GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

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

Breast magnetic resonance imaging as a problem solving tool in women recalled at biennial screening mammography:A population-based study in the Netherlands

PURPOSE: Problem solving magnetic resonance imaging (MRI) is used to exclude malignancy in women with equivocal findings on conventional imaging. However, recommendations on its use for women recalled after screening are lacking. This study evaluates the impact of problem solving MRI on diagnostic workup among women recalled from the Dutch screening program, as well as time trends and inter-hospital variation in its use. METHODS: Women who were recalled at screening mammography in the South of the Netherlands (2008–2017) were included. Two-year follow-up data were collected. Diagnostic-workup and accuracy of problem solving MRI were evaluated and time trends and inter-hospital variation in its use were examined. RESULTS: In the study period 16,175 women were recalled, of whom 906 underwent problem solving MRI. Almost half of the women (45.4%) who underwent problem solving MRI were referred back to the screening program without further workup. The sensitivity, specificity, and positive and negative predictive values of problem solving MRI were 98.2%, 70.0%, 31.1%, and 99.6%, respectively. The percentage of recalled women receiving problem solving MRI fluctuated over time (4.7%–7.2%) and significantly varied among hospitals (2.2%–7.0%). CONCLUSION: The use of problem solving MRI may exclude malignancy in recalled women. The use of problem solving MRI varied over time and among hospitals, which indicates the need for guidelines on problem solving MRI

Effects of nonparticipation at previous screening rounds on the characteristics of screen-detected breast cancers

PURPOSE: We determined the incidence and effects of different screening intervals prior to a true positive recall on the tumour characteristics of screen-detected cancers (SDC) and interval cancers (ICs) at biennial screening mammography. METHODS: A consecutive series of 553020 subsequent screens was included, obtained in a Dutch screening region between January 2009 and July 2019. During 2-year follow-up, we obtained data on radiological procedures, pathology and surgical interventions of all recalled women. RESULTS: A total of 13,221 women were recalled (2.4% recall rate), yielding 3662 women with a SDC (6.6 SDCs per 1000 screen). Of these, 3477 (94.9%) had attended their two most recent screens as scheduled (i.e., 2-year screening interval), whereas the interval between the two most recent screens was four years or at least six years in respectively 132 (3.6%) and 53 (1.4%) women. There was a trend of higher cancer detection rates in case of longer screening intervals. The proportions of DCIS versus invasive cancer, as well as tumour histology, tumour size, axillary lymph node status, B&R grading, hormone receptor status and type of surgical treatment (breast conserving surgery or mastectomy) were comparable for women with a 2-year or 4-year interval between their two latest screens. SDCs in women with at least six years between their two latest screens were more frequently estrogen receptor negative or triple negative and were more frequently treated by mastectomy. All tumour characteristics mentioned above were less favourable for ICs than SDCs. CONCLUSIONS: A vast majority of women with a SDC had a 2-year screening interval between their two latest screens. A screening interval of at least six years had a slight negative influence on the tumour characteristics and treatment of SDCs