Objective
The primary aim was assessing the cost‐effectiveness of an internet‐based self‐help program, expert‐patient support, and the combination of both compared to a care‐as‐usual condition.
...Method
An economic evaluation from a societal perspective was conducted alongside a randomized controlled trial. Participants aged 16 or older with at least mild eating disorder symptoms were randomly assigned to four conditions: (1) Featback, an online unguided self‐help program, (2) chat or e‐mail support from a recovered expert patient, (3) Featback with expert‐patient support, and (4) care‐as‐usual. After a baseline assessment and intervention period of 8 weeks, five online assessments were conducted over 12 months of follow‐up. The main result constituted cost‐utility acceptability curves with quality‐of‐life adjusted life years (QALYs) and societal costs over the entire study duration.
Results
No significant differences between the conditions were found regarding QALYs, health care costs and societal costs. Nonsignificant differences in QALYs were in favor of the Featback conditions and the lowest societal costs per participant were observed in the Featback only condition (€16,741) while the highest costs were seen in the care‐as‐usual condition (€28,479). The Featback only condition had the highest probability of being efficient compared to the alternatives for all acceptable willingness‐to‐pay values.
Discussion
Featback, an internet‐based unguided self‐help intervention, was likely to be efficient compared to Featback with guidance from an expert patient, guidance alone and a care‐as‐usual condition. Results suggest that scalable interventions such as Featback may reduce health care costs and help individuals with eating disorders that are currently not reached by other forms of treatment.
Public significance statement
Internet‐based interventions for eating disorders might reach individuals in society who currently do not receive appropriate treatment at low costs. Featback, an online automated self‐help program for eating disorders, was found to improve quality of life slightly while reducing costs for society, compared to a do‐nothing approach. Consequently, implementing internet‐based interventions such as Featback likely benefits both individuals suffering from an eating disorder and society as a whole.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Intellectual disability (ID) disorders are genetically and phenotypically highly heterogeneous and present a major challenge in clinical genetics and medicine. Although many genes involved in ID have ...been identified, the etiology is unknown in most affected individuals. Moreover, the function of most genes associated with ID remains poorly characterized. Evidence is accumulating that the control of gene transcription through epigenetic modification of chromatin structure in neurons has an important role in cognitive processes and in the etiology of ID. However, our understanding of the key molecular players and mechanisms in this process is highly fragmentary. Here, we identify a chromatin-modification module that underlies a recognizable form of ID, the Kleefstra syndrome phenotypic spectrum (KSS). In a cohort of KSS individuals without mutations in EHMT1 (the only gene known to be disrupted in KSS until now), we identified de novo mutations in four genes, MBD5, MLL3, SMARCB1, and NR1I3, all of which encode epigenetic regulators. Using Drosophila, we demonstrate that MBD5, MLL3, and NR1I3 cooperate with EHMT1, whereas SMARCB1 is known to directly interact with MLL3. We propose a highly conserved epigenetic network that underlies cognition in health and disease. This network should allow the design of strategies to treat the growing group of ID pathologies that are caused by epigenetic defects.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective
Economic evaluations of treatments help to inform decisions on allocating health care resources. These evaluations involve comparing costs and effectiveness in terms of quality of life. To ...calculate quality‐adjusted life years, generic health related quality of life is often used, but is criticized for not being sensitive to change in mental health populations. Another approach, using experienced well‐being measured through capabilities with the ICECAP‐A, has been proposed as an alternative. The aim of this study was to investigate whether changes in individuals with eating disorder (ED) symptoms can be better captured using health related quality of life (EQ‐5D‐5L) or well‐being (ICECAP‐A).
Method
Measurements at two time points with an interval of 1 year were used from a sample of 233 participants with self‐reported ED symptoms. An analysis of variance was used to test whether the EQ‐5D‐5L and ICECAP‐A differed in sensitivity to change over time. In order to compare the two questionnaires in terms of clinically significant outcome, the reliable change index and clinical cut‐off score were calculated.
Results
The two questionnaires did not differ in sensitivity to change. More individuals had recovered but also more had deteriorated according to the EQ‐5D‐5L compared to the ICECAP.
Discussion
The present study revealed no differences in sensitivity to change in health‐related quality of life or well‐being in individuals with ED symptoms in the context of mild clinical change. Results corroborated the pervasiveness of low quality of life in this population, even after alleviation of ED symptoms.
Public significance statement
Measuring treatment benefits in terms of improvements in quality of life is an integral part of economic evaluations in health care. It was expected that these treatment benefits would be better captured as changes in well‐being (measured with the ICECAP‐A) than as changes in health‐related quality of life (measured with the EQ‐5D‐5L) for individuals with ED symptoms. Based on the results of this study, no preference for one of the two approaches was found.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Given the major structural role phosphodiesters play in the organism it is surprising they have not been more widely adopted as a building block in sophisticated biomimetic hydrogels and other ...biomaterials. The potential benefits are substantial: phosphoester‐based materials show excellent compatibility with blood, cells, and a remarkable resistance to protein adsorption that may trigger a foreign‐body response. In this work, a novel class of phosphodiester‐based ionic hydrogels is presented which are crosslinked via a phosphodiester moiety. The material shows good compatibility with blood, supports the growth and proliferation of tissue and presents opportunities for use as a drug release matrix as shown with fluorescent model compounds. The final gel is produced via base‐induced elimination from a phosphotriester precursor, which is made by the free‐radical polymerization of a phosphotriester crosslinker. This crosslinker is easily synthesized via multigram one‐pot procedures out of common laboratory chemicals. Via the addition of various comonomers the properties of the final gel may be tuned leading to a wide range of novel applications for this exciting class of materials.
Novel phosphodiester hydrogels are produced via a convenient precursor approach. The method uses a phosphotriester crosslinker which is easily synthesized via multigram one‐pot procedures. Their compatibility with cells and blood is shown to be excellent; and an exploratory study indicates possible utilty as a drug release matrix.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objective
To study the preferences of women with deep endometriosis (DE) with bowel involvement when they have to choose between conservative (medication) or surgical treatment.
Design
Labelled ...discrete choice experiment (DCE).
Setting
Dutch academic and non‐academic hospitals and online recruitment.
Population or Sample
A total of 169 women diagnosed with DE of the bowel.
Methods
Baseline characteristics and the fear of surgery were collected. Women were asked to rank attributes and choose between hypothetical conservative or surgical treatment in different choice sets (scenarios). Each choice set offered different levels of all treatment attributes. Data were analysed by using multinomial logistic regression.
Main Outcome Measures
The following attributes – effect on/risk of pain, fatigue, pregnancy, endometriosis lesions, mood swings, osteoporosis, temporary stoma and permanent intestinal symptoms – were used in this DCE.
Results
In the ranking, osteoporosis was ranked with low importance, whereas in the DCE, a lower chance of osteoporosis was one of the most important drivers when choosing a conservative treatment. Women with previous surgery showed less fear of surgery compared with women without surgery. Low anterior resection syndrome was almost equally important for patients as the chance of pain reduction. Pain reduction had higher importance than improving fertility chances, even in women with desire for a future child.
Conclusions
The risk of developing low anterior resection syndrome as a result of treatment is almost equally important as the reduction of pain symptoms. Women with previous surgery experience less fear of surgery compared with women without a surgical history.
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First discrete choice experiment in patients with deep endometriosis.
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First discrete choice experiment in patients with deep endometriosis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In light of the significant morbidity and mortality of cutaneous invasive squamous cell carcinomas (SCCs) in renal transplant recipients, we investigated whether conversion to sirolimus-based ...immunosuppression from standard immunosuppression could diminish the recurrence rate of these skin cancers.
In a 2-year randomized controlled trial, 155 renal transplant recipients with at least one biopsy-confirmed SCC were stratified according to age (< 55 v ≥ 55 years) and number of previous SCCs (one to nine v ≥ 10) and randomly assigned to conversion to sirolimus (n = 74) or continuation of their original immunosuppression (n = 81). Development of a new SCC within 2 years after random assignment was the primary end point.
After 2 years of follow-up, the risk reduction of new SCCs in the multivariable analysis was not significant, with a hazard ratio (HR) of 0.76 (95% CI, 0.48 to 1.2; P = .255), compared with a non-sirolimus-based regimen. After the first year, there was a significant 50% risk reduction, with an HR of 0.50 (95% CI, 0.28 to 0.90; P = .021) for all patients together and an HR of 0.11 (95% CI, 0.01 to 0.94; P = .044) for patients with only one previous SCC. The tumor burden of SCC was reduced during the 2-year follow-up period in those receiving sirolimus (0.82 v 1.38 per year; HR, 0.51; 95% CI, 0.32 to 0.82; P = .006) if adjusted for the number of previous SCCs and age. Twenty-nine patients stopped taking sirolimus because of various adverse events.
Conversion to sirolimus-based immunosuppression failed to show a benefit in terms of SCC-free survival at 2 years.
The biocompatibility, tunable degradability and broad functionalities of polyphosphoesters and their potential for biomedical applications have stimulated a renewed interest from Chemistry, Medicinal ...Chemistry and Polymer Sciences. Commercial applications of polyphosphoesters as biomaterials are still hampered because of the time and resource-intensive sourcing of their corresponding monomers, in addition to the corrosive and sensitive nature of their intermediates and by-products. Here, we present a groundbreaking challenge for sourcing the corresponding cyclic phosphate monomers by a different approach. This approach relies on the use of continuous flow technologies to intensify the end-to-end preparation of cyclic phosphate monomers with a semi-continuous modular flow platform. The applied flow technology mitigates both safety and instability issues related to the more classical production of cyclic phosphate monomers. The first flow module allows safe synthesis of a library of cyclic chlorophosphite building blocks and features in-line
31
P NMR real-time monitoring. After optimization on the microfluidic scale, this first module is successfully transposed toward mesofluidic scale with a daily throughput of 1.88 kg. Downstream of the first module, a second module is present, allowing the quantitative conversion of cyclic chlorophosphites with molecular oxygen toward chlorophosphate derivatives within seconds. The two modules are concatenable with a downstream semi-batch quench of intermediate chlorophosphate with alcohols, hence affording the corresponding cyclic phosphate monomers. Such a continuous flow setup provides considerable unprecedented advantages to safely and efficiently synthesize a library of versatile high value-added cyclic phosphate monomers at large scale. These freshly produced monomers can be successfully (co)polymerized, using either batch or flow protocols, into well-defined polyphosphoesters with assessed thermal properties and cytotoxicity.
A semi-continuous flow platform allows the safer end-to-end production of cyclic phosphate monomers providing an easier access to polyphosphoesters and their applications.
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IJS, KILJ, NUK, UL, UM, UPUK
Objective
The aim of this study is to identify items of economic evaluation guidelines that are frequently not complied within obstetric economic evaluations and to search for reasons for ...non‐adherence.
Design
Scoping review and qualitative study.
Setting
Literature on economic evaluations in obstetric care and interviews with experts.
Population or sample
The sample included 229 scientific articles and five experts.
Methods
A systematic literature search was performed. All types of literature about economic evaluations in obstetric care were included. The adherence to guidelines was assessed and articles were qualitatively analysed on additional information about reasons for non‐adherence. Issues that arose from the scoping review were discussed with experts.
Main outcome measures
Adherence to guideline items of the included economic evaluations studies. Analytical themes describing reasons for non‐adherence, resulting from qualitative analysis of articles and interviews with experts.
Results
A total of 184 economic evaluations and 45 other type of articles were included. Guideline items frequently not complied with were time horizon, type of economic evaluation and effect measure. Reasons for non‐adherence had to do with paucity of long‐term health data and assessing and combining outcomes for mother and child resulting from obstetric interventions.
Conclusions
This study identified items of guidelines that are frequently not complied with and the reasons behind this. The results are a starting point for a broad consensus building on how to deal with these challenges that can result in special guidance for the conduct of economic evaluations in obstetric care.
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Non‐adherence to guidelines in obstetric economic evaluation studies: the difficulties in detail.
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Non‐adherence to guidelines in obstetric economic evaluation studies: the difficulties in detail.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Genetic causes for autosomal recessive forms of dilated cardiomyopathy (DCM) are only rarely identified, although they are thought to contribute considerably to sudden cardiac death and heart ...failure, especially in young children. Here, we describe 11 young patients (5-13 years) with a predominant presentation of dilated cardiomyopathy (DCM). Metabolic investigations showed deficient protein N-glycosylation, leading to a diagnosis of Congenital Disorders of Glycosylation (CDG). Homozygosity mapping in the consanguineous families showed a locus with two known genes in the N-glycosylation pathway. In all individuals, pathogenic mutations were identified in DOLK, encoding the dolichol kinase responsible for formation of dolichol-phosphate. Enzyme analysis in patients' fibroblasts confirmed a dolichol kinase deficiency in all families. In comparison with the generally multisystem presentation in CDG, the nonsyndromic DCM in several individuals was remarkable. Investigation of other dolichol-phosphate dependent glycosylation pathways in biopsied heart tissue indicated reduced O-mannosylation of alpha-dystroglycan with concomitant functional loss of its laminin-binding capacity, which has been linked to DCM. We thus identified a combined deficiency of protein N-glycosylation and alpha-dystroglycan O-mannosylation in patients with nonsyndromic DCM due to autosomal recessive DOLK mutations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
Evaluate possibilities to reduce the number of infants screened for retinopathy of prematurity (ROP) and investigate costs and number of infants detected of current and alternative screening ...strategies in the Netherlands.
Methods
Prospective population‐based study including clinical data from all infants born in 2017 and referred for ROP screening (NEDROP‐2 study). Cost and effects of screening strategies were evaluated that differed on the criteria gestational age (GA), birth weight (BW) and presence of one or more specific risk factor(s) (RF): mechanical ventilation, sepsis, necrotizing enterocolitis, postnatal corticoids and/or hypotension treated with inotropic agents. RF obtained from the Dutch perinatal registry (Perined).
Results
Of the possible efficient strategies, the annual costs varied from €137 966 (inclusion of BW < 700, 63 infants eligible for screening, detection of 17/39 treated ROP) to €492 689 (GA < 30 weeks and BW < 1250 grams, together with infants with GA 30–32 and BW 1250–1500 grams with presence of one more RF, 744 infants eligible for screening, all treated infants detected). Total annual costs of the current Dutch guideline that detects all infants that need treatment for ROP amount to €552 143).
Conclusion
The current Dutch ROP guideline can be improved by implementing new screening inclusion criteria. The most effective strategy detecting all severe and treated infants, reduces the number of screened infants by 24% compared to the current guideline and the overall annual costs by €59454.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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