Tranexamic acid to prevent operation in chronic subdural haematoma (TORCH): study protocol for a randomised placebo-controlled clinical trial.

BACKGROUND: Chronic subdural haematoma (cSDH) occurs mainly in the elderly. Surgical evacuation is effective, but in these old, often frail, patients with multi-comorbidity, surgery carries significant risks for future cognitive functioning and loss of independency. Therefore, a growing interest is noted for a non-surgical treatment with medication such as tranexamic acid (TXA). In five small retrospective series, this antifibrinolytic drug showed a beneficial effect on the spontaneous resolution of the haematoma, and with that, the necessity for surgery. METHODS: For this randomised, placebo-controlled clinical multicentre trial, all cSDH patients, over 50 years old with mild symptoms (Glasgow Coma Score (GCS) ≥ 14, modified National Institutes of Health Stroke Scale (mNIHSS) ≤ 4), a midline shift of ≤ 10 mm and in whom a primary conservative treatment is chosen, are eligible for study participation. After informed consent, 140 patients will be randomised to receive either TXA 500 mg or placebo two times daily for 28 days. The primary outcome is the necessity for surgery within 12 weeks; secondary outcomes are cSDH volume, neurological impairment (mNIHSS), falling incidents, cognitive functioning (Montreal Cognitive Assessment (MOCA)), performance in activities of daily living (Barthel and Lawton score), functional outcome (modified Rankin Scale (mRS)), quality of life (Short Form Health Survey (SF-36) and EuroQol 5-Dimension Health Survey (EQ-5D)), mortality and the use of care and health-related costs (Medical Consumption Questionnaire (iMCQ) and Productivity Cost Questionnaire (iPCQ)) at 12 weeks and 6 months. DISCUSSION: This phase III trial investigating the efficacy of TXA to prevent surgery for cSDH is the first in including patients using anticoagulants and mentally incompetent patients, since these comprise a significant part of the target population. Also, this study is one of the first to prospectively measure functional outcome and quality of life in cSDH patients. Final results of this study are expected in 2024. TRIAL REGISTRATION: Dutch Trial Registry (Nederlands Trial Register) NL6584 . Registered on 11 November 2017 ClinicalTrials.gov NCT03582293 . Registered on 11 July 2018 EU Clinical Trials Register 2017-004311-40 . Registered on 29 March 2018.

Maternal and paternal family history of diabetes in second-degree relatives and metabolic outcomes at age 5-6 years: The ABCD Study.

AIM: To investigate whether children with a family history of diabetes (FHD) in second-degree relatives (grandparents, aunts/uncles) are at increased risk of developing obesity and diabetes, and whether the risk differs between maternal or paternal transmission. METHODS: In the multiethnic population-based cohort Amsterdam-Born Children and Their Development (ABCD) Study, body mass index (BMI), waist-to-height ratio (WHR), fat percentage (fat%), fasting glucose and C-peptide in 5- or 6-year-old children with no second-degree FHD (n=2226) were compared with children with maternal-only (n=353), paternal-only (n=281) or both maternal and paternal (n=164) second-degree FHD. Children of diabetic mothers or fathers were excluded. RESULTS: None of the children in any of our FHD categories differed in body composition after adjusting for maternal, paternal and childhood lifestyle covariates. However, children with both maternal and paternal second-degree FHD had increased C-peptide levels (0.03nmol, 95% CI: 0.01-0.05) compared with those in the other three study groups. Results were similar when analyses were restricted to only the Dutch children. CONCLUSION: Children with FHD in second-degree relatives on both maternal and paternal sides already have higher C-peptide levels at an early age. This might be the result of a double burden of a shared obesogenic lifestyle, or of more diverse diabetogenic genes compared to children without FHD or with only FHD in one side of the family. In any case, second-degree FHD could be used as a public-health screening tool to identify children at risk of adverse metabolic outcomes and of possible future disease.