ObjectiveTo assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease.BackgroundMigraine has been linked to IBD and celiac... Show moreObjectiveTo assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease.BackgroundMigraine has been linked to IBD and celiac disease in observational studies, but whether this link may be explained by a shared genetic basis or could be causal has not been established. The presence of a causal association could be clinically relevant, as treating one of these medical conditions might mitigate the symptoms of a causally linked condition.MethodsLinkage disequilibrium score regression and two-sample bidirectional Mendelian randomization analyses were performed using summary statistics from cohort-based genome-wide association studies of migraine (59,674 cases; 316,078 controls), IBD (25,042 cases; 34,915 controls) and celiac disease (11,812 or 4533 cases; 11,837 or 10,750 controls). Migraine with and without aura were analyzed separately, as were the two IBD subtypes Crohn's disease and ulcerative colitis. Positive control analyses and conventional Mendelian randomization sensitivity analyses were performed.ResultsMigraine was not genetically correlated with IBD or celiac disease. No evidence was observed for IBD (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.99–1.02, p = 0.703) or celiac disease (OR 1.00, 95% CI 0.99–1.02, p = 0.912) causing migraine or migraine causing either IBD (OR 1.08, 95% CI 0.96–1.22, p = 0.181) or celiac disease (OR 1.08, 95% CI 0.79–1.48, p = 0.614) when all participants with migraine were analyzed jointly. There was some indication of a causal association between celiac disease and migraine with aura (OR 1.04, 95% CI 1.00–1.08, p = 0.045), between celiac disease and migraine without aura (OR 0.95, 95% CI 0.92–0.99, p = 0.006), as well as between migraine without aura and ulcerative colitis (OR 1.15, 95% CI 1.02–1.29, p = 0.025). However, the results were not significant after multiple testing correction.ConclusionsWe found no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease, although we obtained some indications of causal associations with migraine subtypes. Show less
Sustainability-focused research networks and communities of practice have emerged as a key response and strategy to build capacity and knowledge to support transformation towards more sustainable,... Show moreSustainability-focused research networks and communities of practice have emerged as a key response and strategy to build capacity and knowledge to support transformation towards more sustainable, just and equitable futures. This paper synthesises insights from the development of a community of practice on social-ecological systems (SES) research in southern Africa over the past decade, linked to the international Programme on Ecosystem Change and Society (PECS). This community consists of a network of researchers who carry out place-based SES research in the southern African region. They interact through various cross-cutting working groups and also host a variety of public colloquia and student and practitioner training events. Known as the Southern African Program on Ecosystem Change and Society (SAPECS), its core objectives are to: (1) derive new approaches and empirical insights on SES dynamics in the southern African context; (2) have a tangible impact by mainstreaming knowledge into policy and practice; and (3) grow the community of practice engaged in SES research and governance, including researchers, students and practitioners. This paper reflects on experiences in building the SAPECS community, with the aim of supporting the development of similar networks elsewhere in the world, particularly in the Global South. Show less
Sustainability-focused research networks and communities of practice have emerged as a key response and strategy to build capacity and knowledge to support transformation towards more sustainable,... Show moreSustainability-focused research networks and communities of practice have emerged as a key response and strategy to build capacity and knowledge to support transformation towards more sustainable, just and equitable futures. This paper synthesises insights from the development of a community of practice on social-ecological systems (SES) research in southern Africa over the past decade, linked to the international Programme on Ecosystem Change and Society (PECS). This community consists of a network of researchers who carry out place-based SES research in the southern African region. They interact through various cross-cutting working groups and also host a variety of public colloquia and student and practitioner training events. Known as the Southern African Program on Ecosystem Change and Society (SAPECS), its core objectives are to: (1) derive new approaches and empirical insights on SES dynamics in the southern African context; (2) have a tangible impact by mainstreaming knowledge into policy and practice; and (3) grow the community of practice engaged in SES research and governance, including researchers, students and practitioners. This paper reflects on experiences in building the SAPECS community, with the aim of supporting the development of similar networks elsewhere in the world, particularly in the Global South. Show less
Jansen, A.J.G.; Mcdonald, V.; Newland, A.; Morgan, M.; Bastiaanse, M.; Wilson, K.; ... ; Zwaginga, J.J. 2023
Objective:Identify patient experience and preference towards thrombopoietin-receptor agonists (TPO-RAs) in treatment of immune thrombocytopenia (ITP) in the Netherlands.Methods:The Thrombopoietin... Show moreObjective:Identify patient experience and preference towards thrombopoietin-receptor agonists (TPO-RAs) in treatment of immune thrombocytopenia (ITP) in the Netherlands.Methods:The Thrombopoietin-Receptor Agonist Patient experience (TRAPeze) survey used a discrete choice experiment (DCE) to elicit patient preferences and a patient burden survey (PBS) to evaluate the clinical and social impact of ITP. TRAPeze collected responses from 6th October to 19th November 2021.Results:Seventy-six respondents completed the DCE: treatment preference appeared to be driven by method of administration (odds ratio [OR] 4.33; 95% confidence interval [CI] 2.88–6.52), frequency of dosing (OR 2.33; 95% CI 1.86–2.92) and drug–food interactions (OR 1.91; 95% CI 1.54–2.37). Respondents preferred therapies delivered orally over subcutaneous injection (OR 4.22; 95% CI 2.76–6.46), dosed once weekly over once daily (OR 2.37; 95% CI 1.58–3.54) and without food restrictions over with restrictions (OR 1.90; 95% CI 1.52–2.38). Sixty-nine respondents completed the DCE and PBS (mean [range] age 53 [19–83] years, 65% female). Seven incomplete PBS responses were excluded from analysis. Respondents were currently, or most recently, receiving eltrombopag (n = 43) or romiplostim (n = 26), of which 30% (n = 21/69) had previously received another TPO-RA. Loss (29%, n = 6/21) and lack (29%, n = 6/21) of response were the most common reasons for switching TPO-RA. Only 28% (n = 18/65) of respondents felt their TPO-RA increased energy levels.Conclusion:Patients preferred therapies delivered orally, dosed less frequently and without food restrictions. QoL of ITP patients on TPO-RAs can be improved; the burden analyses presented can inform future efforts towards this. Show less
Children with intellectual disabilities have consistently occupied a marginalisedposition within the digital landscape. While they might reap benefits from usingdigital products and services, they... Show moreChildren with intellectual disabilities have consistently occupied a marginalisedposition within the digital landscape. While they might reap benefits from usingdigital products and services, they are also particularly vulnerable to online risks dueto cognitive deficiencies and lower critical literacy skills. As a result, children withintellectual impairments frequently encounter various predicaments, encompassingonline sexual solicitation, exposure to inaccurate information and manipulativebehavioural designs, as well as various privacy and data protection concerns.Regarding these challenges, utilising data protection by design under Article 25(1)GDPR can play a pivotal role in dismantling certain barriers. This approach allowsdigital service providers to take children’s evolving capacities into account andimplement technical and organisational measures appropriate for their age anddevelopmental stage. The aim of this article is to explore what challenges childrenwith intellectual disabilities might confront in the digital environment and examinehow data protection by design can help prevent or mitigate these challenges.Specifically, the article proposes a series of potential measures as the following: (1)presenting information transparently and in a manner accessible to children withintellectual disabilities; (2) crafting an inclusive user interface that enables thesechildren to actively and autonomously engage with the digital environment; (3)integrating interactive assistive tools, such as AI bots, to offer guidance and support;and (4) introducing parental control mechanisms that allow parents to provideassistance in alignment with their children's needs and preferences. Show less
In lieu of an abstract:In 2018, three anonymous and hitherto unpublished, unexhibited drawings of Istanbul by the same hand, previously part of Dr. Müfid Ekdal’s collection, were donated to the... Show moreIn lieu of an abstract:In 2018, three anonymous and hitherto unpublished, unexhibited drawings of Istanbul by the same hand, previously part of Dr. Müfid Ekdal’s collection, were donated to the Suna and İnan Kıraç Foundation by his son Oral Ekdal, upon Dr. Ekdal’s passing. One of them, a 360-degree, threeand- a-half-meter-long panorama, inspired researchers and curators working at the Istanbul Research Institute and Pera Museum to work on an exhibition on the history of Istanbul panoramas. Four years after preparations began, On the Spot: Panoramic Gaze on Istanbul, a History, curated by Çiğdem Kafescioğlu, K. Mehmet Kentel, and M. Baha Tanman, opened on October 26, 2023, at the Pera Museum, and greets its visitors with the aforementioned panorama. While the exhibition and its accompanying catalog explore various facets of Istanbul’s panoramic imaginaries through the centuries and firmly locate Istanbul as a crucial spot within the global history of panoramas, this short piece aims to briefly introduce these three recent additions to the Suna and İnan Kıraç Foundation collections to the scholarly community. Show less
Alberts, N.; Blanken, M. den; Bruinen, R.; Dammers, D.; Dijk, A.-C. van; Geboers, L.; ... ; Timorason, A. 2023
Purpose The purpose of this study was to explore the lived experience of dancing with Parkinson's and Multiple Sclerosis in an inclusive dance group called ReDiscoverMe (RDM). Methods Participatory... Show morePurpose The purpose of this study was to explore the lived experience of dancing with Parkinson's and Multiple Sclerosis in an inclusive dance group called ReDiscoverMe (RDM). Methods Participatory research approaches and interpretative phenomenological analysis were used to make sense of the lived experience captured in interviews and observations. Arthur Frank's conceptual framework on embodied storytelling from his book The Wounded Storyteller was the study's theoretical lens. Themes are both described and represented in images made by an RDM participant. Findings Dancing in a nonjudgmental environment was described by participants as a way to rediscover themselves while continually adapting to living with chronic illness. We interpreted this experience of rediscovery as an active, recursive process involving three "movements": escaping, expanding, and embracing. Through these movements, participants could rise above the self and illness. Conclusions The lived experience of dancing in this group was characterized by transformations of the body, self, and life. Through escaping, expanding, and embracing, participants could more easily embrace the body's contingency, integrate the self and body by becoming dancers, connect with others living with illness, and produce desire through passion. Participants could therefore experience illness as a journey and gain something from the experience. Show less
Kullberg, M.L.J.; Schoorl, M.; Oprel, D.A.C.; Hoeboer, C.M.; Smit, F.; Does, W. van der; ... ; Hout, W. van den 2023
Background: Prolonged exposure (PE) is an effective treatment for post-traumatic stress disorder (PTSD).Objective: This study aimed to analyse the cost-effectiveness of three exposure-based... Show moreBackground: Prolonged exposure (PE) is an effective treatment for post-traumatic stress disorder (PTSD).Objective: This study aimed to analyse the cost-effectiveness of three exposure-based treatments in patients with childhood abuse-related PTSD.Method: A net–benefit analysis was conducted alongside a pragmatic randomized controlled trial with participants (N = 149) randomized to three conditions: PE (n = 48), intensified PE (i-PE, n = 51), and phase-based PE [Skills Training in Affective and Interpersonal Regulation (STAIR) + PE, n = 50]. Assessments took place at baseline (T0), post-treatment (T3), 6 month follow-up (T4), and 12 month follow-up (T5). Costs stemming from healthcare utilization and productivity losses were estimated using the Trimbos/iMTA questionnaire for Costs associated with Psychiatric Illness. Quality-adjusted life-years (QALYs) were based on the 5-level EuroQoL 5 Dimensions (EQ-5D-5L) using the Dutch tariff. Missing values of costs and utilities were multiply imputed. To compare i-PE to PE and STAIR + PE to PE, pair-wise unequal-variance t-tests were conducted. Net–benefit analysis was used to relate costs to QALYs and to draw acceptability curves.Results: Intervention costs did not differ across the three treatment conditions. Total medical costs, productivity losses, total societal costs, and EQ-5D-5L-based QALYs did not differ between treatment conditions either (all p > .10). At the relevant €50,000/QALY threshold, the probability of one treatment being more cost-effective than another was 32%, 28%, and 40% for PE, i-PE, and STAIR-PE, respectively.Conclusion: Three equally effective treatments were compared and no differences in cost-effectiveness between treatments were found. Therefore, we advocate the implementation and adoption of any of the treatments and endorse shared decision making. Show less
Mutations in the DMD gene are causative for Duchenne muscular dystrophy (DMD). Antisense oligonucleotide (AON) mediated exon skipping to restore disrupted dystrophin reading frame is a therapeutic... Show moreMutations in the DMD gene are causative for Duchenne muscular dystrophy (DMD). Antisense oligonucleotide (AON) mediated exon skipping to restore disrupted dystrophin reading frame is a therapeutic approach that allows production of a shorter but functional protein. As DMD causing mutations can affect most of the 79 exons encoding dystrophin, a wide variety of AONs are needed to treat the patient population. Design of AONs is largely guided by trial-and-error, and it is yet unclear what defines the skippability of an exon. Here, we use a library of phosphorodiamidate morpholino oligomer (PMOs) AONs of similar physical properties to test the skippability of a large number of DMD exons. The DMD transcript is non-sequentially spliced, meaning that certain introns are retained longer in the transcript than downstream introns. We tested whether the relative intron retention time has a significant effect on AON efficiency, and found that targeting an out-of-frame exon flanked at its 5'-end by an intron that is retained in the transcript longer ('slow' intron) leads to overall higher exon skipping efficiency than when the 5'-end flanking intron is 'fast'. Regardless of splicing speed of flanking introns, we find that positioning an AON closer to the 5'-end of the target exon leads to higher exon skipping efficiency opposed to targeting an exons 3'-end. The data enclosed herein can be of use to guide future target selection and preferential AON binding sites for both DMD and other disease amenable by exon skipping therapies. Show less
During the COVID-19 pandemic the number of hospital admissions due to chronic obstructive pulmonary disease (COPD) exacerbations was significantly reduced. The reason for this decline is not fully... Show moreDuring the COVID-19 pandemic the number of hospital admissions due to chronic obstructive pulmonary disease (COPD) exacerbations was significantly reduced. The reason for this decline is not fully understood. Governmental non-pharmaceutical interventions (NPI's), an increase in community treated exacerbations, or healthcare avoidance by patients, are potential reasons. For the current study, the impact of Dutch governmental NPI's on the COPD exacerbations and respiratory infections rate in patients with severe alpha-1 antitrypsin deficiency (AATD) was analyzed. The patients participated in the NCT04204252 study, a randomized controlled trial evaluating the efficacy and safety of inhaled alpha-1 antitrypsin. Data collected in the time-period from March 2020 until February 2022 was analyzed. In this period the Dutch government imposed variable NPI's to contain the spread of SARS-CoV-2. Patients were required to document their daily symptoms in an electronic diary. The strictness of the governmental NPI's was measured by the COVID-19 Stringency Index. 19 patients participated in this study during the analysis period. A total of 40 respiratory infections and COPD exacerbations occurred. The Spearman's correlation coefficient of the monthly average COVID-19 Stringency Index and respiratory infections and COPD exacerbations rate was -0.316 (p = 0.132). When months known for a low respiratory infection rate were excluded, the correlation coefficient was -0.625 (p = 0.010). This study showed a significant negative correlation between the COPD exacerbations and respiratory infection rate and the COVID-19 Stringency Index in patients with AATD related COPD in the autumn-winter months. Show less
Borm, F.J.; Smit, J.; Bakker, J.; Wondergem, M.; Smit, E.F.; Langen, A.J. de; Gruijl, T.D. de 2023
Better biomarkers for programmed death - (ligand) 1 (PD-(L)1) checkpoint blockade in non-small cell lung cancer (NSCLC) are needed. We explored the predictive value of early response evaluation... Show moreBetter biomarkers for programmed death - (ligand) 1 (PD-(L)1) checkpoint blockade in non-small cell lung cancer (NSCLC) are needed. We explored the predictive value of early response evaluation using Fluor-18-deoxyglucose positron emission tomography and pre- and on-treatment flowcytometric T-cell profiling in peripheral blood and tumor-draining lymph nodes (TDLN). The on-treatment evaluation was performed 7–14 days after the start of PD-1 blockade in NSCLC patients. These data were related to (pathological) tumor response, progression-free survival, and overall survival (OS). We found that increases in total lesion glycolysis (TLG) had a strong reverse correlation with OS (r = −0.93, p = 0.022). Additionally, responders showed decreased and progressors increased Treg frequencies on-treatment. Frequencies of detectable PD-1-expressing CD8+ T cells decreased in responders but remained stable in progressors. This was especially found in the TDLN. Changes in activated Treg rates in TDLN were strongly but, due to low numbers of data points, non-significantly correlated with ΔTLG and reversely correlated with OS. Show less
BackgroundDiagnostics are increasingly shifting to patients’ home environment, facilitated by new digital technologies. Digital diagnostics (diagnostic services enabled by digital technologies) can... Show moreBackgroundDiagnostics are increasingly shifting to patients’ home environment, facilitated by new digital technologies. Digital diagnostics (diagnostic services enabled by digital technologies) can be a tool to better respond to the challenges faced by primary care systems while aligning with patients’ and healthcare professionals’ needs. However, it needs to be clarified how to determine the success of these interventions.ObjectivesWe aim to provide practical guidance to facilitate the adequate development and implementation of digital diagnostics.StrategyHere, we propose the quadruple aim (better patient experiences, health outcomes and professional satisfaction at lower costs) as a framework to determine the contribution of digital diagnostics in primary care. Using this framework, we critically analyse the advantages and challenges of digital diagnostics in primary care using scientific literature and relevant casuistry.ResultsTwo use cases address the development process and implementation in the Netherlands: a patient portal for reporting laboratory results and digital diagnostics as part of hybrid care, respectively. The third use case addresses digital diagnostics for sexually transmitted diseases from an international perspective.ConclusionsWe conclude that although evidence is gathering, the often-expected value of digital diagnostics needs adequate scientific evidence. We propose striving for evidence-based ‘responsible digital diagnostics’ (sustainable, ethically acceptable, and socially desirable digital diagnostics). Finally, we provide a set of conditions necessary to achieve it. The analysis and actionable guidance provided can improve the chance of success of digital diagnostics interventions and overall, the positive impact of this rapidly developing field. Show less