ABSTRACT
PURPOSE OF REVIEW: Outpatient and perioperative therapeutic decision making for patients with diabetes involves increasingly complex medical-decision making due to rapid advances in knowledge and treatment modalities. We sought to review mobile decision support tools available to clinicians for this essential and increasingly difficult task, and to highlight the development and implementation of novel mobile applications for these purposes. RECENT FINDINGS: We found 211 mobile applications related to diabetes from the search, but only five were found to provide clinical decision support for outpatient diabetes management and none for perioperative decision support. We found a dearth of tools for clinicians to navigate these tasks. We highlight key aspects for effective development of future diabetes decision support. These include just-in-time availability, respect for the five rights of clinical decision support, and integration with clinical workflows including the electronic medical record.
Subject(s)
Decision Support Systems, Clinical , Diabetes Mellitus , Mobile Applications , Diabetes Mellitus/drug therapy , Electronic Health Records , Humans , OutpatientsABSTRACT
IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility loci on Chr.6p21 (HLA-DQB1/DRB1, PSMB9/TAP1, and DPA1/DPB2 loci), Chr.1q32 (CFHR3/R1 locus), and Chr.22q12 (HORMAD2 locus). These IgAN loci are associated with risk of other immune-mediated disorders such as type I diabetes, multiple sclerosis, or inflammatory bowel disease. We tested association of these loci in eight new independent cohorts of Asian, European, and African-American ancestry (Nâ=â4,789), followed by meta-analysis with risk-score modeling in 12 cohorts (Nâ=â10,755) and geospatial analysis in 85 world populations. Four susceptibility loci robustly replicated and all five loci were genome-wide significant in the combined cohort (Pâ=â5×10⻳²-3×10⻹°), with heterogeneity detected only at the PSMB9/TAP1 locus (I²â=â0.60). Conditional analyses identified two new independent risk alleles within the HLA-DQB1/DRB1 locus, defining multiple risk and protective haplotypes within this interval. We also detected a significant genetic interaction, whereby the odds ratio for the HORMAD2 protective allele was reversed in homozygotes for a CFHR3/R1 deletion (Pâ=â2.5×10â»4). A seven-SNP genetic risk score, which explained 4.7% of overall IgAN risk, increased sharply with Eastward and Northward distance from Africa (râ=â0.30, Pâ=â3×10⻹²8). This model paralleled the known East-West gradient in disease risk. Moreover, the prediction of a South-North axis was confirmed by registry data showing that the prevalence of IgAN-attributable kidney failure is increased in Northern Europe, similar to multiple sclerosis and type I diabetes. Variation at IgAN susceptibility loci correlates with differences in disease prevalence among world populations. These findings inform genetic, biological, and epidemiological investigations of IgAN and permit cross-comparison with other complex traits that share genetic risk loci and geographic patterns with IgAN.
Subject(s)
Blood Proteins/genetics , Cysteine Endopeptidases/genetics , Genome-Wide Association Study , Glomerulonephritis, IGA/genetics , HLA-DQ beta-Chains/genetics , Africa , Black or African American/genetics , Alleles , Asia , Asian People/genetics , Cohort Studies , Diabetes Mellitus, Type 1/genetics , Europe , Genetic Predisposition to Disease , Haplotypes , Humans , Linkage Disequilibrium , Multiple Sclerosis/genetics , Risk Factors , White People/geneticsABSTRACT
A chromosome 22q13 locus strongly associates with increased risk for idiopathic focal segmental glomerulosclerosis (FSGS), HIV-1-associated nephropathy (HIVAN), and hypertensive ESRD among individuals of African descent. Although initial studies implicated MYH9, more recent analyses localized the strongest association within the neighboring APOL1 gene. In this replication study, we examined the six top-most associated variants in APOL1 and MYH9 in an independent cohort of African Americans with various nephropathies (44 with FSGS, 21 with HIVAN, 32 with IgA nephropathy, and 74 healthy controls). All six variants associated with FSGS and HIVAN (additive ORs, 1.8 to 3.0; P values 3 × 10(-2) to 5 × 10(-5)) but not with IgA nephropathy. In conditional and haplotype analyses, two APOL1 haplotypes accounted for virtually all of the association with FSGS and HIVAN on chromosome 22q13 (haplotype P value = 5.6 × 10(-8)). To assess the role of MYH9 deficiency in nephropathy, we crossbred Myh9-haploinsufficient mice (Myh9(+/-)) with HIV-1 transgenic mice. Myh9(+/-) mice were healthy and did not demonstrate overt proteinuria or nephropathy, irrespective of the presence of the HIV-1 transgene. These data further support the strong association of genetic variants in APOL1 with susceptibility to FSGS and HIVAN among African Americans.
Subject(s)
AIDS-Associated Nephropathy/genetics , Apolipoproteins/genetics , Black or African American/genetics , Glomerulonephritis, IGA/genetics , Glomerulosclerosis, Focal Segmental/genetics , Lipoproteins, HDL/genetics , AIDS-Associated Nephropathy/ethnology , Black or African American/statistics & numerical data , Animals , Apolipoprotein L1 , Disease Models, Animal , Genetic Variation , Glomerulonephritis, IGA/ethnology , Glomerulosclerosis, Focal Segmental/ethnology , Haplotypes , Humans , Mice , Mice, Transgenic , Molecular Motor Proteins/genetics , Myosin Heavy Chains/genetics , Nonmuscle Myosin Type IIA/genetics , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN.