Objectives To compare the effectiveness of longstanding (>52 weeks), supervised exercise therapy with usual care in adults with rheumatoid arthritis (RA) and severe functional limitations.Methods P... Show moreObjectives To compare the effectiveness of longstanding (>52 weeks), supervised exercise therapy with usual care in adults with rheumatoid arthritis (RA) and severe functional limitations.Methods Participants were randomised 1:1 to the intervention (individualised goal-setting, active exercises, education and self-management regarding physical activity) or usual care. Primary endpoint was the change in the Patient-Specific Complaints activity ranked 1 (PSC1, 0–10) at 52 weeks. Secondary endpoints included the PSC activities ranked 2 and 3 (PSC2, PSC3), Health Assessment Questionnaire-Disability Index (HAQ-DI), Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL), 6-minute walk test (6MWT), Patient Reported Outcome Measurement Information System Physical Function-10 (PROMIS PF-10) and the Short Form-36 Physical and Mental Component Summary Scales (SF-36 PCS and MCS). (Serious) Adverse events (AEs) were recorded. Measurements were done by blinded assessors. Analyses at 52 weeks were based on the intention-to-treat principle.Results In total, 217 people (90% female, age 58.8 (SD 12.9) years) were randomised (n=104 intervention, n=98 usual care available for analyses). At 52 weeks, the improvement of the PSC1 was significantly larger in the intervention group (mean difference (95% CI) −1.7 (−2.4, –1.0)). Except for the SF-36 MCS, all secondary outcomes showed significantly greater improvements favouring the intervention (PSC2 −1.8 (−2.4, –1.1), PSC3 −1.7 (−2.4, −1.0), PROMIS PF-10 +3.09 (1.80, 4.38), HAQ-DI −0.17 (−0.29, –0.06), RAQoL −2.03 (−3.39, –0.69), SF-36 PCS +3.83 (1.49, 6.17) and 6MWT +56 (38, 75) m). One mild, transient AE occurred in the intervention group.Conclusion Longstanding, supervised exercise therapy was more effective than usual care in people with RA and severe functional limitations. Show less
BackgroundAutoimmune hepatitis (AIH) is a rare, chronic inflammatory disease of the liver. The treatment goal is reaching complete biochemical response (CR), defined as the normalisation of... Show moreBackgroundAutoimmune hepatitis (AIH) is a rare, chronic inflammatory disease of the liver. The treatment goal is reaching complete biochemical response (CR), defined as the normalisation of aspartate and alanine aminotransferases and immunoglobulin gamma. Ongoing AIH activity can lead to fibrosis and (decompensated) cirrhosis. Incomplete biochemical response is the most important risk factor for liver transplantation or liver-related mortality. First-line treatment consists of a combination of azathioprine and prednisolone. If CR is not reached, tacrolimus (TAC) or mycophenolate mofetil (MMF) can be used as second-line therapy. Both products are registered for the prevention of graft rejection in solid organ transplant recipients. The aim of this study is to compare the effectiveness and safety of TAC and MMF as second-line treatment for AIH.MethodsThe TAILOR study is a phase IIIB, multicentre, open-label, parallel-group, randomised (1:1) controlled trial performed in large teaching and university hospitals in the Netherlands. We will enrol 86 patients with AIH who have not reached CR after at least 6 months of treatment with first-line therapy. Patients are randomised to TAC (0.07 mg/kg/day initially and adjusted by trough levels) or MMF (max 2000 mg/day), stratified by the presence of cirrhosis at inclusion. The primary endpoint is the difference in the proportion of patients reaching CR after 12 months. Secondary endpoints include the difference in the proportion of patients reaching CR after 6 months, adverse effects, difference in fibrogenesis, quality of life and cost-effectiveness.DiscussionThis is the first randomised controlled trial comparing two second-line therapies for AIH. Currently, second-line treatment is based on retrospective cohort studies. The rarity of AIH is the main issue in clinical research for alternative treatment options. The results of this trial can be implemented in existing international clinical guidelines.Trial registrationClinicalTrials.gov NCT05221411. Retrospectively registered on 3 February 2022; EudraCT number 2021-003420-33. Prospectively registered on 16 June 2021. Show less
Introduction Vasoplegia is a common complication after cardiac surgery and is associated with poor prognosis. It is characterised by refractory hypotension despite normal or even increased cardiac... Show moreIntroduction Vasoplegia is a common complication after cardiac surgery and is associated with poor prognosis. It is characterised by refractory hypotension despite normal or even increased cardiac output. The pathophysiology is complex and includes the systemic inflammatory response caused by cardiopulmonary bypass (CPB) and surgical trauma. Patients with end-stage heart failure (HF) are at increased risk for developing vasoplegia. The CytoSorb adsorber is a relatively new haemoadsorption device which can remove circulating inflammatory mediators in a concentration based manner. The CytoSorb-HF trial aims to evaluate the efficacy of CytoSorb haemoadsorption in limiting the systemic inflammatory response and preventing postoperative vasoplegia in HF patients undergoing cardiac surgery with CPB. Methods and analysis This is an investigator-initiated, single-centre, randomised, controlled clinical trial. In total 36 HF patients undergoing elective cardiac surgery with an expected CPB duration of more than 120 min will be randomised to receive CytoSorb haemoadsorption along with standard surgical treatment or standard surgical treatment alone. The primary endpoint is the change in systemic vascular resistance index with phenylephrine challenge after CPB. Secondary endpoints include inflammatory markers, sublingual microcirculation parameters and 30-day clinical indices. In addition, we will assess the cost-effectiveness of using the CytoSorb adsorber. Vascular reactivity in response to phenylephrine challenge will be assessed after induction, after CPB and on postoperative day 1. At the same time points, and before induction and on postoperative day 4 (5 time points in total), blood samples will be collected and the sublingual microcirculation will be recorded. Study participants will be followed up until day 30.Ethics and dissemination The trial protocol was approved by the Medical Ethical Committee of Leiden The Hague Delft (METC LDD, registration number P20.039). The results of the trial will be published in peer-reviewed medical journals and through scientific conferences. Show less
Wouden, C.H. van der; Marck, H.; Guchelaar, H.J.; Swen, J.J.; Hout, W.B. van den 2022
Aim: Prospective studies support the clinical impact of pharmacogenomics (PGx)-guided prescribing to reduce severe and potentially fatal adverse effects. Drug-gene interactions (DGIs) preventing... Show moreAim: Prospective studies support the clinical impact of pharmacogenomics (PGx)-guided prescribing to reduce severe and potentially fatal adverse effects. Drug-gene interactions (DGIs) preventing potential drug-related deaths have been categorized as "essential" by the Dutch Pharmacogenetics Working Group (DPWG). The collective clinical impact and cost-effectiveness of this sub-set is yet undetermined. Therefore, we aim to assess impact and cost-effectiveness of "essential" PGx tests for prevention of gene-drug-related deaths, when adopted nation-wide. Methods: We used a decision-analytic model to quantify the number and cost per gene-drug-related death prevented, from a 1-year Dutch healthcare perspective. The modelled intervention is a single gene PGx-test for CYP2C19, DPYD, TPMT or UGT1A1 to guide prescribing based on the DPWG recommendations among patients in the Netherlands initiating interacting drugs (clopidogrel, capecitabine, systemic fluorouracil, azathioprine, mercaptopurine, tioguanine or irinotecan). Results: For 148,128 patients initiating one of seven drugs in a given year, costs for PGx-testing, interpretation, and drugs would increase by euro21.4 million. Of these drug initiators, 35,762 (24.1%) would require an alternative dose or drug. PGx-guided prescribing would relatively reduce gene-drug related mortality by 10.6% (range per DGI: 8.1-14.5%) and prevent 419 (0.3% of initiators) deaths a year. Cost-effectiveness is estimated at euro51,000 per prevented gene-drug-related death (range per DGI: euro-752,000-euro633,000). Conclusion: Adoption of PGx-guided prescribing for "essential" DGIs potentially saves the lives of 0.3% of drug initiators, at reasonable costs. Show less
Poort, E.K.J. van der; Akker-van Marle, E. van den; Stiggelbout, A.M.; Hout, W.B. van den 2022
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
Chung, J.E.R.E.W.; Geet, R. van; Helmond, N. van; Kastoer, C.; Bohringer, S.; Hout, W.B. van den; ... ; Blom, H.M. 2022
IMPORTANCE Carbon dioxide laser tonsillotomy performed under local anesthesia may be an effective and less invasive alternative than dissection tonsillectomy for treatment of tonsil-related... Show moreIMPORTANCE Carbon dioxide laser tonsillotomy performed under local anesthesia may be an effective and less invasive alternative than dissection tonsillectomy for treatment of tonsil-related afflictions.OBJECTIVE To compare functional recovery and symptom relief among adults undergoing tonsillectomy or tonsillotomy.DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial was conducted at 5 secondary and tertiary hospitals in the Netherlands from January 2018 to December 2019. Participants were 199 adult patients with an indication for surgical tonsil removal randomly assigned to either the tonsillectomy or tonsillotomy group.INTERVENTIONS For tonsillotomy, the crypts of the palatine tonsil were evaporated using a carbon dioxide laser under local anesthesia, whereas tonsillectomy consisted of total tonsil removal performed under general anesthesia.MAIN OUTCOMES AND MEASURES The primary outcome was time to functional recovery measured within 2 weeks after surgery assessed for a modified intention-to-treat population. Secondary outcomes were time to return to work after surgery, resolution of primary symptoms, severity of remaining symptoms, surgical complications, postoperative pain and analgesics use, and overall patient satisfaction assessed for the intention-to-treat population.RESULTS Of 199 patients (139 (70%] female; mean [SD] age, 29 [9] years), 98 were randomly assigned to tonsillotomy and 101v were randomly assigned to tonsillectomy. Recovery within 2 weeks after surgery was significantly shorter after tonsillotomy than after tonsillectomy (hazard ratio for recovery after tonsillectomy vs tonsillotomy, 0.3; 95% CI, 0.2-0.5). Two weeks after surgery, 72 (77%) patients in the tonsillotomy group were fully recovered compared with 26 (57%) patients in the tonsillectomy group. Time until return to work within 2 weeks was also shorter after tonsillotomy (median [IQR], 4.5 [3.0-7.0] days vs 12.0 [9.0-14.0] days; hazard ratio for return after tonsillectomy vs tonsillotomy, 0.3; 95% CI, 0.2-0.4.). Postoperative hemorrhage occurred in 2 patients (2%) in the tonsillotomy group and 8 patients (12%) in the tonsillectomy group. At 6 months after surgery, fewer patients in the tonsillectomy group (25; 35%) than in the tonsillotomy group (54; 57%) experienced persistent symptoms (difference of 22%; 95% CI, 7%-37%). Most patients with persistent symptoms in both the tonsillotomy (32 of 54; 59%) and tonsillectomy (16 of 25; 64%) groups reported mild symptoms 6 months after surgery.CONCLUSIONS AND RELEVANCE This randomized clinical trial found that compared with tonsillectomy performed under general anesthesia, laser tonsillotomy performed under local anesthesia had a significantly shorter and less painful recovery period. A higher percentage of patients had persistent symptoms after tonsillotomy, although the intensity of these symptoms was lower than before surgery. These results suggest that laser tonsillotomy performed under local anesthesia may be a feasible alternative to conventional tonsillectomy in this population. Show less
Background Aggression and violent incidents are a major concern in psychiatric in-patient care. Nutritional supplementation has been found to reduce aggressive incidents and rule violations in... Show moreBackground Aggression and violent incidents are a major concern in psychiatric in-patient care. Nutritional supplementation has been found to reduce aggressive incidents and rule violations in forensic populations and children with behavioural problems. Aims To assess whether multivitamin, mineral and n-3 polyunsaturated fatty acid supplementation would reduce the number of aggressive incidents among long-stay psychiatric in-patients. Method The trial was a pragmatic, multicentre, randomised, double-blind placebo-controlled study. Data were collected from 25 July 2016 to 29 October 2019, at eight local sites for mental healthcare in The Netherlands and Belgium. Participants were randomised (1:1) to receive 6-month treatment with either three supplements containing multivitamins, minerals and n-3 polyunsaturated fatty acid, or placebo. The primary outcome was the number of aggressive incidents, determined by the Staff Observation Aggression Scale - Revised (SOAS-R). Secondary outcomes were patient quality of life, affective symptoms and adverse events. Results In total, 176 participants were randomised (supplements, n = 87; placebo, n = 89). Participants were on average 49.3 years old (s.d. 14.5) and 64.2% were male. Most patients had a psychotic disorder (60.8%). The primary outcome of SOAS-R incidents was similar in supplement (1.03 incidents per month, 95% CI 0.74-1.37) and placebo groups (0.90 incidents per month, 95% CI 0.65-1.19), with a rate ratio of 1.08 (95% CI 0.67-1.74, P = 0.75). Differential effects were not found in sensitivity analyses on the SOAS-R or on secondary outcomes. Conclusions Six months of nutritional supplementation did not reduce aggressive incidents among long-stay psychiatric in-patients. Show less
Purpose To assess the impact of an [F-18]FDG-PET/CT-driven diagnostic workup to rule out malignancy, avoid futile diagnostic surgeries, and improve patient outcomes in thyroid nodules with... Show morePurpose To assess the impact of an [F-18]FDG-PET/CT-driven diagnostic workup to rule out malignancy, avoid futile diagnostic surgeries, and improve patient outcomes in thyroid nodules with indeterminate cytology.Methods In this double-blinded, randomised controlled multicentre trial, 132 adult euthyroid patients with scheduled diagnostic surgery for a Bethesda III or IV thyroid nodule underwent [F-18]FDG-PET/CT and were randomised to an [F-18] FDG-PET/CT-driven or diagnostic surgery group. In the [F-18]FDG-PET/CT-driven group, management was based on the [F-18]FDG-PET/CT result: when the index nodule was visually [F-18]FDG-positive, diagnostic surgery was advised; when [F-18]FDG-negative, active surveillance was recommended. The nodule was presumed benign when it remained unchanged on ultrasound surveillance. In the diagnostic surgery group, all patients were advised to proceed to the scheduled surgery, according to current guidelines. The primary outcome was the fraction of unbeneficial patient management in one year, i.e., diagnostic surgery for benign nodules and active surveillance for malignant/borderline nodules. Intention-to-treat analysis was performed. Subgroup analyses were performed for non-Hurthle cell and Hurthle cell nodules.Results Patient management was unbeneficial in 42% (38/91 [95% confidence interval [CI], 32-53%]) of patients in the [F-18] FDG-PET/CT-driven group, as compared to 83% (34/41 [95% CI, 68-93%]) in the diagnostic surgery group (p < 0.001). [F-18]FDG-PET/CT-driven management avoided 40% (25/63 [95% CI, 28-53%]) diagnostic surgeries for benign nodules: 48% (23/48 [95% CI, 33-63%]) in non-Hurthle cell and 13% (2/15 [95% CI, 2-40%]) in I-Liable cell nodules (p = 0.02). No malignant or borderline tumours were observed in patients under surveillance. Sensitivity, specificity, negative and positive predictive value, and benign call rate (95% CI) of [F-18]FDG-PET/CT were 94.1% (80.3-99.3%), 39.8% (30.0-50.2%), 95.1% (83.5-99.4%), 35.2% (25.4-45.9%), and 31.1% (23.3-39.7%), respectively.Conclusion An [F-18]FDG-PET/CT-driven diagnostic workup of indeterminate thyroid nodules leads to practice changing management, accurately and oncologically safely reducing futile surgeries by 40%. For optimal therapeutic yield, application should be limited to non-Hurthle cell nodules. Show less
Manson, L.E.N.; Hout, W.B. van den; Guchelaar, H.J. 2022
Human Leukocyte Antigen (HLA) variants can be a risk factor for developing potentially fatal drug hypersensitivity reactions. Our aim was to estimate the potential impact of genotyping for the HLA... Show moreHuman Leukocyte Antigen (HLA) variants can be a risk factor for developing potentially fatal drug hypersensitivity reactions. Our aim was to estimate the potential impact of genotyping for the HLA risk alleles incorporated in the Dutch Pharmacogenetics Working Group (DPWG) guidelines in The Netherlands. We estimated the number of hypersensitivity reactions and associated deaths that can be avoided annually by genotyping for these HLA risk alleles. Additionally, the cost-effectiveness was estimated. Nationwide implementation of genotyping HLA risk alleles before initiating drugs with an actionable drug-gene interaction can potentially save the life of seven allopurinol initiators and two flucloxacillin initiators each year in The Netherlands. Besides these deaths, 28 cases of abacavir hypersensitivity, 24 cases of allopurinol induced SCARs, 6 cases of carbamazepine induced DRESS and 22 cases of flucloxacillin induced DILI can be prevented. Genotyping HLA-B*5701 in abacavir initiators has a number needed to genotype of 31 to prevent one case of abacavir hypersensitivity and is cost-saving. Genotyping HLA-B*5801 in allopurinol initiators has a number needed to genotype of 1149 to prevent one case of SCAR but is still cost-effective. Genotyping before initiating antiepileptic drugs or flucloxacillin is not cost-effective. Our results confirm the need for mandatory testing of HLA-B*5701 in abacavir initiators, as indicated in the drug label, and show genotyping of HLA-B*5801 in allopurinol initiators should be considered. Show less
Markus-Doornbosch, F. van; Meesters, J.J.; Volker, G.; Ijzereef, W.A.; Hout, W.B. van den; Vlieland, T.P.V.; Kloet, A.J. de 2022
BACKGROUND: Persons with disabilities are at risk for unemployment with negative long-term consequences.OBJECTIVE: This study aimed to explore the process and outcomes of a novel vocational... Show moreBACKGROUND: Persons with disabilities are at risk for unemployment with negative long-term consequences.OBJECTIVE: This study aimed to explore the process and outcomes of a novel vocational rehabilitation (VR) program based on the concept of mentorship.METHODS: Observational, retrospective study including unemployed young adults with acquired brain injury (ABI) taking part in a VR program including assessment, training, individual counselling and mentor support from volunteering professionals. Adherence to the program and work status were registered and at follow-up all patients were invited to complete a general questionnaire and EuroQol 5D.RESULTS: 49 patients started the program, with 41 completing the follow-up. Median age was 31 years and 19 were male. Median duration of the program was 8 months. At follow-up, 9 patients had acquired paid employment, 7 with the support of a mentor; 6 of whom were bothered by health problems at work. Nine patients left the program prematurely, with insufficient financial support for continuation being the primary reason for withdrawal (n = 6).CONCLUSIONS: A VR program including a mentor may be a promising program for patients who are unemployed at onset of ABI. Lack of financial support to complete the program and concurrent health problems were found to hamper the process and outcomes of the program, respectively. Show less
Birkenhager-Gillesse, E.G.; Achterberg, W.P.; Janus, S.I.M.; Zuidema, S.U.; Hout, W.B. van den 2022
Introduction: We evaluated the cost-effectiveness of the "More at Home with Dementia" intervention, a multicomponent training program for co-residing caregivers of people with dementia (PwDs).... Show moreIntroduction: We evaluated the cost-effectiveness of the "More at Home with Dementia" intervention, a multicomponent training program for co-residing caregivers of people with dementia (PwDs). Methods: We performed a two-armed randomized controlled trial with an intervention and a control group. Participants were community-dwelling caregivers living with a person with dementia (59 randomized to intervention and 50 to control arm). The training program lasted 5 days and took place in a holiday accommodation. Quality-adjusted life-years (QALYs) were calculated using the EuroQol-5 Dimensions 3 Levels (EQ-5D-3L) for caregivers and PwDs. Costs for informal and formal social care, as well as health care, were collected at four times over a 6-month period from baseline. Information on nursing home admission or death was collected for 2 years after baseline. Results: QALYs for caregivers and PwDs added together were 0.12 higher in the intervention group compared with the control group (P = .11). After 1 year, there tended to be fewer nursing home admissions in the intervention group, but this difference was lost by 2 years (P = .19). The cost of the intervention was estimated at euro1000 (USD 1090) per dyad. Compared with the control group, the intervention group used other health care and formal social care significantly less for a year after baseline (P = .02 and .001, respectively). The estimated decrease in total costs was euro10,437 (P = .07), with an estimated 96% probability that the intervention was cost-effective vs usual care. Discussion: The multicomponent "More at Home with Dementia" training program is effective and appears to save costs compared with usual care. Savings appear to be achieved by delaying nursing home admissions and by reducing the use of other care resources. Further research is also needed to clarify if this intervention is effective for caregivers who do not live with a PwD, such as adult children, and for the caregivers of patients with other debilitating chronic diseases. At the same time, effort is advised to implement caregiver training in standard care programs. Show less
Study Design: Literature review.Objective: To describe whether practice variation studies on surgery in patients with lumbar degenerative disc disease used adequate study methodology to identify... Show moreStudy Design: Literature review.Objective: To describe whether practice variation studies on surgery in patients with lumbar degenerative disc disease used adequate study methodology to identify unwarranted variation, and to inform quality improvement in clinical practice. Secondary aim was to describe whether variation changed over time.Methods: Literature databases were searched up to May 4th, 2021. To define whether study design was appropriate to identify unwarranted variation, we extracted data on level of aggregation, study population, and case-mix correction. To define whether studies were appropriate to achieve quality improvement, data were extracted on outcomes, explanatory variables, description of scientific basis, and given recommendations. Spearman's rho was used to determine the association between the Extreme Quotient (EQ) and year of publication.Results: We identified 34 articles published between 1990 and 2020. Twenty-six articles (76%) defined the diagnosis. Prior surgery cases were excluded or adjusted for in 5 articles (15%). Twenty-three articles (68%) adjusted for case-mix. Variation in outcomes was analyzed in 7 articles (21%). Fourteen articles (41%) identified explanatory variables. Twenty-six articles (76%) described the evidence on effectiveness. Recommendations for clinical practice were given in 9 articles (26%). Extreme Quotients ranged between 1-fold and 15-fold variation and did not show a significant change over time (rho= -.33, P= .09).Conclusions: Practice variation research on surgery in patients with degenerative disc disease showed important limitations to identify unwarranted variation and to achieve quality improvement by public reporting. Despite the availability of new evidence, we could not observe a significant decrease in variation over time. Show less
Suvaal, I.; Hummel, S.B.; Mens, J.W.M.; Doorn, H.C. van; Hout, W.B. van den; Creutzberg, C.L.; Kuile, M.M. ter 2021
Background: Sexual problems are frequently reported after treatment with radiotherapy (RT) for gynaecological cancer (GC), in particular after combined external beam radiotherapy and brachytherapy ... Show moreBackground: Sexual problems are frequently reported after treatment with radiotherapy (RT) for gynaecological cancer (GC), in particular after combined external beam radiotherapy and brachytherapy (EBRT+BT). Studies demonstrate that psychosexual support should include cognitive behavioural interventions and involvement of the patient's partner, if available. Therefore, we developed a nurse-led sexual rehabilitation intervention, including these key components. The intervention was previously pilot-tested and results demonstrated that this intervention improves women's sexual functioning and increases dilator compliance. The objective of the current study is to investigate the (cost-)effectiveness of the intervention compared to optimal care as usual (CAU). We expect that women who receive the intervention will report a statistically significant greater improvement in sexual functioning and - for women who receive EBRT+BT - higher compliance with dilator use, from baseline to 12 months post-RT than women who receive optimal care as usual (CAU).Methods/design: The intervention is evaluated in the SPARC (Sexual rehabilitation Programme After Radiotherapy for gynaecological Cancer) study, a multicentre, randomized controlled trial (RCT). The primary endpoint is sexual functioning. Secondary outcomes include body image, fear of sexual activity, sexual-, treatment-related- and psychological distress, health-related quality of life and relationship satisfaction. A cost-effectiveness analysis (CEA) will be conducted in which the costs of the intervention will be related to shifts in other health care costs and the impact on patient outcome. The study sample will consist of 220 women with GC treated with RT in specialized GC treatment centres (N = 10). Participants are randomized to either the intervention- or CAU control group (1:1), and within each centre stratified by type of radiotherapy (EBRT+BT vs. EBRT only) and having a partner (yes/no). All women complete questionnaires at baseline (T1) and at 1, 3, 6, and 12 months post-RT (T2, T3, T4 and T5, respectively).Discussion: There is a need to improve sexual functioning after RT for GC. This RCT will provide evidence about the (cost-)effectiveness of a nurse-led sexual rehabilitation intervention. If proven effective, the intervention will be a much needed addition to care offered to GC survivors and will result in improved quality of life. Show less
Wissen, M.A.T. van; Teuwen, M.M.H.; Ende, C.H.M. van den; Vlieland, T.P.M.V.; Broeder, A.A. den; Hout, W.B. van den; ... ; Weely, S.F.E. van 2021
Objectives Research on effectiveness and cost-effectiveness of longstanding exercise therapy in patients with axial SpondyloArthritis (axSpA) or Rheumatoid Arthritis (RA) is scarce, and mainly... Show moreObjectives Research on effectiveness and cost-effectiveness of longstanding exercise therapy in patients with axial SpondyloArthritis (axSpA) or Rheumatoid Arthritis (RA) is scarce, and mainly concerned patients with a relatively favorable health status. We aim to evaluate the effectiveness and cost-effectiveness of longstanding exercise therapy compared to usual care in the subgroup of patients with axSpA or RA and severe limitations in functioning. Methods In two separate, parallel randomized controlled trials the effectiveness and cost-effectiveness of longstanding, active exercise therapy (52 weeks) compared with usual care (1:1) will be evaluated. The longstanding, active exercise therapy will focus on improving individual limitations in daily activities and participation and will be given by a trained physical therapist in the vicinity of the participant. For each diagnosis, 215 patients with severe limitations in activities and participation will be included. Assessments are performed at baseline, 12, 26, and 52 weeks. The primary outcome measure of effectiveness is the individual level of functioning (activities and participation), as measured with the Patient-Specific Complaints instrument at 52 weeks. For cost-effectiveness analyses, the EuroQol (EQ-5D-5L) and questionnaires on healthcare use and productivity will be administered. The economic evaluation will be a cost-utility analysis from a societal perspective. After 52 weeks, the patients in the usual care group are offered longstanding, active exercise therapy as well. Follow-up assessments are done at 104, 156, and 208 weeks. Conclusion The results of these studies will provide insights in the effectiveness and cost-effectiveness of longstanding exercise therapy in the subgroup of axSpA and RA patients with severe functional limitations. Show less
Neve, O.M.; Boerman, J.A.; Hout, W.B. van den; Briaire, J.J.; Benthem, P.P.G. van; Frijns, J.H.M. 2021
Objectives: While the costs and outcomes of cochlear implantation (CI) have been widely assessed, most of these analyses were solely performed from the perspective of healthcare costs. This study... Show moreObjectives: While the costs and outcomes of cochlear implantation (CI) have been widely assessed, most of these analyses were solely performed from the perspective of healthcare costs. This study assesses the costs and benefits of CI in the Netherlands from a broader societal perspective, including health outcomes, healthcare cost, educational cost, and productivity losses and gains. Design: The cost and benefits of CI were analyzed in this cost-benefit analysis, in which a monetary value is put on both the resources needed and the outcomes of CI. The costs and benefits were analyzed by prototypical instances of three groups, representing the majority of cochlear implant patients: prelingually deaf children implanted at the age of 1, adults with progressive profound hearing loss implanted at the age of 40 and seniors implanted at the age of 70 with progressive profound hearing loss. Costs and benefits were estimated over the expected lifetimes of the members of each group, using a Markov state transition model. Model parameters and assumptions were based on published literature. Probabilistic and one-way sensitivity analyses were performed. Results: In all three patient groups, the total benefits of CI exceeded the total cost, leading to a net benefit of CI. Prelingually deaf children with a bilateral CI had a lifetime positive outcome net benefit of euro433,000. Adults and seniors with progressive profound hearing loss and a unilateral CI had a total net benefit of euro275,000 and euro76,000, respectively. These results ensue from health outcomes expressed in monetary terms, reduced educational cost, and increased productivity. Conclusions: Based on estimates from modeling, the increased healthcare costs due to CI were more than compensated by the value of the health benefits and by savings in educational and productivity costs. In particular, for children and working adults, the societal benefit was positive even without taking health benefits into account. Therefore, CI generates an advantage for both patients and society. Show less
Boon, G.J.A.M.; Hout, W.B. van den; Barco, S.; Bogaard, H.J.; Delcroix, M.; Huisman, M.V.; ... ; Klok, F.A. 2021
Background Diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) exceeds 1 year, contributing to higher mortality. Health economic consequences of late CTEPH diagnosis are... Show moreBackground Diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) exceeds 1 year, contributing to higher mortality. Health economic consequences of late CTEPH diagnosis are unknown. We aimed to develop a model for quantifying the impact of diagnosing CTEPH earlier on survival, quality-adjusted life-years (QALYs) and healthcare costs.Material and methods A Markov model was developed to estimate lifelong outcomes, depending on the degree of delay. Data on survival and quality of life were obtained from published literature. Hospital costs were assessed from patient records (n=498) at the Amsterdam UMC - VUmc, which is a Dutch CTEPH referral center. Medication costs were based on a mix of standard medication regimens.Results For 63-year-old CTEPH patients with a 14-month diagnostic delay of CTEPH (median age and delay of patients in the European CTEPH Registry), lifelong healthcare costs were estimated at EUR 117100 for a mix of treatment options. In a hypothetical scenario of maximal reduction of current delay, improved survival was estimated at a gain of 3.01 life-years and 2.04 QALYs. The associated cost increase was EUR 44654, of which 87% was due to prolonged medication use. This accounts for an incremental cost-utility ratio of EUR 21900/QALY.Conclusion Our constructed model based on the Dutch healthcare setting demonstrates a substantial health gain when CTEPH is diagnosed earlier. According to Dutch health economic standards, additional costs remain below the deemed acceptable limit of EUR 50000/QALY for the particular disease burden. This model can be used for evaluating cost-effectiveness of diagnostic strategies aimed at reducing the diagnostic delay. Show less
Objective: To estimate societal costs and changes in health-related quality of life in stroke patients, up to one year after start of medical specialist rehabilitation.& nbsp; Design:... Show moreObjective: To estimate societal costs and changes in health-related quality of life in stroke patients, up to one year after start of medical specialist rehabilitation.& nbsp; Design: Observational.& nbsp; Patients: Consecutive patients who received med ical specialist rehabilitation in the Stroke Cohort Out-comes of REhabilitation (SCORE) study.& nbsp; Methods: Participants completed questionnaires on health-related quality of life (EuroQol EQ-5D-3L), absenteeism, out-of-pocket costs and healthcare use at start and end of rehabilitation and 6 and 12 months after start. Clinical characteristics and reha-bilitation costs were extracted from the medical and financial records, respectively.& nbsp; Results: From 2014 to 2016 a total of 313 stroke patients completed the study. Mean age was 59 (standard deviation (SD) 12) years, 185 (59%) were male, and 244 (78%) inpatients. Mean costs for inpatient and outpatient rehabilitation were US$70,601 and US$27,473, respectively. For in-patients, utility (an expression of quality of life) in-creased significantly between baseline and 6 months (EQ-5D-3L 0.66 & ndash;0.73, p = 0.01; visual analogue scale 0.77 & ndash;0.82, p < 0.001) and between baseline and 12 months (visual analogue scale 0.77 & ndash;0.81, p < 0.001).& nbsp; Conclusion: One-year societal costs from after the start of rehabilitation in stroke patients were con-siderable. Future research should also include costs prior to rehabilitation. For inpatients, health-related quality of life, expressed in terms of utility, improved significantly over time. Show less
Hendriks, S.V.; Hout, W.B. van den; Bemmel, T. van; Bistervels, I.M.; Eijsvogel, M.; Faber, L.M.; ... ; YEARS Investigators 2021
Background Venous thromboembolism constitutes substantial health care costs amounting to approximately 60 million euros per year in the Netherlands. Compared with initial hospitalization, home... Show moreBackground Venous thromboembolism constitutes substantial health care costs amounting to approximately 60 million euros per year in the Netherlands. Compared with initial hospitalization, home treatment of pulmonary embolism (PE) is associated with a cost reduction. An accurate estimation of cost savings per patient treated at home is currently lacking.Aim The aim of this study was to compare health care utilization and costs during the first 3 months after a PE diagnosis in patients who are treated at home versus those who are initially hospitalized.Methods Patient-level data of the YEARS cohort study, including 383 normotensive patients diagnosed with PE, were used to estimate the proportion of patients treated at home, mean hospitalization duration in those who were hospitalized, and rates of PE-related readmissions and complications. To correct for baseline differences within the two groups, regression analyses was performed. The primary outcome was the average total health care costs during a 3-month follow-up period for patients initially treated at home or in hospital.Results Mean hospitalization duration for the initial treatment was 0.69 days for those treated initially at home ( n =181) and 4.3 days for those initially treated in hospital ( n =202). Total average costs per hospitalized patient were Euro3,209 and Euro1,512 per patient treated at home. The adjusted mean difference was Euro1,483 (95% confidence interval: Euro1,181-1,784).Conclusion Home treatment of hemodynamically stable patients with acute PE was associated with an estimated net cost reduction of Euro1,483 per patient. This difference underlines the advantage of triage-based home treatment of these patients. Show less
Dam, L.F. van; Hout, W.B. van den; Gautam, G.; Dronkers, C.E.A.; Ghanima, W.; Gleditsch, J.; ... ; Klok, F.A. 2021
The diagnostic workup of recurrent ipsilateral deep vein thrombosis (DVT) using compression ultrasonography (CUS) can be complicated by persistent intravascular abnormalities after a previous DVT.... Show moreThe diagnostic workup of recurrent ipsilateral deep vein thrombosis (DVT) using compression ultrasonography (CUS) can be complicated by persistent intravascular abnormalities after a previous DVT. We showed that magnetic resonance direct thrombus imaging (MRDTI) can exclude recurrent ipsilateral DVT. However, it is unknown whether the application of MRDTI in daily clinical practice is cost effective. The aim of this study was to evaluate the cost effectiveness of MRDTI-based diagnosis for suspected recurrent ipsilateral DVT during first year of treatment and follow-up in the Dutch health care setting. Patientlevel data of the Theia study (NCT02262052) were analyzed in 10 diagnostic scenarios, including a clinical decision rule and D-dimer test and imaging with CUS and/or MRDTI. The total costs of diagnostic tests and treatment during 1-year follow-up, including costs of false-positive and false-negative diagnoses, were compared and related to the associated mortality. The 1-year health care costs with MRDTI (range, (sic)1219-1296) were generally lower than strategies without MRDTI (range, (sic)1278-1529). This was because of superior specificity, despite higher initial diagnostic costs. Diagnostic strategies including CUS alone and CUS followed by MRDTI in case of an inconclusive CUS were potential optimal cost-effective strategies, with estimated average costs of (sic)1529 and (sic)1263 per patient and predicted mortality of 1 per 737 patients and 1 per 609 patients, respectively. Our model shows that diagnostic strategies with MRDTI for suspected recurrent ipsilateral DVT have generally lower 1-year health care costs than strategies without MRDTI. Therefore, compared with CUS alone, applying MRDTI did not increase health care costs. Show less
