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To assess the cost-effectiveness of app-based treatment for female stress, urgency or mixed urinary incontinence (UI) compared with care-as-usual in Dutch primary care.A pragmatic, randomised controlled, superiority trial.Primary care in the Netherlands from 2015 to 2018, follow-up at 12 months.Women with ≥2 UI-episodes per week, access to mobile apps, wanting treatment.The standalone app included conservative management for UI with motivation aids (e.g. reminders). Care-as-usual delivered according to the Dutch GP guideline for UI.Costs and cost-effectiveness and -utility were assessed from a societal perspective, based on incontinence impact adjusted life years (IIALYs), quality adjusted life years (QALYs) and medical, non-medical and productivity costs. Information on costs was obtained with the iMCQ and iPCQ questionnaires (medical consumption and productivity cost questionnaires).In all, 262 women were andomised equally to app or care-as-usual; 89 (68%) and 83 (63%) attended follow-up, respectively. Costs were lower for app-based treatment with € -161 (95% confidence interval [CI -180 to -151) per year. Cost-effectiveness showed small mean differences in effect for IIALY (0.04) and QALY (-0.03) and thus larger incremental cost-effectiveness ratios (ICER: -€3696) and incremental cost-utility ratios (ICUR: €6379).App-based treatment is a cost-effective alternative to care-as-usual for women with UI in Dutch primary care.App-treatment for female urinary incontinence cost-effective compared to care-as-usual in general practice after 12 months.

Objective Health care expenditures for children with functional constipation (FC) are high, while conservative management is successful in only 50% of the children. The aim is to evaluate whether adding physiotherapy to conventional treatment (CT) is a cost-effective strategy in the management of children with FC aged 4–18 years in primary care. Methods A cost-effectiveness analysis was performed alongside a randomized controlled trial (RCT) with 8-month follow-up. Costs were assessed from a societal perspective, effectiveness included both the primary outcome (treatment success defined as the absence of FC and no laxative use) and the secondary outcome (absence of FC irrespective of laxative use). Uncertainty was assessed by bootstrapping and cost-effectiveness acceptability curves (CEACs) were displayed. Results One hundred and thirty-four children were randomized. The incremental cost-effectiveness ratio (ICER) for one additional successfully treated child in the physiotherapy group compared with the CT group was €24,060 (95% confidence interval [CI] €−16,275 to €31,390) and for the secondary outcome €1,221 (95% CI €−12,905 to €10,956). Subgroup analyses showed that for children with chronic laxative use the ICER was €2,134 (95% CI −24,975 to 17,192) and €571 (95% CI 11 to 3,566), respectively. At a value of €1,000, the CEAC showed a probability of 0.53 of cost-effectiveness for the primary outcome, and 0.90 for the secondary outcome. Conclusions Physiotherapy added to CT as first-line treatment for all children with FC is not cost-effective compared with CT alone. Future studies should consider the cost-effectiveness of physiotherapy added to CT in children with chronic laxative use. Trial registration The RCT is registered in the Netherlands Trial Register (NTR4797), on the 8th of September 2014. The first child was enrolled on the 2nd of December 2014. https://www.trialregister.nl/trial/4654.

Background Wound healing and scar formation depends on a plethora of factors. Given the impact of abnormal scar formation, interventions aimed to improve scar formation would be most advantageous. The tissue stromal vascular fraction (tSVF) of adipose tissue is composed of a heterogenous mixture of cells embedded in extracellular matrix. It contains growth factors and cytokines involved in wound-healing processes, eg, parenchymal proliferation, inflammation, angiogenesis, and matrix remodeling. Objectives The aim of this study was to investigate the hypothesis that tSVF reduces postsurgical scar formation. Methods This prospective, double-blind, placebo-controlled, randomized trial was conducted between 2016 and 2020. Forty mammoplasty patients were enrolled and followed for 1 year. At the end of the mammoplasty procedure, all patients received tSVF in the lateral 5 cm of the horizontal scar of 1 breast and a placebo injection in the contralateral breast to serve as an intrapatient control. Primary outcome was scar quality measure by the Patient and Observer Scar Assessment Scale (POSAS). Secondary outcomes were obtained from photographic evaluation and histologic analysis of scar tissue samples. Results Thirty-four of 40 patients completed follow-up. At 6 months postoperation, injection of tSVF had significantly improved postoperative scar appearance as assessed by the POSAS questionnaire. No difference was observed at 12 months postoperation. No improvement was seen based on the evaluation of photographs and histologic analysis of postoperative scars between both groups. Conclusions Injection of tSVF resulted in improved wound healing and reduced scar formation at 6 months postoperation, without any noticeable advantageous effects seen at 12 months. Level of Evidence: 2

Contains fulltext : 291794.pdf (Publisher’s version ) (Open Access) PURPOSE: This study reports on survival and health related quality of life (HRQOL) after extracorporeal membrane oxygenation (ECMO) treatment and the associated costs in the first year. MATERIALS AND METHODS: Prospective observational cohort study patients receiving ECMO in the intensive care unit during August 2017 and July 2019. We analyzed all healthcare costs in the first year after index admission. Follow-up included a HRQOL analysis using the EQ-5D-5L at 6 and 12 months. RESULTS: The study enrolled 428 patients with an ECMO run during their critical care admission. The one-year mortality was 50%. Follow up was available for 124 patients at 12 months. Survivors reported a favorable mean HRQOL (utility) of 0.71 (scale 0-1) at 12 months of 0.77. The overall health status (VAS, scale 0-100) was reported as 73.6 at 12 months. Mean total costs during the first year were $204,513 ± 211,590 with hospital costs as the major factor contributing to the total costs. Follow up costs were $53,752 ± 65,051 and costs of absenteeism were $7317 ± 17,036. CONCLUSIONS: At one year after hospital admission requiring ECMO the health-related quality of life is favorable with substantial costs but considering the survival might be acceptable. However, our results are limited by loss of follow up. So it may be possible that only the best-recovered patients returned their questionnaires. This potential bias might lead to higher costs and worse HRQOL in a real-life scenario.

Contains fulltext : 251525.pdf (Publisher’s version ) (Open Access) OBJECTIVES: Knowledge on long-term outcomes in patients with Hirschsprung disease is progressing. Nevertheless, differences in outcomes according to aganglionic lengths are unclear. We compared long-term bowel function and generic quality of life in Hirschsprung patients with total colonic or long-segment versus rectosigmoid aganglionosis. METHODS: In this nationwide, cross-sectional study participants with proven Hirschsprung disease received the Defecation and Fecal Continence questionnaire, and the Child Health Questionnaire Child Form-87, or the WHO Quality of Life-100. We excluded deceased patients, patients who were younger than 8 years, lived abroad, had a permanent enterostomy, or were intellectually impaired. RESULTS: The study population (n = 334) was operated for rectosigmoid (83.9%), long-segment (8.7%), or total colonic aganglionosis (7.5%). Fecal incontinence in general was not significantly different between the three groups, but liquid fecal incontinence was significantly associated with total colonic aganglionosis (odds ratio [OR] = 6.00, 95% confidence interval [CI] 2.07-17.38, P = 0.001). Regarding constipation, patients with total colonic or long-segment aganglionosis were less likely to suffer from constipation than the rectosigmoid group (OR = 0.21, 95% CI, 0.05-0.91, P = 0.038 and OR = 0.11, 95% CI, 0.01-0.83, P = 0.032). Quality of life was comparable between the three groups, except for a lower physical score in children with total colonic aganglionosis (P = 0.016). CONCLUSIONS: Over time Hirschsprung patients with total colonic or long-segment aganglionosis do not suffer from worse fecal incontinence in general. A difference in stool consistency may underlie the association between liquid fecal incontinence and total colonic aganglionosis and constipation in patients with rectosigmoid aganglionosis. Despite these differences, generic quality of life is comparable on reaching adulthood.

Patients with the genetic blistering skin condition epidermolysis bullosa (EB) report severe pain as a consequence of skin and mucous membrane lesions including blisters, wounds, and scars. Adequate symptom alleviation is not often achieved using conventional pharmacologic interventions. Finding novel approaches to pain care in EB is imperative to improve the quality of life of patients living with EB. There are several anecdotal reports on the use of cannabinoid-based medicines (CBMs) by EB patients to reduce the burden of symptoms. However, controlled clinical investigations assessing these reported effects are lacking. As the pain quality “unpleasantness” delineates EB pain, we hypothesize the modulation of affective pain processing in the brain by way of intervention with CBMs comprising the cannabinoids Δ-9-tetrahydrocannabinol and cannabidiol—objectified by functional magnetic resonance imaging (fMRI). The C4EB study is an investigator-initiated, single-centre, randomized, double-blind, placebo-controlled and crossover trial. Adult patients with the diagnosis epidermolysis bullosa, reporting chronic pain will be eligible to participate. Following baseline measurements, participants will be randomized to receive the sublingually administered interventions placebo and Transvamix® in forward or reversed orders, each for two weeks and separated by a washout. The primary outcome is the difference in numeric rating scale pain scores between grouped interventions, using affective descriptors within the Short-form McGill Pain Questionnaire-2. Secondary outcomes include pain self-efficacy, concomitant analgesic medication-use and adverse events. Additionally, fMRI will be employed to assess brain connectivity related to neuroanatomic pain circuits at baseline, placebo and Transvamix® interventions. The study was approved by the ethical committee at the University Medical Center of Groningen in the Netherlands. Results will be submitted for publication in a peer-reviewed journal. Trial registration number: Netherlands Trial Register: NL9347 (Acronym: C4EB).

BackgroundAcute gastroenteritis is a common childhood condition with substantial medical and indirect costs, mostly because of referral, hospitalisation, and parental absence from work.AimTo determine the cost-effectiveness of adding oral ondansetron to care as usual (CAU) for children with acute gastroenteritis presenting to out-of-hours primary care (OOH-PC).Design and settingA pragmatic randomised controlled trial from December 2015 to January 2018, at three OOHPC centres in the north of the Netherlands (Groningen, Zwolle, and Assen) with a follow-up of 7 days.MethodChildren were recruited at the OOH-PC and parents kept a parental diary. Inclusion criteria were: aged 6 months–6 years; diagnosis of acute gastroenteritis; at least four reported episodes of vomiting 24 hours before presentation, at least one of which was in the 4 hours before presentation; and written informed consent from both parents. Children were randomly allocated at a 1:1 ratio to either CAU (oral rehydration therapy) or CAU plus one dose of 0.1 mg/kg oral ondansetron.ResultsIn total, 194 children were included for randomisation. One dose of oral ondansetron decreased the proportion of children who continued vomiting within the first 4 hours from 42.9% to 19.5%, (a decrease of 54.5%), with an odds ratio of 0.4 (95% confidence interval [CI] = 0.2 to 0.7; number needed to treat: four). Total mean costs in the ondansetron group were 31.2% lower (€488 [£420] versus €709 [£610]), and the total incremental mean costs for an additional child free of vomiting in the first 4 hours was −€9 (£8) (95% CI = −€41 [£35] to €3 [£3]).ConclusionA single oral dose of ondansetron for children with acute gastroenteritis, given in OOH-PC settings, is both clinically beneficial and cost-effective.

Background To improve participation in the Dutch cervical cancer screening, a self-sampling device (SSD) was introduced in 2017 into the Dutch population-based screening programme (PBS) for the early detection of cervical cancer. The aim of this study was to gather potential preferences and experiences that might influence a woman's decision to use the SSD in the Dutch PBS. Methods A scoping review was performed in the PubMed database. Studies that assessed preferences and experiences of women regarding the SSD were included, and preferences and experiences were extracted. In addition, in a qualitative study, the list of potential preferences and experiences specific for the Dutch PBS was extended based on semi-structured interviews with SSD users as well as non-SSD users who recently participated in the PBS, analysed in a structured manner by translating full sentences to key words. Results Ninety-eight studies were included in the scoping review and 16 interviews were performed. Frequently mentioned reasons for using the SSD, in both the interviews and the literature, were practicality and comfort. Frequently mentioned reasons for not using the SSD were fear of not performing the SSD procedure correctly and doubts on whether the results of the high-risk human papillomavirus (hrHPV) test will be reliable. A new positive experience elicited in the interviews was accessibility. Negative preferences and experiences were not being aware the SSD was an option, and the inconvenience that after an hrHPV-positive test result of the SSD, an additional smear test at the GP is necessary. Conclusion Several preferences and experiences play a role in the choice whether or not to use the SSD. Based on the currently found preferences and experiences, an app will be developed in order to assess which of these are the most important for women participating in the Dutch population-based cervical screening programme.

Background Lipofilling has become popular as a treatment to improve aging-related skin characteristics (eg, wrinkles, pigmentation spots, pores, or rosacea). Different additives such as platelet-rich plasma (PRP) or stromal vascular fraction (SVF) have been combined with lipofilling to increase the therapeutic effect of adipose-derived stromal cells (ASCs). Objectives The aim of this study was to examine the hypothesis that mechanically isolated SVF augments the therapeutic effect of PRP-supplemented lipofilling to improve facial skin quality. Methods This prospective, double-blind, placebo-controlled, randomized trial was conducted between 2016 and 2019. In total, 28 female subjects were enrolled; 25 completed the follow-up. All patients received PRP-supplemented lipofilling with either mechanically isolated SVF or saline. SVF was isolated by fractionation of adipose tissue (tSVF). Results were evaluated by changes in skin elasticity and transepidermal water loss, changes in skin-aging-related features, ie, superficial spots, wrinkles, skin texture, pores, vascularity, and pigmentation, as well as patient satisfaction (FACE-Q), recovery, and number of complications up to 1 year postoperative. Results The addition of tSVF to PRP-supplemented lipofilling did not improve skin elasticity, transepidermal water loss, or skin-aging-related features. No improvement in patient satisfaction with overall facial appearance or facial skin quality was seen when tSVF was added to PRP-supplemented lipofilling. Conclusions In comparison to PRP-supplemented lipofilling, PRP-supplemented lipofilling combined with tSVF does not improve facial skin quality or patient satisfaction in a healthy population. PRP-supplemented lipofilling combined with tSVF can be considered a safe procedure. Level of Evidence: 2

ObjectivesTo improve continence care in the Netherlands, a new framework has been developed in which a shift has been made from incontinence severity as the sole criterion for selecting incontinence products to a focus on patient need for daily life activities. The impact of the framework on daily care has not been assessed. We aimed to compare treatment effectiveness and costs between participants who did and did not undergo re-evaluation according to the new framework.DesignCohort studySettingTwelve pharmacies in the NetherlandsParticipantsExisting users of absorbent incontinence materials for urinary incontinence.InterventionsParticipants were offered the option to have their incontinence products re-evaluated within the new framework at their pharmacy.Primary and secondary outcome measuresEffectiveness and cost outcomes were assessed at 3 and 6 months through questionnaires. These questionnaires included the International Consultation on Incontinence Questionnaire (ICIQ) Lower Urinary Tract Symptoms Quality of Life Module, ICIQ Urinary Incontinence Short Form, ICIQ Absorbent Pads, questions about satisfaction and the iPCQ and iMCQ.Results303 users consented and 279 completed the baseline questionnaire. Of these participants, 72 agreed to a re-evaluation of their incontinence materials. There was a small improvement at 3 months in the re-evaluation group compared with the other group on most outcomes. However, these improvements were not clinically relevant. Moreover, these differences did not change much from 3 to 6 months. Small differences were also observed in the changes in costs, but with very wide CIs on both sides of zero (€99.38; 95% CI −633.48 to 832.23).ConclusionsThe current study showed no clinically relevant effect of a newly implemented framework for selecting incontinence materials in pharmacies when compared with an existing method. Given that the study also showed no differences in effectiveness and costs, introducing the new framework in pharmacies may not lead to better incontinence care.

Objective To evaluate the costs and non‐inferiority of a strategy starting with the levonorgestrel intrauterine system (LNG‐IUS) compared with endometrial ablation (EA) in the treatment of heavy menstrual bleeding (HMB). Design Cost‐effectiveness analysis from a societal perspective alongside a multicentre randomised non‐inferiority trial. Setting General practices and gynaecology departments in the Netherlands. Population In all, 270 women with HMB, aged ≥34 years old, without intracavitary pathology or wish for a future child. Methods Randomisation to a strategy starting with the LNG‐IUS (n = 132) or EA (n = 138). The incremental cost‐effectiveness ratio was estimated. Main outcome measures Direct medical costs and (in)direct non‐medical costs were calculated. The primary outcome was menstrual blood loss after 24 months, measured with the mean Pictorial Blood Assessment Chart (PBAC)‐score (non‐inferiority margin 25 points). A secondary outcome was successful blood loss reduction (PBAC‐score ≤75 points). Results Total costs per patient were €2,285 in the LNG‐IUS strategy and €3,465 in the EA strategy (difference: €1,180). At 24 months, mean PBAC‐scores were 64.8 in the LNG‐IUS group (n = 115) and 14.2 in the EA group (n = 132); difference 50.5 points (95% CI 4.3–96.7). In the LNG‐IUS group, 87% of women had a PBAC‐score ≤75 points versus 94% in the EA group (relative risk [RR] 0.93, 95% CI 0.85–1.01). The ICER was €23 (95% CI €5–111) per PBAC‐point. Conclusions A strategy starting with the LNG‐IUS was cheaper than starting with EA, but non‐inferiority could not be demonstrated. The LNG‐IUS is reversible and less invasive and can be a cost‐effective treatment option, depending on the success rate women are willing to accept. Tweetable abstract Treatment of heavy menstrual bleeding starting with LNG‐IUS is cheaper but slightly less effective than endometrial ablation., Tweetable abstract Treatment of heavy menstrual bleeding starting with LNG‐IUS is cheaper but slightly less effective than endometrial ablation.

Background Autologous lipofilling is an emerging procedure to treat and possibly reverse dermal scars and to reduce scar-related pain, but its efficacy and mechanisms are poorly understood. Objectives The aim of this study was to test the hypothesis that repeated lipografts reverse dermal scars by reinitiation of wound healing. Methods In a prospective, non-placebo-controlled clinical study, 27 adult patients with symptomatic scars were given 2 lipofilling treatments at 3-month intervals. As primary outcome, clinical effects were measured with the Patient and Observer Scar Assessment Scale (POSAS). Scar biopsies were taken before and after treatments to assess scar remodeling at a cellular level. Results Twenty patients completed the study. Patients’ scars improved after lipofilling. The total POSAS scores (combined patient and observer scores) decreased from 73.2 [14.7] points (mean [standard deviation]) pretreatment to 46.1 [14.0] and 32.3 [13.2] points after the first and second lipofilling treatment, respectively. Patient POSAS scores decreased from 37.3 [8.8] points to 27.2 [11.3] and 21.1 [11.4] points, whereas observer POSAS scores decreased from 35.9 [9.5] points to 18.9 [6.0] and 11.3 [4.5] points after the first and second treatment, respectively. After each lipofilling treatment, T lymphocytes, mast cells, and M2 macrophages had invaded scar tissue and were associated with increased vascularization. In addition, the scar-associated epidermis showed an increase in epidermal cell proliferation to levels similar to that normal in skin. Moreover, lipofilling treatment caused normalization of the extracellular matrix organization towards that of normal skin. Conclusions Autologous lipofilling improves the clinical outcome of dermal scars through the induction of a pro-regenerative immune response, increased vascularization, and epidermal proliferation and remodeling of scar tissue extracellular matrix. Level of Evidence: 4

Background There is an increasing demand for home mechanical ventilation (HMV) in patients with chronic respiratory insufficiency. At present, noninvasive ventilation is exclusively initiated in a clinical setting at all four centers for HMV in the Netherlands. In addition to its high societal costs and patient discomfort, commencing HMV is often delayed because of a lack of hospital bed capacity. Research Question Is HMV initiation at home, using a telemonitoring approach, noninferior to in-hospital initiation in a nationwide study? Study Design and Methods We conducted a nationwide, randomized controlled noninferiority trial, in which every HMV center recruited 24 patients (home [n = 12] vs hospital [n = 12]) with a neuromuscular disease or thoracic cage disorder, all with an indication to start HMV. Change in arterial CO2 (Pa co 2) over a 6-month period was considered the primary outcome, and quality of life and costs were assessed as secondary outcomes. Results A total of 96 patients were randomized, most of them diagnosed with neuromuscular disease. We found a significant improvement in Pa co 2 within both groups (home: from 6.1 to 5.6 kPa [P Interpretation This nationwide, multicenter study shows that HMV initiation at home is noninferior to hospital initiation, as it shows the same improvement in gas exchange and health-related quality of life. In fact, from a patient’s perspective, it might even be a more attractive approach. In addition, starting at home saves over €3,200 ($3,793) per patient over a 6-month period. Trial Registry ClinicalTrials.gov; No.: NCT03203577; URL: www.clinicaltrials.gov

OBJECTIVES: Patient-reported outcome measures (PROMs) are widely applied to assess perceived health status. To date, no transplant-specific PROM is available for generating a single, standardized score regarding the health status of transplant recipients. The objective of this study is to generate health items for a new patient-centered PROM for organ recipients: the Transplant PROM (TXP).STUDY DESIGN AND SETTING: A five-phase, mixed-method approach was applied to identify and select the health items: scoping literature review, expert meetings, focus-group meetings with organ recipients, a special judgmental task within an online survey, and expert meetings for final selection of health items.RESULTS: Based on a previously published scoping literature review, a first round of expert meetings, and a total of four focus-group meetings with kidney, lung, and liver transplant recipients (N = 18), a list of 83 relevant health items relating to post-transplant life was selected. In an online survey, 183 transplant recipients selected the 10 most important health items from this list. After evaluating the frequency of selected health items and combining items that assess closely related or similar concepts in the second round of expert meetings, nine health items were chosen to be included in TXP: fatigue, skin, worry/anxiety, self-reliance, activities, weight, sexuality, stooling, and memory/concentration.CONCLUSION: The nine TXP health items reflect the most prominent issues transplant recipients experience. The TXP can be administered by means of a mobile phone app.

OBJECTIVE: To assess the long-term effectiveness of app-based treatment for female stress, urgency, or mixed urinary incontinence (UI) compared to care-as-usual in primary care.DESIGN: A pragmatic, randomised controlled, superiority trial.SETTING: Primary care in the Netherlands from 2015 to 2018, follow-up at 12 months.POPULATION: Women with ≥2 UI-episodes per week, access to mobile apps, wanting treatment. 262 women randomised equally to app or care-as-usual; 89 (68%) and 83 (63%) attended one year follow-up.INTERVENTIONS: The standalone app included conservative management for UI with motivation aids (e.g., reminders). Care-as-usual delivered according to the Dutch GP guideline for UI.MAIN OUTCOME MEASURES: Effectiveness assessed by the change in symptom severity score (ICIQ-UI-SF) and the change in quality of life (ICIQ-LUTS-QoL) with linear regression on an intention-to-treat basis.RESULTS: Clinically relevant improvement of UI severity for both app (-2.17 ± 2.81) and care-as-usual (-3.43 ± 3.6), with a non-significant mean difference of 0.903 (-0.66 to 1.871).CONCLUSION: App-based treatment is a viable alternative to care-as-usual for UI in primary care in terms of effectiveness after one year.

Research has long since confirmed the benefits of regular cervical cancer screening (CCS) worldwide. However, some developed countries have low participation rates despite well-organized screening programs. Given that studies in Europe typically define participation in 12-month windows from an invitation, we evaluated both whether extending this defined time window could reveal the true participation rate and how sociodemographic determinants affect participation delays. This involved linking data from the Lifelines population-based cohort with CCS-related data from the Dutch Nationwide Pathology Databank and including data for 69 185 women eligible for screening in the Dutch CCS program between 2014 and 2018. We then estimated and compared the participation rates for 15- and 36-month time windows and categorized women by the primary screening window into timely participation (within 15 months) and delayed participation (within 15–36 months) groups, before performing multivariable logistic regression to evaluate the association between delayed participation and the sociodemographic determinants. Participation rates for the 15- and 36-month windows were 71.1% and 77.0%, respectively, with participation considered timely in 49 224 cases and delayed in 4047 cases. Delayed participation was associated with age 30–35 years (odds ratio [OR]: 2.88, 95 %CI: 2.67–3.11), higher education (OR: 1.50, 95 %CI: 1.35–1.67), the high-risk human papillomavirus test-based program (OR: 1.67, 95 %CI: 1.56–1.79), and pregnancy (OR: 4.61, 95 %CI: 3.88–5.48). These findings show that a 36-month window for monitoring attendance at CCS better reflects the actual participation rate by accommodating possible delayed uptake among younger, pregnant, and highly educated women.

Objectives: Efforts to evaluate the health of solid organ transplant recipients are hampered by the lack of adequate patient-reported outcome measures (PROMs) targeting this group. We developed the Transplant ePROM (TXP), which is based on a novel measurement model and administered through a mobile application to fill this gap. The main objective of this article is to elucidate how we derived the weights for different items, and to report initial empirical results. Study design and setting: The nine health items in the TXP were fatigue, skin, worry, self-reliance, activities, weight, sexuality, stooling, and memory. Via an online survey solid organ recipient participating in the TransplantLines Biobank and Cohort study (NCT03272841) were asked to describe and then compare their own health state with six other health states. Coefficients for item levels were obtained using a conditional logit model. Results: A total of 232 solid organ transplant recipients (mean age: 54 years) participated. The majority (106) were kidney recipients, followed by lung, liver, and heart recipients. Fatigue was the most frequent complaint (54%). The strongest negative coefficients were found for activities and worry, followed by self-reliance and memory. Conclusion: A set of coefficients and values were developed for TXP. The TXP score approximated an optimal health state for the majority of respondents and recipients of different organs reported comparable health states. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

IntroductionChildren with chronic gastrointestinal symptoms are frequently seen in primary care, yet general practitioners (GPs) often experience challenges distinguishing functional gastrointestinal disorders (FGID) from organic disorders. We, therefore, aim to evaluate whether a test strategy that includes point-of-care testing (POCT) for faecal calprotectin (FCal) can reduce the referral rate to paediatric specialist care among children with chronic gastrointestinal symptoms. The study findings will contribute to improving the recommendations on FCal use among children in primary care.Methods and analysisIn this pragmatic cluster randomised controlled trial, we will randomise general practices into intervention and control groups. The intervention group will use FCal-POCT when indicated, after completing online training about its indication, interpretation and follow-up as well as communicating an FGID diagnosis. The control group will test and treat according to Dutch GP guidelines, which advise against FCal testing in children. GPs will include children aged 4–18 years presenting to primary care with chronic diarrhoea and/or recurrent abdominal pain. The primary outcome will be the referral rate for children with chronic gastrointestinal symptoms within 6 months after the initial assessment. Secondary outcomes will be evaluated by questionnaires completed at baseline and at 3- and 6-month follow-up. These outcomes will include parental satisfaction and concerns, gastrointestinal symptoms, impact of symptoms on daily function, quality of life, proportion of children with paediatrician-diagnosed FGID referred to secondary care, health service use and healthcare costs. A sample size calculation indicates that we need to recruit 158 GP practices to recruit 406 children.Ethics and disseminationThe Medical Research Ethics Committee (MREC) of the University Medical Center Groningen (The Netherlands) approved this study (MREC number: 201900309). The study results will be made available to patients, GPs, paediatricians and laboratories via peer-reviewed publications and in presentations at (inter)national conferences.Trial registration numberThe Netherlands Trial Register: NL7690 (Pre-results)

BACKGROUND: To decrease the burden of breast cancer (BC), the Chinese government recently introduced biennial mammography screening for women aged 45-70 years. In this study, we assess the effectiveness and cost-effectiveness of implementing this programme in urban China using a micro-simulation model.METHODS: The 'Simulation Model on radiation Risk and breast cancer Screening' (SiMRiSc) was applied, with parameters updated based on available data for the Chinese population. The base scenario was biennial mammography screening for women aged 45-70 years, and this was compared to a reference population with no screening. Seven alternative scenarios were then simulated by varying the screening intervals and participant ages. This analysis was conducted from a societal perspective. The discounted incremental cost-effectiveness ratio (ICER) was compared to a threshold of triple the gross domestic product (GDP) per life years gained (LYG), which was 30 785 USD/LYG. Univariate sensitivity analyses were conducted to evaluate model robustness. In addition, a budget impact analysis was performed by comparing biennial screening with no screening at a time horizon of 10 years.RESULTS: Compared with no screening, the base scenario was cost-effective in urban China, giving a discounted average cost-effectiveness ratio (ACER) of 17 309 USD/LYG. The model was most sensitive to the cost of mammography per screen, followed by mean size of self-detected tumours, mammographic breast density and the cumulative lifetime risk of BC. The efficient frontier showed that at a threshold of 30 785 USD/LYG, the base scenario was the optimal scenario with a discounted ICER of 25 261 USD/LYG. Over 10 years, screening would incur a net cost of almost 38.1 million USD for a city with 1 million citizens.CONCLUSION: Compared to no screening, biennial mammography screening for women aged from 45-70 is cost-effective in urban China.

STUDY OBJECTIVES: Limited evidence exists on the cost-effectiveness of mandibular advancement device (MAD) compared to continuous positive airway pressure (CPAP) therapy in moderate obstructive sleep apnea (OSA). Therefore, this study compares the clinical and cost-effectiveness of MAD therapy with CPAP therapy in moderate OSA. METHODS: In a multicentre randomized controlled trial, patients with an apnea-hypopnea index (AHI) of 15 to 30 events/h were randomized to either MAD or CPAP. Incremental cost-effectiveness and cost-utility ratios (ICER/ICUR, in terms of AHI reduction and quality-adjusted life-years [QALYs, based on the EuroQol Five-Dimension Quality of Life questionnaire]) were calculated after 12 months, all from a societal perspective. RESULTS: In the 85 randomized patients (n = 42 CPAP, n = 43 MAD), AHI reduction was significantly greater with CPAP (median reduction AHI 18.3 [14.8–22.6] events/h) than with MAD therapy (median reduction AHI 13.5 [8.5–18.4] events/h) after 12 months. Societal costs after 12 months were higher for MAD than for CPAP (mean difference €2.156). MAD was less cost-effective than CPAP after 12 months (ICER −€305 [−€3.003 to €1.572] per AHI point improvement). However, in terms of QALY, MAD performed better than CPAP after 12 months (€33.701 [−€191.106 to €562.271] per QALY gained). CONCLUSIONS: CPAP was more clinically effective (in terms of AHI reduction) and cost-effective than MAD. However, costs per QALY was better with MAD as compared to CPAP. Therefore, CPAP is the first-choice treatment option in moderate OSA and MAD may be a good alternative. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Identifier: NCT01588275. CITATION: de Vries GE, Hoekema A, Vermeulen KM, Claessen J, JacobsW, van derMaten J, van der Hoeven JH, Stegenga B, Kerstjens HAM,Wijkstra PJ. Clinicaland cost-effectiveness of a mandibular advancement device versus continuous positive airway pressure in moderate obstructive sleep apnea. J Clin Sleep Med. 2019;15(10):1477-1485.

OBJECTIVES: Efforts to evaluate HRQoL and calculate quality-adjusted life years (QALYs) for infants less than 12 months of age are hampered by the lack of preference-based HRQoL instruments for this group. To fill this gap, we developed the Infant Quality of life Instrument (IQI), which is administered through a mobile application. This article explains how weights were derived for the 4 levels of each health item.METHODS: The IQI includes 7 health items: sleeping, feeding, breathing, stooling/poo, mood, skin, and interaction. In an online survey, respondents from the general population (n = 1409) and primary caregivers (n = 1229) from China, the United Kingdom, and the United States were presented with 10 discrete choice scenarios. Coefficients for the item levels were obtained with a conditional logit model.RESULTS: The highest coefficients were found for sleeping, feeding, and breathing. All coefficients for these items were negative and logically ordered, meaning that more extreme levels were less preferred. Stooling, mood, skin, and interaction showed some irregularities in the ordering of coefficients. Results for caregivers and the general population were about the same.CONCLUSIONS: The IQI is the first generic instrument to assess overall HRQoL in infants up to 1 year of age. It is short and easy to administer through a mobile application. We demonstrated how to derive values for infant health states with a discrete choice methodology. Our next step will be to normalize these values into utilities ranging from 0 (dead) to 1 (best health state) and to collect IQI values in a clinical population.

Background: Valuing hypothetical health states is a demanding personal process, since it involves the psychological evaluation of hypothetical health states. It seems plausible that elderly individuals will value hypothetical health states differently than the general population. It is, however, important to understand the psychological division that oldest old subgroups construct between acceptable and unacceptable health states. This information can produce important evidence regarding well-being and disability conceptualization. Objective: To investigate how Dutch oldest old, conceptualize health-related quality of life health states when compared to well-being health states. In addition, we aim to compare subgroups, based on dependency classification. Methods: Ninety-nine elderly living in the Groningen, Hoogeveen and Veendam areas of the Netherlands participated in the study. Respondents were classified into three groups based on dependency levels. The respondents were asked to value hypothetical health states, a generic preference-based HRQoL and a well-being instrument, using a visual analog scale. Results: All three groups ranked the same health states, from both questionnaires, below the average across the health states. The health-related quality of life health states was consistently ranked lower than the current well-being health states. Conclusions: Health state valuations performed by the oldest old indicate that conceptually, respondents view below average health-related and well-being health states as undesirable. The results indicated that the oldest old do view deficits in health-related health states as more important than deficits in well-being health states. Since the oldest old performed the valuations, focused interventions to improve below average health-related outcomes might be the most cost-effective way to increase oldest old well-being outcomes.

The overall aim of this scoping review of the literature is twofold: (1) to provide an overview of all instruments that have been used to assess health-related quality of life (HRQoL) after solid organ transplantation and (2) to provide a list of health items they include to support future studies on the development of a new-generation HRQoL instrument. All studies that administered any form of HRQoL instrument to post-transplant solid organ recipients were identified in a comprehensive search of PubMed (MEDLINE), Embase, and Web of Science, with a cut-off date of May 2018. The search used various combinations of the following keywords: lung, heart, liver, kidney, or pancreas transplantation; quality of life; well-being; patient-reported outcome; instrument; questionnaire; and health survey. In total, 8013 distinct publications were identified and 1218 of these were selected for review. Among the instruments applied, 53 measured generic, 51 organ-specific, 271 domain-specific, and 43 transplant-specific HRQoL. A total of 78 distinct health items grouped into 16 sub-domains were identified and depicted graphically. The majority of publications did not report a logical rationale for the choice of specific HRQoL instrument. The most commonly used types of instruments were generic health instruments, followed by domain-specific instruments. Despite the availability of transplant-specific instruments, few studies applied these types of instruments. Based on the 78 items, further research is planned to develop a patient-centered, transplant-specific HRQoL instrument that is concise, easy to apply (mobile application), and specifically related to the health issues of solid organ recipients. Electronic supplementary material The online version of this article (10.1007/s40271-018-0335-3) contains supplementary material, which is available to authorized users.

BackgroundResearch in primary care is essential, but recruiting children in this setting can be complex and may cause selection bias. Challenges surrounding informed consent, particularly in an acute clinical setting, can undermine feasibility. The off-protocol use of an intervention nearing implementation has become common in pragmatic randomised controlled trials (RCTs) set in primary care.AimTo describe how the informed consent procedure affects study inclusion and to assess how off-protocol medication prescribing affects participant selection in a paediatric RCT.Design & settingA pragmatic RCT evaluating the cost-effectiveness of oral ondansetron in children diagnosed with acute gastroenteritis (AGE) in primary care out-of-hours services and a parallel cohort study.MethodConsecutive children aged 6 months to 6 years attending primary care out-of-hours services with AGE were evaluated to assess the feasibility of obtaining informed consent, the off-protocol use of ondansetron, and other inclusion and exclusion criteria.ResultsThe RCT's feasibility was reduced by the informed consent procedure because 39.0% (n = 325/834) of children were accompanied by only one parent. GPs prescribed ondansetron off-protocol to 34 children (4.1%) of which 19 children were eligible for the RCT. RCT-eligible children included in the parallel cohort study had fewer risk factors for dehydration than children in the RCT despite similar dehydration assessments by GPs.ConclusionThe informed consent procedure and off-protocol use of study medication affect the inclusion rate, but had little effect on selection. A parallel cohort study alongside the RCT can help evaluate selection bias, and a pilot study can reveal potential barriers to inclusion.

Objective: Long-term cost-effectiveness of app-based treatment for female stress, urgency, or mixed urinary incontinence (UI) compared to care-as-usual in primary care. Design: A pragmatic, randomised controlled, superiority trial. Setting: Primary care in the Netherlands from 2015 to 2018, follow-up at 12 months. Population: Women with ≥2 UI-episodes per week, access to mobile apps, wanting treatment. 262 women randomised equally to app or care-as-usual; 89 (68%) and 83 (63%) attended follow-up. Methods: The standalone app included conservative management for UI with motivation aids (e.g., reminders). Care-as-usual delivered according to the Dutch GP guideline for UI. Main outcome measures: Effectiveness assessed by the change in symptom severity score (ICIQ-UI-SF) and the change in quality of life (ICIQ-LUTS-QoL, EQ-5D-5L) on superiority with linear regression on an intention-to-treat basis. Cost-effectiveness and -utility from a societal perspective, based on Incontinence Impact Adjusted Life Years (IIALYs) and Quality Adjusted Life years (QALYs). Results: Clinically relevant improvement of UI severity for both app (-2.17 ± 2.81) and care-as-usual (-3.43 ± 3.6), with a non-significant mean difference of 0.903 (-0.66 to 1.871). Costs were lower for app-based treatment with \euro-161 (95%CI: -180 to -151) per year. Cost-effectiveness showed small mean differences in effect for IIALY (0.04) and QALY (-0.03) and thus larger ICER (-3,696) and ICUR (\euro6,379). Conclusion: App-based treatment is a viable alternative to care-as-usual for UI in primary care in terms of long-term cost-effectiveness. Funding: Dutch Organisation for Health Research and Development (ZonMw: 837001508), sub-funding P.W. Boer Foundation Dutch Trial Register identifier: Trial NL4948 (www.trialregister.nl/trial/4948).

Background Lung cancer screening with low-dose computed tomography (LDCT) reduces lung cancer mortality. The aim of this study was to evaluate the cost-effectiveness of lung cancer screening with LDCT in a high-risk population. Methods The study used an adapted microsimulation model in a cohort of Dutch heavy smokers for a lifetime horizon from a health insurance perspective. The main outcomes included average cost-effectiveness ratio (ACER), incremental cost-effectiveness ratio (ICER) and lung cancer mortality reduction. The comparator was no screening. Scenarios with different screening intervals and starting and stopping ages were evaluated for 100,000 male heavy smokers and 100,000 female heavy smokers. A cost-effectiveness threshold of 60 k€ per life year gained (LYG) was assumed acceptable. Results The evaluated screening scenarios yielded ACERs ranging from 17.7 to 32.4 k€/LYG for men and from 17.8 to 32.1 k€/LYG for women. The lung cancer mortality reduction ranged from 9.3% to 16.8% for men and from 7.8% to 13.7% for women. The optimal screening scenario was annual screening from 55 to 80 years for men and biennial screening from 50 to 80 years for women, with an ICER of 51.6 and 45.8 k€ per LYG compared with its previous efficient alternative, respectively. Compared with no screening, the optimal screening scenario yielded an ICER of 27.6 k€/LYG for men and 21.1 k€/LYG for women. The mortality reduction of lung cancer was 15.9% for men and 10.6% for women. Conclusions Lung cancer LDCT screening is cost-effective in a high-risk population. The optimal screening scenario is dependent on sex.

This supplementary data is supportive to the research article entitled ‘Cost-effectiveness of lung cancer screening with low-dose computed tomography (LDCT) in heavy smokers: A micro-simulation modelling study’ (Yihui Du et al. 2020). This supplementary contains a description of the model input and the related model output data that were not included in the research article. The input data used for the tumour growth model and the self-detected tumour size model are provided. The output data of this article include the data used for cost-effectiveness analysis of lung cancer LDCT screening with the Dutch and international discount rates, the data of the sensitivity analysis, and the data of the model validation.

BackgroundIn many countries, medical interventions are reimbursed on the basis of recommendations made by advisory boards and committees that apply multiple criteria in their assessment procedures. Given the diversity of these criteria, it is difficult to find common ground to determine what information is required for setting priorities.ObjectiveTo investigate whether society and patients share the same interests and views concerning healthcare priorities.MethodsWe applied a framework of discrete choice models in which respondents were presented with judgmental tasks to elicit their preferences. They were asked to choose between two hypothetical scenarios of patients receiving a new treatment. The scenarios graphically presented treatment outcomes and patient characteristics. Responses were collected through an online survey administered among respondents from the general population (N = 1,253) and patients (N = 1,389) and were analyzed using conditional logit and mixed logit models.ResultsThe respondents' preferences regarding new medical treatments revealed that they attached the most relative importance to additional survival years, age at treatment, initial health condition, and the cause of disease. Minor differences in the relative importance assigned to three criteria: age at treatment, initial health, and cause of disease were found between the general population and patient samples. Health scenarios in which patients had higher initial health-related quality of life (i.e., a lower burden of disease) were favored over those in which patients' initial health-related quality of life was lower.ConclusionsOverall, respondents within the general population expressed preferences that were similar to those of the patients. Therefore, priority-setting studies that are based on the perspectives of the general population may be useful for informing decisions on reimbursement and other types of priority-setting processes in health care. Incorporating the preferences of the general population may simultaneously increase public acceptance of these decisions.

Objectives To evaluate at which sensitivity digital breast tomosynthesis (DBT) would become cost-effective compared to digital mammography (DM) in a population breast cancer screening program, given a constant estimate of specificity. Methods In a microsimulation model, the cost-effectiveness of biennial screening for women aged 50–75 was simulated for three scenarios: DBT for women with dense breasts and DM for women with fatty breasts (scenario 1), DBT for the whole population (scenario 2) or maintaining DM screening (reference). For DM, sensitivity was varied depending on breast density from 65 to 87%, and for DBT from 65 to 100%. The specificity was set at 96.5% for both DM and DBT. Direct medical costs were considered, including screening, biopsy and treatment costs. Scenarios were considered to be cost-effective if the incremental cost-effectiveness ratio (ICER) was below €20,000 per life year gain (LYG). Results For both scenarios, the ICER was more favourable at increasing DBT sensitivity. Compared with DM screening, 0.8–10.2% more LYGs were found when DBT sensitivity was at least 75% for scenario 1, and 4.7–18.7% when DBT sensitivity was at least 80% for scenario 2. At €96 per DBT, scenario 1 was cost-effective at a DBT sensitivity of at least 90%, and at least 95% for scenario 2. At €80 per DBT, these values decreased to 80% and 90%, respectively. Conclusion DBT is more likely to be a cost-effective alternative to mammography in women with dense breasts. Whether DBT could be cost-effective in a general population highly depends on DBT costs. Key Points • DBT could be a cost-effective screening modality for women with dense breasts when its sensitivity is at least 90% at a maximum cost per screen of €96. • DBT has the potential to be cost-effective for screening all women when sensitivity is at least 90% at a maximum cost per screen of €80. • Whether DBT could be used as an alternative to mammography for screening all women is highly dependent on the cost of DBT per screen.

There is an increasing demand for home mechanical ventilation (HMV) in patients with chronic respiratory insufficiency. At present, noninvasive ventilation is exclusively initiated in a clinical setting at all four centers for HMV in the Netherlands. In addition to its high societal costs and patient discomfort, commencing HMV is often delayed because of a lack of hospital bed capacity.Is HMV initiation at home, using a telemonitoring approach, noninferior to in-hospital initiation in a nationwide study?We conducted a nationwide, randomized controlled noninferiority trial, in which every HMV center recruited 24 patients (home [n = 12] vs hospital [n = 12]) with a neuromuscular disease or thoracic cage disorder, all with an indication to start HMV. Change in arterial COA total of 96 patients were randomized, most of them diagnosed with neuromuscular disease. We found a significant improvement in PacoThis nationwide, multicenter study shows that HMV initiation at home is noninferior to hospital initiation, as it shows the same improvement in gas exchange and health-related quality of life. In fact, from a patient's perspective, it might even be a more attractive approach. In addition, starting at home saves over €3,200 ($3,793) per patient over a 6-month period.ClinicalTrials.gov; No.: NCT03203577; URL: www.clinicaltrials.gov.