Integration of a fasting-mimicking diet programme in primary care for type 2 diabetes reduces the need for medication and improves glycaemic control: a 12-month randomised controlled trial.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the impact on metabolic control of periodic use of a 5-day fasting-mimicking diet (FMD) programme as an adjunct to usual care in people with type 2 diabetes under regular primary care surveillance. METHODS: In this randomised, controlled, assessor-blinded trial, people with type 2 diabetes using metformin as the only glucose-lowering drug and/or diet for glycaemic control were randomised to receive 5-day cycles of an FMD monthly as an adjunct to regular care by their general practitioner or to receive regular care only. The primary outcomes were changes in glucose-lowering medication (as reflected by the medication effect score) and HbA1c levels after 12 months. Moreover, changes in use of glucose-lowering medication and/or HbA1c levels in individual participants were combined to yield a clinically relevant outcome measure ('glycaemic management'), which was categorised as improved, stable or deteriorated after 1 year of follow-up. Several secondary outcome measures were also examined, including changes in body weight. RESULTS: One hundred individuals with type 2 diabetes, age 18-75 years, BMI ≥27 kg/m2, were randomised to the FMD group (n=51) or the control group (n=49). Eight FMD participants and ten control participants were lost to follow-up. Intention-to-treat analyses, using linear mixed models, revealed adjusted estimated treatment effects for the medication effect score (-0.3; 95% CI -0.4, -0.2; p<0.001), HbA1c (-3.2 mmol/mol; 95% CI -6.2, -0.2 and -0.3%; 95% CI -0.6, -0.0; p=0.04) and body weight (-3.6 kg; 95% CI -5.2, -2.1; p<0.001) at 12 months. Glycaemic management improved in 53% of participants using FMD vs 8% of control participants, remained stable in 23% vs 33%, and deteriorated in 23% vs 59% (p<0.001). CONCLUSIONS/INTERPRETATION: Integration of a monthly FMD programme in regular primary care for people with type 2 diabetes who use metformin as the only glucose-lowering drug and/or diet for glycaemic control reduces the need for glucose-lowering medication, improves HbA1c despite the reduction in medication use, and appears to be safe in routine clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03811587 FUNDING: The project was co-funded by Health~Holland, Top Sector Life Sciences & Health, the Dutch Diabetes Foundation and L-Nutra.

Tailored anticoagulant treatment after a first venous thromboembolism: protocol of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study - cohort-based randomised controlled trial.

INTRODUCTION: Patients with a first venous thromboembolism (VTE) are at risk of recurrence. Recurrent VTE (rVTE) can be prevented by extended anticoagulant therapy, but this comes at the cost of an increased risk of bleeding. It is still uncertain whether patients with an intermediate recurrence risk or with a high recurrence and high bleeding risk will benefit from extended anticoagulant treatment, and whether a strategy where anticoagulant duration is tailored on the predicted risks of rVTE and bleeding can improve outcomes. The aim of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study is to evaluate the outcomes of tailored duration of long-term anticoagulant treatment based on individualised assessment of rVTE and major bleeding risks. METHODS AND ANALYSIS: The L-TRRiP study is a multicentre, open-label, cohort-based, randomised controlled trial, including patients with a first VTE. We classify the risk of rVTE and major bleeding using the L-TRRiP and VTE-BLEED scores, respectively. After 3 months of anticoagulant therapy, patients with a low rVTE risk will discontinue anticoagulant treatment, patients with a high rVTE and low bleeding risk will continue anticoagulant treatment, whereas all other patients will be randomised to continue or discontinue anticoagulant treatment. All patients will be followed up for at least 2 years. Inclusion will continue until the randomised group consists of 608 patients; we estimate to include 1600 patients in total. The primary outcome is the combined incidence of rVTE and major bleeding in the randomised group after 2 years of follow-up. Secondary outcomes include the incidence of rVTE and major bleeding, functional outcomes, quality of life and cost-effectiveness in all patients. ETHICS AND DISSEMINATION: The protocol was approved by the Medical Research Ethics Committee Leiden-Den Haag-Delft. Results are expected in 2028 and will be disseminated through peer-reviewed journals and during (inter)national conferences. TRIAL REGISTRATION NUMBER: NCT06087952.

(Cost-)effectiveness of an individualised risk prediction tool (PERSARC) on patient's knowledge and decisional conflict among soft-tissue sarcomas patients: protocol for a parallel cluster randomised trial (the VALUE-PERSARC study).

INTRODUCTION: Current treatment decision-making in high-grade soft-tissue sarcoma (STS) care is not informed by individualised risks for different treatment options and patients' preferences. Risk prediction tools may provide patients and professionals insight in personalised risks and benefits for different treatment options and thereby potentially increase patients' knowledge and reduce decisional conflict. The VALUE-PERSARC study aims to assess the (cost-)effectiveness of a personalised risk assessment tool (PERSARC) to increase patients' knowledge about risks and benefits of treatment options and to reduce decisional conflict in comparison with usual care in high-grade extremity STS patients. METHODS: The VALUE-PERSARC study is a parallel cluster randomised control trial that aims to include at least 120 primarily diagnosed high-grade extremity STS patients in 6 Dutch hospitals. Eligible patients (≥18 years) are those without a treatment plan and treated with curative intent. Patients with sarcoma subtypes or treatment options not mentioned in PERSARC are unable to participate. Hospitals will be randomised between usual care (control) or care with the use of PERSARC (intervention). In the intervention condition, PERSARC will be used by STS professionals in multidisciplinary tumour boards to guide treatment advice and in patient consultations, where the oncological/orthopaedic surgeon informs the patient about his/her diagnosis and discusses benefits and harms of all relevant treatment options. The primary outcomes are patients' knowledge about risks and benefits of treatment options and decisional conflict (Decisional Conflict Scale) 1 week after the treatment decision has been made. Secondary outcomes will be evaluated using questionnaires, 1 week and 3, 6 and 12 months after the treatment decision. Data will be analysed following an intention-to-treat approach using a linear mixed model and taking into account clustering of patients within hospitals. ETHICS AND DISSEMINATION: The Medical Ethical Committee Leiden-Den Haag-Delft (METC-LDD) approved this protocol (NL76563.058.21). The results of this study will be reported in a peer-review journal. TRIAL REGISTRATION NUMBER: NL9160, NCT05741944.

Cost reduction in screening for retinopathy of prematurity in the Netherlands by comparing different screening strategies.

PURPOSE: Evaluate possibilities to reduce the number of infants screened for retinopathy of prematurity (ROP) and investigate costs and number of infants detected of current and alternative screening strategies in the Netherlands. METHODS: Prospective population-based study including clinical data from all infants born in 2017 and referred for ROP screening (NEDROP-2 study). Cost and effects of screening strategies were evaluated that differed on the criteria gestational age (GA), birth weight (BW) and presence of one or more specific risk factor(s) (RF): mechanical ventilation, sepsis, necrotizing enterocolitis, postnatal corticoids and/or hypotension treated with inotropic agents. RF obtained from the Dutch perinatal registry (Perined). RESULTS: Of the possible efficient strategies, the annual costs varied from €137 966 (inclusion of BW < 700, 63 infants eligible for screening, detection of 17/39 treated ROP) to €492 689 (GA < 30 weeks and BW < 1250 grams, together with infants with GA 30-32 and BW 1250-1500 grams with presence of one more RF, 744 infants eligible for screening, all treated infants detected). Total annual costs of the current Dutch guideline that detects all infants that need treatment for ROP amount to €552 143). CONCLUSION: The current Dutch ROP guideline can be improved by implementing new screening inclusion criteria. The most effective strategy detecting all severe and treated infants, reduces the number of screened infants by 24% compared to the current guideline and the overall annual costs by €59454.

Development and psychometric evaluation of a Positive Health measurement scale: a factor analysis study based on a Dutch population.

OBJECTIVES: The My Positive Health (MPH) dialogue tool is increasingly adopted by healthcare professionals in the Netherlands as well as abroad to support people in their health. Given this trend, the need arises to measure effects of interventions on the Positive Health dimensions. However, the dialogue tool was not developed for this purpose. Therefore, this study aims to work towards a suitable measurement scale using the MPH dialogue tool as starting point. DESIGN: A cross-sectional study design. PARTICIPANTS AND SETTINGS: A total of 708 respondents, who were all members of the municipal health service panel in the eastern part of the Netherlands, completed the MPH dialogue tool. METHODS: The factor structure of the MPH dialogue tool was explored through exploratory factor analysis using maximum likelihood extraction. Next, the fit of the extracted factor structure was tested through confirmatory factor analysis. Reliability and discriminant validity of both a new model and the MPH scales were assessed through Cronbach's alpha tests. RESULTS: Similar to the MPH dialogue tool, the extracted 17-item model has a six-factor structure but named differently, comprising the factors physical fitness, mental functions, future perspectives, contentment, social relations and health management. The reliability tests suggest good to very good reliability of the aimed measurement tool and MPH model (Cronbach's alpha values ranging from, respectively, 0.820 to 0.920 and 0.882 to 0.933). The measurement model shows acceptable discriminant validity, whereas the MPH model suggests overlap between domains. CONCLUSION: The results suggest that the current MPH dialogue tool seems reliable as a dialogue, but it is not suitable as a measurement scale. We therefore propose a 17-item model with improved, acceptable psychometric properties which can serve as a basis for further development of a measurement scale.

Societal preferences for standard health insurance coverage in the Netherlands: a cross-sectional study.

INTRODUCTION: Cost-effectiveness is an important criterion in the decision to cover interventions in health insurance packages. One of the outcome measures, the quality-adjusted life year, has been criticised on its assumptions and implications concerning life expectancy and quality of life. Several studies have been conducted that measured societal preferences concerning healthcare rationing decisions. These studies mainly focused on one attribute. To adjust quality-adjusted life year maximisation in accordance with societal preferences, the relative importance of attributes should be studied. The present study aims to measure the relative importance of age, gender, socioeconomic status, pre-intervention health state, treatment effect, chance of treatment success and number of people in need of the intervention. A secondary objective is to compare the validity of the willingness to pay method with the validity of a relatively new preference elicitation method, best-worst scaling. METHODS AND ANALYSIS: A representative sample of 2000 Dutch citizens, over 18 years of age, are recruited to complete a web-based survey containing treatment scenarios. The scenarios present different levels of attributes. Respondents are asked to select one of the four scenarios that they prefer to be covered by the Dutch standard health insurance package and one that they prefer not to be covered. They are also asked to indicate how much they are willing to pay for each treatment scenario. At the end of the survey, respondents are asked to rate every attribute on a 1-10 scale. Two versions of the questionnaire are developed which differ on the framing, that is, treatments can be added to or removed from the insurance package. The data will be analysed by means of sequential conditional logit analysis (best-worst scaling) and analysis of variance (willingness to pay). ETHICS AND DISSEMINATION: The protocol is reviewed and approved by the medical ethical committee of the University Medical Center Leiden.