A two arm randomized controlled trial comparing the short and long term effects of an elimination diet and a healthy diet in children with ADHD (TRACE study). Rationale, study design and methods.

BACKGROUND: Food may trigger Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms. Therefore, an elimination diet (ED) might be an effective treatment for children with ADHD. However, earlier studies were criticized for the nature of the control group, potential confounders explaining the observed effects, unsatisfactory blinding, potential risks of nutritional deficiencies and unknown long term and cost-effectiveness. To address these issues, this paper describes the rationale, study design and methods of an ongoing two arm randomized controlled trial (RCT) comparing the short (5 week) and long term (1 year) effects of an elimination diet and a healthy diet compared with care as usual (CAU) in children with ADHD. METHODS: A total of N = 162 children (5-12 years) with ADHD will be randomized to either an ED or a healthy diet. A comparator arm including N = 60 children being solely treated with CAU (e.g. medication) is used to compare the effects found in both dietary groups. The two armed RCT is performed in two youth psychiatry centers in the Netherlands, with randomization within each participating center. The primary outcome measure is response to treatment defined as a ≥ 30% reduction on an ADHD DSM-5 rating scale (SWAN) and/or on an emotion dysregulation rating scale (SDQ: dysregulation profile). This is assessed after 5 weeks of dietary treatment, after which participants continue the diet or not. Secondary outcome measures include the Disruptive Behavior Diagnostic Observational Schedule (DB-DOS), parent and teacher ratings of comorbid symptoms, cognitive assessment (e.g. executive functions), school functioning, physical measurements (e.g. weight), motor activity, sleep pattern, food consumption, nutritional quality of the diet, adherence, parental wellbeing, use of health care resources and cost-effectiveness. Assessments take place at the start of the study (T0), after five weeks (T1), four months (T2), eight months (T3) and 12 months of treatment (T4). T0, T1 and T4 assessments take place at one of the psychiatric centers. T2 and T3 assessments consist of filling out online questionnaires by the parents only. DISCUSSION: This RCT will likely contribute significantly to clinical practice for ADHD by offering insight into the feasibility, nutritional quality, (cost-)effectiveness and long term effects of dietary treatments for ADHD. TRIAL REGISTRATION: www.trialregister.nl, NTR5434. Registered at October 11th, 2015.

Fast-track Radioiodine Ablation Therapy After Thyroidectomy Reduces Sick Leave in Patients With Differentiated Thyroid Cancer (FASTHYNA Trial).

BACKGROUND: Recombinant human thyroid stimulating hormone (RhTSH) aided radioiodine ablative therapy (RIT) is current-day practice in the treatment of differentiated thyroid cancer (DTC). It is often planned 4 to 6 weeks after surgery or sometimes even longer (standard protocol). The RhTSH-aided RIT, however, has the advantage that it can be planned shortly after thyroidectomy. The FASTHYNA trial was designed to test the hypothesis that RIT 1 week after thyroidectomy (fast-track protocol) results in a significant reduction of sick leave with lower societal costs and with a better quality of life (QOL) compared with the current standard treatment. METHODS: In a randomized, multicenter trial, we included patients with differentiated thyroid cancer, stage T1-3 N0-1 M0-x, who were treated with a total or completion thyroidectomy, with a paid job of at least 12 hours per week. The primary study end point was days of sick leave reported from time of surgery. Secondary end points were QOL and societal costs associated with absence from work. RESULTS: Twenty patients were eligible for inclusion between November 2013 and May 2016. Significant decreases in mean duration of sick leave in the fast-track group versus the standard care group (115 and 280 hours, respectively, P = 0.02) and in costs associated with productivity losses (&OV0556;4070.77 vs &OV0556;9202.90, P = 0.02) were found. There were no significant differences in QOL between both groups. CONCLUSIONS: The trial showed a significant reduction in sick leave and in societal costs in the fast-track group without a deterioration of QOL. Therefore, fast-track ablation is desirable. TRIAL REGISTRATION: Netherlands trial register: NTR 3933.

Economic evaluations of cholesterol-lowering drugs: a critical and systematic review.

The wide availability of economic evaluations and their increasing importance for decision making emphasises the need for economic evaluations that are methodologically sound. The aim of this review was to provide users of economic evaluations of cholesterol-lowering drugs with an insight into the quality of these evaluations. By focusing on the most relevant studies, the gap between research and policy making may be narrowed. A systematic review was conducted. All Dutch and English publications on economic evaluations of cholesterol-lowering drugs were identified by searching PubMed, the Centre for Reviews and Dissemination database (CRD), the NHS Economic Evaluation Database (NHS EED), the Health Technology Assessment database (HTA) and the Database of Abstracts of Reviews of Effects (DARE). A search strategy was set up to identify the articles to be included. The quality of these articles was assessed using Drummond's checklists. The scoring was performed by at least two reviewers. When necessary, disagreement between these reviewers was decided upon in a consensus meeting. We calculated an average quality score for the included articles. The search identified 1390 articles, of which 23 were included. Most studies measured the costs per life-year gained. The overall score per study was disappointing and varied between 2.7 and 7.7, with an average of 5.5. Most studies scored high on the measurement of costs and consequences, whereas the establishment of effectiveness left room for improvement. Only two studies included a well performed incremental analysis. This study noted an increase of quality of economic evaluations over time, suggesting the value of cost-effectiveness studies for policy decisions increases over time. In general, piggy-back evaluations tended to score higher on quality and may therefore be more valuable in decision making.

Effectiveness and cost-effectiveness of nationwide campaigns for awareness and case finding of hepatitis C targeted at people who inject drugs and the general population in the Netherlands.

BACKGROUND: Hepatitis C virus infection (HCV) is a serious, but underdiagnosed disease that can generally be treated successfully. Therefore, a nationwide HCV awareness campaign was implemented in the Netherlands targeting people who inject drugs (PWID) in addiction care ('PWID intervention') and high-risk groups in the general population ('public intervention'). The objective of this study is to assess the effectiveness and cost-effectiveness of the interventions used in this campaign. METHODS: For the 'PWID' intervention, all addiction care centres in the Netherlands provided proactive individual HCV consultation and testing. The 'public intervention' consisted of health education through mass media and instruction of health care professionals. A Markov chain model was used to estimate incremental cost-effectiveness ratios (ICER, cost per QALY gained). We included a 'DAA treatment' scenario to estimate the effect of these treatment strategies on cost-effectiveness. RESULTS: The 'PWID intervention' identified 257 additional HCV-carriers. The ICER was €9056 (95% CI: €6043-€13,523) when compared to 'no intervention'. The 'public intervention' identified 38 additional HCV-carriers. The ICER was €18,421 (95% CI: €7376-€25,490,119) when compared to 'no intervention'. Probabilistic sensitivity analysis showed that the probability that the 'PWID intervention' was cost-effective was 100%. It also showed a probability of 34% that the 'public intervention' did not exceed the Dutch threshold for cost-effectiveness (€20,000). New treatment regimens are likely to improve cost-effectiveness of this strategy. CONCLUSION: In a nationwide HCV awareness and case finding campaign, the intervention targeting PWID was effective and cost-effective. An intervention targeting risk groups in the general population showed only a modest effect and is therefore less likely to be cost-effective.

Drug costs associated with non-adherence to cholesterol management guidelines for primary prevention of cardiovascular disease in an elderly population: the Rotterdam study.

BACKGROUND: In The Netherlands, costs of HMG-CoA reductase inhibitor (statin) use have recently increased sharply compared with costs of other drugs. However, several studies have established both undertreatment and non-guidelines-indicated treatment with statins, suggesting a suboptimal use of resources. OBJECTIVE: To estimate the drug costs associated with non-guidelines-indicated treatment and undertreatment with statins in an elderly population. PATIENTS AND SETTING: Data were obtained from the Rotterdam Study, a population-based prospective cohort study which began in 1990 with 7983 participants aged > or =55 years. Subjects with a history of cardiovascular disease (CVD) were excluded. Pharmacy records were used to assess patterns of medication use in daily medical practice. MAIN OUTCOME MEASURE: Non-guidelines-indicated treatment and undertreatment with statins were established in relation to Dutch cholesterol management guidelines for all participants. We calculated the costs of statin therapy associated with non-guidelines-indicated treatment, and the costs of statins if all those undertreated were to receive statins. The results were projected on to the Dutch population to determine the economic implications of non-adherence to cholesterol management guidelines in the elderly. RESULTS: Of the participants who started treatment with statins for the primary prevention of CVD during follow-up, 69% received non-guidelines-indicated treatment. More men (7.5%) were undertreated than women (1.6%) and more women (6.2%) received non-guidelines-indicated treatment than men (1.5%). Among the participants without CVD who were still alive at 1 January 2002, 14% were eligible for statin therapy but were untreated. After projection of the prevalence of non-guidelines-indicated treatment and undertreatment to the Dutch population, the absolute costs for non-guidelines-indicated treatment with statins in 2005 were estimated to be approximately 23 million euro(uncertainty limits [UL]: 19-28 million euro), while the cost to eliminate undertreatment was also 23 million euro (UL: 19-28 million euro). CONCLUSION: Reallocation of resources used for statin therapy from those receiving non-guidelines-indicated treatment to those being undertreated could lead to a more efficient use of resources.

A literature review of assumptions on test characteristics and adherence in economic evaluations of colonoscopy and CT-colonography screening.

Colorectal cancer screening is an effective public health strategy for decreasing colorectal cancer mortality. Since many screening modalities exist, it needs to be determined what the most cost-effective strategy is. The aim of this review is to summarise the available cost-effectiveness evidence for colonoscopy versus CT-colonography screening, and to pay special attention to assumptions regarding test characteristics and adherence. A literature search resulted in twelve economic evaluations that could be included in the review. The incremental cost-effectiveness ratios of colonoscopy and CT-colonography versus no screening remained under 20,000 euro and 30,000 euro per life year gained, respectively. Although, both screening modalities were cost-effective according to most international thresholds, in most of the economic evaluations colonoscopy seemed more cost-effective than colonography screening. In many studies, model assumptions on major parameters (e.g. screening uptake) were more positive than real life data suggest. None of the models included indirect costs, which disproportionally favoured the relative cost-effectiveness of colonoscopy. For a good comparison of both screening methods, it is necessary that the assumptions used in economic evaluations are realistic, and include all costs.