BackgroundRecently, a large group of patients with persistent dyspnea, poor physical capacity, and reduced health-related quality of life (HRQoL) following pulmonary embolism (PE) has been... Show moreBackgroundRecently, a large group of patients with persistent dyspnea, poor physical capacity, and reduced health-related quality of life (HRQoL) following pulmonary embolism (PE) has been identified and clustered under the name "post pulmonary embolism syndrome" (PPS). These patients seem good candidates for pulmonary rehabilitation. The aim of the study is to explore whether a pulmonary rehabilitation program can improve physical capacity, dyspnea, and HRQoL in PPS patients.MethodsA two-center randomized controlled trial (RCT) is being performed at Ostfold Hospital and Akershus University Hospital in Norway. Patients with PPS are 1:1 randomized into an intervention or a control group. The intervention consists of a supervised, outpatient rehabilitation program twice weekly (1h) for 8weeks provided by experienced physiotherapists. The intervention involves individually adapted exercises based on existing pulmonary rehabilitation programs (relaxation, interval, and resistance training), and an educational session including topics such as normal anatomy and physiology of the respiratory and circulatory system, information on PE/PPS, breathing strategies, and benefits of exercise/physical activity. Patients randomized to the control group receive usual care without specific instructions to exercise.Participants in the intervention and control groups will be compared based on assessments conducted at baseline, 12weeks, and 36weeks after inclusion using the incremental shuttle walk test (primary outcome) and endurance shuttle walk test (exercise capacity), Sensewear activity monitor (daily physical activity), the modified Medical Research Council scale, the Shortness of Breath Questionnaire (dyspnea), and EQ-5D-5L and the Pulmonary Embolism Quality of Life Questionnaire (HRQoL).Recruitment of 190 patients is currently ongoing.DiscussionResults from this study may provide a currently untreated group of PPS patients with an effective treatment resulting in reduced symptoms of dyspnea, improved exercise capacity, and better HRQoL following PE.Trial registrationClinical Trials NCT03405480. Registered prospectively on September 2017.Protocol version 1 (from original protocol September 2017).The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 1). Show less
Meij, A. van der; Walderveen, M.A.A. van; Kruyt, N.D.; Zwet, E.W. van; Liebler, E.J.; Ferrari, M.D.; Wermer, M.J.H. 2020
BackgroundSecondary damage due to neurochemical and inflammatory changes in the penumbra in the first days after ischemic stroke contributes substantially to poor clinical outcome. In animal models... Show moreBackgroundSecondary damage due to neurochemical and inflammatory changes in the penumbra in the first days after ischemic stroke contributes substantially to poor clinical outcome. In animal models, vagus nerve stimulation (VNS) inhibits these detrimental changes and thereby reduces tissue injury. The aim of this study is to investigate whether non-invasive cervical VNS (nVNS) in addition to the current standard treatment can improve penumbral recovery and limit final infarct volume.MethodsNOVIS is a single-center prospective randomized clinical trial with blinded outcome assessment. One hundred fifty patients will be randomly allocated (1:1) within 12h from clinical stroke onset to nVNS for 5 days in addition to standard treatment versus standard treatment alone. The primary endpoint is the final infarct volume on day 5 assessed with MRI.DiscussionWe hypothesize that nVNS will result in smaller final infarct volumes as compared to standard treatment due to improved penumbral recovery. The results of this study will be used to assess the viability and approach to power a larger trial to more definitively assess the clinical efficacy of nVNS after stroke.Trial registrationClinicalTrials.govNCT04050501. Registered on 8 August 2019 Show less
Niemantsverdriet, E.; Dakkak, Y.J.; Burgers, L.E.; Bonte-Mineur, F.; Steup-Beekman, G.M.; Kooij, S.M. van der; ... ; Helm-van Mil, A.H.M. van der 2020
Background: We present a study protocol for a randomized, double-blind, placebo-controlled trial that investigates the hypothesis if intervention in the symptomatic phase preceding clinical... Show moreBackground: We present a study protocol for a randomized, double-blind, placebo-controlled trial that investigates the hypothesis if intervention in the symptomatic phase preceding clinical arthritis (clinically suspect arthralgia (CSA)) is effective in preventing progression from subclinical inflammation to clinically apparent persistent arthritis. Currently, rheumatoid arthritis (RA) can be recognized and diagnosed when arthritis (joint swelling) has become detectable at physical examination. Importantly, at this time, the immune processes have already matured, chronicity is established, and patients require long-standing treatment with disease-modifying anti-rheumatic drugs. The TREAT EARLIER trial studies the hypothesis that intervention in the symptomatic phase preceding clinical arthritis is more often successful in permanent disease modification because of less matured underlying disease processes.Methods: A two-level definition to identify patients that are prone to develop RA is used. First, patients should have CSA and recent-onset arthralgia (< 1 year) that is suspect to progress to RA according to the expertise of the treating rheumatologist. Second, patients need to have subclinical inflammation of the hand or foot joints at 1.5 T MRI. The trial aims to recruit 230 participants from secondary care hospital settings across the south-west region of The Netherlands. Intervention will be randomly assigned and includes a single-dose of intramuscular 120 mg methylprednisolon followed by methotrexate (increasing dose to 25 mg/week orally) or placebo (both; injection and tablets) over the course of 1 year. Thereafter, participants are followed for another year. The primary endpoint is the development of clinically detectable arthritis, either fulfilling the 2010 criteria for RA or unclassified clinical arthritis of >= 2 joints, which persists for at least 2 weeks. DMARD-free status is a co-primary endpoint. The patient-reported outcomes functioning, along with workability and symptoms, are key secondary endpoints. Participants, caregivers (including those assessing the endpoints), and scientific staff are all blinded to the group assignment.Discussion: This proof-of-concept study is the logical consequence of pre-work on the identification of patients with CSA with MRI-detected subclinical joint inflammation. It will test the hypothesis whether intervention in patients in this early phase with the cornerstone treatment of classified RA (methotrexate) hampers the development of persistent RA and reduce the disease burden of RA. Show less
Background: Despite evidence of a quite large beneficial effect of endovascular treatment (EVT) for ischemic stroke caused by anterior circulation large vessel occlusion, many patients do not... Show moreBackground: Despite evidence of a quite large beneficial effect of endovascular treatment (EVT) for ischemic stroke caused by anterior circulation large vessel occlusion, many patients do not recover even after complete recanalization. To some extent, this may be attributable to incomplete microvascular reperfusion, which can possibly be improved by antiplatelet agents and heparin. It is unknown whether periprocedural antithrombotic medication in patients treated with EVT improves functional outcome. The aim of this study is to assess the effect of acetylsalicylic acid (ASA) and unfractionated heparin (UFH), alone, or in combination, given to patients with an ischemic stroke caused by an intracranial large vessel occlusion in the anterior circulation during EVT.Methods: MR CLEAN-MED is a multicenter phase III trial with a prospective, 2 x 3 factorial randomized, open label, blinded end-point (PROBE) design, which aims to enroll 1500 patients. The trial is designed to evaluate the effect of intravenous ASA (300 mg), UFH (low or moderate dose), both or neither as adjunctive therapy to EVT. We enroll adult patients with a clinical diagnosis of stroke (NIHSS >= 2) and with a confirmed intracranial large vessel occlusion in the anterior circulation on CTA or MRA, when EVT within 6 h from symptom onset is indicated and possible. The primary outcome is the score on the modified Rankin Scale (mRS) at 90 days. Treatment effect on the mRS will be estimated with ordinal logistic regression analysis, with adjustment for main prognostic variables. Secondary outcomes include stroke severity measured with the NIHSS at 24 h and at 5-7 days, follow-up infarct volume, symptomatic intracranial hemorrhage (sICH), and mortality.Discussion: Clinical equipoise exists whether antithrombotic medication should be administered during EVT for a large vessel occlusion, as ASA and/or UFH may improve functional outcome, but might also lead to an increased risk of sICH. When one or both of the study treatments show the anticipated effect on outcome, we will be able to improve outcome of patients treated with EVT by 5%. This amounts to more than 50 patients annually in the Netherlands, more than 1800 in Europe, and more than 1300 in the USA. Show less
Background The global health challenge of dementia is exceptional in size, cost and impact. It is the only top ten cause of death that cannot be prevented, cured or substantially slowed, leaving... Show moreBackground The global health challenge of dementia is exceptional in size, cost and impact. It is the only top ten cause of death that cannot be prevented, cured or substantially slowed, leaving disease management, caregiver support and service innovation as the main targets for reduction of disease burden. Institutionalization of persons with dementia is common in western countries, despite patients preferring to live longer at home, supported by caregivers. Such complex health challenges warrant multicomponent interventions thoroughly implemented in daily clinical practice. This article describes the rationale, development, feasibility testing and implementation process of the LIVE@Home.Path trial. Methods The LIVE@Home.Path trial is a 2-year, multicenter, mixed-method, stepped-wedge randomized controlled trial, aiming to include 315 dyads of home-dwelling people with dementia and their caregivers, recruited from 3 municipalities in Norway. The stepped-wedge randomization implies that all dyads receive the intervention, but the timing is determined by randomization. The control group constitutes the dyads waiting for the intervention. The multicomponent intervention was developed in collaboration with user-representatives, researchers and stakeholders to meet the requirements from the national Dementia Plan 2020. During the 6-month intervention period, the participants will be allocated to a municipal coordinator, the core feature of the intervention, responsible for regular contact with the dyads to facilitate L: Learning, I: Innovation, V: Volunteering and E: Empowerment (LIVE). The primary outcome is resource utilization. This is measured by the Resource Utilization in Dementia (RUD) instrument and the Relative Stress Scale (RSS), reflecting that resource utilization is more than the actual time required for caring but also how burdensome the task is experienced by the caregiver. Discussion We expect the implementation of LIVE to lead to a pathway for dementia treatment and care which is cost-effective, compared to treatment as usual, and will support high-quality independent living, at home. Show less
Spencer-Bonilla, G.; Thota, A.; Organick, P.; Ponce, O.J.; Kunneman, M.; Giblon, R.; ... ; Shared Decision Making Atrial Fibr 2020
BackgroundShared decision making (SDM) implementation remains challenging. The factors that promote or hinder implementation of SDM tools for use during the consultation, including contextual... Show moreBackgroundShared decision making (SDM) implementation remains challenging. The factors that promote or hinder implementation of SDM tools for use during the consultation, including contextual factors such as clinician burnout and organizational support, remain unclear. We explored these factors in the context of a practical multicenter randomized trial evaluating the effectiveness of an SDM conversation tool for patients with atrial fibrillation considering anticoagulation therapy.MethodsIn this cross-sectional study, we recruited clinicians who were regularly involved in conversations with patients regarding anticoagulation for atrial fibrillation. Clinicians reported their characteristics and burnout symptoms using the two-item Maslach Burnout Inventory. Clinicians were trained in using the SDM tool, and they recorded their perceptions of the tool's normalization potential using the Normalization MeAsure Development (NoMAD) survey instrument and verbally reflected on their answers to these survey questions. When possible, the training sessions and clinicians' verbal responses to the conversation tool were recorded.ResultsOur study comprised 183 clinicians recruited into the trial (168 with survey responses and 112 with recordings). Overall, clinicians gave high scores to the normalization potential of the intervention; they endorsed all domains of normalization to the same extent, regardless of site, clinician characteristics, or burnout ratings. In interviews, clinicians paid significant attention to making sense of the tool. Tool buy-in seemed to depend heavily on their ability to see the tool as accurate and "evidence-based" and their perceptions of having time in the consultation to use it.ConclusionsWhile time in the consultation remains a barrier, we did not find a significant association between burnout symptoms and normalization of an SDM conversation tool. Possible areas for improving the normalization of SDM conversation tools in clinical practice include enabling collaboration among clinicians to implement the tool and reporting how clinicians elsewhere use the tool. Direct measures of normalization (i.e., observing how often clinicians access the tool in practice outside of the clinical trial) may further elucidate the role that contextual factors, such as clinician burnout, play in the implementation of SDM.Trial registrationClinicalTrials.gov, NCT02905032. Registered on 9 September 2016. Show less
BackgroundPancreatic resection is a major abdominal operation with 50% risk of postoperative complications. A common complication is pancreatic fistula, which may have severe clinical consequences... Show moreBackgroundPancreatic resection is a major abdominal operation with 50% risk of postoperative complications. A common complication is pancreatic fistula, which may have severe clinical consequences such as postoperative bleeding, organ failure and death. The objective of this study is to investigate whether implementation of an algorithm for early detection and minimally invasive management of pancreatic fistula may improve outcomes after pancreatic resection.MethodsThis is a nationwide stepped-wedge, cluster-randomized, superiority trial, designed in adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. During a period of 22months, all Dutch centers performing pancreatic surgery will cross over in a randomized order from current practice to best practice according to the algorithm. This evidence-based and consensus-based algorithm will provide daily multilevel advice on the management of patients after pancreatic resection (i.e. indication for abdominal imaging, antibiotic treatment, percutaneous drainage and removal of abdominal drains). The algorithm is designed to aid early detection and minimally invasive step-up management of postoperative pancreatic fistula. Outcomes of current practice will be compared with outcomes after implementation of the algorithm. The primary outcome is a composite of major complications (i.e. post-pancreatectomy bleeding, new-onset organ failure and death) and will be measured in a sample size of at least 1600 patients undergoing pancreatic resection. Secondary endpoints include the individual components of the primary endpoint and other clinical outcomes, healthcare resource utilization and costs analysis. Follow up will be up to 90days after pancreatic resection.DiscussionIt is hypothesized that a structured nationwide implementation of a dedicated algorithm for early detection and minimally invasive step-up management of postoperative pancreatic fistula will reduce the risk of major complications and death after pancreatic resection, as compared to current practice.Trial registrationNetherlands Trial Register: NL 6671. Registered on 16 December 2017. Show less
BackgroundPancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in... Show moreBackgroundPancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life.Methods/designPACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide.DiscussionThe PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life.Trial registrationClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018. Show less
Background Acute respiratory distress syndrome (ARDS) is caused by rapid-onset (within hours) acute inflammatory processes in lung tissue, and it is a life-threatening condition with high mortality... Show moreBackground Acute respiratory distress syndrome (ARDS) is caused by rapid-onset (within hours) acute inflammatory processes in lung tissue, and it is a life-threatening condition with high mortality. The treatment of ARDS to date is focused on the prevention of further iatrogenic damage of the lung rather than the treatment of the initial inflammatory process. Several preclinical studies have revealed a beneficial effect of iloprost on the control of pulmonary inflammation, and in a small number of patients with ARDS, iloprost treatment resulted in improved oxygenation. Therefore, we plan to conduct a large multicenter trial to evaluate the effect of iloprost on ARDS. Methods The Therapeutic Iloprost during ARDS trial (ThIlo trial) is a multicenter, randomized, single blinded, clinical phase II trial assessing the efficacy of inhaled iloprost for the prevention of the development and progression of ARDS in critically ill patients. One hundred fifty critically ill patients suffering from acute ARDS will be treated either by nebulized iloprost or NaCl 0.9% for 5 days. Blood samples will be drawn at defined time points to elucidate the serum levels of iloprost and inflammatory markers during treatment. Mechanical ventilation will be standardized. In follow-up visits at days 28 and 90 as well as 6 months after enrollment, functional status according to the Barthel Index and a health care-related questionnaire, and frailty (Vulnerable Elders Survey) will be evaluated. The primary endpoint is the improvement of oxygenation, defined as the ratio of PaO2/FiO(2). Secondary endpoints include 90-day all-cause mortality, Sequential Organ Failure Assessment scores during the study period up to day 90, the duration of mechanical ventilation, the length of intensive care unit (ICU) stay, ventilator-associated pneumonia, delirium, ICU-acquired weakness, and discharge localization. The study will be conducted in three university ARDS centers in Germany. Discussion The results of the ThIlo trial will highlight the anti-inflammatory effect of iloprost on early inflammatory processes during ARDS, resulting in the improvement of outcome parameters in patients with ARDS. Show less
Michielsens, C.A.J.; Boers, N.; Broeder, N. den; Wenink, M.H.; Maas, A. van der; Mahler, E.A.M.; ... ; Broeder, A.A. den 2020
Background Tumour necrosis factor inhibitors (TNFi) are effective in the treatment of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).... Show moreBackground Tumour necrosis factor inhibitors (TNFi) are effective in the treatment of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). However, these drugs come with some disadvantages such as adverse events, practical burden for patients and high costs. Dose optimisation of TNFi after patients have reached low disease activity (LDA) has been shown feasible and safe in rheumatoid arthritis (RA). However, data on TNFi dose optimisation in PsA and axSpA are scarce, especially pragmatic, randomised strategy studies. Methods We developed an investigator-driven, pragmatic, open-label, randomised, controlled, non-inferiority trial (DRESS-PS) to compare the effects of a disease activity-guided treat-to-target strategy with or without a tapering attempt in patients with SpA (PsA and axSpA combined), >= 16 years of age, who are being treated with TNFi, and have had at least 6 months of low disease activity. The primary outcome is the percentage of patients in LDA after 12 months of follow up. Patients are assessed at baseline, 3, 6, 9, and 12 months of follow up. Bayesian power analyses with a weakened prior based on a similar study performed in RA resulted in a sample size of 95 patients in total. Discussion More knowledge on disease activity-guided treatment algorithms would contribute to better treatment choices and cost savings and potentially decrease the risk of side effects. In this article we elucidate some of our design choices on TNFi dose optimisation and its clinical and methodological consequences. Show less
Manaï, M.; Middendorp, H. van; Veldhuijzen, D.S.; Pol, J.A. van der; Huizinga, T.W.J.; Evers, A.W.M. 2020
Background In pharmacological conditioning associations are formed between the effects of medication and contextual factors related to the medication. Pharmacological conditioning with placebo... Show moreBackground In pharmacological conditioning associations are formed between the effects of medication and contextual factors related to the medication. Pharmacological conditioning with placebo medication can result in comparable treatment effects and reduced side effects compared to regular treatment in various clinical populations, and may be applied to achieve enhanced drug effects. In the current study protocol, pharmacological conditioning is applied to achieve enhanced treatment effects in patients with recent-onset rheumatoid arthritis (RA). The results from this study broaden the knowledge on the potential of pharmacological conditioning and provide a potential innovative treatment option to optimize long-term pharmacological treatment effectiveness for patients with inflammatory conditions, such as recent-onset RA. Methods A multicenter, randomized controlled clinical trial is conducted in patients with recent-onset RA. Participants start on standardized pharmacological treatment for 16 weeks, which consists of methotrexate (MTX) 15 mg/week and a tapered schedule of prednisone 60 mg or 30 mg. After 4 months, participants in clinical remission (based on the rheumatologist's opinion and a targeted score below 1.6 on a 44-joint disease activity score (DAS44)) are randomized to 1 of 2 groups: (1) the control group (C), which continues with a standardized treatment schedule of MTX 15 mg/week or (2) the pharmacological conditioning group (PC), which receives an MTX treatment schedule in alternating high and low dosages. In the case of persistent clinical remission after 8 months, treatment is tapered and discontinued linearly in the C group and variably in the PC group. Both groups receive the same cumulative amount of MTX during each period. Logistic regression analysis is used to compare the proportion of participants with drug-free clinical remission after 12 months between the C group and the PC group. Secondary outcome measures include clinical functioning, laboratory assessments, and self-reported measures after each 4-month period up to 18 months after study start. Discussion The results from this study broaden the knowledge on the potential of pharmacological conditioning and provide a potential innovative treatment option to optimize long-term pharmacological treatment effectiveness in patients with inflammatory conditions, such as recent-onset RA. Show less
Rohrbach, P.J.; Dingemans, A.E.; Spinhoven, P.; Akker-Van Marle, E. van den; Ginkel, J.R. van; Fokkema, M.; ... ; Furth, E.F. van 2019
Background: E-mental health has become increasingly popular in interventions for individuals with eating disorders (EDs). It has the potential to offer low-threshold interventions and guide... Show moreBackground: E-mental health has become increasingly popular in interventions for individuals with eating disorders (EDs). It has the potential to offer low-threshold interventions and guide individuals to the needed care more promptly. Featback is such an Internet-based intervention and consists of psychoeducation and a fully automated monitoring and feedback system. Preliminary findings suggest Featback to be (cost-)effective in reducing ED symptomatology. Additionally, e-mail or chat support by a psychologist did not enhance theeffectiveness of Featback. Support by an expert patient (someone with a lived experience of an ED) might be more effective, since that person can effectively model healthy behavior and enhance self-efficacy in individuals struggling with an ED. The present study aims to replicate and build on earlier findings by further investigating the (cost-)effectiveness of Featback and the added value of expert-patient support.Methods: The study will be a randomized controlled trial with a two-by-two factorial design with repeatedmeasures. The four conditions will be (1) Featback, in which participants receive automated feedback on a short monitoring questionnaire weekly, (2) Featback with weekly e-mail or chat support from an expert patient, (3) weekly support from an expert patient, and (4) a waiting list. Participants who are 16 years or older and have at least mild self-reported ED symptoms receive a baseline measure. Subsequently, they are randomized to one of the four conditions for 8 weeks. Participants will be assessed again post-intervention and at 3, 6, 9, and 12 months follow-up. The primary outcome measure will be ED psychopathology. Secondary outcome measures are experienced social support, self-efficacy, symptoms of anxiety and depression, user satisfaction, intervention usage, and help-seeking attitudes and behaviors.Discussion: The current study is the first to investigate e-mental health in combination with expert-patient support for EDs and will add to the optimization of the delivery of Internet-based interventions and expert-patient support.Trial registration: Netherlands Trial Register, NTR7065. Registered on 7 June 2018.Keywords: Eating disorders, Internet, Internet-based, E-mental health, Intervention, Treatment, Prevention, Expert patient, Peer support, Cost-effectiveness Show less
Rohrbach, P.J.; Dingemans, A.E.; Spinhoven, P.; Van den Akker-Van Marle, E.; Ginkel, J.R. van; Fokkema, M.; ... ; Van Furth, E.F. 2019
BackgroundE-mental health has become increasingly popular in interventions for individuals with eating disorders (EDs). It has the potential to offer low-threshold interventions and guide... Show moreBackgroundE-mental health has become increasingly popular in interventions for individuals with eating disorders (EDs). It has the potential to offer low-threshold interventions and guide individuals to the needed care more promptly. Featback is such an Internet-based intervention and consists of psychoeducation and a fully automated monitoring and feedback system. Preliminary findings suggest Featback to be (cost-)effective in reducing ED symptomatology. Additionally, e-mail or chat support by a psychologist did not enhance the effectiveness of Featback. Support by an expert patient (someone with a lived experience of an ED) might be more effective, since that person can effectively model healthy behavior and enhance self-efficacy in individuals struggling with an ED. The present study aims to replicate and build on earlier findings by further investigating the (cost-)effectiveness of Featback and the added value of expert-patient support.MethodsThe study will be a randomized controlled trial with a two-by-two factorial design with repeated measures. The four conditions will be (1) Featback, in which participants receive automated feedback on a short monitoring questionnaire weekly, (2) Featback with weekly e-mail or chat support from an expert patient, (3) weekly support from an expert patient, and (4) a waiting list. Participants who are 16 years or older and have at least mild self-reported ED symptoms receive a baseline measure. Subsequently, they are randomized to one of the four conditions for 8 weeks. Participants will be assessed again post-intervention and at 3, 6, 9, and 12 months follow-up. The primary outcome measure will be ED psychopathology. Secondary outcome measures are experienced social support, self-efficacy, symptoms of anxiety and depression, user satisfaction, intervention usage, and help-seeking attitudes and behaviors.DiscussionThe current study is the first to investigate e-mental health in combination with expert-patient support for EDs and will add to the optimization of the delivery of Internet-based interventions and expert-patient support.Trial registrationNetherlands Trial Register, NTR7065. Registered on 7 June 2018. Show less
Vavani, B.; Kraaij, V.; Spinhoven, P.; Garnefski, N. 2019
BackgroundThe treatment of mental health issues among people living with HIV (PLH) in Botswana is yet to be addressed. A recent study revealed that depressive symptoms are highly prevalent in a... Show moreBackgroundThe treatment of mental health issues among people living with HIV (PLH) in Botswana is yet to be addressed. A recent study revealed that depressive symptoms are highly prevalent in a sample of PLH in Botswana. Based on empirical findings of a study that investigated intervention targets for PLH in Botswana, a self-help program with coaching in booklet format in the Setswana and English languages was developed, composed of cognitive behavioral techniques, coping skills interventions, and goal adjustment training. We will investigate the program for effectiveness in the treatment of depressive symptoms among PLH. Additionally, we will investigate treatment moderators and mediators. This paper describes the study protocol.Methods/designA randomized controlled trial will be conducted to compare the booklet self-help program with coaching with an attention-only control condition, by including pre-test, post-test, and follow-up assessments. We aim to enroll 200 participants with mild to moderate depressive symptoms into the study. The self-help program contains the following main components: activation, relaxation, changing maladaptive cognitions, and the attainment of new personal goals. This content is covered over six lessons to be completed in a maximum of 8 weeks. It uses a combination of psycho-education, assignments, and exercises. The participants will work on the program 1–2 h every week for 6 weeks (maximum 8 weeks). Coaches will offer support and motivate the participants. For both groups, depressive symptoms and possible mediators will be measured three times during the intervention, and at pre-test, post-test, and follow-up.DiscussionIf the intervention is found to effectively treat depressive symptoms, it will be implemented and thus help improve the psychological health of PLH in Botswana. Show less
Al-Laith, M.; Jasenecova, M.; Abraham, S.; Bosworth, A.; Bruce, I.N.; Buckley, C.D.; ... ; Cope, A.P. 2019
Trial designWe present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of... Show moreTrial designWe present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis.MethodsThe study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants who were at least 18 years old, who reported inflammatory sounding joint pain (clinically suspicious arthralgia) and who were found to be positive for serum autoantibodies associated with rheumatoid arthritis (RA) were eligible for enrolment. All study subjects were randomly assigned to receive weekly injections of investigational medicinal product, either abatacept or placebo treatment over the course of a 52-week period. Participants were followed up for a further 52weeks. The primary endpoint was defined as the time to development of at least three swollen joints or to the fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA using swollen but not tender joints, whichever endpoint was met first. In either case, swollen joints were confirmed by ultrasonography. Participants, care givers, and those assessing the outcomes were all blinded to group assignment. Clinical assessors and ultrasonographers were also blinded to each other's assessments for the duration of the study.ConclusionsThere is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. We discuss the rationale behind choice and duration of treatment and the challenges associated with defining the at risk state and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA.Trial registrationCurrent Controlled Trials, ID: ISRCTN46017566. Registered on 4 July 2014. Show less
BackgroundSome studies have suggested that transdermal administration of glyceryl trinitrate (GTN; nitroglycerin) in the first few hours after symptom onset increases the chance of a favourable... Show moreBackgroundSome studies have suggested that transdermal administration of glyceryl trinitrate (GTN; nitroglycerin) in the first few hours after symptom onset increases the chance of a favourable outcome after ischaemic stroke or intracerebral haemorrhage, possibly through an increase in intracranial collateral blood flow and a reduction in blood pressure. The Multicentre Randomised trial of Acute Stroke treatment in the Ambulance with a nitroglycerin Patch (MR ASAP) aims to assess the effect of transdermal GTN, started within 3 h after stroke onset in the prehospital setting, on functional outcome at 90days in patients with acute ischaemic stroke or intracerebral haemorrhage.MethodsMR ASAP is a phase III, multicentre, randomised, open-label clinical trial with a blinded outcome assessment. A total of 1400 adult patients with suspected stroke and a systolic blood pressure140mmHg will be randomised to transdermal GTN (5mg/day), administered as a transdermal patch by paramedics in the prehospital setting within 3h of stroke onset and continued for 24h or to standard care. The primary outcome is the score on the modified Rankin Scale (mRS) at 90days, analysed with ordinal logistic regression. Secondary outcomes include blood pressure and collateral circulation at hospital admission, neurological deficit measured with the National Institutes of Health Stroke Scale at 24h, and mortality and poor outcome (mRS score 3 to 6) at 90days. This trial will be conducted in the Netherlands and will use a deferred consent procedure. The trial is part of the Collaboration for New Treatments of Acute Stroke (CONTRAST) programme.DiscussionMR ASAP will assess whether very early administration of GTN improves outcome after stroke in a setting where rates of intravenous thrombolysis and endovascular treatment for acute ischaemic stroke are high. The deferred consent procedure facilitates prompt GTN treatment and will prevent delay to revascularisation therapies. If early transdermal GTN treatment proves to be effective, this low-cost treatment can be readily implemented into daily clinical practice.Trial registrationISRCTN Registry, ISRCTN99503308. Registered on 2 January 2018. Show less
School absenteeism (SA) is associated with anxiety, depression, and disruptive behavior. It is a risk factor for academic difficulties and school dropout, which predict problems in adulthood such... Show moreSchool absenteeism (SA) is associated with anxiety, depression, and disruptive behavior. It is a risk factor for academic difficulties and school dropout, which predict problems in adulthood such as social, work-related, and health problems. The main goal of this study is to examine the initial effectiveness of a modular transdiagnostic cognitive behavioral therapy (CBT) intervention (Back2School) for increasing school attendance and decreasing psychological problems, relative to a comparator control arm (treatment as usual [TAU]).\nOne hundred sixty children, aged 7 to 16 years, will be randomly assigned to either Back2School or TAU. The design is a two (Back2School and TAU) by four (preassessment [T1], postassessment [T2], and 3-month [T3] and 1-year [T4] assessments) mixed between-within design. The primary outcome is school attendance based on daily registration. Secondary outcomes pertain to youth psychosocial functioning, quality of life, bullying, self-efficacy, and teacher-parent collaboration. These secondary outcomes are measured via youth, parent, and teacher reports.\nThis study will provide critically needed empirical evidence on the initial effectiveness of a manualized treatment program for youth with SA. If the intervention is found to be effective, the program can be further implemented and tested in a larger school health effectiveness trial.\nClinicalTrials.gov, NCT03459677 . Retrospectively registered on 9 March 18.\nBACKGROUND\nMETHODS/DESIGN\nDISCUSSION\nTRIAL REGISTRATION Show less
