Induction versus expectant monitoring for intrauterine growth restriction at term: Randomised equivalence trial (DIGITAT)

Objective: To compare the effect of induction of labour with a policy of expectant monitoring for intrauterine growth restriction near term. Design: Multicentre randomised equivalence trial (the Disproportionate Intrauterine Growth Intervention Trial At Term (DIGITAT)). Setting: Eight academic and 44 non-academic hospitals in the Netherlands between November 2004 and November 2008. Participants: Pregnant women who had a singleton pregnancy beyond 36+0 weeks' g

Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal.

The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. We observe up to 30 driver events per tumor and show that subclonal diversification is associated with known prognostic parameters. By resolving the patterns of driver event ordering, co-occurrence, and mutual exclusivity at clone level, we show the deterministic nature of clonal evolution. ccRCC can be grouped into seven evolutionary subtypes, ranging from tumors characterized by early fixation of multiple mutational and copy number drivers and rapid metastases to highly branched tumors with >10 subclonal drivers and extensive parallel evolution associated with attenuated progression. We identify genetic diversity and chromosomal complexity as determinants of patient outcome. Our insights reconcile the variable clinical behavior of ccRCC and suggest evolutionary potential as a biomarker for both intervention and surveillance

Disproportionate Intrauterine Growth Intervention Trial At Term: DIGITAT

Contains fulltext : 65628.pdf ( ) (Open Access)BACKGROUND: Around 80% of intrauterine growth restricted (IUGR) infants are born at term. They have an increase in perinatal mortality and morbidity including behavioral problems, minor developmental delay and spastic cerebral palsy. Management is controversial, in particular the decision whether to induce labour or await spontaneous delivery with strict fetal and maternal surveillance. We propose a randomised trial to compare effectiveness, costs and maternal quality of life for induction of labour versus expectant management in women with a suspected IUGR fetus at term. METHODS/DESIGN: The proposed trial is a multi-centre randomised study in pregnant women who are suspected on clinical grounds of having an IUGR child at a gestational age between 36+0 and 41+0 weeks. After informed consent women will be randomly allocated to either induction of labour or expectant management with maternal and fetal monitoring. Randomisation will be web-based. The primary outcome measure will be a composite neonatal morbidity and mortality. Secondary outcomes will be severe maternal morbidity, maternal quality of life and costs. Moreover, we aim to assess neurodevelopmental and neurobehavioral outcome at two years as assessed by a postal enquiry (Child Behavioral Check List-CBCL and Ages and Stages Questionnaire-ASQ). Analysis will be by intention to treat. Quality of life analysis and a preference study will also be performed in the same study population. Health technology assessment with an economic analysis is part of this so called Digitat trial (Disproportionate Intrauterine Growth Intervention Trial At Term). The study aims to include 325 patients per arm. DISCUSSION: This trial will provide evidence for which strategy is superior in terms of neonatal and maternal morbidity and mortality, costs and maternal quality of life aspects. This will be the first randomised trial for IUGR at term. TRIAL REGISTRATION: Dutch Trial Register and ISRCTN-Register: ISRCTN10363217

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Clinical characteristics of women captured by extending the definition of severe postpartum haemorrhage with 'refractoriness to treatment': a cohort study

Background: The absence of a uniform and clinically relevant definition of severe postpartum haemorrhage hampers comparative studies and optimization of clinical management. The concept of persistent postpartum haemorrhage, based on refractoriness to initial first-line treatment, was proposed as an alternative to common definitions that are either based on estimations of blood loss or transfused units of packed red blood cells (RBC). We compared characteristics and outcomes of women with severe postpartum haemorrhage captured by these three types of definitions. Methods: In this large retrospective cohort study in 61 hospitals in the Netherlands we included 1391 consecutive women with postpartum haemorrhage who received either ≥4 units of RBC or a multicomponent transfusion. Clinical characteristics and outcomes of women with severe postpartum haemorrhage defined as persistent postpartum haemorrhage were compared to definitions based on estimated blood loss or transfused units of RBC within 24 h following birth. Adverse maternal outcome was a composite of maternal mortality, hysterectomy, arterial embolisation and intensive care unit admission. Results: One thousand two hundred sixty out of 1391 women (90.6%) with postpartum haemorrhage fulfilled the definition of persistent postpartum haemorrhage. The majority, 820/1260 (65.1%), fulfilled this definition within 1 h following birth, compared to 819/1391 (58.7%) applying the definition of ≥1 L blood loss and 37/845 (4.4%) applying the definition of ≥4 units of RBC. The definition persistent postpartum haemorrhage captured 430/471 adverse maternal outcomes (91.3%), compared to 471/471 (100%) for ≥1 L blood loss and 383/471 (81.3%) for ≥4 units of RBC. Persistent postpartum haemorrhage did not capture all adverse outcomes because of missing data on timing of initial, first-line treatment. Conclusion: The definition persistent postpartum haemo

Analysis of the key themes in the healthcare of older people with multimorbidity in Germany: a framework analysis as part of the LoChro trial

Objectives Multimorbidity challenges healthcare systems. In Germany, coordination of healthcare for older multimorbid patients remains unstructured.This study aims to identify key themes in the healthcare of these patients and the inter-relationships between them.Design Framework analysis of six cases based on 1-year data of primary and secondary care, patient-answered questionnaires and video material.Setting Southern Germany.Participants Six multimorbid older patients participating in a randomised controlled trial that compared usual care with a local, collaborative, stepped and personalised care management approach for older people with chronic diseases (LoChro-trial). The LoChro care intervention involved a care manager who assisted participants in self-management. The primary outcome was a composite of functional health and depressive symptoms at 12 and 18 months. The LoChro-intervention had no effect on the primary outcome.Primary outcome measure Key themes in the healthcare of older patients with multimorbidity and the inter-relationships between them.Methods One-year data included diagnoses, treatment plans, examinations, assessments and discharge reports. Patient perspectives were assessed using the Patient Assessment of Chronic Illness Care. In three cases, videos of the LoChro intervention showed patients describing their health needs. These data were evaluated by three doctors and public health researchers. Using framework analysis, recurring themes influencing the healthcare situation of multimorbid older patients and their inter-relationships were identified.Results Participants had an average age of 77, with 13 diagnoses, taking eight medications regularly. The five key themes describing the healthcare situation of these multimorbid patients were as follows: insufficient coordination, overuse and underuse of medical care, doctor and patient roles. Each theme covered three to four subcategories. The most significant inter-relationships between these themes were a lack of coordination leading to overuse and underuse of medical care. These were characterised by redundant inpatient stays, potential prescribing omissions and missed examinations. Deficiencies in vaccinations and secondary prevention were also demonstrated.Conclusion Coordination of care for multimorbid older patients in Germany is still deficient. Future healthcare arrangements should be explored with the participation of physicians and patients.Trial registration number LoChro trial: DRKS00013904

Local, collaborative, stepped and personalised care management for older people with chronic diseases (LoChro): study protocol of a randomised comparative effectiveness trial

Abstract Background Multimorbid older adults suffering from a long-term health condition like depression, diabetes mellitus type 2, dementia or frailty are at high risk of losing their autonomy. Disability and multimorbidity in the older population are associated with social inequality and lead to soaring costs. Our local, collaborative, stepped and personalised care management for older people with chronic diseases (LoChro-Care) aims at improving outcomes for older multimorbid patients with chronic conditions whose social and medical care must be improved. Methods The study will evaluate the effects of LoChro-Care on functional health, depressive symptoms and satisfaction with care, resource utilisation as well as health costs in older persons with long-term conditions. The trial will compare the effectiveness of LoChro-Care and usual care in a cross-sectoral setting from hospital to community care. We will recruit 606 older adults (65+) admitted to local hospital inpatient or outpatient departments who are at risk of loss of independence. Half of them will be randomised to receive the LoChro-Care intervention, comprising seven to 16 contacts with chronic care managers (CCM) within 12 months. The hypothesis that LoChro-Care will result in better patient-centred outcomes will be tested through mixed-method process and outcome evaluation and valid measures completed at baseline and at 12 and 18 months. Cost-effectiveness analyses from the healthcare perspective will include incremental cost-effectiveness ratios. Discussion The trial will provide evidence about the effectiveness of local, collaborative, stepped and personalised care management for multimorbid patients with more than one functional impairment or chronic condition. Positive results will be a first step towards the implementation of a systematic cross-sectoral chronic care management to facilitate the appropriate use of available medical and nursing services and to enhance self-management of older people. Trial registration German Clinical Trials Register (DRKS): DRKS00013904; Trial registration date: 02. February 2018