Global Research Priorities to Better Understand the Burden of Iatrogenic Harm in Primary Care: An International Delphi Exercise

There is a need to identify and reach agreement on key foci for patient safety research in primary care contexts and understand how these priorities differ between low-, middle-, and high-income settings. We conducted a modified Delphi exercise, which was distributed to an international panel of experts in patient safety and primary care. Family practice and pharmacy were considered the main contexts on which to focus attention in order to advance patient safety in primary care across all income categories. Other clinical contexts prioritised included community midwifery and nursing in low-income countries and care homes in high-income countries. The sources of patient safety incidents requiring further study across all economic settings that were identified were communication between health care professionals and with patients, teamwork within the health care team, laboratory and diagnostic imaging investigations, issues relating to data management, transitions between different care settings, and chart/patient record com- pleteness. This work lays the foundation for a range of research initiatives that aim to promote a more comprehensive appreciation of the burden of unsafe primary care, develop understanding of the main areas of risk, and identify interventions that can enhance the safety of primary care provision internationall

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction.

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

Identification of genetic elements in metabolism by high-throughput mouse phenotyping.  

Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no previous link to metabolism and 51 genes remain functionally completely unannotated. We compared human orthologues of these uncharacterized genes in five GWAS consortia and indeed 23 candidate genes are associated with metabolic disease. We further identify common regulatory elements in promoters of candidate genes. As each regulatory element is composed of several transcription factor binding sites, our data reveal an extensive metabolic phenotype-associated network of co-regulated genes. Our systematic mouse phenotype analysis thus paves the way for full functional annotation of the genome