The work described in this thesis had two objectives, specifically focusing on people aged 70 years and older: first, we aimed to investigate the associations between several thrombosis-related... Show moreThe work described in this thesis had two objectives, specifically focusing on people aged 70 years and older: first, we aimed to investigate the associations between several thrombosis-related risk factors described in young and middle-aged populations and the risk of venous thrombosis (VT) in the elderly; second, we aimed to provide insight into several long-term consequences (i.e., health-related quality of life (HRQoL) and long-term risk of mortality) after a first VT at old age. Show less
Dam, P.H. van; Achterberg, W.P.; Husebo, B.S.; Caljouw, M.A. 2024
BackgroundPain medication may have an impact on the quality of life (QoL) in persons with dementia, but may also influence care dependency and daily functioning. The aim of this study is to... Show moreBackgroundPain medication may have an impact on the quality of life (QoL) in persons with dementia, but may also influence care dependency and daily functioning. The aim of this study is to investigate the effect of regularly scheduled paracetamol on care dependency and daily functioning in persons with advanced dementia with low QoL living in long-term care facilities.MethodsThe Quality of life and Paracetamol In advanced Dementia (Q-PID) study was a (block) randomized double-blind placebo-controlled crossover trial with paracetamol and placebo across seventeen long-term care facilities across 9 care organizations in the western region of the Netherlands. Participants were >= 65 years, had advanced dementia (Global Deterioration Scale 5-7), and low QoL (QUALIDEM-6D score <= 70). Measurements were performed by nursing staff at the start and at the end of each treatment period of six weeks. Repeated linear mixed models were used to compute differences between randomization groups, with adjustment for period and order effects, and psychotropic use.ResultsNinety-five persons (mean age of 83.9 years, 57.4% female) were enrolled in the Q-PID study. The mean Care Dependency Scale total score was 37.8 (Standard Deviation [SD] 12.9) and the mean Katz-15 total score was 11.9 (SD 2.4). Repeated linear mixed models showed no difference in mean differences of care dependency (paracetamol - 1.0 [95% Confidence Interval (CI) -2.4-0.3], placebo + 0.1 [-1.3-1.5]), and daily functioning (paracetamol + 0.2 [95% CI -0.2-0.6], placebo + 0.1 [-0.3-0.4]).ConclusionsCompared to placebo, no effect of scheduled administration of paracetamol was found on care dependency and daily functioning in persons with advanced dementia with low QoL. Future research should focus on which specific items of care dependency need special attention to improve the care for persons with advanced dementia. A multi-domain approach is needed to enhance and/or maintain QoL of persons with advanced dementia.Trial registrationNetherlands Trial Register (NTR6766); http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6766; Trial registration date: 20/10/2017. Show less
Patients with chronic obstructive pulmonary disease (COPD) may benefit from palliative care including advance care planning, because of their severe symptom burden and high mortality rates. However... Show morePatients with chronic obstructive pulmonary disease (COPD) may benefit from palliative care including advance care planning, because of their severe symptom burden and high mortality rates. However, this care is poorly implemented due to various reasons. Therefore, this thesis aimed to study the effectiveness of palliative care for patients with COPD and how a palliative care approach can be successfully integrated into regular COPD care.A national survey among pulmonologists and general practitioners was conducted to identify the current content and organization of palliative care in COPD in the Netherlands (Chapter 2). A systematic review revealed that very little was known about the effectiveness of palliative care interventions in COPD and how best to implement it in practice (Chapter 3). To close this knowledge gap, the COMPASSION study was designed (Chapter 4). In a cluster randomized controlled trial in eight hospital regions, health care providers of intervention regions were trained to identify palliative patients with COPD using the ProPal-COPD tool, do advance care planning conversations, and manage dyspnea. The effectiveness on patient outcomes was studied (Chapter 5) and factors for successful implementation identified (Chapter 6). Finally, the ProPal-COPD tool was externally validated and user experiences examined (Chapter 7). Show less
Webers, C.; Grimm, S.; Tubergen, A. van; Gaalen, F. van; Heijde, D. van der; Joore, M.; Boonen, A. 2023
ObjectiveTo demonstrate the value of diagnosing axSpA, by comparing health and costs associated with available diagnostic algorithms and perfect diagnosis.MethodsUsing data from SPACE and other... Show moreObjectiveTo demonstrate the value of diagnosing axSpA, by comparing health and costs associated with available diagnostic algorithms and perfect diagnosis.MethodsUsing data from SPACE and other cohorts, a model was developed to estimate health (quality-adjusted life-years, QALYs) and costs (healthcare consumption and work productivity losses) of different diagnostic algorithms for axSpA amongst patients with low back pain referred to a rheumatologist, over a 60-year horizon. The model combined a decision-tree (diagnosis) with a state-transition model (treatment). The three algorithms (Berlin [BER, highest specificity], Modification 1 [M1; less strict inflammatory back pain (IBP) criterion] and Modification 2 [M2; IBP not mandatory as entry criterion, highest sensitivity]) were compared. Changes in sensitivity/specificity were explored and the value of perfect diagnosis was investigated.ResultsFor each correctly diagnosed axSpA patient, up to 4.7 QALYs and €60,000 could be gained/saved, considering a societal perspective. Algorithm M2 resulted in more health and lower costs per patient (24.23 QALYs; €157,469), compared to BER (23.96 QALYs; €159,423) and M1 (24.15 QALYs; €158,417). Hypothetical improvements in M2 sensitivity resulted in slightly more value compared to improvements in specificity. Perfect diagnosis can cost €7,500 per patient and still provide enough value.ConclusionCorrect diagnosis of axSpA results in substantial health and cost benefits for patients and society. Not requiring IBP as mandatory for diagnosis of axSpA (algorithm M2) provides more value and would be preferable. A considerably more expensive diagnostic algorithm with better accuracy than M2 would still be considered good value for money. Show less
Aims/hypothesis There is a lack of e-health systems that integrate the complex variety of aspects relevant for diabetes self-management. We developed and field-tested an e-health system (POWER2DM)... Show moreAims/hypothesis There is a lack of e-health systems that integrate the complex variety of aspects relevant for diabetes self-management. We developed and field-tested an e-health system (POWER2DM) that integrates medical, psychological and behavioural aspects and connected wearables to support patients and healthcare professionals in shared decision making and diabetes self-management.Methods Participants with type 1 or type 2 diabetes (aged >18 years) from hospital outpatient diabetes clinics in the Netherlands and Spain were randomised using randomisation software to POWER2DM or usual care for 37 weeks. This RCT assessed the change in HbA(1c) between the POWER2DM and usual care groups at the end of the study (37 weeks) as a primary outcome measure. Participants and clinicians were not blinded to the intervention. Changes in quality of life (QoL) (WHO-5 Well-Being Index [WHO-5]), diabetes self-management (Diabetes Self-Management Questionnaire - Revised [DSMQ-R]), glycaemic profiles from continuous glucose monitoring devices, awareness of hypoglycaemia (Clarke hypoglycaemia unawareness instrument), incidence of hypoglycaemic episodes and technology acceptance were secondary outcome measures. Additionally, sub-analyses were performed for participants with type 1 and type 2 diabetes separately.Results A total of 226 participants participated in the trial (108 with type 1 diabetes; 118 with type 2 diabetes). In the POWER2DM group (n=111), HbA(1c) decreased from 60.6 +/- 14.7 mmol/mol (7.7 +/- 1.3%) to 56.7 +/- 12.1 mmol/mol (7.3 +/- 1.1%) (means +/- SD, p<0.001), compared with no change in the usual care group (n=115) (baseline: 61.7 +/- 13.7 mmol/mol, 7.8 +/- 1.3%; end of study: 61.0 +/- 12.4 mmol/mol, 7.7 +/- 1.1%; p=0.19) (between-group difference 0.24%, p=0.008). In the sub-analyses in the POWER2DM group, HbA(1c) in participants with type 2 diabetes decreased from 62.3 +/- 17.3 mmol/mol (7.9 +/- 1.6%) to 54.3 +/- 11.1 mmol/mol (7.1 +/- 1.0%) (p<0.001) compared with no change in HbA(1c) in participants with type 1 diabetes (baseline: 58.8 +/- 11.2 mmol/mol [7.5 +/- 1.0%]; end of study: 59.2 +/- 12.7 mmol/mol [7.6 +/- 1.2%]; p=0.84). There was an increase in the time during which interstitial glucose levels were between 3.0 and 3.9 mmol/l in the POWER2DM group, but no increase in clinically relevant hypoglycaemia (interstitial glucose level below 3.0 mmol/l). QoL improved in participants with type 1 diabetes in the POWER2DM group compared with the usual care group (baseline: 15.7 +/- 3.8; end of study: 16.3 +/- 3.5; p=0.047 for between-group difference). Diabetes self-management improved in both participants with type 1 diabetes (from 7.3 +/- 1.2 to 7.7 +/- 1.2; p=0.002) and those with type 2 diabetes (from 6.5 +/- 1.3 to 6.7 +/- 1.3; p=0.003) within the POWER2DM group. The POWER2DM integrated e-health support was well accepted in daily life and no important adverse (or unexpected) effects or side effects were observed.Conclusions/interpretation POWER2DM improves HbA(1c) levels compared with usual care in those with type 2 diabetes, improves QoL in those with type 1 diabetes, improves diabetes self-management in those with type 1 and type 2 diabetes, and is well accepted in daily life.Trial registration ClinicalTrials.gov NCT03588104.Funding This study was funded by the European Union's Horizon 2020 Research and Innovation Programme (grant agreement number 689444). Show less
Ekels, A.; Oerlemans, S.; Schagen, S.B.; Issa, D.E.; Thielen, N.; Nijziel, M.R.; ... ; Poll-franse, L.V. van de 2023
Purpose To investigate the proportion of patients with lymphoma with persistent clinically relevant cognitive impairment, and its relation to treatment, fatigue, and psychological distress.Methods... Show morePurpose To investigate the proportion of patients with lymphoma with persistent clinically relevant cognitive impairment, and its relation to treatment, fatigue, and psychological distress.Methods Patients with diffuse-large-B-cell-lymphoma (DLBCL), follicular-lymphoma (FL), and chronic-lymphocytic-leukemia (CLL)/small-lymphocytic-lymphoma (SLL), diagnosed between 2004-2010 or 2015-2019, were followed up to 8 years post-diagnosis. Sociodemographic and clinical data were obtained from the Netherlands Cancer Registry and the Population-based HAematological Registry for Observational Studies. The EORTC QLQ-C30 was used to assess cognitive functioning and fatigue, and the HADS to assess psychological distress. Individual growth curve models were performed. Results were compared with an age- and sex-matched normative population.Results A total of 924 patients were included (70% response rate). Persistent cognitive impairment was twice as high in patients (30%) compared to the normative population (15%). Additionally, 74% of patients reported co-occurring symptoms of persistent fatigue and/or psychological distress. Patients with FL (- 23 points, p < 0.001) and CLL/SLL (- 10 points, p < 0.05) reported clinically relevant deterioration of cognitive functioning, as did the normative population (FLnorm - 5 points, DLBCLnorm - 4 points, both p < 0.05). Younger age, higher fatigue, and/or psychological distress at inclusion were associated with worse cognitive functioning (all p's < 0.01). Treatment appeared less relevant.Conclusion Almost one-third of patients with lymphoma report persistent cognitive impairment, remaining present up to 8 years post-diagnosis. Early onset and co-occurrence of symptoms highlight the need for clinicians to discuss symptoms with patients early.Implications for Cancer Survivors Early recognition of cognitive impairment could increase timely referral to suitable supportive care (i.e., lifestyle interventions) and reduce (long-term) symptom burden. Show less
Persons with dementia may not always be able to set their own goals and expectations. When persons with dementia are no longer able to assess their own Quality of life (QoL), family, friends and... Show morePersons with dementia may not always be able to set their own goals and expectations. When persons with dementia are no longer able to assess their own Quality of life (QoL), family, friends and professional caregivers need to be their voice, as they are most familiar with their values, goals and needs. QoL in persons with advanced dementia is influenced by many factors, such as environment, background and psychological factors such as depression and agitation.The Q-PID study was a 13-week double-blind, randomised, placebo-controlled crossover trial that assessed the effect of paracetamol on QoL, discomfort, pain, neuropsychiatric symptoms, care dependency and daily functioning in 95 persons with moderate to advanced dementia living in long-term care facilities (LTCF).This thesis provides evidence that administration of paracetamol or placebo alone is not effective, i.e., no ‘panacea’, for improving QoL, discomfort, pain, neuropsychiatric symptoms, care dependency and dailyfunctioning in persons with advanced dementia living in LTCF. Personalizing interventions, collaborationbetween different health care workers and family/friends, and combining pharmacological and non-pharmacological interventions are important to maintain the best QoL possible, and we recognize that this will be challenging, but not impossible. Show less
Introduction: As the population is ageing, the number of older patients with multimorbidity including cancer continues to increase. To improve care for these patients, the European Union-funded... Show moreIntroduction: As the population is ageing, the number of older patients with multimorbidity including cancer continues to increase. To improve care for these patients, the European Union-funded project "Streamlined Geriatric and Oncological evaluation based on IC Technology" (GERONTE) was initiated to develop a new, patientcentred, holistic care pathway. The aim of this paper is to analyse what challenges are encountered in everyday clinical practice according to patients, their informal caregivers, and healthcare professionals as a starting point for the development of the care pathway.Materials and Methods: An expert panel of cancer and geriatrics specialists participated in an online survey to answer what challenges they experience in caring for older patients with multimorbidity including cancer and what treatment outcomes could be improved. Furthermore, in-depth interviews with older patients and their informal caregivers were organised to assess what challenges they experience.Results: Healthcare professionals (n = 36) most frequently mentioned the challenge of choosing the best treatment in light of the lack of evidence in this population and how to handle interactions between the (cancer) treatment and multimorbidities. Twelve patients and caregivers participated, and they most frequently mentioned challenges related to treatment outcomes, such as how to deal with symptoms of disease or treatment and how to maintain quality of life. From the challenges, five main themes emerged that should be taken into account when developing a new care pathway for older patients with multimorbidity including cancer. Two themes focus on decision making aspects such as personalized treatment recommendations and inclusion of nononcologic information, two focus on patient support and monitoring to maintain quality of life and functioning, and one overarching theme addresses care coordination to prevent fragmentation of care.Discussion: In conclusion, the management of older patients with multimorbidity including cancer is complex and although progress has been made on improving aspects of their care, challenges remain and patients are at risk of receiving inappropriate, unnecessary, and potentially harmful treatment. A patient-centred care pathway that integrates solutions to the five main themes and that moves away from a single-disease centred approach is needed. Show less
Seghers, P.A.L.; Alibhai, S.M.H.; Battisti, N.M.L.; Kanesvaran, R.; Extermann, M.; O'Donovan, A.; ... ; O'Hanlon, S. 2023
Most cancers occur in older people and the burden in this age group is increasing. Over the past two decades the evidence on how best to treat this population has increased rapidly. However,... Show moreMost cancers occur in older people and the burden in this age group is increasing. Over the past two decades the evidence on how best to treat this population has increased rapidly. However, implementation of new best practices has been slow and needs involvement of policymakers. This perspective paper explains why older people with cancer have different needs than the wider population. An overview is given of the recommended approach for older people with cancer and its benefits on clinical outcomes and cost-effectiveness. In older patients, the geriatric assessment (GA) is the gold standard to measure level of fitness and to determine treatment tolerability. The GA, with multiple domains of physical health, functional status, psychological health and socio-environmental factors, prevents initiation of inappropriate oncologic treatment and recommends geriatric interventions to optimize the patient's general health and thus resilience for receiving treatments. Multiple studies have proven its benefits such as reduced toxicity, better quality of life, better patient-centred communication and lower healthcare use. Although GA might require investment of time and resources, this is relatively small compared to the improved outcomes, possible cost-savings and compared to the large cost of oncologic treatments as a whole. Show less
Pape, M.; Vissers, P.A.J.; Slingerland, M.; Mohammad, N.H.; Rossum, P.S.N. van; Verhoeven, R.H.A.; ... ; Dutch Upper GI Canc Grp DUCG 2023
PurposeTo investigate the effect of systemic therapy on health-related quality of life (HRQoL) in patients with advanced esophagogastric cancer in daily clinical practice. This study assessed the... Show morePurposeTo investigate the effect of systemic therapy on health-related quality of life (HRQoL) in patients with advanced esophagogastric cancer in daily clinical practice. This study assessed the HRQoL of patients with esophagogastric cancer during first-line systemic therapy, at disease progression, and after progression in a real-world context.MethodsPatients with advanced esophagogastric cancer (2014-2021) receiving first-line systemic therapy registered in the Prospective Observational Cohort Study of Oesophageal-gastric cancer (POCOP) were included (n = 335). HRQoL was measured with the EORTC QLQ-C30 and QLQ-OG25. Outcomes of mixed-effects models were presented as adjusted mean changes.ResultsResults of the mixed-effect models showed the largest significant improvements during systemic therapy for odynophagia (- 18.9, p < 0.001), anxiety (- 18.7, p < 0.001), and dysphagia (- 13.8, p < 0.001) compared to baseline. After progression, global health status (- 6.3, p = 0.002) and cognitive (- 6.2, p = 0.001) and social functioning (- 9.7, p < 0.001) significantly worsened. At and after progression, physical (- 9.0, p < 0.001 and - 8.8, p < 0.001) and role functioning (- 15.2, p = 0.003 and - 14.7, p < 0.001) worsened, respectively. Trouble with taste worsened during systemic therapy (11.5, p < 0.001), at progression (12.0, p = 0.004), and after progression (15.3, p < 0.001).ConclusionIn general, HRQoL outcomes in patients with advanced esophagogastric cancer improved during first-line therapy. Deterioration in outcomes was mainly observed at and after progression.Implications for cancer survivorsIdentification of HRQoL aspects is important in shared decision-making and to inform patients on the impact of systemic therapy on their HRQoL. Show less
Alanay, Y.; Mohnike, K.; Nilsson, O.; Alves, I.; AlSayed, M.; Appelman-Dijkstra, N.M.; ... ; Irving, M. 2023
BackgroundCollection of real-world evidence (RWE) is important in achondroplasia. Development of a prospective, shared, international resource that follows the principles of findability,... Show moreBackgroundCollection of real-world evidence (RWE) is important in achondroplasia. Development of a prospective, shared, international resource that follows the principles of findability, accessibility, interoperability, and reuse of digital assets, and that captures long-term, high-quality data, would improve understanding of the natural history of achondroplasia, quality of life, and related outcomes.MethodsThe Europe, Middle East, and Africa (EMEA) Achondroplasia Steering Committee comprises a multidisciplinary team of 17 clinical experts and 3 advocacy organization representatives. The committee undertook an exercise to identify essential data elements for a standardized prospective registry to study the natural history of achondroplasia and related outcomes.ResultsA range of RWE on achondroplasia is being collected at EMEA centres. Whereas commonalities exist, the data elements, methods used to collect and store them, and frequency of collection vary. The topics considered most important for collection were auxological measures, sleep studies, quality of life, and neurological manifestations. Data considered essential for a prospective registry were grouped into six categories: demographics; diagnosis and patient measurements; medical issues; investigations and surgical events; medications; and outcomes possibly associated with achondroplasia treatments.ConclusionsLong-term, high-quality data are needed for this rare, multifaceted condition. Establishing registries that collect predefined data elements across age spans will provide contemporaneous prospective and longitudinal information and will be useful to improve clinical decision-making and management. It should be feasible to collect a minimum dataset with the flexibility to include country-specific criteria and pool data across countries to examine clinical outcomes associated with achondroplasia and different therapeutic approaches. Show less
With the introduction of population-based screening, early-stage colorectal cancers (T1CRCs) are increasingly detected. The treatment of patients with T1CRC is complex, as these tumors have... Show moreWith the introduction of population-based screening, early-stage colorectal cancers (T1CRCs) are increasingly detected. The treatment of patients with T1CRC is complex, as these tumors have metastatic potential despite their early stage. As a result, local organ-sparing endoscopic tumor resection is not always sufficient, thereby giving rise to various challenges throughout the entire treatment process.The overarching goal of this thesis is to improve clinical care for T1CRC patients. Part 1 is centered around the biology and translational potential of the tumor microenvironment, and in particular cancer-associated fibroblasts (CAFs), in T1CRC. The studies in this part show that CAFs in T1CRCs exhibit T1 stage-specific phenotypic traits and can promote cancer cell invasion in T1CRC through diverse mechanisms. These findings provide promising leads for developing better predictors of metastasis, which can be used to determine which T1CRC patients will (not) benefit from major bowel surgery.Part 2 focuses on the clinical aspects of T1CRC treatment. The studies in this part show that local endoscopic tumor resection has become a mature alternative to surgery, from both the patient’s and oncological perspective. However, further optimizations of local resection techniques and surveillance thereafter are needed to increase the use of organ-sparing treatment for T1CRC patients. Show less
Maas, A.; Maurice-Stam, H.; Aa-van Delden, A.M. van der; Dalen, E.C. van; Dulmen-den Broeder, E. van; Tissing, W.J.E.; ... ; Dutch LATER Study Group 2023
Purpose: Numerous studies investigated generic psychosocial outcomes in survivors of childhood cancer (CCS). The present study aimed to describe survivor-specific psychosocial consequences in CCS,... Show morePurpose: Numerous studies investigated generic psychosocial outcomes in survivors of childhood cancer (CCS). The present study aimed to describe survivor-specific psychosocial consequences in CCS, and to identify socio-demographic and medical associated factors. Methods: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed 1963-2001) part 2 (age >= 18 years, diagnosed < 18 years, >= 5 years since diagnosis) completed the Benefit & Burden Scale (BBSC) and the Impact of Cancer-Childhood Cancer (IOC-CS). Items were scored on a 5-point Likert scale (range 1-5). We examined outcomes with descriptive statistics, and socio-demographic and medical associated factors with regression analyses, corrected for multiple testing (p < 0.004). Results: CCS, N = 1713, age mean (M) 36 years, 49% female, >= 15 years since diagnosis, participated. On average, CCS reported 'somewhat' Benefit (M = 2.9), and 'not at all' to 'a little' Burden (M = 1.5) of childhood cancer. Average scores on IOC-CS' positive impact scales ranged from 2.5 (Personal Growth) to 4.1 (Socializing), and on the negative impact scales from 1.4 (Financial Problems) to 2.4 (Thinking/Memory). Apart from cognitive problems, CCS reported challenges as worries about relationship status, fertility, and how cancer had affected siblings. Female sex was associated with more Personal Growth, and more negative impact. CCS more highly educated, partnered, and employed had higher positive and lower negative impact. CCS older at diagnosis reported more positive impact. CNS tumor survivors and those who had head/cranium radiotherapy had higher negative impact. CNS tumor survivors reported less positive impact. Conclusion and implications: The majority of CCS reported positive impact of cancer while most CCS reported little negative impact. While this may indicate resiliency in most CCS, health care providers should be aware that they can also experience survivor-specific challenges that warrant monitoring/screening, information provision and psychosocial support. Show less
BackgroundNon-communicable diseases are currently the leading cause of death in the Netherlands. Meeting the increasingly complex care needs of patients with these diseases is demanding for society... Show moreBackgroundNon-communicable diseases are currently the leading cause of death in the Netherlands. Meeting the increasingly complex care needs of patients with these diseases is demanding for society and our healthcare services.Specialist palliative care diminishes inappropriate end-of-life care and improves quality of life for patients with advanced cancer and other life-limiting diseases.Aims & MethodsUsing 2 national cross-sectional surveys and 2 population-based observational studies, we assessed the value, availability and accessibility of palliative care in the Dutch healthcare system. Using a modified Delphi technique, we developed a national quality framework for palliative care with key elements for integration with regular care.ResultsTimely provision of generalist and specialist palliative care is associated with significantly less potentially inappropriate end-of-life care for patients with advanced cancer.The majority of patients with cancer received no palliative care or only in their last weeks or days of life. Specialist palliative care teams were found to be available in almost all hospitals, but referrals to these teams were consistently low. Our findings implicate a limited availability and accessibility of palliative care.Eight key elements of the Netherlands Quality Framework for Palliative Care were prioritised to improve availability and accessibility to quality palliative care. Show less
Hoydonckx, Y.; Singh, M.; Gilron, I.; Khan, J.; Narouze, S.; Dahan, A.; ... ; Bhatia, A. 2023
BackgroundChronic daily headaches (CDH) are common and associated with significant morbidity, poor quality of life, and substantial burden on the healthcare system. CDH tends to be refractory to... Show moreBackgroundChronic daily headaches (CDH) are common and associated with significant morbidity, poor quality of life, and substantial burden on the healthcare system. CDH tends to be refractory to conventional medical management and/or patients cannot afford expensive treatments. It is stipulated that CDH share a mechanism of central sensitization in the trigeminocervical complex, mediated by activation of the N-methyl-d-aspartate (NMDA) receptors. Ketamine, a non-competitive NMDA antagonist, has been used in the treatment of chronic pain, but its role in CDH has not been completely established. This trial aims to evaluate the effect of high-dose IV ketamine infusions (compared to placebo) on the number of headache days at 28 days post-infusion.MethodsA multicenter, placebo-controlled, randomized controlled trial will be conducted with two parallel groups and blinding of participants and outcome assessors. The study will include 56 adults with a CDH diagnosis as per ICHD-3 criteria. Participants will be randomized (1:1) to either ketamine (1 mg. kg−1 bolus followed by infusion of 1 mg. kg−1. h−1 for 6 h) or placebo (0.9% saline in the same volume and infusion rate as the trial medication) bolus and infusion for 6 h. The impact on the number of monthly headache days, headache intensity, physical activity, mood, sleep, quality of life, analgesic consumption, and adverse effects will be recorded at baseline, immediately post-infusion, and from 1 to 28 days, 29 to 56 days, and 57 to 84 days after the infusionDiscussionDespite advancements in treatment, many patients continue to suffer from CDH. This trial investigates whether high-dose IV ketamine infusions can effectively and safely improve the CDH burden as compared to a placebo infusion. This treatment could become a safe, affordable, and widely available option for patients living with refractory headache. Show less
Objective: To analyze the effect of dizziness-related symptoms on the long-term quality of life (QoL) of patients with unilateral vestibular schwannoma. Methods: In this cross-sectional study,... Show moreObjective: To analyze the effect of dizziness-related symptoms on the long-term quality of life (QoL) of patients with unilateral vestibular schwannoma. Methods: In this cross-sectional study, patients with a unilateral vestibular schwannoma diagnosed between 2004 and 2013 completed a disease-specific QoL questionnaire (Penn Acoustic Neuroma Quality of Life [PANQOL]) and the Dizziness Handicap Inventory (DHI) in 2020. Linear regression was performed to assess the correlation between QoL and the DHI total score, and the scores of the DHI functional, emotional, and physical subdomains. Potential confounders such as age, sex, tumor size at baseline, and treatment modality (active surveillance, surgery, or radiotherapy) were included in the model. Results: In total, 287 of 479 patients (59%) experienced dizziness with a median follow-up of 10 years. The DHI total score was significantly associated with the PANQOL total score. On average, we found a reduction of 0.7 points on the PANQOL for each additional point on the DHI. The DHI emotional subdomain was the most prominent determinant of poorer QoL. Each point on the DHI emotional subscale was associated with a reduction of 1.3 on the PANQOL score. Treatment modality did not have a clinically relevant effect on dizziness-related QoL. Conclusions: Even mild dizziness can have a significant and clinically relevant effect on the QoL of patients with unilateral vestibular schwannoma in the long term. This holds true for all treatment modalities. Addressing the vestibular problems may improve QoL in vestibular schwannoma patients, and DHI subscale analysis may help tailor the optimal vestibular intervention. Show less
Background: Huntington's disease (HD) is a genetic, neurodegenerative disease. Due to the progressive nature of HD and the absence of a cure, (health-related) quality of life ((HR)QoL) is an... Show moreBackground: Huntington's disease (HD) is a genetic, neurodegenerative disease. Due to the progressive nature of HD and the absence of a cure, (health-related) quality of life ((HR)QoL) is an important topic. Several studies have investigated (HR)QoL in HD, yet a clear synthesis of the existing literature is lacking to date. We performed a systematic review on self-reported (HR)QoL, and factors and intervention effects associated with (HR)QoL in premanifest and manifest HD gene expansion carriers (pHDGECs and mHDGECs, respectively). Methods: PubMed, EMBASE, Web of Science, and PsycINFO were searched systematically from September 17th, 2021, up to August 11th, 2022. Methodological and conceptual quality of the included studies was assessed with two appraisal tools.Results: 30 out of 70 eligible articles were included. mHDGECs experienced lower (HR)QoL compared to pHDGECs and controls, whereas mixed findings were reported when compared to other neurological diseases. Several factors were associated with (HR)QoL that might contribute to lower (HR)QoL in mHDGECs, including depressive symptoms, physical and psychological symptoms, lower functional capacity, lower support, and unmet needs. Multidisciplinary rehabilitation programs and a respiratory muscle training were beneficial for (HR)QoL in mHDGECs. Discussion: (HR)QoL is experienced differently across the course of the disease. Although (HR)QoL is key for understanding the impact of HD and the effect of symptomatic treatment, there is a need to improve the methodological and conceptual shortcomings that were found in most studies, especially regarding the conceptual clarity when reporting on QoL and HRQoL. Suggestions for strengthening these shortcomings are provided in this review. Show less
In the current dissertation the effectiveness and cost-effectiveness of Featback, an internet-based self-help intervention for eating disorders, and online support by individuals with a lived... Show moreIn the current dissertation the effectiveness and cost-effectiveness of Featback, an internet-based self-help intervention for eating disorders, and online support by individuals with a lived experience of an eating disorder were investigated. The findings suggest that low-threshold internet-based interventions for eating disorders, such as Featback, can complement existing treatment options in three ways. First, they have been repeatedly found to be effective in reducing eating disorder symptomatology. Second, such interventions can reach individuals that are currently not reached by other forms of treatment and stimulate them to get professional help. Finally, internet-based interventions are likely to be cost-effective compared to care as usual. Concordantly, implementing highly scalable and easily accessible interventions like Featback likely helps to reduce both the individual and societal burden of eating disorders. Show less
Background: Chronic pancreatitis (CP) is an inflammatory disease that may be complicated by abdominal pain, pancreatic dysfunction, nutritional deficiencies, and diminished bone density.... Show moreBackground: Chronic pancreatitis (CP) is an inflammatory disease that may be complicated by abdominal pain, pancreatic dysfunction, nutritional deficiencies, and diminished bone density. Importantly, it is also associated with a substantially impaired quality of life and reduced life expectancy. This may partly be explained by suboptimal treatment, in particular the long-term management of this chronic condition, despite several national and international guidelines. Standardization of care through a structured implementation of guideline recommendations may improve the level of care and lower the complication rate of these patients. Therefore, the aim of the present study is to evaluate to what extent patient education and standardization of care, through the implementation of an evidence-based integrated management algorithm, improve quality of life and reduce pain severity in patients with CP. Methods: The COMBO trial is a nationwide stepped-wedge cluster-randomized controlled trial. In a stepwise manner, 26 centers, clustered in 6 health regions, cross-over from current practice to care according to an evidence-based integrated management algorithm. During the current practice phase, study participants are recruited and followed longitudinally through questionnaires. Individual patients contribute data to both study periods. Co-primary study endpoints consist of quality of life (assessed by the PANQOLI score) and level of pain (assessed by the Izbicki questionnaire). Secondary outcomes include process measure outcomes, clinical outcomes (e.g., pancreatic function, nutritional status, bone health, interventions, medication use), utilization of healthcare resources, (in) direct costs, and the level of social participation. Standard follow-up is 35 months from the start of the trial. Discussion: This is the first stepped-wedge cluster-randomized controlled trial to investigate whether an evidence-based integrated therapeutic approach improves quality of life and pain severity in patients with CP as compared with current practice. Show less
There are substantial disease and health-related quality-of-life (HRQoL) burdens for many patients with myasthenia gravis (MG), especially for those whose disease symptoms are not well controlled.... Show moreThere are substantial disease and health-related quality-of-life (HRQoL) burdens for many patients with myasthenia gravis (MG), especially for those whose disease symptoms are not well controlled. HRQoL measures such as the Myasthenia Gravis Quality of Life 15-item revised (MG-QOL15r) and EuroQoL 5-Dimensions 5-Levels (EQ-5D-5L) are vital for evaluating the clinical benefit of therapeutic interventions in patients with MG, as they assess the burden of disease and the effectiveness of treatment, as perceived by patients. The phase 3 ADAPT study (NCT03669588) demonstrated that efgartigimod-a novel neonatal Fc receptor inhibitor-was well tolerated and that acetylcholine receptor antibody-positive (AChR-Ab+) participants who received efgartigimod had statistically significant improvements in MG-specific clinical scale scores. The ancillary data reported here, which cover an additional treatment cycle, show that these participants had similar significant improvements in HRQoL measures, the MG-QOL15r and EQ-5D-5L utility and visual analog scales, and that these improvements were maintained in the second treatment cycle. Positive effects on HRQoL were rapid, seen as early as the first week of treatment in both treatment cycles, and maintained for up to 4 weeks in the follow-up-only portion of treatment cycles. The pattern of improvements in HRQoL paralleled changes in immunoglobulin G level, and correlational analyses show that improvements were consistent across HRQoL measures and with clinical efficacy measures in the ADAPT study. The substantial and durable improvements in HRQoL end points in this study demonstrate the broader benefit of treatment with efgartigimod beyond relief of immediate signs and symptoms of gMG. Show less
