Abstract Background: Antipsychotic-induced Weight Gain (AiWG) is a debilitating and common adverse effect of antipsychotics. AiWG negatively impacts life expectancy, quality of life, treatment adherence, likelihood of developing type-2 diabetes and readmission. Treatment of AiWG is currently challenging, and there is no consensus on the optimal management strategy. In this study, we aim to evaluate the use of metformin for the treatment of AiWG by comparing metformin with placebo in those receiving treatment as usual, which includes a lifestyle intervention. Methods: In this randomized, double-blind, multicenter, placebo-controlled, pragmatic trial with a follow-up of 52 weeks, we aim to include 256 overweight participants (Body Mass Index (BMI) > 25 kg/m2) of at least 16years of age. Patients are eligible if they have been diagnosed with schizophrenia spectrum disorder and if they have been using an antipsychotic for at least three months. Participants will be randomized with a 1:1 allocation to placebo or metformin, and will be treated for a total of 26 weeks. Metformin will be started at 500 mg b.i.d. and escalated to 1000 mg b.i.d. 2 weeks thereafter (up to a maximum of 2000mg daily). In addition, all participants will undergo a lifestyle intervention as part of the usual treatment consisting of a combination of an exercise program and dietary consultations. The primary outcome measure is difference in body weight as a continuous trait between the two arms from treatment inception until 26 weeks of treatment, compared to baseline. Secondary outcome measures include: 1) Any element of metabolic syndrome (MetS); 2) Response, defined as ≥5% body weight loss at 26 weeks relative to treatment inception; 3) Quality of life; 4) General mental and physical health; and 5) Cost-effectiveness. Finally, we aim to assess whether genetic liability to BMI and MetS may help estimate the amount of weight reduction following initiation of metformin treatment. Discussion: The pragmatic design of the current trial allows for a comparison of the efficacy and safety of metformin in combination with a lifestyle intervention in the treatment of AiWG, facilitating the development of guidelines on the interventions for this major health problem.
DOCUMENT
Background: To facilitate adherence to adaptive pain management behaviors after interdisciplinary multimodal pain treatment, we developed a mobile health app (AGRIPPA app) that contains two behavior regulation strategies. Objective: The aims of this project are (1) to test the effectiveness of the AGRIPPA app on pain disability; (2) to determine the cost-effectiveness; and (3) to explore the levels of engagement and usability of app users. Methods: We will perform a multicenter randomized controlled trial with two parallel groups. Within the 12-month inclusion period, we plan to recruit 158 adult patients with chronic pain during the initial stage of their interdisciplinary treatment program in one of the 6 participating centers. Participants will be randomly assigned to the standard treatment condition or to the enhanced treatment condition in which they will receive the AGRIPPA app. Patients will be monitored from the start of the treatment program until 12 months posttreatment. In our primary analysis, we will evaluate the difference over time of pain-related disability between the two conditions. Other outcome measures will include health-related quality of life, illness perceptions, pain self-efficacy, app system usage data, productivity loss, and health care expenses. Results: The study was approved by the local Medical Research Ethics Committee in October 2019. As of March 20, 2020, we have recruited 88 patients. Conclusions: This study will be the first step in systematically evaluating the effectiveness and efficiency of the AGRIPPA app. After 3 years of development and feasibility testing, this formal evaluation will help determine to what extent the app will influence the maintenance of treatment gains over time. The outcomes of this trial will guide future decisions regarding uptake in clinical practice.
LINK
Background:Tobacco consumption is a leading cause of death and disease, killing >8 million people each year. Smoking cessation significantly reduces the risk of developing smoking-related diseases. Although combined treatment for addiction is promising, evidence of its effectiveness is still emerging. Currently, there is no published research comparing the effectiveness of blended smoking cessation treatments (BSCTs) with face-to-face (F2F) treatments, where web-based components replace 50% of the F2F components in blended treatment.Objective:The primary objective of this 2-arm noninferiority randomized controlled trial was to determine whether a BSCT is noninferior to an F2F treatment with identical ingredients in achieving abstinence rates.Methods:This study included 344 individuals who smoke (at least 1 cigarette per day) attending an outpatient smoking cessation clinic in the Netherlands. The participants received either a blended 50% F2F and 50% web-based BSCT or only F2F treatment with similar content and intensity. The primary outcome measure was cotinine-validated abstinence rates from all smoking products at 3 and 15 months after treatment initiation. Additional measures included carbon monoxide–validated point prevalence abstinence; self-reported point prevalence abstinence; and self-reported continuous abstinence rates at 3, 6, 9, and 15 months after treatment initiation.Results:None of the 13 outcomes showed statistically confirmed noninferiority of the BSCT, whereas 4 outcomes showed significantly (P<.001) inferior abstinence rates of the BSCT: cotinine-validated point prevalence abstinence rate at 3 months (difference 12.7, 95% CI 6.2-19.4), self-reported point prevalence abstinence rate at 6 months (difference 19.3, 95% CI 11.5-27.0) and at 15 months (difference 11.7, 95% CI 5.8-17.9), and self-reported continuous abstinence rate at 6 months (difference 13.8, 95% CI 6.8-20.8). The remaining 9 outcomes, including the cotinine-validated point prevalence abstinence rate at 15 months, were inconclusive.Conclusions:In this high-intensity outpatient smoking cessation trial, the blended mode was predominantly less effective than the traditional F2F mode. The results contradict the widely assumed potential benefits of blended treatment and suggest that further research is needed to identify the critical factors in the design of blended interventions.Trial Registration:Netherlands Trial Register 27150; https://onderzoekmetmensen.nl/nl/trial/27150
DOCUMENT
Background: Early childhood caries is considered one of the most prevalent diseases in childhood, affecting almost half of preschool-age children globally. In the Netherlands, approximately one-third of children aged 5 years already have dental caries, and dental care providers experience problems reaching out to these children. Objective: Within the proposed trial, we aim to test the hypothesis that, compared to children who receive usual care, children who receive the Toddler Oral Health Intervention as add-on care will have a reduced cumulative caries incidence and caries incidence density at the age of 48 months. Methods: This pragmatic, 2-arm, individually randomized controlled trial is being conducted in the Netherlands and has been approved by the Medical Ethics Research Board of University Medical Center Utrecht. Parents with children aged 6 to 12 months attending 1 of the 9 selected well-baby clinics are invited to participate. Only healthy children (ie, not requiring any form of specialized health care) with parents that have sufficient command of the Dutch language and have no plans to move outside the well-baby clinic region are eligible. Both groups receive conventional oral health education in well-baby clinics during regular well-baby clinic visits between the ages of 6 to 48 months. After concealed random allocation of interventions, the intervention group also receives the Toddler Oral Health Intervention from an oral health coach. The Toddler Oral Health Intervention combines behavioral interventions of proven effectiveness in caries prevention. Data are collected at baseline, at 24 months, and at 48 months. The primary study endpoint is cumulative caries incidence for children aged 48 months, and will be analyzed according to the intention-to-treat principle. For children aged 48 months, the balance between costs and effects of the Toddler Oral Health Intervention will be evaluated, and for children aged 24 months, the effects of the Toddler Oral Health Intervention on behavioral determinants, alongside cumulative caries incidence, will be compared. Results: The first parent-child dyads were enrolled in June 2017, and recruitment was finished in June 2019. We enrolled 402 parent-child dyads. Conclusions: All follow-up interventions and data collection will be completed by the end of 2022, and the trial results are expected soon thereafter. Results will be shared at international conferences and via peer-reviewed publication.
LINK
Purpose – Self-efficacy has often been found to play a significant role in healthy dietary behaviours. However, self-efficacy interventions most often consist of intensive interventions. The authors aim to provide more insight into the effect of brief self-efficacy interventions on healthy dietary behaviours. Design/methodology/approach – In the present article, two randomized controlled trials are described. In study 1, a brief self-efficacy intervention with multiple self-efficacy techniques integrated on a flyer is tested, and in study 2, an online brief self-efficacy intervention with a single self-efficacy technique is tested. Findings – The results show that a brief self-efficacy intervention can directly increase vegetable intake and indirectly improve compliance to a diet plan to eat healthier. Originality/value – These findings suggest that self-efficacy interventions do not always have to be intensive to change dietary behaviours and that brief self-efficacy interventions can also lead to more healthy dietary behaviours.
DOCUMENT
Study design: A secondary analysis of a systematic review. Background: Manipulations or mobilizations are commonly used interventions in patients with mechanical neck pain. The treatment effects have often been studied in randomized controlled trials (RCT) which are generally considered the gold standard in evaluating the treatment effects, mainly due to its high internal validity. External validity is defined as the extent to which the effects can be generalised to clinical practice. An important prerequisite for this is that interventions used in clinical trials can be replicated in clinical practice. It can be questioned if interventions utilized in randomized controlled trials can be translated into clinical practice. Objectives: The overall aim of this study is to examine whether the quality of the description of manipulation and mobilization interventions is sufficient for to replication of these interventions in clinical practice. Methods: A comprehensive literature search was performed. Two independent researchers used the Template for Intervention Description and Replication (TIDieR) which is a 12-item checklist for describing the completeness of the interventions. Results: Sixty-seven articles were included that used manipulation and/or mobilization interventions for patients with mechanical neck pain. None of the articles describe the intervention e.g. all the items on the TIDieR list. Considering item 8 (a-f) of the TIDieR checklist only one article described the used techniques completely. Conclusion: Manipulation or a mobilization interventions are poorly reported in RCTs, which jeopardize the external validity of RCTs, making it difficult for clinicians and researchers to replicate these interventions.
LINK
Mounting evidence supports the use of face-to-face pain neuroscience education for the treatment of chronic pain patients. This study aimed at examining whether written education about pain neuroscience improves illness perceptions, catastrophizing, and health status in patients with fibromyalgia. A double-blind, multicenter randomized controlled clinical trial with 6-month follow-up was conducted. Patients with FM (n = 114) that consented to participate were randomly allocated to receive either written pain neuroscience education or written relaxation training. Written pain neuroscience education comprised of a booklet with pain neuroscience education plus a telephone call to clarify any difficulties; the relaxation group received a booklet with relaxation education and a telephone call. The revised illness perception questionnaire, Pain Catastrophizing Scale, and fibromyalgia impact questionnaire were used as outcome measures. Both patients and assessors were blinded. Repeated-measures analyses with last observation carried forward principle were performed. Cohen's d effect sizes (ES) were calculated for all within-group changes and between-group differences. The results reveal that written pain neuroscience education does not change the impact of FM on daily life, catastrophizing, or perceived symptoms of patients with FM. Compared with written relaxation training, written pain neuroscience education improved beliefs in a chronic timeline of FM (P = 0.03; ES = 0.50), but it does not impact upon other domains of illness perceptions. Compared with written relaxation training, written pain neuroscience education slightly improved illness perceptions of patients with FM, but it did not impart clinically meaningful effects on pain, catastrophizing, or the impact of FM on daily life. Face-to-face sessions of pain neuroscience education are required to change inappropriate cognitions and perceived health in patients with FM.
LINK
Background: In 2009, the Steering Committee for Pregnancy and Childbirth in the Netherlands recommended the implementation of continuous care during labor in order to improve perinatal outcomes. However, in current care, routine maternity caregivers are unable to provide this type of care, resulting in an implementation rate of less than 30%. Maternity care assistants (MCAs), who already play a nursing role in low risk births in the second stage of labor and in homecare during the postnatal period, might be able to fill this gap. In this study, we aim to explore the (cost) effectiveness of adding MCAs to routine first- and second-line maternity care, with the idea that these MCAs would offer continuous care to women during labor. Methods: A randomized controlled trial (RCT) will be performed comparing continuous care (CC) with care-as-usual (CAU). All women intending to have a vaginal birth, who have an understanding of the Dutch language and are > 18 years of age, will be eligible for inclusion. The intervention consists of the provision of continuous care by a trained MCA from the moment the supervising maternity caregiver establishes that labor has started. The primary outcome will be use of epidural analgesia (EA). Our secondary outcomes will be referrals from primary care to secondary care, caesarean delivery, instrumental delivery, adverse outcomes associated with epidural (fever, augmentation of labor, prolonged labor, postpartum hemorrhage, duration of postpartum stay in hospital for mother and/or newborn), women’s satisfaction with the birth experience, cost-effectiveness, and a budget impact analysis. Cost effectiveness will be calculated by QALY per prevented EA based on the utility index from the EQ-5D and the usage of healthcare services. A standardized sensitivity analysis will be carried out to quantify the outcome in addition to a budget impact analysis. In order to show a reduction from 25 to 17% in the primary outcome (alpha 0.05 and bèta 0.20), taking into account an extra 10% sample size for multi-level analysis and an attrition rate of 10%, 2 × 496 women will be needed (n = 992). Discussion: We expect that adding MCAs to the routine maternity care team will result in a decrease in the use of epidural analgesia and subsequent costs without a reduction in patient satisfaction. It will therefore be a costeffective intervention. Trial registration: Trial Registration: Netherlands Trial Register, NL8065. Registered 3 October 2019 - Retrospectively registered.
DOCUMENT
Abstract Background: Patients with glioma often suffer from cognitive deficits. Physical exercise has been effective in ameliorating cognitive deficits in older adults and neurological patients. This pilot randomized controlled trial (RCT) explored the possible impact of an exercise intervention, designed to improve cognitive functioning in glioma patients, regarding cognitive test performance and patient-reported outcomes (PROs). Methods: Thirty-four clinically stable patients with World Health Organization grades II/III glioma were randomized to a home-based remotely coached exercise group or an active control group. Patients exercised 3 times per week for 20-45 minutes, with moderate to vigorous intensity, during 6 months. At baseline and immediate follow-up, cognitive performance and PROs were assessed with neuropsychological tests and questionnaires, respectively. Linear regression analyses were used to estimate effect sizes of potential between-group differences in cognitive performance and PROs at 6 months. Results: The exercise group (n = 21) had small- to medium-sized better follow-up scores than the control group (n = 11) on several measures of attention and information processing speed, verbal memory, and executive function, whereas the control group showed a slightly better score on a measure of sustained selective attention. The exercise group also demonstrated small- to medium-sized better outcomes on measures of self-reported cognitive symptoms, fatigue, sleep, mood, and mental health-related quality of life. Conclusions: This small exploratory RCT in glioma patients provides a proof of concept with respect to improvement of cognitive functioning and PROs after aerobic exercise, and warrants larger exercise trials in brain tumor patients.
DOCUMENT
Background: A pragmatic, stepped wedge trial design can be an appealing design to evaluate complex interventions in real-life settings. However, there are certain pitfalls that need to be considered. This paper reports on the experiences and lessons learned from the conduct of a cluster randomized, stepped wedge trial evaluating the effect of the Hospital Elder Life Program (HELP) in a Dutch hospital setting to prevent older patients from developing delirium. Methods: We evaluated our trial which was conducted in eight departments in two hospitals in hospitalized patients aged 70 years or older who were at risk for delirium by reflecting on the assumptions that we had and on what we intended to accomplish when we started, as compared to what we actually realized in the different phases of our study. Lessons learned on the design, the timeline, the enrollment of eligible patients and the use of routinely collected data are provided accompanied by recommendations to address challenges. Results: The start of the trial was delayed which caused subsequent time schedule problems. The requirement for individual informed consent for a quality improvement project made the inclusion more prone to selection bias. Most units experienced major difficulties in including patients, leading to excluding two of the eight units from participation. This resulted in failing to include a similar number of patients in the control condition versus the intervention condition. Data on outcomes routinely collected in the electronic patient records were not accessible during the study, and appeared to be often missing during analyses. Conclusions: The stepped wedge, cluster randomized trial poses specific risks in the design and execution of research in real-life settings of which researchers should be aware to prevent negative consequences impacting the validity of their results. Valid conclusions on the effectiveness of the HELP in the Dutch hospital setting are hampered by the limited quantity and quality of routine clinical data in our pragmatic trial. Executing a stepped wedge design in a daily practice setting using routinely collected data requires specific attention to ethical review, flexibility, a spacious time schedule, the availability of substantial capacity in the research team and early checks on the data availability and quality.
DOCUMENT
