data and a multidimensional methodology including clinical, genetic and metabolic analyses., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

This study proposes a framework for mining temporal patterns from Electronic Medical Records. A new scoring scheme based on the Wilson interval is provided to obtain frequent and predictive patterns, as well as to accelerate the mining process by reducing the number of patterns mined. This is combined with a case study using data from general practices in the Netherlands to identify children at risk of suffering from mental disorders. To develop an accurate model, feature engineering methods such as one hot encoding and frequency transformation are proposed, and the pattern selection is tailored to this type of clinical data. Six machine learning models are trained on five age groups, with XGBoost achieving the highest AUC values (0.75-0.79) with sensitivity and specificity above 0.7 and 0.6 respectively. An improvement is demonstrated by the models learning from patterns in addition to non-temporal features., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The treatment of older, unfit patients with acute myeloid leukemia (AML) is challenging. Based on preclinical data of Bruton tyrosine kinase expression/phosphorylation and ibrutinib cytotoxicity in AML blasts, we conducted a randomized phase 2 multicenter study to assess the tolerability and efficacy of the addition of ibrutinib to 10-day decitabine in unfit (ie, Hematopoietic Cell Transplantation Comorbidity Index ≥3) AML patients and higher risk myelodysplasia patients (HOVON135/SAKK30/15 trial). In total, 144 eligible patients were randomly (1:1) assigned to either 10-day decitabine combined with ibrutinib (560 mg; sequentially given, starting the day after the last dose of decitabine) (n = 72) or to 10-day decitabine (n = 72). The addition of ibrutinib was well tolerated, and the number of adverse events was comparable for both arms. In the decitabine plus ibrutinib arm, 41% reached complete remission/complete remission with incomplete hematologic recovery (CR/CRi), the median overall survival (OS) was 11 months, and 2-year OS was 27%; these findings compared with 50% CR/CRi, median OS of 11.5 months, and 2-year OS of 21% for the decitabine group (not significant). Extensive molecular profiling at diagnosis revealed that patients with STAG2, IDH2, and ASXL1 mutations had significantly lower CR/CRi rates, whereas patients with mutations in TP53 had significantly higher CR/CRi rates. Furthermore, multicolor flow cytometry revealed that after 3 cycles of treatment, 28 (49%) of 57 patients with available bone marrow samples had no measurable residual disease. In this limited number of cases, measurable residual disease revealed no apparent impact on event-free survival and OS. In conclusion, the addition of ibrutinib does not improve the therapeutic efficacy of decitabine. This trial was registered at the Netherlands Trial Register (NL5751 [NTR6017]) and has EudraCT number 2015-002855-85., (© 2020 by The American Society of Hematology.)

Rituximab-containing induction followed by autologous stem cell transplantation (ASCT) is the standard first-line treatment for young mantle cell lymphoma patients. However, most patients relapse after ASCT. We investigated in a randomised phase II study the outcome of a chemo-immuno regimen and ASCT with or without maintenance therapy with bortezomib. Induction consisted of three cycles R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), two cycles high-dose cytarabine, BEAM (carmustine, etoposide, cytarabine, melphalan) and ASCT. Patients responding were randomised between bortezomib maintenance (1·3 mg/m 2 intravenously once every 2 weeks, for 2 years) and observation. Of 135 eligible patients, 115 (85%) proceeded to ASCT, 60 (44%) were randomised. With a median follow-up of 77·5 months for patients still alive, 5-year event-free survival (EFS) was 51% (95% CI 42-59%); 5-year overall survival (OS) was 73% (95% CI 65-80%). The median follow-up of randomised patients still alive was 71·5 months. Patients with bortezomib maintenance had a 5-year EFS of 63% (95% CI 44-78%) and 5-year OS of 90% (95% CI 72-97%). The patients randomised to observation had 5-year PFS of 60% (95% CI, 40-75%) and OS of 90% (95% CI 72-97%). In conclusion, in this phase II study we found no indication of a positive effect of bortezomib maintenance after ASCT., (© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

An observational population-based cohort study was performed to investigate the role of comorbidity on outcome and treatment-related toxicity in patients with newly diagnosed advanced-stage diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Data for the clinical characteristics of 154 patients (median age 69 years), including Charlson Comorbidity Index (CCI), treatment, toxicity and outcome were evaluated. Forty-five percent of the patients had an International Prognistic index ≥3 and 16% had a CCI ≥2. The planned R-CHOP schedule was completed by 84% and 75% reached complete remission (CR). In those with CCI ≥2, 67% completed treatment with 46% CR. In patients with a CCI <2, overall survival (OS) after 1, 2 and 5 years was 84%, 79% and 65% respectively and it was 64%, 48% and 48% for those with CCI ≥2. Grade III/IV toxicity was documented in 53%, most frequently febrile neutropenia (27%) and infections (23%). In multivariate analysis CCI ≥2 and IPI ≥3 were independent risk indicators for OS and grade III/IV toxicity. In conclusion, comorbidity is an independent risk indicator for worse OS in patients with advanced DLBCL treated with R-CHOP by interference with intensive treatment schedules and more grade III/IV toxicity. Future studies are warranted to determine the optimal treatment approach in patients with significant comorbidities., (© 2014 John Wiley & Sons Ltd.)

Background: Elderly patients with non-Hodgkin's lymphoma (NHL) are often not treated with standard immunochemotherapy and this might have a negative impact on their survival. Little is known about the determinants that play a role in treatment decision-making of clinicians regarding elderly patients with NHL. The objective of this study was to gain more insight into these determinants., Methods: A survey was conducted amongst haematologists in the Netherlands. The survey contained questions about comorbidity, polypharmacy, social setting, nutritional status, depression, mild cognitive impairment, dementia, activities of daily living (ADL) and instrumental activities of daily living (IADL) in relation to treatment decisions in elderly NHL patients., Results: Of all comorbidities, respondents designated cognitive disorders and cardiovascular comorbidity as the most important factors when assessing whether an older patient with NHL is eligible for curative treatment. Also in decreasing degree of importance ADL, IADL and depressive disorder are frequently included in treatment decision-making. Almost half of the respondents feel that treatment of the elderly person is complicated as a result of a lack of scientific evidence., Conclusion: Haematologists are aware of coexisting problems in elderly patients and they frequently take comorbidities, cognitive disorders and functional status into consideration in treatment decision-making. Future studies are needed to determine the exact role that these factors should play in the treatment of elderly patients. Furthermore, haematologists feel that treatment of the elderly is complicated and there is a lack of scientific evidence, and therefore older adults should be better represented in clinical trials.

Objectives: To determine the prevalence of antibiotic resistance and multiresistance of Escherichia coli and Staphylococcus aureus in nursing homes and to determine which factors are associated with this prevalence., Design: Cohort study., Setting: Nursing homes., Participants: Residents of long-stay somatic care wards and rehabilitation patients were recruited from five nursing homes and two rehabilitation wards in hospitals in the central region of the Netherlands., Measurements: From each included patient, an anal swab was analyzed for E. coli and its antibiotic susceptibility and extended spectrum β-lactamase-producing Enterobacteriaceae. Nasal swabs were analyzed for S. aureus and its susceptibility, including methicillin-resistant S. aureus (MRSA). Associations were determined between resistance of E. coli to amoxicillin/co-amoxiclav and recent use (previous 6 months) of these antibiotics, hospital admission (previous 3 months), and presence of a urinary catheter., Results: A total of 125 patients were included in the study. The resistance and intermediate susceptibility of E. coli varied from 4% (ceftriaxone) to 43% (amoxicillin). Extended spectrum β-lactamase-producing Enterobacteriaceae were found in 6% of the patients. Amoxicillin and/or co-amoxiclav users were significantly more resistant to these antibiotics (69%) than nonusers (38%). No associations were found between amoxicillin and/or co-amoxiclav resistance and hospital admission or presence of a urine catheter. The resistance of S. aureus varied from 0% to 69% (penicillin). No MRSA was found. The ciprofloxacin resistance in E. coli and S. aureus was 14% and 39%, respectively., Conclusion: The prevalence of antibiotic-resistant E. coli and S. aureus in nursing homes was considerably high in this study, although no MRSA was found. This may lead to failing of empiric therapy of infections in patients in nursing homes. In particular, the high resistance to ciprofloxacin may make empiric quinolone therapy unreliable. Antibiotic use was associated with antibiotic resistance of E. coli. Therefore, antibiotic use should be restricted as much as possible. Analysis of risk factors for antibiotic resistance should be extended to be able to prevent further development of antibiotic resistance in nursing homes., (Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.)

An urgent need for new treatment modalities is emerging in elderly patients with acute myeloid leukemia (AML). We hypothesized that targeting VEGF might furnish an effective treatment modality in this population. Elderly patients with AML were randomly assigned in this phase 2 study (n = 171) to receive standard chemotherapy (3 + 7) with or without bevacizumab at a dose of 10 mg/kg intravenously at days 1 and 15. In the second cycle, patients received cytarabine 1000 mg/m(2) twice daily on days 1-6 with or without bevacizumab. The complete remission rates in the 2 arms were not different (65%). Event-free survival at 12 months was 33% for the standard arm versus 30% for the bevacizumab arm; at 24 months, it was 22% and 16%, respectively (P = .42). The frequencies of severe adverse events (SAEs) were higher in the bevacizumab arm (n = 63) compared with the control arm (n = 28; P = .043), but the percentages of death or life-threatening SAEs were lower in the bevacizumab arm (60% vs 75% of SAEs). The results of the present study show that the addition of bevacizumab to standard chemotherapy does not improve the therapeutic outcome of older AML patients. This trial is registered as number NTR904 in The Nederlands Trial Register (www.trialregister.nl).

Background: The aim of this study was to estimate the cost-effectiveness of tiotropium versus salmeterol to inform decision making within the Dutch healthcare setting., Methods: A previously published, validated COPD progression model was updated with new exacerbation data and adapted to the Dutch setting by including Dutch estimates of healthcare use for COPD maintenance treatment and Dutch unit costs. Exacerbation data from the POET-COPD trial were combined with evidence from earlier tiotropium studies using Bayesian meta-analysis. The model-based analysis was performed using a one- and five-year time horizon. Main health outcomes were the number of exacerbations and quality-adjusted life years (QALYs)., Results: One-year costs per patient from the healthcare perspective were v1370 for tiotropium and v1359 for salmeterol; a difference of v11 (95% uncertainty interval (UI): -198-212). The annual number of exacerbations was 0.068 (-0.005-0.140) lower in the tiotropium group. The number of QALYs in the tiotropium group was 0.011 (-0.019-0.049) higher, resulting in an incremental cost-effectiveness ratio (ICER) of v1015 per QALY. After five years, the difference in exacerbations, QALYs and costs between the tiotropium and salmeterol group were -0.435 (-0.915-0.107), 0.079 (-0.272-0.520) and v-277 (-1586-1074), respectively, indicating that tiotropium was more effective and less costly. Using a societal perspective, tiotropium dominated salmeterol both after one and five years., Conclusion: Tiotropium reduced exacerbations and exacerbation-related costs. After one year the cost per QALY of tiotropium compared with salmeterol was very low, while after five years tiotropium was found to dominate salmeterol.

The efficacy of azacitidine in the treatment of high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20-30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors for response, we analysed a cohort of 90 MDS, CMML and AML patients who have been treated in a Dutch compassionate named patient programme. Patients received azacitidine for a median of five cycles (range 1-19). The overall response rate (complete/partial/haematological improvement) was 57% in low risk MDS, 53% in high risk MDS, 50% in CMML, and 39% in AML patients. Median overall survival (OS) was 13·0 (9·8-16·2) months. Multivariate analysis confirmed circulating blasts [Hazard Ratio (HR) 0·48, 95% confidence interval (CI) 0·24-0·99; P = 0·05] and poor risk cytogenetics (HR 0·45, 95% CI 0·22-0·91; P = 0·03) as independent predictors for OS. Interestingly, this analysis also identified platelet doubling after the first cycle of azacitidine as a simple and independent positive predictor for OS (HR 5·4, 95% CI 0·73-39·9; P = 0·10). In conclusion, routine administration of azacitidine to patients with variable risk groups of MDS, CMML and AML is feasible, and subgroups with distinct efficacy of azacitidine treatment can be identified., (© 2011 Blackwell Publishing Ltd.)

Objective: To examine the cost-effectiveness of varenicline, a new pharmacotherapy to support smoking cessation, compared with the currently available pharmacologic alternatives in the Netherlands., Methods: The BENESCO-model was used to estimate the long-term health and economic benefits of smoking cessation for a cohort of smokers making a one-time quit attempt. The cohort represented the population of Dutch smokers with respect to gender, age, and prevalence of the smoking-related diseases included in the model: COPD, lung cancer, CHD, stroke, and asthma exacerbations. The model compared the cumulative incidence of smoking-related diseases, (quality-adjusted) life years, intervention costs, and direct medical costs between the cohort treated with varenicline and the same cohort either untreated (unaided cessation) or treated with bupropion, nortriptyline or NRT. The time horizon was lifetime. Future costs were discounted at 4%, health outcomes at 1.5%., Results: The cost of varenicline per additional quitter ranged from 1030 Euro compared with NRT to 4270 Euro compared with nortriptyline. When including the savings due to the reduction in incidence of smoking-related diseases, varenicline generated net savings compared with bupropion and NRT. Compared with nortriptyline and unaided cessation, varenicline was estimated to cost 1650 Euro/QALY and 320 Euro/QALY gained, respectively. At a willingness-to-pay as low as 5000/QALY gained, the probability that varenicline was cost-effective was more than 80% compared to bupropion, NRT, and unaided cessation and about 60% compared to nortriptyline., Conclusion: Treatment with varenicline for smoking cessation is cost-effective compared with nortriptyline and unaided cessation and even cost-saving compared with bupropion and NRT.

Objective: To determine the health-care utilisation and associated costs for asthma and chronic obstructive pulmonary disease (COPD) in the Netherlands for the year 2000 and to estimate future costs by means of projections., Design: Descriptive and explorative., Method: The costs were based on data regarding resource use in 2000 obtained from representative national registries and surveys. The costs were specified by gender and age category and for COPD also by severity. Three projections for the costs of asthma and COPD were made by means of prevalence projections: first assuming constant resource use and constant prices, second assuming asthma- and COPD-specific trends in the costs for hospital care (asthma, -4.7% and COPD, -4.1% per year) and medication (+4.9% per year), and third by adding general trends for the remaining types of care., Results: Total costs for the year 2000 for asthma (452,000 patients) and COPD (306,000 patients) were estimated to be 141 and 280 million Euros, amounting to 313 en 915 Euros per patient or 9 and 18 Euros per inhabitant, respectively. Projections of total prevalence for the year 2025 varied between 478,000 and 568,000 patients for asthma and between 479,000 and 494,000 patients for COPD. Assuming constant resource use and prices, the costs in 2025 were projected to increase to amounts between 167 and 181 million Euros for asthma and 443 and 495 million Euros for COPD. Projections including the estimated trends in costs for hospital care, medication and the costs for other types of care predicted a sharper increase., Conclusion: Costs for asthma and COPD together (421 million Euros) amounted to 1.3% of the total Dutch health-care budget in 2000. Almost 70% of these costs were for COPD. Projections for 2025 showed that the costs for COPD will increase more than the costs for asthma.

The actual burden of chronic obstructive pulmonary disease (COPD) in terms of health care use and costs strongly depends on the distribution of disease severity. For the Netherlands, the distribution of diagnosed COPD was estimated by classifying all patients with a physician diagnosis of COPD from two different sources of general practitioners (GP)-data into mild (27%), moderate (55%), severe (15%) or very severe COPD (3%) based on their post-bronchodilator FEV1% predicted, according to the GOLD-guidelines. This distribution will most likely shift to the less severe stages when under-reporting and under-diagnosis are reduced.

To contribute to evidence-based policy making, a dynamic Dutch population model of chronic obstructive pulmonary disease (COPD) progression was developed. The model projects incidence, prevalence, mortality, progression and costs of diagnosed COPD by the Global Initiative for Chronic Obstructive Lung Disease-severity stage for 2000-2025, taking into account population dynamics and changes in smoking prevalence over time. It was estimated that of all diagnosed COPD patients in 2000, 27% had mild, 55% moderate, 15% severe and 3% very severe COPD. The severity distribution of COPD incidence was computed to be 40% mild, 55% moderate, 4% severe and 0.1% very severe COPD. Disease progression was modelled as decline in forced expiratory volume in one second (FEV1) % predicted depending on sex, age, smoking and FEV1 % pred. The relative mortality risk of a 10-unit decrease in FEV1 % pred was estimated at 1.2. Projections of current practice were compared with projections assuming that each year 25% of all COPD patients receive either minimal smoking cessation counselling or intensive counselling plus bupropion. In the projections of current practice, prevalence rates between 2000-2025 changed from 5.1 to 11 per 1,000 inhabitants for mild, 11 to 14 per 1,000 for moderate, 3.0 to 3.9 per 1,000 for severe and from 0.5 to 1.3 per 1,000 for very severe COPD. Costs per inhabitant increased from 1.40 Euro to 3.10 for mild, 6.50 Euro to 9.00 for moderate, 6.20 Euro to 8.50 for severe and from 3.40 Euro to 9.40 for very severe COPD (price level 2000). Both smoking cessation scenarios were cost-effective with minimal counselling generating net savings. In conclusion, the chronic obstructive pulmonary disease progression model is a useful instrument to give detailed information about the future burden of chronic obstructive pulmonary disease and to assess the long-term impact of interventions on this burden.

Objective: To ascertain the correlation between chills, bacteraemia, infection type and clinical progress in patients presenting with fever to the casualty department., Design: Prospective, descriptive., Method: Anamnestic, clinical and microbiological data were registered from patients with fever (> 38.2 degrees C rectal) presenting to the Casualty Department of the Leiden University Hospital and the Bronovo Hospital, in the period 1 February 1994-31 July 1995 respectively 1 February 1996-31 July 1997., Results: A total of 764 patients (424 men and 340 women; median age: 66 years) were included in the study. A chill was reported by 270 patients (35%). Bacteria were isolated from the blood culture in the case of 141 patients (18%). The relative risk (RR) for bacteraemia in the case of a chill was 2.8 (95% CI: 2.1-3.8); the positive predictive value of a chill for bacteraemia was 31% and the negative predictive value 89%. For 683 (89%) of the 764 patients the cause of the fever was probably or certainly an infection, which was mostly pulmonary (319 patients; 42%) or urogenital (112 patients; 15%) in origin. The positive predictive value was 24% for patients with respiratory tract infections and 48% for patients with urinary tract infections. Mortality occurred in the case of 62 patients (8%) after a median admission period of 11 days. The patients who died were older than the patients discharged (p < 0.01) and there was a statistically significant correlation between mortality with bacteraemia (RR: 1.1) and serious comorbidity (RR: 6.1)., Conclusion: There was a strong correlation between the chill indicated in the anamnesis and bacteraemia, especially in patients with a urinary tract infection. Bacteraemia, advanced age and serious comorbidity were unfavourable prognostic factors.