BACKGROUND: Digital inhalers can monitor inhaler usage, support difficult-to-treat asthma management, and inform step-up treatment decisions yet their economic value is unknown, hampering wide... Show moreBACKGROUND: Digital inhalers can monitor inhaler usage, support difficult-to-treat asthma management, and inform step-up treatment decisions yet their economic value is unknown, hampering wide-scale implementation.OBJECTIVE: We aimed to assess the long-term cost-effective-ness of digital inhalerebased medication adherence management in difficult-to-treat asthma.METHODS: A model-based cost-utility analysis was performed. The Markov model structure was determined by biological and clinical understanding of asthma and was further informed by guideline-based assessment of model development. Internal and external validation was performed using the Assessment of the Validation Status of Health-Economic (AdViSHE) tool. The INCA (Inhaler Compliance Assessment) Sun randomized clinical trial data were incorporated into the model to evaluate the cost-effectiveness of digital inhalers. Several long-term clin-ical case scenarios were assessed (reduced number of exacer-bations, increased asthma control, introduction of biosimilars [25% price-cut on biologics]). RESULTS: The long-term modelled cost-effectiveness based on a societal perspective indicated 1-year per-patient costs for digital inhalers and usual care (ie, regular inhalers) of euro7,546 ($7,946) and euro10,752 ($11,322), respectively, reflecting cost savings of euro3,207 ($3,377) for digital inhalers. Using a 10-year interven-tion duration and time horizon resulted in cost savings of euro26,309 ($27,703) for digital inhalers. In the first year, add-on biologic therapies accounted for 69% of the total costs in the usual care group and for 49% in the digital inhaler group. Scenario analyses indicated consistent cost savings ranging from euro2,287 ($2,408) (introduction biosimilars) to euro4,581 ($4,824) (increased control, decreased exacerbations). CONCLUSIONS: In patients with difficult-to-treat asthma, digital inhaler -based interventions can be cost-saving in the long-term by optimizing medication adherence and inhaler technique and reducing add-on biologic prescriptions.(c) 2023 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/) Show less
Webers, C.; Grimm, S.; Tubergen, A. van; Gaalen, F. van; Heijde, D. van der; Joore, M.; Boonen, A. 2023
ObjectiveTo demonstrate the value of diagnosing axSpA, by comparing health and costs associated with available diagnostic algorithms and perfect diagnosis.MethodsUsing data from SPACE and other... Show moreObjectiveTo demonstrate the value of diagnosing axSpA, by comparing health and costs associated with available diagnostic algorithms and perfect diagnosis.MethodsUsing data from SPACE and other cohorts, a model was developed to estimate health (quality-adjusted life-years, QALYs) and costs (healthcare consumption and work productivity losses) of different diagnostic algorithms for axSpA amongst patients with low back pain referred to a rheumatologist, over a 60-year horizon. The model combined a decision-tree (diagnosis) with a state-transition model (treatment). The three algorithms (Berlin [BER, highest specificity], Modification 1 [M1; less strict inflammatory back pain (IBP) criterion] and Modification 2 [M2; IBP not mandatory as entry criterion, highest sensitivity]) were compared. Changes in sensitivity/specificity were explored and the value of perfect diagnosis was investigated.ResultsFor each correctly diagnosed axSpA patient, up to 4.7 QALYs and €60,000 could be gained/saved, considering a societal perspective. Algorithm M2 resulted in more health and lower costs per patient (24.23 QALYs; €157,469), compared to BER (23.96 QALYs; €159,423) and M1 (24.15 QALYs; €158,417). Hypothetical improvements in M2 sensitivity resulted in slightly more value compared to improvements in specificity. Perfect diagnosis can cost €7,500 per patient and still provide enough value.ConclusionCorrect diagnosis of axSpA results in substantial health and cost benefits for patients and society. Not requiring IBP as mandatory for diagnosis of axSpA (algorithm M2) provides more value and would be preferable. A considerably more expensive diagnostic algorithm with better accuracy than M2 would still be considered good value for money. Show less
BackgroundCardiovascular diseases and especially Acute Coronary Syndrome (ACS) constitute a major health issue impacting millions of patients worldwide. Being a leading cause of death and hospital... Show moreBackgroundCardiovascular diseases and especially Acute Coronary Syndrome (ACS) constitute a major health issue impacting millions of patients worldwide. Being a leading cause of death and hospital admissions in many European countries including Spain, it accounts for enormous amounts of healthcare expenditures for its management. Clopidogrel is one of the oldest antiplatelet medications used as standard of care in ACS.MethodsIn this study, we performed an economic evaluation study to estimate whether a genome-guided clopidogrel treatment is cost-effective compared to conventional one in a large cohort of 243 individuals of Spanish origin suffering from ACS and treated with clopidogrel. Data were derived from the U-PGx PREPARE clinical trial. Effectiveness was measured as survival of individuals while study data on safety and efficacy, as well as on resource utilization associated with each adverse drug reaction were used to measure costs to treat these adverse drug reactions. A generalized linear regression model was used to estimate cost differences for both study groups.ResultsBased on our findings, PGx-guided treatment group is cost-effective. PGx-guided treatment demonstrated to have 50% less hospital admissions, reduced emergency visits and almost 13% less ADRs compared to the non-PGx approach with mean QALY 1.07 (95% CI, 1.04-1.10) versus 1.06 (95% CI, 1.03-1.09) for the control group, while life years for both groups were 1.24 (95% CI, 1.20-1.26) and 1.23 (95% CI, 1.19-1.26), respectively. The mean total cost of PGx-guided treatment was 50% less expensive than conventional therapy with clopidogrel [euro883 (95% UI, euro316-euro1582), compared to euro1,755 (95% UI, euro765-euro2949)].ConclusionThese findings suggest that PGx-guided clopidogrel treatment represents a cost-effective option for patients suffering from ACS in the Spanish healthcare setting. Show less
Prooije, T. van; Ruigrok, S.; Berkmortel, N. van den; Maas, R.P.P.W.M.; Wijn, S.; Roon-Mom, W.M.C. van; ... ; Grutters, J.P.C. 2023
ObjectiveThere currently is no disease-modifying therapy for spinocerebellar ataxia type 1 (SCA1). Genetic interventions, such as RNA-based therapies, are being developed but those currently... Show moreObjectiveThere currently is no disease-modifying therapy for spinocerebellar ataxia type 1 (SCA1). Genetic interventions, such as RNA-based therapies, are being developed but those currently available are very expensive. Early evaluation of costs and benefits is, therefore, crucial. By developing a health economic model, we aimed to provide first insights into the potential cost-effectiveness of RNA-based therapies for SCA1 in the Netherlands.MethodsWe simulated disease progression of individuals with SCA1 using a patient-level state-transition model. Five hypothetical treatment strategies with different start and endpoints and level of effectiveness (5-50% reduction in disease progression) were evaluated. Consequences of each strategy were measured in terms of quality-adjusted life years (QALYs), survival, healthcare costs, and maximum costs to be cost effective.ResultsMost QALYs (6.68) are gained when therapy starts during the pre-ataxic stage and continues during the entire disease course. Incremental costs are lowest (- euro14,048) if therapy is stopped when the severe ataxia stage is reached. The maximum costs per year to be cost-effective are euro19,630 in the "stop after moderate ataxia stage" strategy at 50% effectiveness.DiscussionOur model indicates that the maximum price for a hypothetical therapy to be cost-effective is considerably lower than currently available RNA-based therapies. Most value for money can be gained by slowing progression in the early and moderate stages of SCA1 and by stopping therapy upon entering the severe ataxia stage. To allow for such a strategy, it is crucial to identify individuals in early stages of disease, preferably just before symptom onset. Show less
In the current dissertation the effectiveness and cost-effectiveness of Featback, an internet-based self-help intervention for eating disorders, and online support by individuals with a lived... Show moreIn the current dissertation the effectiveness and cost-effectiveness of Featback, an internet-based self-help intervention for eating disorders, and online support by individuals with a lived experience of an eating disorder were investigated. The findings suggest that low-threshold internet-based interventions for eating disorders, such as Featback, can complement existing treatment options in three ways. First, they have been repeatedly found to be effective in reducing eating disorder symptomatology. Second, such interventions can reach individuals that are currently not reached by other forms of treatment and stimulate them to get professional help. Finally, internet-based interventions are likely to be cost-effective compared to care as usual. Concordantly, implementing highly scalable and easily accessible interventions like Featback likely helps to reduce both the individual and societal burden of eating disorders. Show less
Ankle and distal radius fractures are two of the most common musculoskeletal injuries. Over the last decades their incidences have risen due to increasing participation in athletic activities and... Show moreAnkle and distal radius fractures are two of the most common musculoskeletal injuries. Over the last decades their incidences have risen due to increasing participation in athletic activities and ageing of the population. Current national and international protocols recommend frequent outpatient clinic visits in which radiographs of the fractured extremity are obtained. The general aim of this thesis was to evaluate the added value of routine radiography in the follow-up of ankle and distal radius fractures. Specifically, we were interested in investigating whether a follow-up protocol which focuses on reducing the number of routine follow-up radiographs was able to deliver care that was comparable to the current standard of care, but without sacrificing quality nor safety, whilst increasing cost-effectiveness. Chapter 1 provides background information on the epidemiology of ankle and distal radius fractures. It also outlines the current standard of care during treatment and follow-up of the affected patients. In chapter 2 an overview of the current literature on routine radiography in extremity fractures is given. Despite the common occurrence of extremity fractures, limited data were available on the added value of routine radiography at the time that our systematic review was performed in 2018. We identified eleven studies; however, due to theirretrospective design and thus incumbent biases, the resultant quality or certainty of the evidence was considered low. Despite this, the treatment plan was modified in a very small percentage of the cases (ranging from 0 to 2.6%); therefore, the added value of routine radiography seems limited.Following our review in 2018, we conducted a retrospective analysis in four level 1 trauma centres in the Netherlands in order to determine the impact of routine radiographs on treatment strategy for patients with ankle fractures. Chapter 3 illustrates that, in accordance with studies outlined in chapter 2, the use of routine radiographs in the follow-up of ankle fracture patients in the Netherlands was common. In total, 80% of radiographs obtained after more than three weeks of follow-up were considered routine,and only 1.2% of these radiographs resulted in a change of treatment strategy. However, due to its retrospective design, the strength of the evidence was also considered low given its limitations.Chapters 4 and 5 report on the results of a multi-centre randomized controlled trial (RCT) in which participants with an ankle fracture were randomized between the current standard of care consisting of routine follow-up radiography (routine care) and a reduced imaging follow-up regimen. The clinical and functional outcomes outlined in chapter 4 suggest that routine radiographs at week 6 and 12 can be omitted without compromising treatment outcomes. Specifically, functional outcome measured with the Olerud and Molander Ankle Score was non-inferior in the reduced imaging group, while secondary outcomes, such as American Association of Orthopedic Surgeons (AAOS) foot and ankle scores, Health-Related Quality of Life (HRQoL), pain, health perception and self-perceived recovery did not differ between groups. The median number of radiographs obtained was 4 in the reduced imaging group and 5 in the routine care group (a reduction of 20%). Similar numbers and types of complications were observed in both groups; therefore, modifying the current standard of care can be implemented without sacrificing quality nor safety. In chapter 5 the results of the economic evaluation of the reduced-imaging follow-up strategy for ankle fracture patients are presented. Patients randomized to reduced imaging had a similar HRQoL in comparison with patients randomized to routine care. Costs for radiographic imaging were significantly lower in the reduced imaging group (a difference of €48 (95% CI: €-72 to €-28)). Other costs, including overall costs did not statistically differ between the groups. The probability of cost-effectiveness was 0.45 at a willingness-to-pay of €20,000 per QALY. Chapters 6 and 7 report on the outcomes from the same RCT, but which focused on patients with a fracture of the distal radius. Similar to the results of the RCT on anklefractures, functional outcome (measured with the Disabilities of Arm, Shoulder and Hand questionnaire [DASH]) was no worse than the reduced imaging group (chapter 6). Secondary outcomes such as HRQoL, pain and complications demonstrated similar outcomes between the groups. The number of radiographs obtained per patient decreased 25% to median 3 in the reduced imaging group from median 4 in the routine care group. The results of the economic evaluation described in chapter 7 demonstrated similarities to the results of the study on ankle fractures. HRQoL was similar, and costs for radiographic imaging were significantly lower in the reduced imaging group (this reduction was €48 per patient (95% CI: -68 to -27)). The probability of cost-effectiveness was 0.8 to 0.9 at willingness-to-pay of €20,000 to €80,000 per QALY.Following these analyses, we investigated which factors could encourage or discourage physicians to modify their practice behaviours, namely reduce their reliance on routine follow-up radiographs of extremities. These so-called “barriers and facilitators” were queried among orthopaedic trauma surgeons in the Netherlands (chapter 8). In total, 130 respondents (57%) completed the questionnaire, 71% indicated that they would stop ordering routine radiographs if they demonstrated no added value. In short, we identified three facilitators which were found to be independent predictors for the intention to de-implement routine radiographs: 1) ‘the reduced imaging follow-up protocol will lead to lower healthcare costs’; 2) ‘incorporation of the reduced imaging follow-up in regional protocols’; and 3) ‘reduced imaging will result in time-savings for the patient’. There was no barrier that was found to be an independent predictor for the intention to reduce the reliance on routine radiographs. With the three facilitators in mind, a proper de-implementation strategy can be drafted for the Netherlands, and other populations similar as ours. In chapter 9, I present general conclusions and discuss the clinical implications and future perspectives regarding the effectiveness and cost-effectiveness of routine radiography in ankle and distal radius fractures. This large multi-center study demonstrates that the number of routine radiographs in those with ankle and distal radius fractures can be reduced without sacrificing quality nor safety, while resulting in more cost-effective care Show less
Purpose To evaluate cost-effectiveness of an [F-1(8)]FDG-PET/CT-driven diagnostic workup as compared to diagnostic surgery, for thyroid nodules with Bethesda III/IV cytology. [F-1(8)]FDG-PET/CT... Show morePurpose To evaluate cost-effectiveness of an [F-1(8)]FDG-PET/CT-driven diagnostic workup as compared to diagnostic surgery, for thyroid nodules with Bethesda III/IV cytology. [F-1(8)]FDG-PET/CT avoids 40% of futile diagnostic surgeries for benign Bethesda III/IV nodules.Methods Lifelong societal costs and quality-adjusted life years (QALYs) were assessed for 132 patients participating in a randomised controlled multicentre trial comparing [F-18]FDG-PET/CT to diagnostic surgery. The observed 1-year trial results were extrapolated using a Markov model. The probability of cost-effectiveness was estimated using cost-effectiveness acceptability curves, taking uncertainty about sampling, imputation, and parameters into account.Results The observed 1-year cost difference of [F-18]FDG-PET/CT as compared to diagnostic surgery was - (sic)1000 (95% CI: - (sic)2100 to CO) for thyroid nodule-related care (p = 0.06). From the broader societal perspective, the 1-year difference in total societal costs was - (sic)4500 (- (sic)9200 to (sic)150) (p = 0.06). Over the modelled lifelong period, the cost difference was - (sic)9900 (- C23,100 to (sic)3200) (p =0.14). The difference in QALYs was 0.019 (- 0.045 to 0.083) at 1 year (p =0.57) and 0.402 (- 0.581 to 1.385) over the lifelong period (p =0.42). For a willingness to pay of (sic)50,000 per QALY, an [F-18] FDG-PET/CT-driven work-up was the cost-effective strategy with 84% certainty.Conclusion Following the observed reduction in diagnostic surgery, an [F-18]FDG-PET/CT-driven diagnostic workup reduced the 1-year thyroid nodule-related and societal costs while sustaining quality of life. It is very likely cost-effective as compared to diagnostic surgery for Bethesda III/IV nodules. Show less
Aims Non-acute chest pain is a common complaint and can be caused by various conditions. With the rising healthcare expenditures of today, it is necessary to use our healthcare resources... Show moreAims Non-acute chest pain is a common complaint and can be caused by various conditions. With the rising healthcare expenditures of today, it is necessary to use our healthcare resources effectively. This study aims to give insight into the diagnostic effort and costs for patients with non-acute chest pain.Methods and results Financial data of patients without a cardiac history from four hospitals (January 2012-October 2018), who were registered with the national diagnostic code 'no cardiac pathology' (ICD-10 Z13.6), 'chest wall syndrome' (ICD-10 R07.4), or 'stable angina pectoris' (ICD-10 I20.9) were extracted. In total, 74 091 patients were included for analysis and divided into the following final diagnosis groups: no cardiac pathology: N=19 688 (age 5318), 46% male; chest wall syndrome: N=40 858 (age 56 +/- 15), 45% male; and stable angina pectoris (AP): N=13 545 (age 67 +/- 11), 61% male. A total of approximately (sic)142.7 million was spent during diagnostic work-up. The total expenditure during diagnostic effort was (sic)1.97, (sic)8.13, and (sic)10.7 million, respectively for no cardiac pathology, chest wall syndrome, and stable AP per year. After 8years of follow-up, >= 95% of the patients diagnosed with no cardiac pathology or chest wall syndrome had an (cardiac) ischaemic-free survival.Conclusion The diagnostic expenditure and clinical effort to ascertain non-cardiac chest pain are high. We should define what we as society find acceptable as 'assurance costs' with an increasing pressure on the healthcare system and costs. Show less
Wingen-Heimann, S.M.; Prehn, J. van; Kuijper, E.J.; Vehreschild, M.J.G.T. 2021
Pharmacogenomics (PGx) utilizes an individual’s germline genetic profile to identify those who are at higher risk for ADRs or lack of efficacy. This information can be used by healthcare... Show morePharmacogenomics (PGx) utilizes an individual’s germline genetic profile to identify those who are at higher risk for ADRs or lack of efficacy. This information can be used by healthcare professionals (HCPs) to guide dose and drug selection before drug initiation in an effort to optimize drug therapy through precision medicine. Despite both the promise of and the progress in the field of PGx to achieve precision medicine, it is still not routinely applied in patient care. As such, a number of barriers preventing implementation have been identified. These include the undetermined model for delivering PGx, the lack of evidence supporting a PGx panel approach and the lack of tools supporting implementation. Therefore, the work of this thesis aims to support the implementation of precision medicine using PGx panel testing. It reports on generating evidence for PGx panel testing (Part I) and the development of tools facilitating implementation (Part II), evaluates the implementation process utilizing these tools (Part III) and quantifies the impact of PGx implementation on patient outcomes and cost-effectiveness (Part IV). Show less
Background There is an ongoing debate regarding optimal fixation of total knee arthroplasty (TKA), however cost has not been addressed as profoundly. Therefore, the current study primarily aimed to... Show moreBackground There is an ongoing debate regarding optimal fixation of total knee arthroplasty (TKA), however cost has not been addressed as profoundly. Therefore, the current study primarily aimed to compare costs and cost-effectiveness 1 year after cemented or uncemented TKA. A secondary objective was to compare short-term functional outcomes between both groups. Methods A posthoc prospective observational multicenter cohort study of 60 cemented and 50 uncemented Low Contact Stress (LCS) knee systems. Outcome was evaluated using the EuroQol5D-3 L (EQ5D) index, in order to calculate quality adjusted life years (QALYs). Total costs were calculated considering direct costs within the hospital setting (inpatient cost) as well as direct and indirect costs outside the hospital. Cost-effectiveness (total costs per QALY), Oxford Knee Score (OKS) and Numeric Rating Scale (NRS) were compared between cemented and uncemented cases at 1 year after surgery. HealthBASKET project, a micro-costing approach, represents the Dutch costs and situation and was used to calculate hospital stay. (In) direct costs outside the healthcare (medical cost and productivity cost) were determined using two validated questionnaires. Results Median costs per QALY were similar between cemented and uncemented TKA patients (euro16,269 and euro17,727 respectively;p = 0.50). Median OKS (44 and 42;p = 0.79), EQ5D (0.88 and 0.90;p = 0.82) and NRS for pain (1.0 and 1.0;p = 0.48) and satisfaction (9.0 and 9.0;p = 0.15) were also comparable between both groups. Conclusion For this type of knee implant (LCS), inpatient hospital costs and costs after hospitalization were comparable between groups. Show less
Burg, E.L. van den; Schoonakker, M.P.; Peet, P.G. van; Akker-van Marle, M.E. van den; Dijk, K.W. van; Longo, V.D.; ... ; Pijl, H. 2020
Background Caloric restriction is an effective way to treat Type 2 diabetes (T2D). However, chronic and severe restriction of food intake is difficult to sustain and is known to promote slower... Show moreBackground Caloric restriction is an effective way to treat Type 2 diabetes (T2D). However, chronic and severe restriction of food intake is difficult to sustain and is known to promote slower metabolism. Intermittent and frequent fasting can exert similar metabolic effects, but may be even more challenging for most patients. A fasting-mimicking diet (FMD) is low in calories, sugars and proteins, but includes relatively high levels of plant based complex carbohydrates and healthy fats. The metabolic effects of such a diet mimic the benefits of water-only fasting. The effects of a FMD applied periodically in T2D patients are still unknown. The Fasting In diabetes Treatment (FIT) trial was designed to determine the effect of intermittent use (5 consecutive days a month during a year) of a FMD in T2D patients on metabolic parameters and T2D medication use compared to usual care. Methods One hundred T2D patients from general practices in the Netherlands with a BMI >= 27 kg/m(2), treated with lifestyle advice only or lifestyle advice plus metformin, will be randomised to receive the FMD plus usual care or usual care only. Primary outcomes are HbA1c and T2D medication dosage. Secondary outcomes are anthropometrics, blood pressure, plasma lipid profiles, quality of life, treatment satisfaction, metabolomics, microbiome composition, MRI data including cardiac function, fat distribution and ectopic fat storage, cost-effectiveness, and feasibility in clinical practice. Discussion This study will establish whether monthly 5-day cycles of a FMD during a year improve metabolic parameters and/or reduce the need for medication in T2D. Furthermore, additional health benefits and the feasibility in clinical practice will be measured and a cost-effectiveness evaluation will be performed. Show less
Background The present study aims to assess the cost-effectiveness of an influenza vaccination program for children in the Netherlands. This requires an evaluation of the long-term impact of such a... Show moreBackground The present study aims to assess the cost-effectiveness of an influenza vaccination program for children in the Netherlands. This requires an evaluation of the long-term impact of such a program on the burden of influenza across all age groups, using a transmission model that accounts for the seasonal variability in vaccine effectiveness and the shorter duration of protection following vaccination as compared to natural infection. Methods We performed a cost-effectiveness analysis based on a stochastic dynamic transmission model that has been calibrated to reported GP visits with influenza-like illness in the Netherlands over 11 seasons (2003/2004 to 2014/2015). We analyzed the costs and effects of extending the current program with vaccination of children aged 2-16 years at 50% coverage over 20 consecutive seasons. We measured the effects in quality-adjusted life-years (QALYs) and we adopted a societal perspective. Results The childhood vaccination program is estimated to have an average incremental cost-effectiveness ratio (ICER) of euro3944 per QALY gained and is cost-effective in the general population (across 1000 simulations; conventional Dutch threshold of euro20,000 per QALY gained). The childhood vaccination program is not estimated to be cost-effective for the target-group itself with an average ICER of euro57,054 per QALY gained. Uncertainty analyses reveal that these ICERs hide a wide range of outcomes. Even though introduction of a childhood vaccination program decreases the number of infections, it tends to lead to larger epidemics: in 23.3% of 1000 simulations, the childhood vaccination program results in an increase in seasons with a symptomatic attack rate larger than 5%, which is expected to cause serious strain on the health care system. In 6.4% of 1000 simulations, the childhood vaccination program leads to a net loss of QALYs. These findings are robust across different targeted age groups and vaccination coverages. Conclusions Modeling indicates that childhood influenza vaccination is cost-effective in the Netherlands. However, childhood influenza vaccination is not cost-effective when only outcomes for the children themselves are considered. In approximately a quarter of the simulations, the introduction of a childhood vaccination program increases the frequency of seasons with a symptomatic attack rate larger than 5%. The possibility of an overall health loss cannot be excluded. Show less
Aim This study aimed at evaluating the cost-effectiveness of different non-invasive imaging-guided strategies for the diagnosis of obstructive coronary artery disease (CAD) in a European population... Show moreAim This study aimed at evaluating the cost-effectiveness of different non-invasive imaging-guided strategies for the diagnosis of obstructive coronary artery disease (CAD) in a European population of patients from the Evaluation of Integrated Cardiac Imaging in Ischemic Heart Disease (EVINCI) study. Methods and results Cost-effectiveness analysis was performed in 350 patients (209 males, mean age 59 +/- 9 years) with symptoms of suspected stable CAD undergoing computed tomography coronary angiography (CTCA) and at least one cardiac imaging stress-test prior to invasive coronary angiography (ICA) and in whom imaging exams were analysed at dedicated core laboratories. Stand-alone stress-tests or combined non-invasive strategies, when the first exam was uncertain, were compared. The diagnostic end-point was obstructive CAD defined as > 50% stenosis at quantitative ICA in the left main or at least one major coronary vessel. Effectiveness was defined as the percentage of correct diagnosis (cd) and costs were calculated using country-specific reimbursements. Incremental cost-effectiveness ratios (ICERs) were obtained using per-patient data and considering "no-imaging" as reference. The overall prevalence of obstructive CAD was 28%. Strategies combining CTCA followed by stress ECHO, SPECT, PET, or stress CMR followed by CTCA, were all cost-effective. ICERs values indicated cost saving from - 969euro/cd for CMR-CTCA to - 1490euro/cd for CTCA-PET, - 3092euro/cd for CTCA-SPECT and - 3776euro/cd for CTCA-ECHO. Similarly when considering early revascularization as effectiveness measure. Conclusion In patients with suspected stable CAD and low prevalence of disease, combined non-invasive strategies with CTCA and stress-imaging are cost-effective as gatekeepers to ICA and to select candidates for early revascularization. Show less
Background Only a minority of dialysis patients with depressive symptoms are diagnosed and receive treatment. Depressive symptoms are highly prevalent in this population and are associated with... Show moreBackground Only a minority of dialysis patients with depressive symptoms are diagnosed and receive treatment. Depressive symptoms are highly prevalent in this population and are associated with adverse clinical outcomes. Underlying factors for this undertreatment may be the lack of evidence for the safety and effectivity of antidepressant medication, the reluctance of patients to adhere to antidepressant medication, the lack of mental healthcare provision in somatic healthcare environments and end-stage renal disease (ESRD) related physical limitations that complicate face-to-face psychotherapy. Guided Internet-based self-help treatment has demonstrated to be effective for depressive symptoms in other chronic patient populations and may overcome these barriers. The aim of this study is to investigate the (cost) effectiveness of a guided Internet-based self-help intervention for symptoms of depression in dialysis patients. Methods This study is a cluster randomized controlled trial (RCT) that investigates the effectiveness of a 5-week Internet-based self-help Problem Solving Therapy (PST) for depressive symptoms in dialysis patients. Depressive symptoms will be measured using the Beck Depression Inventory - second edition (BDI-II), with a cut-off score of >= 10. We aim to include 206 dialysis patients with depressive symptoms who will be cluster randomized to the intervention or the Care as Usual (CAU) control group. Secondary outcomes will include anxiety symptoms, quality of life, economic costs and clinical outcomes, such as inflammatory factors and hair cortisol levels. Assessments will take place at baseline (T0), 2 weeks after intervention (T1) and 6 months (T2), 12 months (T3) and 18 months (T4) after intervention. The control group will be measured at the same time points. Analysis will be based on the intention-to-treat principle. Mixed models will be used to assess the changes within each condition between pre-treatment and post-treatment. Discussion If demonstrated to be (cost) effective, Internet-based PST will offer new possibilities to treat dialysis patients with depressive symptoms and to improve their quality of care. Show less
Introduction The primary aim was to assess and compare the total costs (direct health care costs and indirect costs due to loss of production) after early mobilization versus plaster immobilization... Show moreIntroduction The primary aim was to assess and compare the total costs (direct health care costs and indirect costs due to loss of production) after early mobilization versus plaster immobilization in patients with a simple elbow dislocation. It was hypothesized that early mobilization would not lead to higher direct and indirect costs. Materials and methods This study used data of a multicenter randomized clinical trial (FuncSiE trial). From August 25, 2009 until September 18, 2012, 100 adult patients with a simple elbow dislocation were recruited and randomized to early mobilization (immediate motion exercises; n = 48) or 3 weeks plaster immobilization (n = 52). Patients completed questionnaires on health-related quality of life [EuroQoL-5D (EQ-5D) and Short Form-36 (SF-36 PCS and SF-36 MCS)], health care use, and work absence. Follow-up was 1 year. Primary outcome were the total costs at 1 year. Analysis was by intention to treat. Results There were no significant differences in EQ-5D, SF-36 PCS, and SF-36 MCS between the two groups. Mean total costs per patient were euro3624 in the early mobilization group versus euro7072 in the plaster group (p = 0.094). Shorter work absenteeism in the early mobilization group (10 versus 18 days; p = 0.027) did not lead to significantly lower costs for loss of productivity (euro1719 in the early mobilization group versus euro4589; p = 0.120). Conclusion From a clinical and a socio-economic point of view, early mobilization should be the treatment of choice for a simple elbow dislocation. Plaster immobilization has inferior results at almost double the cost. Show less
This thesis on systemic treatment options in soft tissue sarcomas consists of two parts. In part I, the pharmacogenetics of systemic gastro-intestinal stromal tumors (GIST) treatment is... Show moreThis thesis on systemic treatment options in soft tissue sarcomas consists of two parts. In part I, the pharmacogenetics of systemic gastro-intestinal stromal tumors (GIST) treatment is investigated. SNPs related to the pharmacokinetics and pharmacodynamics of imatinib and sunitinib have been associated to survival and to toxicity. SNPs in VEGFA and SLCO1B3 have been associated to worse progression free survival during imatinib treatment of advanced GIST. SNPs in ABCG2 and CYP1A2 have been associated with the need for dose reduction in patients receiving imatinib for GIST. A SNP in POR was associated with better progression free survival during sunitinib treatment of advanced GIST . In part II the usage of trabectedin is soft tissue sarcomas (STS) in the Netherlands is studied. Trabectedin as second line treatment of soft tissue sarcoma was compared to ifosfamide monotherapy. The Incremental Cost-Effectiveness Ratio for leiomyosarcomas and liposarcomas was at the top end of what is considered acceptable in the Netherlands. For other soft tissue sarcomas subtypes, ifosfamide dominated trabectedin. The venous access related adverse events of trabectedin have been described. The research in this thesis contributes towards personalised treatment for advanced soft tissue sarcomas. Show less
Verheijen, E.; Munts, A.G.; Haagen, O. van; Vries, D. de; Dekkers, O.; Hout, W. van den; Vleggeert-Lankamp, C. 2019
This dissertation contains the results of an RCT into the effectiveness of an online self-help intervention for people living with HIV (PLWH) and depressive symptoms. Many PLWH suffer from... Show moreThis dissertation contains the results of an RCT into the effectiveness of an online self-help intervention for people living with HIV (PLWH) and depressive symptoms. Many PLWH suffer from depressive symptoms. Online interventions to treat depression may have benefits, such as less perceived stigma, a large reach and high accessibility. The online self-help intervention that we investigated is based on cognitive behavioral therapy and contains 4 components: stimulating activities, relaxation exercises, changing negative thoughts and goal attainment. Two meta-analyses were conducted and the results point to the effectiveness of psychosocial interventions for PLWH to improve depressive symptoms, anxiety symptoms, quality of life, psychological well-being, and medication adherence. The most important result of the RCT was that the intervention together with telephone coaching is effective in reducing depressive symptoms, compared to an attention-only control group. It was also found that the intervention may be effective for all PLWH, regardless of certain baseline characteristics. Furthermore, behavioral activation and goal reengagement were found to be mediators of the intervention effect. Also, the intervention is likely to be cost-effective compared to attention only. As eHealth interventions have benefits compared to face-to-face interventions, they should be more widely implemented in the mental healthcare for PLWH. Show less
