BackgroundBased on observational studies and randomised controlled trials (RCTs), the benefit–harm balance of antihypertensive treatment in older adults with dementia is unclear.ObjectiveTo assess... Show moreBackgroundBased on observational studies and randomised controlled trials (RCTs), the benefit–harm balance of antihypertensive treatment in older adults with dementia is unclear.ObjectiveTo assess whether discontinuing antihypertensive treatment reduces neuropsychiatric symptoms (NPSs) and maintains quality of life (QoL) in nursing home residents with dementia.DesignOpen-label, blinded-outcome RCT. Randomisation 1:1, stratified by nursing home organisation and baseline NPS. Trial registration: NL7365.SubjectsDutch long-term care residents with moderate-to-severe dementia and systolic blood pressure (SBP) ≤160 mmHg during antihypertensive treatment. Exclusion criteria included heart failure NYHA-class-III/IV, recent cardiovascular events/procedures or life expectancy <4 months (planned sample size n = 492).MeasurementsCo-primary outcomes NPS (Neuropsychiatric Inventory-Nursing Home [NPI-NH]) and QoL (Qualidem) at 16 weeks.ResultsFrom 9 November 2018 to 4 May 2021, 205 participants (median age 85.8 [IQR 79.6–89.5] years; 79.5% female; median SBP 134 [IQR 123–146] mmHg) were randomised to either antihypertensive treatment discontinuation (n = 101) or usual care (n = 104). Safety concerns, combined with lacking benefits, prompted the data safety and monitoring board to advice a premature cessation of randomisation. At 16-week follow-up, no significant differences were found between groups for NPI-NH (adjusted mean difference 1.6 [95% CI –2.3 to 5.6]; P = 0.42) or Qualidem (adjusted mean difference − 2.5 [95% CI –6.0 to 1.0]; P = 0.15). Serious adverse events (SAEs) occurred in 36% (discontinuation) and 24% (usual care) of the participants (adjusted hazard ratio 1.65 [95% CI 0.98–2.79]). All 32-week outcomes favoured usual care.ConclusionHalfway through this study, a non-significant increased SAE risk associated with discontinuing antihypertensive treatment was observed, and an associated interim analysis showed that significant worthwhile health gain for discontinuation of antihypertensive treatment was unlikely. This unbeneficial benefit–harm balance shows that discontinuation of antihypertensive treatment in this context does not appear to be either safe or beneficial enough to be recommended in older adults with dementia. Show less
Hanssen, I.; Huijbers, M.; Regeer, E.; Bennekom, M.L. van; Stevens, A.; Dijk, P. van; ... ; Speckens, A.E. 2023
BackgroundMindfulness-based cognitive therapy (MBCT) seems a promising intervention for bipolar disorder (BD), but there is a lack of randomised controlled trials (RCT) investigating this. The... Show moreBackgroundMindfulness-based cognitive therapy (MBCT) seems a promising intervention for bipolar disorder (BD), but there is a lack of randomised controlled trials (RCT) investigating this. The purpose of this multicentre, evaluator blinded RCT was to investigate the added value of MBCT to treatment as usual (TAU) in BD up to 15 months follow-up (NCT03507647). MethodsA total of 144 participants with BD type I and II were randomised to MBCT + TAU (n = 72) and TAU (n = 72). Primary outcome was current depressive symptoms. Secondary outcomes were current (hypo)manic and anxiety symptoms, recurrence rates, rumination, dampening of positive affect, functional impairment, mindfulness skills, self-compassion, and positive mental health. Potential moderators of treatment outcome were examined. ResultsMBCT + TAU was not more efficacious than TAU in reducing current depressive symptoms at post-treatment (95% CI [-7.0 to 1.8], p = 0.303, d = 0.24) or follow-up (95% CI [-2.2 to 6.3], p = 0.037, d = 0.13). At post-treatment, MBCT + TAU was more effective than TAU in improving mindfulness skills. At follow-up, TAU was more effective than MBCT + TAU in reducing trait anxiety and improving mindfulness skills and positive mental health. Exploratory analysis revealed that participants with higher depressive symptoms and functional impairment at baseline benefitted more from MBCT + TAU than TAU. ConclusionsIn these participants with highly recurrent BD, MBCT may be a treatment option in addition to TAU for those who suffer from moderate to severe levels of depression and functional impairment. Show less
Gast, D.A.A.; Didden, R.; Westera, J.J.; Rest, O. van de; Hemert, A.M. van; Giltay, E.J. 2022
BackgroundAggressive incidents are common in people with intellectual disabilities. Therefore, we aimed to assess whether supplementation of multivitamins, minerals, and omega-3 fatty acids (FA)... Show moreBackgroundAggressive incidents are common in people with intellectual disabilities. Therefore, we aimed to assess whether supplementation of multivitamins, minerals, and omega-3 fatty acids (FA) reduces aggressive incidents.MethodsWe conducted a randomised, triple blind, placebo controlled, single crossover intervention trial. People with intellectual disabilities or borderline intellectual functioning, between 12 and 40 years of age, and showing aggressive behaviour were included. Participants received either a daily dose of dietary supplements, or placebo. Primary outcome was the number of aggressive incidents, measured using the Modified Overt Aggression Scale (MOAS).Resultsthere were 113 participants (placebo, n = 56), of whom 24 (placebo, n = 10) participated in the crossover phase of the trial. All 137 trajectories were included in the analyses. There was no significant difference in mean number of aggressive incidents per day between those assigned to supplements and those who received placebo (rate ratio = 0.93: 95% Confidence Interval [CI] = 0.59–1.45).ConclusionIn this pragmatic trial, we did not find significant differences in the outcomes between the supplement and placebo arms. The COVID-19 pandemic started midway through our trial, this may have affected the results. Show less
Nielsen, P.; Christensen, M.; Henderson, C.; Liddle, H.A.; Croquette-Krokar, M.; Favez, N.; Rigter, H. 2021
Background and aims: Social variables including parental and family factors may serve as risk factors for Internet Gaming Disorder (IGD) in adolescents. An IGD treatment programme should address... Show moreBackground and aims: Social variables including parental and family factors may serve as risk factors for Internet Gaming Disorder (IGD) in adolescents. An IGD treatment programme should address these factors. We assessed two family therapies multidimensional family therapy (MDFT) and family therapy as usual (FTAU) - on their impact on the prevalence of IGD and IGD symptoms. Methods: Eligible for this randomised controlled trial comparing MDFT (N = 12) with FrAu (N = 30) were adolescents of 12-19 years old meeting at least 5 of the 9 DSM-5 IGD criteria and with at least one parent willing to participate in the study. The youths were recruited from the Centre Phenix-Mail, which offers outpatient adolescent addiction care in Geneva. Assessments occurred at baseline and 6 and 12 months. Results: Both family therapies decreased the prevalence of IGD across the one-year period. Both therapies also lowered the number of IGD criteria met, with MDFT outperforming FTAU. There was no effect on the amount of time spent on gaming. At baseline, parents judged their child's gaming problems to be important whereas the adolescents thought these problems were minimal. This discrepancy in judgment diminished across the study period as parents became milder in rating problem severity. MDFT better retained families in treatment than FTAU. Discussion and Conclusions: Family therapy, especially MDFT, was effective in treating adolescent IGD. Improvements in family relationships may contribute to the treatment success. Our findings are promising but need to be replicated in larger study. Show less
BackgroundThe cardiovascular effects of treating older adults with subclinical hypothyroidism (SCH) are uncertain. Although concerns have been raised regarding a potential increase in... Show moreBackgroundThe cardiovascular effects of treating older adults with subclinical hypothyroidism (SCH) are uncertain. Although concerns have been raised regarding a potential increase in cardiovascular side effects from thyroid hormone replacement, undertreatment may also increase the risk of cardiovascular events, especially for patients with cardiovascular disease (CVD).ObjectiveTo determine the effects of levothyroxine treatment on cardiovascular outcomes in older adults with SCH.MethodsCombined data of two parallel randomised double-blind placebo-controlled trials TRUST (Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial) and IEMO80+ (the Institute for Evidence-Based Medicine in Old Age 80-plus thyroid trial) were analysed as one-stage individual participant data. Participants aged >= 65 years for TRUST (n=737) and >= 80 years for IEMO80+ (n=105) with SCH, defined by elevated TSH with fT4 within the reference range, were included. Participants were randomly assigned to receive placebo or levothyroxine, with titration of the dose until TSH level was within the reference range. Cardiovascular events and cardiovascular side effects of overtreatment (new-onset atrial fibrillation and heart failure) were investigated, including stratified analyses according to CVD history and age.ResultsThe median [IQR] age was 75.0 [69.7-81.1] years, and 448 participants (53.2%) were women. The mean TSH was 6.38 +/- SD 5.7 mIU/L at baseline and decreased at 1 year to 5.66 +/- 3.3 mIU/L in the placebo group, compared with 3.66 +/- 2.1 mIU/L in the levothyroxine group (p<0.001), at a median dose of 50 mu g. Levothyroxine did not significantly change the risk of any of the prespecified cardiovascular outcomes, including cardiovascular events (HR 0.74 [0.41-1.25]), atrial fibrillation (HR 0.69 [0.32-1.52]), or heart failure (0.41 [0.13-1.35]), or all-cause mortality (HR 1.28 [0.54-3.03]), irrespective of history of CVD and age.ConclusionTreatment with levothyroxine did not significantly change the risk of cardiovascular outcomes in older adults with subclinical hypothyroidism, irrespective of a history of cardiovascular disease and age. Show less
Verdoorn, S.; Pol, J. van de; Hovels, A.M.; Kwint, H.F.; Blom, J.W.; Gussekloo, J.; Bouvy, M.L. 2020
Aims The ageing society may lead to increasing healthcare expenditure. A clinical medication review (CMR) could potentially reduce costs. The aim of this study is to perform a cost-utility and cost... Show moreAims The ageing society may lead to increasing healthcare expenditure. A clinical medication review (CMR) could potentially reduce costs. The aim of this study is to perform a cost-utility and cost-effectiveness analysis from a societal perspective of a patient-centred CMR. Methods A trial-based cost-utility and cost-effectiveness analysis was performed as part of the DREAMeR study, a pragmatic controlled trial that randomised patients aged >= 70 years using at least seven drugs to either CMR or usual care. Over six months, healthcare consumption and drug use were collected to estimate costs, and effects were collected in terms of quality-adjusted life years (QALYs) measured with EQ-5D-5 L and EQ-VAS and as reduced health-related complaints with impact on patients' daily lives. Results The total mean costs per patient (n= 588) over six months were euro4,189 +/- 6,596 for the control group (n= 294) and euro4,008 +/- 6,678 for the intervention group (n= 294), including estimated intervention costs of euro199 +/- 67, which resulted in a mean incremental total cost savings of euro181 for the intervention group compared to the control group. Compared to the control group, for the intervention group, the mean incremental QALYs over six months were: -0.00217 measured with EQ-5D and 0.003 measured with EQ-VAS. The incremental effect of reduced health-related complaints with impact was -0.34. There was a likelihood of >90% that the intervention was cost-saving. Conclusions The benefits of a patient-centred CMR were inconsistent with no benefits on HR-QoL measured with EQ-5D-5 L and small benefits on HR-QoL measured with EQ-VAS and health-related complaints with impact on patients' daily lives. Additionally, a CMR could potentially be cost saving from a societal perspective. Show less
Ghert, M.; Bhandari, M.; Bozzo, A.; Dijkstra, P.D.S.; Griffin, A.; Grimer, R.; ... ; SAFETY Investigators 2019
Introduction Following the treatment of patients with soft tissue sarcomas (STS) that are not metastatic at presentation, the high risk for local and systemic disease recurrence necessitates post... Show moreIntroduction Following the treatment of patients with soft tissue sarcomas (STS) that are not metastatic at presentation, the high risk for local and systemic disease recurrence necessitates post-treatment surveillance. Systemic recurrence is most often detected in the lungs. The most appropriate surveillance frequency and modality remain unknown and, as such, clinical practice is highly varied. We plan to assess the feasibility of conducting a multi-centre randomised controlled trial (RCT) that will evaluate the effect on overall 5-year survival of two different surveillance frequencies and imaging modalities in patients with STS who undergo surgical excision with curative intent.Methods and analysis The Surveillance After Extremity Tumor Surgery trial will be a multi-centre 2x2 factorial RCT. Patients with non-metastatic primary Grade II or III STS treated with excision will be allocated to one of four treatment arms(1): chest radiograph (CXR) every 3 months for 2 years(2); CXR every 6 months for 2 years(3); chest CT every 3 months for 2 years or(4) chest CT every 6 months for 2years. The primary outcome of the pilot study is the feasibility of a definitive RCT based on a combination of feasibility endpoints. Secondary outcomes for the pilot study include the primary outcome of the definitive trial (overall survival), patient-reported outcomes on anxiety, satisfaction and quality of life, local recurrence-free survival, metastasis-free survival, treatment-related complications and net healthcare costs related to surveillance.Ethics and dissemination This trial received provisional ethics approval from the McMaster/Hamilton Health Sciences Research Ethics Board on 7 August 2019 (Project number 7562). Final ethics approval will be obtained prior to commencing patient recruitment. Once feasibility has been established and the definitive protocol is finalised, the study will transition to the definitive study. Show less
Moonen, J.E.F.; Foster-Dingley, J.C.; Ruijter, W. de; Grond, J. van der; Craen, A.J.M. de; Mast, R.C. van der 2016
