This thesis provides an overview of the current epidemiology of neonatal NI, including CLABSI. While highlighting the importance of this complication, it has laid the foundation for the development... Show moreThis thesis provides an overview of the current epidemiology of neonatal NI, including CLABSI. While highlighting the importance of this complication, it has laid the foundation for the development and evaluation of several prevention and reduction strategies. The incidence of sepsis among certain neonatal subpopulations such as neonates with hemolytic disease of the fetus and newborn remains high, illustrating the need to re-calibrate indications for central-line placement and CLABSI prevention measures. In contrast to what was hypothesized, a significant positive effect of several interventions and changes in clinical practice, including the implementation of single-room care and a multi-modal strategy, could not be supported. On the other hand, support was found for behavioral change tools such as ‘nudges’ which seem to be a more promising avenue in the reduction of NI, providing such tools can be tailored to the clinical micro-system and context-specific needs of NICU-healthcare workers. Furthermore, nationwide CLABSI surveillance provided a unique insight into the current burden of neonatal CLABSI in The Netherlands, although the optimization of digital infrastructures, data availability and accessibility are urgently needed to perform forthcoming benchmarking initiatives. Even though much progress has been made, we are far from done in the battle against neonatal NI. Show less
Mertens, E.C.A.; Siezenga, A.M.; Tettero, T.; Gelder, J.L. van 2022
Background: Short-term mindsets are associated with self-defeating behaviors, such as delinquency and alcohol use. In contrast, people who consider the longer-term consequences of their decisions... Show moreBackground: Short-term mindsets are associated with self-defeating behaviors, such as delinquency and alcohol use. In contrast, people who consider the longer-term consequences of their decisions tend to report positive outcomes, like feeling more competent and enhanced goal achievement. We evaluate an intervention, FutureU, that aims to stimulate future-oriented thinking, increase goal achievement, and reduce self-defeating behavior, by strengthening people’s identification with their future self. The intervention will be delivered through a smartphone application (app) or immersive Virtual Reality (VR). We test the effectiveness of FutureU for both delivery methods, examine working mechanisms, and identify potential moderators of intervention effects. Methods: In this Randomized Controlled Trial, a total of 240 first-year university students (n=80 per condition) will be randomized into one of three conditions: (1) a smartphone condition, (2) a VR condition, and (3) an active control condition. We will assess proximal (i.e., future self-identification) and distal intervention outcomes (e.g., future orientation, self-defeating behaviors, goal achievement), user engagement, and examine usage data and goal content. Assessments will take place at baseline, during the intervention, immediately after the intervention, and at 3- and 6-months follow-up. Discussion: This study will provide information on the effectiveness of the intervention and allows for comparisons between delivery methods using novel technologies, a smartphone app versus immersive VR. Knowledge gained through this study can be used for further intervention development as well as theory building. Trial registration: This trial is registered on Clinicaltrials.gov (NCT05578755) on 13 October 2022. Show less
Ali, M.; Meij, A. van der; Os, H.J.A. van; Zwet, E.W. van; Spaander, F.H.M.; Hofmeijer, J.; ... ; MR CLEAN Registry Investigators 2022
BackgroundWomen have been reported to have worse outcomes after endovascular treatment (EVT), despite a similar treatment effect in non-clinical trial populations. We aimed to assess sex... Show moreBackgroundWomen have been reported to have worse outcomes after endovascular treatment (EVT), despite a similar treatment effect in non-clinical trial populations. We aimed to assess sex differences at hospital presentation with respect to workflow metrics, prestroke disability, and presenting clinical symptoms. MethodsWe included consecutive patients from the Multicentre Randomised Controlled Trial of Endovascular Treatment for Acute Ischaemic Stroke in The Netherlands (MR CLEAN) Registry (2014-2018) who received EVT for anterior circulation large vessel occlusion (LVO). We assessed sex differences in workflow metrics, prestroke disability (modified Rankin Scale (mRS) score >= 1), and stroke severity and symptoms according to the National Institutes of Health Stroke Scale (NIHSS) score on hospital admission with logistic and linear regression analyses and calculated the adjusted OR (aOR). ResultsWe included 4872 patients (47.6% women). Compared with men, women were older (median age 76 vs 70 years) and less often achieved good functional outcome at 90 days (mRS <= 2: 35.2% vs 46.4%, aOR 0.70, 95% CI 0.60 to 0.82). Mean onset-to-door time was longer in women (2 hours 16 min vs 2 hours 7 min, adjusted delay 9 min, 95% CI 4 to 13). This delay contributed to longer onset-to-groin times (3 hours 26 min in women vs 3 hours 13 min in men, adjusted delay 13 min, 95% CI 9 to 17). Women more often had prestroke disability (mRS >= 1: 41.1% vs 29.1%, aOR 1.57, 95% CI 1.36 to 1.82). NIHSS on admission was essentially similar in men and women (mean 15 +/- 6 vs 15 +/- 6, NIHSS <10 vs >= 10, aOR 0.91, 95% CI 0.78 to 1.06). There were no clear sex differences in the occurrence of specific stroke symptoms. ConclusionWomen with LVO had longer onset-to-door times and more often prestroke disability than men. Raising awareness of these differences at hospital presentation and investigating underlying causes may help to improve outcome after EVT in women. Show less
This thesis showed that there appears much room for improvement in optimizing physical activity and exercise of people with axial spondyloarthritis (axSpA), both in patients using and not using... Show moreThis thesis showed that there appears much room for improvement in optimizing physical activity and exercise of people with axial spondyloarthritis (axSpA), both in patients using and not using individual physical therapy and axSpA-specific group exercise. Although recommended, only a minority engages in high-intensity aerobic physical activity and in strengthening and mobility exercise with the recommended frequency. This is also the case in people with axSpA using physical therapy. Furthermore, certain evidence-based enhancements in axSpA-specific exercise groups seem warranted. A pilot implementation of these enhancements was found to be partially successful and a number of barriers remain to be overcome in a larger-scale implementation. Because only a small minority of people with axSpA participate in such exercise groups, it is also desired to implement modifications to individual physical therapy as well as interventions in which people with axSpA can participate independently (without supervision). A number of components of such interventions were identified in this thesis. Show less
Mergelsberg, E.L.P.; Ruijter, D. de; Crone, M.R.; Smit, E.S.; Hoving, C. 2022
The objective was to assess active ingredients, change mechanisms, and fidelity in interventions aiming to increase the quality of smoking cessation care in the Dutch primary healthcare setting. We... Show moreThe objective was to assess active ingredients, change mechanisms, and fidelity in interventions aiming to increase the quality of smoking cessation care in the Dutch primary healthcare setting. We conducted a systematic review searching five scientific databases on August 2nd, 2019, updated on October 28th, 2021. We included effect data of behavioural interventions aiming at improving the provision of smoking cessation support by Dutch primary care providers to their patients. We excluded studies published before 2000 and those without a behavioural support intervention for primary care providers targeting smoking cessation in their patients. We found 1939 articles and included 15 distinct interventions in the review. We provided an overview of study characteristics, intervention effects, fidelity, active ingredients and change mechanisms using the Behaviour Change Techniques (BCT) Taxonomy and Mechanisms of Action (MoAs) protocols. Interventions seemed more effective when including a face-to-face component, using active learning strategies and providing a tool to help follow the guidelines in practice (e.g., physical cards with information). BCTs, MoAs, and fidelity were overall poorly reported on. To support the application of smoking cessation practices in Dutch primary care, we recommend implementation of face-to-face training programs incorporating active skill training elements combined with practical tools. Show less
School refusal (SR) signals a young person’s difficulty attending school. It jeopardizes their development, often contributes to distress for parents, and places an extra burden on school personnel... Show moreSchool refusal (SR) signals a young person’s difficulty attending school. It jeopardizes their development, often contributes to distress for parents, and places an extra burden on school personnel. Reviews of empirical studies indicate that intervention for SR helps to increase school attendance, but not for all youths. This practice-based manuscript aims to support practitioners and organisations addressing the needs of youths and families affected by SR. Specifically, we present 14 signposts for the development and delivery of intervention for SR. The signposts represent important conditions for effective intervention based on key findings from the Knowing What Works project in the Netherlands. During that project, 76 professionals shared their views about the important elements in SR interventions they delivered, and 39 youths and 86 parents shared their views about the helpful elements in SR interventions in which they participated. These 201 stakeholders were variously associated with 21 SR interventions across 9 of the 12 Dutch provinces, most situated in mainstream or special education settings. Their responses informed the development of the 14 signposts presented here, supported by the extant literature on SR intervention. Wedescribe the essence of each signpost and conclude with suggestions for using the signposts and evaluating their utility. Show less
Physical activity is effective in preventing and treating many of these age-related diseases. However, two thirds of Dutch older adults do not reach the recommended level of physical activity.... Show morePhysical activity is effective in preventing and treating many of these age-related diseases. However, two thirds of Dutch older adults do not reach the recommended level of physical activity. Current efforts to increase physical activity with professional led physical activity interventions are effective during the intervention period, but do not manage to have a sustainable effect. In this thesis we studied the possibility of peer coaching to sustainably increase physical activity in older adults. We do this by studying the effectiveness, implementation and organization of peer coach physical activity intervention. The conclusion of this thesis is that older adults can effectively and sustainably increase physical activity of older adults through peer coach physical activity interventions. After a small investment for implementation, a sustainable self-organising exercise intervention can be created which exist for years. The reach of the groups can be increased through an exercise referral scheme in primary care, but the effectivity needs to be improved through research. Nationwide implementation of exercise groups for older adults is possible, but it requires effort from a large (governmental) party. Show less
Process evaluations of peer education on the topic of sexuality and relationships pay little attention to the activities implemented by peer educators. Process evaluation with other target groups... Show moreProcess evaluations of peer education on the topic of sexuality and relationships pay little attention to the activities implemented by peer educators. Process evaluation with other target groups indicate clusters of activities that refer to educator skills, offering a safe place to learn, and efforts to change attitudes. An overarching factor named life experiences influences how peer educators implement activities. In this study, a peer education for social acceptance of LGBT was created and implemented in pre-vocational secondary schools. Students trained as peer educators implemented peer education, and after the implementation, they were interviewed about their activities. Sharing the coming-out story appeared to play a central role in the peer education intervention and its perceived outcomes. Show less
Chronic kidney disease (CKD) poses a major challenge to public health. China, a middle-income country, is the largest country globally with a current population of 1.4 billion. China accounts for... Show moreChronic kidney disease (CKD) poses a major challenge to public health. China, a middle-income country, is the largest country globally with a current population of 1.4 billion. China accounts for around one fifth of the global burden of CKD. Hence, eHealth self-management interventions are a great potential to Chinese populations. An extensively studied CKD self-management eHealth intervention is the Dutch ‘Medical Dashboard (MD)’. It has been demonstrated effective in decreasing the burden of CKD. To aim of this thesis is to inform the adaptation and evaluation of a tailored CKD self-management eHealth intervention in China based on the Dutch MD intervention. Specific characteristics and needs (e.g. facilitators and barriers) in Chinese settings need to be addressed to optimize the implementation of CKD self-management eHealth intervention. Emphasis should be placed on addressing the existing paternalistic patient-HCP relationship, stakeholder involvement in the development and implementation process, adjusting eHealth design features to fit the clinical workflows, and providing the needed support and training. This thesis is a vital step towards the design and implementation of a tailored eHealth solution to improve health outcomes of patients with CKD and address the high burden of CKD in China. Show less
Background It is estimated that 20-50% of all radiological examinations are of low value. Many attempts have been made to reduce the use of low-value imaging. However, the comparative effectiveness... Show moreBackground It is estimated that 20-50% of all radiological examinations are of low value. Many attempts have been made to reduce the use of low-value imaging. However, the comparative effectiveness of interventions to reduce low-value imaging is unclear. Thus, the objective of this systematic review was to provide an overview and evaluate the outcomes of interventions aimed at reducing low-value imaging. Methods An electronic database search was completed in Medline - Ovid, Embase-Ovid, Scopus, and Cochrane Library for citations between 2010 and 2020. The search was built from medical subject headings for Diagnostic imaging/Radiology, Health service misuse or medical overuse, and Health planning. Keywords were used for the concept of reduction and avoidance. Reference lists of included articles were also hand-searched for relevant citations. Only articles written in English, German, Danish, Norwegian, Dutch, and Swedish were included. The Mixed Methods Appraisal Tool was used to appraise the quality of the included articles. A narrative synthesis of the final included articles was completed. Results The search identified 15,659 records. After abstract and full-text screening, 95 studies of varying quality were included in the final analysis, containing 45 studies found through hand-searching techniques. Both controlled and uncontrolled before-and-after studies, time series, chart reviews, and cohort studies were included. Most interventions were aimed at referring physicians. Clinical practice guidelines (n = 28) and education (n = 28) were most commonly evaluated interventions, either alone or in combination with other components. Multi-component interventions were often more effective than single-component interventions showing a reduction in the use of low-value imaging in 94 and 74% of the studies, respectively. The most addressed types of imaging were musculoskeletal (n = 26), neurological (n = 23) and vascular (n = 16) imaging. Seventy-seven studies reported reduced low-value imaging, while 3 studies reported an increase. Conclusions Multi-component interventions that include education were often more effective than single-component interventions. The contextual and cultural factors in the health care systems seem to be vital for successful reduction of low-value imaging. Further research should focus on assessing the impact of the context in interventions reducing low-value imaging and how interventions can be adapted to different contexts. Show less
OBJECTIVES: The objective of this study was to assess our 43-year experience with arterial switch operation (ASO) for transposition of the great arteries (TGA) by analysing cardiac outcome measures... Show moreOBJECTIVES: The objective of this study was to assess our 43-year experience with arterial switch operation (ASO) for transposition of the great arteries (TGA) by analysing cardiac outcome measures (hospital and late mortality, reoperations and catheter interventions, significant coronary artery obstruction) and to identify risk factors for reoperation and catheter interventions.METHODS: A total of 490 patients who underwent ASO for TGA from 1977 to 2020 were included in this retrospective, single-centre study. Data on reoperation and catheter intervention of hospital survivors were estimated by the Kaplan-Meier method and compared using a long-rank test. Risk factors for reoperation and/or catheter intervention were assessed by multivariate Cox regression analysis.RESULTS: Hospital mortality occurred in 43 patients (8.8%), late death in 12 patients (2.9%) and 43 patients were lost to follow-up. Median follow-up time of 413 hospital survivors was 15.6 (interquartile range 7.0-22.4) years. Reoperations were performed in 83 patients (117 reoperations). Neoaortic valve regurgitation with root dilatation was the second most common indication for reoperation (15/83 patients, 18.1%) after right ventricular outflow tract obstruction (50/83 patients, 60.2%). Risk factors for any reoperation on multivariable analysis were: TGA morphological subtype [TGA with ventricular septal defect: hazard ratio (HR)=1.99, 95% confidence interval (CI) 1.18-3.36; P=0.010 and Taussig-Bing: HR=2.17, 95% CI 1.02-4.64; P=0.045], aortic arch repair associated with ASO (HR=3.03, 95% CI 1.62-5.69; P=0.001) and a non-usual coronary artery anatomy (HR=2.41, 95% CI 1.45-4.00; P=0.001). One hundred and one catheter interventions were performed in 54 patients, usually for relief of supravalvular pulmonary stenosis (44/54 patients, 81.5%) or arch obstruction (10/54 patients, 18.5%). Main risk factor for catheter intervention on multivariable analysis was aortic arch repair associated with ASO (HR=2.95, 95% CI 1.37-6.36; P=0.006). Significant coronary artery stenosis was relatively uncommon (9/413 patients, 2.2%) but may be underrepresented.CONCLUSIONS: Patients after ASO typically have good long-term clinical outcomes but reoperations and interventions remain necessary in some patients. Neoaortic valve regurgitation with root dilatation is the second most common indication for reoperation after right ventricular outflow tract obstruction and an increasing need for neoaortic valve and root redo surgery in future is to be expected. Show less
Ample research has shown that more household chaos is related to lower parenting quality, but it is yet unknown whether this is a causal relation. This dissertation focuses on two research... Show moreAmple research has shown that more household chaos is related to lower parenting quality, but it is yet unknown whether this is a causal relation. This dissertation focuses on two research questions. The first is whether household chaos has a causal effect on parenting. The second is whether the effect of household chaos on parenting is stronger for parents with certain characteristics, such as high sensory-processing sensitivity (SPS), low self-regulation, and more impulsivity. Two experimental studies were conducted in which household chaos was manipulated. The results show that household chaos affects both positive and negative parenting, but only in demanding parenting situations. Moderation by impulsivity was not found and moderation by SPS and by self-regulation was inconsistent. Regarding SPS, this may exacerbate the effect of household chaos on parenting in case of extreme differences between or high levels of household chaos. Regarding self-regulation, parents with low self-regulation may not have enough self-regulation capacities to simultaneously lower their levels of household chaos and refrain from harsh discipline. These results form a promising vantagepoint for further research, which could eventually lead to prevention and intervention programs to improve parenting by reducing household chaos. 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
This dissertation aimed to contribute to the quality of foster care addressing three main objectives: The first objective was to investigate if existing parenting interventions are effective in... Show moreThis dissertation aimed to contribute to the quality of foster care addressing three main objectives: The first objective was to investigate if existing parenting interventions are effective in supporting/improving parenting and child outcomes in foster care using a meta-analytic approach. The second objective was to study the effectiveness of an adapted version of Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) for foster care, i.e., VIPP-FC. The implementation of VIPP-SD in different types of families and in childcare settings was first reviewed, with special attention to VIPP-FC. Subsequently, the study protocol of the randomized controlled trial (RCT) investigating the effectiveness of VIPP-FC was described. In addition, the results of this RCT regarding the effectiveness of VIPP-FC on parenting behavior and attitudes were presented. The third objective was to examine correlates of indiscriminate friendliness (IF) displayed by foster children. To answer this question, the relations of attachment security, parental sensitivity, and child inhibitory control with IF were examined using data collected during the pretest of the VIPP-FC RCT. Results are described and discussed in different chapters, and implications for clinical practice and recommendations for future research are additionally provided. Show less
This dissertation focused on the role of attachment-based interventions in child protection cases involving young children. The results confirmed that placement decisions are impacted by subjective... Show moreThis dissertation focused on the role of attachment-based interventions in child protection cases involving young children. The results confirmed that placement decisions are impacted by subjective factors, including professionals’ own attitudes and mind-set. Because we argue that the influence of subjective factors can be reduced by inserting relevant evidence into the decision-making process, we tested the effectiveness of one procedure that might produce such information. Evidence for the notion that implementing an attachment-based intervention in parenting capacity assessments can enhance the quality of placement decisions was partially found in this dissertation: We found initial evidence for improved reliability, but not for improved validity, of placement decisions. Taking these findings together with international evidence, we do tentatively conclude that attachment-based interventions can contribute to an improved quality of placement decisions. However, more research is needed to determine what implementation would be most fruitful in the Dutch child protection context. Finally, our finding that maltreating parents with more severe levels of childhood trauma benefited less from an attachment-based intervention implicates that we need to consider families’ individual needs when conducting interventions in this setting. This way, not only more parents will benefit from these interventions, their responses to these interventions might also be a more valid source of information to support placement decisions. Show less
Children with autism spectrum disorders (ASD) experience difficulty with play, and a number of different interventions have been developed and evaluated to address this deficit. This systematic... Show moreChildren with autism spectrum disorders (ASD) experience difficulty with play, and a number of different interventions have been developed and evaluated to address this deficit. This systematic review of randomized controlled trials identified 19 studies reporting on play-based interventions for children with ASD aged 2-12 years. The components of each study, including elements of the interventions and methodological quality, were examined. A meta-analysis was completed for 11 studies, and a small but significant treatment effect was identified (Hedges' g = 0.439). The current review supports future development of interventions with a focus on the child with ASD across social environments. Outcome measures and comprehensive reporting of intervention components are important considerations in future intervention development and testing. Significance for clinicians and future research is discussed. PROSPERO registration number: RD42015026263. Show less
Windhorst, D.A.; Fang, Y.; Fierloos, I.N.; Crone, M.R.; Mourik, K. van; Jonkman, H.; ... ; Raat, H. 2019
Foster and adoptive parents often face challenges while taking care of children who, due to their adverse early life experiences, are at risk of developing insecure attachment relationships,... Show moreFoster and adoptive parents often face challenges while taking care of children who, due to their adverse early life experiences, are at risk of developing insecure attachment relationships, behavior problems, and stress dysregulation. Several intervention programs have been developed to help foster and adoptive parents to overcome these challenges. In the current study, a series of eight meta-analyses were performed to examine the effectiveness of these intervention programs on four parent outcomes (sensitive parenting, k = 11, N = 684; dysfunctional discipline, k = 4, N = 239; parenting knowledge and attitudes, k = 7, N = 535; parenting stress, k = 18, N = 1,306), three child outcomes (attachment security, k = 6, N = 395; behavior problems, k = 33, N = 2,661; diurnal cortisol levels, k = 3, N = 261), and placement disruption (k = 7, N = 1,100). Results show positive effects for the four parent outcomes and child behavior problems, but not for attachment security, child diurnal cortisol levels, or placement disruption. Indirect effects on child outcomes may be delayed, and therefore long-term follow-up studies are needed to examine the effects of parenting interventions on children. 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
