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Background: Patients with Fabry disease (FD, α-galactosidase A deficiency or absence) accumulate glycosphingolipids, leading to progressive dysfunction of kidneys, heart and nervous system. Generalizable real-world outcomes following agalsidase beta treatment initiation outside trials are limited. We investigated the associations of long-term agalsidase beta treatment with estimated glomerular filtration rate (eGFR) changes over time and the risk of developing a composite clinical event in a matched analysis of treated and untreated patients with FD., Methods: Agalsidase beta-treated adult patients (aged ≥16 years) from the Fabry Registry and adult untreated patients from a natural history cohort were matched 1:1 and X:X (with one occurrence and multiple occurrences of each untreated patient, respectively) by sex, phenotype, age and (for eGFR slope analysis) baseline eGFR. Outcomes included eGFR slope over 5 years and composite clinical event risk (cardiovascular, cerebrovascular or renal event, or death) over 10+ years. As a surrogate indicator of therapeutic response in paediatric patients, the percentage experiencing normalization in plasma globotriaosylceramide (GL-3) from treatment initiation was assessed in patients aged 2 to <16 years., Results: Overall, eGFR slopes for 1:1-matched untreated and treated adult patients [122 pairs (72.1% male)] were -3.19 and -1.47 mL/min/1.73 m 2 /year, respectively (reduction in rate of decline = 53.9%, P  = .007), and for X:X-matched [122 untreated/950 treated (59.4% male)] were -3.29 and -1.56 mL/min/1.73 m 2 /year, respectively (reduction in rate of decline = 52.6%, P  < .001). Agalsidase beta treatment was associated with lower risk of clinical events, with hazard ratios of 0.41 ( P  = .003) and 0.67 ( P  = .008) for 1:1-matched and X:X-matched analyses, respectively. Plasma GL-3 declined markedly in paediatric patients and normalized in most within 6 months of treatment initiation., Conclusion: Agalsidase beta treatment preserves kidney function and delays progression to severe clinical events among adult patients with FD. Plasma GL-3 levels analysed in paediatric patients showed normalization of elevated pre-treatment levels in most patients., Competing Interests: J.L.B., A.H., M.M., S.R., B.G., L.A.R. and E.P. are/were full-time employees of Sanofi and may hold/have held stock and/or stock options in that company. C.W. has received honoraria for board meetings and lecturing from Amicus Therapeutics, Chiesi Pharmaceuticals, Idorsia Pharmaceuticals, Sanofi and Takeda. R.J.D. is a consultant for Sanofi., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Objective: Medication adherence is an important aspect of chronic disease management. Electronic health record (EHR) data are often not linked to dispensing data, limiting clinicians' understanding of which of their patients fill their medications, and how to tailor care appropriately. We aimed to develop an algorithm to link EHR prescribing to claims-based dispensing data and use the results to quantify how often patients with diabetes filled prescribed chronic disease medications., Materials and Methods: We developed an algorithm linking EHR prescribing data (RxNorm terminology) to claims-based dispensing data (NDC terminology), within sample of adult (19-64) community health center (CHC) patients with diabetes from a network of CHCs across 12 states. We demonstrate an application of the method by calculating dispense rates for a set of commonly prescribed diabetes and cardio-protective medications. To further inform clinical care, we computed adjusted odds ratios of dispense by patient-, encounter-, and clinic-level characteristics., Results: Seventy-six percent of cardio-protective medication prescriptions and 74% of diabetes medications were linked to a dispensing record. Age, income, ethnicity, insurance, assigned primary care provider, comorbidity, time on EHR, and clinic size were significantly associated with odds of dispensing., Discussion: EHR prescriptions and pharmacy dispense data can be linked at the record level across different terminologies. Dispensing rates in this low-income population with diabetes were similar to other populations., Conclusion: Record linkage resulted in the finding that CHC patients with diabetes largely had their chronic disease medications dispensed. Understanding factors associated with dispensing rates highlight barriers and opportunities for optimal disease management.

Background: It is hypothesized that Affordable Care Act (ACA) Medicaid expansions could substantially improve access to health insurance and healthcare services for patients at risk for diabetes mellitus (DM), with pre-DM, or already diagnosed with DM. The ACA called for every state to expand Medicaid coverage by 2014. In a 2012 legal challenge, the US Supreme Court ruled that states were not required to implement Medicaid expansions. This 'natural experiment' presents a unique opportunity to learn whether and to what extent Medicaid expansion can affect healthcare access and services for patients with DM risk, pre-DM, or DM., Methods/design: Data from electronic health records (EHRs) from the Accelerating Data Value Across a National Community Health Center Network (ADVANCE) clinical data research network, which has data from >700 community health centers (CHCs), was included in the study. EHR data will be linked to Oregon Medicaid claims data. Data collection will include information on changes in health insurance, service receipt, and health outcomes, spanning 9 years (pre- and post-expansion), comparing states that expanded Medicaid, and those that did not. Patients included in this study will be diagnosed with DM, be at risk for DM, or have pre-DM, between the ages of 19 and 64, with ≥1 ambulatory visit. Sample size is estimated to be roughly 275,000 patients. Biostatistical analyses will include the difference-in-differences (DID) methodology and a generalized linear mixed model. Econometric analyses will include a DID two-part method to calculate the difference in Medicaid expenditures in Oregon among newly insured CHC patients., Discussion: Findings will have national relevance on DM health services and outcomes and will be shared through national conferences and publications. The findings will provide information needed to impact the policy as it is related to access to health insurance and receipt of healthcare among a vulnerable population., Trial Registration: This project is registered with ClinicalTrials.gov ( NCT02685384 ). Registered 18 May 2016.

Purpose: Meaningful use (MU) and Uniform Data Systems (UDSs) are calling for the collection of gender identity (GI) in electronic health record (EHR) systems; however, many transgender and nonconforming (TGNC) patients may not feel safe disclosing their GI and the data collection is not designed to guide care provision. This study explores the complexities surrounding the inclusion of GI in EHR data collection and how it can best serve patients and providers. Methods: Using a semistructured interview format, TGNC patients ( n =7) and providers ( n =5) who care for TGNC patients were asked about data collection procedures and the use of these data within community health centers in Oregon. Using a constant comparative data analysis methodology, interview transcripts were coded for emergent concepts until overlapping themes were identified. Results: Both patients and providers expressed a need for the EHR to expand upon MU and UDS-recommended fields to include current pronouns and name and gender identifiers in a forward-facing display to prevent misgendering by clinic staff and providers. Furthermore, they both cited the need for a broader range of birth-assigned sex and gender options. TGNC patients and providers disagreed on the scope of health information to be collected as well as who should be tasked with the data collection. Conclusion: These interviews offer us a glimpse into the structural difficulties of creating an EHR system that serves the needs of clinicians while providing safe and culturally competent care to TGNC patients., Competing Interests: No competing financial interests exist.

Background: The Omaha System is a standardized interface terminology that is used extensively by public health nurses in community settings to document interventions and client outcomes. Researchers using Omaha System data to analyze the effectiveness of interventions have typically calculated p-values to determine whether significant client changes occurred between admission and discharge. However, p-values are highly dependent on sample size, making it difficult to distinguish statistically significant changes from clinically meaningful changes. Effect sizes can help identify practical differences but have not yet been applied to Omaha System data., Methods: We compared p-values and effect sizes (Cohen's d) for mean differences between admission and discharge for 13 client problems documented in the electronic health records of 1,016 young low-income parents. Client problems were documented anywhere from 6 (Health Care Supervision) to 906 (Caretaking/parenting) times., Results: On a scale from 1 to 5, the mean change needed to yield a large effect size (Cohen's d ≥ 0.80) was approximately 0.60 (range = 0.50 - 1.03) regardless of p-value or sample size (i.e., the number of times a client problem was documented in the electronic health record)., Conclusions: Researchers using the Omaha System should report effect sizes to help readers determine which differences are practical and meaningful. Such disclosures will allow for increased recognition of effective interventions.

Many of the genetic variants identified via genome-wide association studies (GWAS) appear to have larger parameter estimates for younger onset cancers compared with adult onset cancers. We used data from the National Human Genome Research Institute (NHRGI) Catalog of Published GWAS to test the hypothesis that the magnitude of the parameter estimates is larger in younger onset compared to adult onset cancers. We found that the odds ratios in individuals categorized as childhood or young adult cancers were significantly higher than the odds ratios in individuals with adult cancers. The presence of larger effect sizes may mean that the variants associated with younger onset cancers explain a greater proportion of the population attributable risk estimates than the SNPs associated with adult onset cancers, which could improve early detection, treatment, and/or prevention., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, we sought to determine how well lipids measured at baseline and at 20 years predict the presence of subclinical atherosclerosis., Methods: Complete risk factor, coronary artery calcification (CAC), and carotid intima media thickness (CIMT) data were available for 2435 participants. Lipids were categorized into quartiles, CAC at Y20 was dichotomized as present/absent, and CIMT was dichotomized as ≥84 or <84th overall percentile. Multivariable logistic regression was used to model the association between lipids and CAC/CIMT. C statistics were used to assess the discriminative value of each lipid measure in predicting the presence of CAC or CIMT at Y20., Results: Lipid levels measured in young adulthood as well as middle age were both associated with subclinical disease in middle age. The discriminatory value of lipids was virtually identical at baseline, when participants were 18-30 years of age, and 20 years later. Neither baseline nor Y20 lipid data were strong predictors of Y20 subclinical disease despite statistically significant associations., Conclusions: These results are consistent with a growing body of evidence that early-life exposure to nonoptimal lipids matters and lifestyle modifications administered earlier in the lifespan could slow the progress of the atherosclerotic plaques., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to determine potential added value of novel risk factors in predicting the development of type 2 diabetes beyond that provided by standard clinical risk factors., Research Design and Methods: The Atherosclerosis Risk in Communities (ARIC) Study is a population-based prospective cohort study in four U.S. communities. Novel risk factors were either measured in the full cohort or in a case-control sample nested within the cohort. We started with a basic prediction model, previously validated in ARIC, and evaluated 35 novel risk factors by adding them independently to the basic model. The area under the curve (AUC), net reclassification index (NRI), and integrated discrimination index (IDI) were calculated to determine if each of the novel risk factors improved risk prediction., Results: There were 1,457 incident cases of diabetes with a mean of >7.6 years of follow-up among 12,277 participants at risk. None of the novel risk factors significantly improved the AUC. Forced expiratory volume in 1 s was the only novel risk factor that resulted in a significant NRI (0.54%; 95% CI: 0.33-0.86%). Adiponectin, leptin, γ-glutamyl transferase, ferritin, intercellular adhesion molecule 1, complement C3, white blood cell count, albumin, activated partial thromboplastin time, factor VIII, magnesium, hip circumference, heart rate, and a genetic risk score each significantly improved the IDI, but net changes were small., Conclusions: Evaluation of a large panel of novel risk factors for type 2 diabetes indicated only small improvements in risk prediction, which are unlikely to meaningfully alter clinical risk reclassification or discrimination strategies.

Aims: Epidemiological evidence shows that diabetes is associated with a reduced risk of prostate cancer. The objective of this study was to identify genes that may contribute to both type 2 diabetes and prostate cancer outcomes and the biological pathways these diseases may share., Methods: The Atherosclerosis Risk in Communities (ARIC) Study is a population-based prospective cohort study in four U.S. communities that included a baseline examination in 1987-89 and three follow-up exams at three year intervals. Participants were 45-64 years old at baseline. We conducted a genomewide association (GWA) study of incident type 2 diabetes in males, summarized variation across genetic loci into a polygenic risk score, and determined if that diabetes risk score was also associated with incident prostate cancer in the same study population. Secondarily we conducted a separate GWA study of prostate cancer, performed a pathway analysis of both type 2 diabetes and prostate cancer, and qualitatively determined if any of the biochemical pathways identified were shared between the two outcomes., Results: We found that the polygenic risk score for type 2 diabetes was not statistically significantly associated with prostate cancer. The pathway analysis also found no overlap between pathways associated with type 2 diabetes and prostate cancer. However, it did find that the growth hormone signaling pathway was statistically significantly associated with type 2 diabetes (p=0.0001)., Conclusion: The inability of this study to find an association between type 2 diabetes polygenic risk scores with prostate cancer or biological pathways in common suggests that shared genetic variants may not contribute significantly to explaining shared etiology.

Objectives/hypothesis: The objective of this analysis was to estimate the genetic contributions to olfactory impairment., Study Design: Population based., Methods: Olfactory impairment was measured using the San Diego Odor Identification Test at the 5-year follow-up examination for the population-based Epidemiology of Hearing Loss study. Subjects were classified as impaired if they correctly identified fewer than six out of eight odorants. To reduce confounding by age, analysis was restricted to subjects who were 60 to 79 years of age. Familial aggregation was evaluated by heritability estimates, tetrachoric correlations, and odds ratios in 207 sibling pairs from 135 sibships., Results: The prevalence of olfactory impairment was 20.2% overall and was higher in men. After adjustment for sex, age, and smoking, heritability of olfactory impairment was moderate (h(2) = 0.55), although not statistically significantly different from 0 (P = .09). By contrast, the adjusted heritability estimate for bubble gum, one of the individual odorants, was significant (h(2) = 0.51; P = .01)., Conclusions: Genetic factors might contribute to general olfactory impairment in older adults, but the strength of familial aggregation differs for individual odorants, a finding consistent with prior research.

Purpose: To estimate the genetic contributions to presbycusis., Method: Presbycusis was assessed by audiometric measurements at 3 waves of the population-based Epidemiology of Hearing Loss Study (EHLS). Measurements from the most recent hearing examination were used, at which time the subjects (3,510 participants from the EHLS study) were between 48 and 100 years of age. Heritability of presbycusis was estimated using maximum likelihood methods in 973 biological relative pairs from 376 families. Familial aggregation was also evaluated by tetrachoric correlations, odds ratios, and lambda statistics in 594 sibling pairs from 373 sibships., Results: The prevalence of presbycusis conformed to previous research, increasing with age and male sex. Heritability estimates for presbycusis adjusted for age, sex, education level, and exposure to work noise exceeded 50%, and siblings of an affected relative were at 30% higher risk. When stratified by sex, estimates of familial aggregation were higher in women than men., Conclusions: There is evidence that genetic factors contribute to age-related hearing loss in this population-based sample. The familial aggregation is stronger in women than in men.