Introduction A major knowledge gap in the treatment of complicated Staphylococcus aureus bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has... Show moreIntroduction A major knowledge gap in the treatment of complicated Staphylococcus aureus bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has the potential to reduce adverse drug events, length of hospital stay and costs. The objective of the SAFE trial is to evaluate whether 4 weeks of antibiotic therapy is non-inferior to 6 weeks in patients with complicated SAB.Methods and analysis The SAFE-trial is a multicentre, non-inferiority, open-label, parallel group, randomised controlled trial evaluating 4 versus 6 weeks of antibiotic therapy for complicated SAB. The study is performed in 15 university hospitals and general hospitals in the Netherlands. Eligible patients are adults with methicillin-susceptible SAB with evidence of deep-seated or metastatic infection and/or predictors of complicated SAB. Only patients with a satisfactory clinical response to initial antibiotic treatment are included. Patients with infected prosthetic material or an undrained abscess of 5 cm or more at day 14 of adequate antibiotic treatment are excluded. Primary outcome is success of therapy after 180 days, a combined endpoint of survival without evidence of microbiologically confirmed disease relapse. Assuming a primary endpoint occurrence of 90% in the 6 weeks group, a non-inferiority margin of 7.5% is used. Enrolment of 396 patients in total is required to demonstrate non-inferiority of shorter antibiotic therapy with a power of 80%. Currently, 152 patients are enrolled in the study.Ethics and dissemination This is the first randomised controlled trial evaluating duration of antibiotic therapy for complicated SAB. Non-inferiority of 4 weeks of treatment would allow shortening of treatment duration in selected patients with complicated SAB. This study is approved by the Medical Ethics Committee VUmc (Amsterdam, the Netherlands) and registered under NL8347 (the Netherlands Trial Register). Results of the study will be published in a peer-reviewed journal. Show less
Alili, M. el; Smaling, H.J.A.; Joling, K.J.; Achterberg, W.P.; Francke, A.L.; Bosmans, J.E.; Steen, J.T. van der 2020
Background: Dementia is a progressive disease that decreases quality of life of persons with dementia and is associated with high societal costs. The burden of caring for persons with dementia also... Show moreBackground: Dementia is a progressive disease that decreases quality of life of persons with dementia and is associated with high societal costs. The burden of caring for persons with dementia also decreases the quality of life of family caregivers. The objective of this study was to assess the societal cost-effectiveness of Namaste Care Family program in comparison with usual care in nursing home residents with advanced dementia.Methods: Nursing homes were randomized to either Namaste Care Family program or usual care. Outcome measures of the cluster-randomized trial in 231 residents included Quality of Life in Late-Stage Dementia (QUALID) and the Gain in Alzheimer Care Instrument (GAIN) for family caregivers over 12 months of follow-up. Health states were measured using the EQ-5D-3L questionnaire which were translated into utilities. QALYs were calculated by multiplying the amount of time a participant spent in a specific health state with the utility score associated with that health state. Healthcare utilization costs were estimated using standard unit costs, while intervention costs were estimated using a bottom-up approach. Missing cost and effect data were imputed using multiple imputation. Bootstrapped multilevel models were used after multiple imputation. Cost-effectiveness acceptability curves were estimated.Results: The Namaste Care Family program was more effective than usual care in terms of QUALID (- 0.062, 95%CI: - 0.40 to 0.28), QALY (0.0017, 95%CI: - 0.059 to 0.063) and GAIN (0.075, 95%CI: - 0.20 to 0.35). Total societal costs were lower for the Namaste Care Family program as compared to usual care (- 552 euro, 95%CI: - 2920 to 1903). However, these differences were not statistically significant. The probability of cost-effectiveness at a ceiling ratio of 0 euro/unit of effect extra was 0.70 for the QUALID, QALY and GAIN.Conclusions: The Namaste Care Family program is dominant over usual care and, thus, cost-effective, although statistical uncertainty was considerable. Show less
OBJECTIVESTo investigate the effectiveness of routine ultrasonography in the third trimester in reducing adverse perinatal outcomes in low risk pregnancies compared with usual care and the effect... Show moreOBJECTIVESTo investigate the effectiveness of routine ultrasonography in the third trimester in reducing adverse perinatal outcomes in low risk pregnancies compared with usual care and the effect of this policy on maternal outcomes and obstetric interventions.DESIGNPragmatic, multicentre, stepped wedge cluster randomised trial.SETTING60 midwifery practices in the Netherlands.PARTICIPANTS13 046 women aged 16 years or older with a low risk singleton pregnancy.INTERVENTIONS60 midwifery practices offered usual care (serial fundal height measurements with clinically indicated ultrasonography). After 3, 7, and 10 months, a third of the practices were randomised to the intervention strategy. As well as receiving usual care, women in the intervention strategy were offered two routine biometry scans at 28-30 and 34-36 weeks' gestation. The same multidisciplinary protocol for detecting and managing fetal growth restriction was used in both strategies.MAIN OUTCOME MEASURESThe primary outcome measure was a composite of severe adverse perinatal outcomes: perinatal death, Apgar score <4, impaired consciousness, asphyxia, seizures, assisted ventilation, septicaemia, meningitis, bronchopulmonary dysplasia, intraventricular haemorrhage, periventricular leucomalacia, or necrotising enterocolitis. Secondary outcomes were two composite measures of severe maternal morbidity, and spontaneous labour and birth.RESULTSBetween 1 February 2015 and 29 February 2016, 60 midwifery practices enrolled 13 520 women in mid-pregnancy (mean 22.8 (SD 2.4) weeks' gestation). 13 046 women (intervention n=7067, usual care n=5979) with data based on the national Dutch perinatal registry or hospital records were included in the analyses. Small for gestational age at birth was significantly more often detected in the intervention group than in the usual care group (179 of 556 (32%) v 78 of 407 (19%), P<0.001). The incidence of severe adverse perinatal outcomes was 1.7% (n=118) for the intervention strategy and 1.8% (n=106) for usual care. After adjustment for confounders, the difference between the groups was not significant (odds ratio 0.88, 95% confidence interval 0.70 to 1.20). The intervention strategy showed a higher incidence of induction of labour (1.16, 1.04 to 1.30) and a lower incidence of augmentation of labour (0.78, 0.71 to 0.85). Maternal outcomes and other obstetric interventions did not differ between the strategies.CONCLUSIONIn low risk pregnancies, routine ultrasonography in the third trimester along with clinically indicated ultrasonography was associated with higher antenatal detection of small for gestational age fetuses but not with a reduced incidence of severe adverse perinatal outcomes compared with usual care alone. The findings do not support routine ultrasonography Show less
Wit, L. de; Rademaker, D.; Voormolen, D.N.; Akerboom, B.M.C.; Kiewiet-Kemper, R.M.; Soeters, M.R.; ... ; Rijn, B.B. van 2019
Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have... Show moreIntroduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM.Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle.Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals.Trial registration number NTR6134; Pre-results. Show less
Lier, L.I. van; Bosmans, J.E.; Hout, H.P.J. van; Mokkink, L.B.; Hout, W.B. van den; Wit, G.A. de; ... ; Roest, H.G. van der 2018
Introduction Quality of life of people with advanced dementia living in nursing homes is often suboptimal. Family caregivers can feel frustrated with limited contact with their relatives, which... Show moreIntroduction Quality of life of people with advanced dementia living in nursing homes is often suboptimal. Family caregivers can feel frustrated with limited contact with their relatives, which results in visits that are perceived as stressful and not very meaningful. Few psychosocial interventions are specifically developed for people with advanced dementia, and actively involve family caregivers or volunteers. Also, interventions usually stop when it becomes difficult for people to participate. The Namaste Care Family programme aims to increase the quality of life of people with advanced dementia, and improve family caregiving experiences through connecting to people and making them comfortable.Methods and analysis Our study will evaluate the effects of the Namaste Care Family programme on quality of life of people with advanced dementia living in nursing homes and family caregiving experiences using a cluster-randomised controlled trial. Longitudinal analyses will be performed taking into account clustering at the nursing home level. Both a cost-effectiveness and a cost-utility analysis from a societal perspective will be performed. We will modify the Namaste Care Family programme to increase family and volunteer involvement in ongoing and end-of-life care. Data collection involves assessments by family caregivers, nursing staff and elderly care physicians using questionnaires, and observations by the researchers at baseline and multiple times over 12 months. The last questionnaire will be sent up to month 24 after the death of the person with dementia. During semistructured interviews, the feasibility, accessibility and sustainability of the Namaste Care Family programme will be assessed.Ethics and dissemination The study protocol is approved by the Medical Ethics Review Committee of the VU University Medical Center in Amsterdam (protocol no. 2016.399) and registered with the Nederlands Trial Register (NTR5692). The findings will be disseminated via publications in peer-reviewed journals, conference presentations and presentations for healthcare professionals where appropriate.Trial registration number NTR5692. Show less
Dongen, J.M. van; Coffeng, J.K.; Wier, M.F. van; Boot, C.R.L.; Hendriksen, I.J.M.; Mechelen, W. van; ... ; Tulder, M.W. van 2017
