Comparative Performance of Comorbidity Indices in Predicting Health Care-Related Behaviors and Outcomes among Medicaid Enrollees with Type 2 Diabetes

Abstract No single gold standard of comorbidity measure has been identified, and the performance of comorbidity indices vary according to the outcome of interest. The authors compared the Charlson Comorbidity Index, Elixhauser Index (EI), Chronic Disease Score (CDS), and Health-related Quality of Life Comorbidity Index (HRQL-CI) in predicting health care-related behaviors (physicians' concordance with diabetes care standards and patients' oral antidiabetic drug [OAD] adherence) and outcomes (health care utilization and expenditures) among Medicaid enrollees with type 2 diabetes. A total of 9832 diabetes patients who used OAD were identified using data from the MarketScan Medicaid database from 2003 to 2007. Predictive performance of the comorbidity index was assessed using multiple regression models controlling for patient demographics, diabetes severity, and baseline health care characteristics. Among the 4 indices, the CDS was best at predicting physician's concordance with care standards. The CDS and HRQL-CI mental index performed better than other indices as predictors of medication adherence. The EI was best at predicting health care utilization and expenditures. These results suggest that, for these low-income diabetes patients, the CDS and HRQL-CI mental index were relatively better risk-adjustment tools for health care-related behavior data evaluation and the EI was the first choice for health care utilization and expenditures data. (Population Health Management 2012;15:220?229)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98469/1/pop%2E2011%2E0037.pd

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Performances of Comorbidity Measures in Healthcare related Behaviors and Outcomes in Type 2 Diabetes.

Background Few research studies directly compare the predictive and discriminative performance of the commonly used comorbidity measures: the Charlson Comorbidity Index, Elixhauser Index (EI), Chronic Disease Score (CDS), and Health related Quality of Life Comorbidity Index (HRQL-CI). The commonly used approach of a single summative comorbidity score provides a limited view of the differential impact of individual comorbidities on healthcare outcomes. Objectives To assess and compare the predictive and discriminative performances of comorbidity measures in healthcare outcomes and evaluate the dimensionality of comorbidity using psychometric techniques. Methods The study conceptual framework drew upon the behavioral model of health services primarily. The study sample was type 2 diabetes patients from the MarketScanTM Medicaid database (2003 to 2007). Multiple regression analyses assessed the predictive performance of comorbidity measures. The c statistic assessed discriminative performance of the comorbidity indices. Confirmatory factor analyses identified dimensionality of the comorbidity indices. Three outcomes of interest were healthcare behaviors, including physician treatment adherence and patient medication adherence, utilization and expenditures. The SAS™, STATA™, and LISREL™ software were utilized for data analyses. Results The final study sample was 9,832 type 2 diabetes patients with a mean age of approximately 45 years. The CDS had the best performance in predicting physician treatment adherence and discriminating medication adherence behavior. The CDS and HRQL-CI mental aspect index had better predictive validity for medication adherence and similar discrimination of physician treatment adherence compared to the other two indices. Diagnosis-driven indexes (e.g., EI) had better predictive and discriminative performance in healthcare utilization and expenditures outcomes. A 7-factor pattern was noticeable in the correlations related to comorbidity and it provided best model fit and predictive performance across different healthcare outcomes. Individual comorbidity dimensions demonstrated differential impact for a given outcome. Conclusion For studying healthcare behaviors, the CDS and HRQL-CI mental aspect index seem to serve as better risk adjustment tools. Diagnosis-driven indexes such as the EI still need to remain the first choice for healthcare utilization and expenditures data. Accounting for comorbidity dimensionality provides better risk adjustment and insightful information regarding the differential impact of different features of comorbidities in predicting patient outcome.Ph.D.Social & Administrative SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/77787/1/huangtz_1.pd

Cost- effectiveness of long- acting insulin analogues vs intermediate/long- acting human insulin for type 1 diabetes: A population- based cohort followed over 10 years

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154921/1/bcp14188.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154921/2/bcp14188_am.pd

Effect of metformin by employing 2-hour postload insulin for measuring insulin resistance in Taiwanese women with polycystic ovary syndrome

Evidence on clinical effectiveness of metformin in ethnic Chinese women with polycystic ovary syndrome (PCOS) remains scarce. Standard diagnostic approaches to identify insulin resistance (IR) cases in PCOS patients might be invasive, labor intensive, and stressful for patients (i.e., euglycemic clamp), or somewhat complicated for clinicians to calculate and monitor in routine practice [i.e., the homeostatic model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI)]. The aim of this study was to evaluate the clinical effects of metformin in Taiwanese women with PCOS and identify the feasible diagnostic measures of IR for Taiwanese women with PCOS. Methods: A total of 114 women from a medical center in Taiwan were studied. All were aged between 18 years and 45 years, diagnosed with PCOS according to the Rotterdam criteria, and treated with metformin. Outcome end points were body mass index (BMI) and 2-hour postload glucose and insulin levels from a 75-g oral glucose tolerance test. Results: BMI in overweight patients were significantly improved with metformin treatment duration (p < 0.001). The 2-hour insulin level statistically improved after treatment (before: 80.7 ± 63.9 μIU/mL vs. after: 65.0 ± 60.4 μIU/mL; p = 0.009). The improved 2-hour insulin level was significantly greater in IR patients than in non-IR patients. Compared with the 2-hour postload insulin level, the fasting insulin level provided 18.15% sensitivity and 94.12% specificity, the HOMA yielded 40% sensitivity and 70.58% specificity, and the QUICKI achieved 63.63% sensitivity and 11.76% specificity. Conclusion: Clinical outcomes in Taiwanese PCOS women were improved with metformin treatment, especially in overweight and IR patients. The 2-hour postload insulin level appears to be a convenient tool for screening IR in Taiwanese patients

Comparative cardiovascular safety of GLP-1 receptor agonists versus other glucose-lowering agents in real-world patients with type 2 diabetes: a nationwide population-based cohort study

Abstract Background Current evidence about the cardiovascular safety of glucagon-like peptide-1 receptor agonist (GLP-1ra) possesses limited generalizability to real-world patients with type 2 diabetes (T2D) in usual practice. This study aimed to investigate the comparative cardiovascular safety of GLP-1ra in comparisons with dipeptidyl peptidase-4 inhibitor (DPP-4i), sulfonylurea (SU), and insulin in a real-world population with T2D. Methods Adults with newly-diagnosed T2D were identified from Taiwan’s National Health Insurance Research Database in 2003–2014. A prevalent new-user cohort design was adopted to include a broad representation of real-world T2D patients being treated with GLP-1ra. The between-group comparability of baseline patient characteristics was achieved by matching on (1) initiation time of study drugs, (2) prior exposure to glucose-lowering agents, and (3) diabetes severity and complications, comorbidities, and concomitant cardiovascular medications using propensity scores. The primary outcome was a composite of cardiovascular disease (CVD) events and assessed up to the end of 2015. Cox modeling was employed to assess the association between study drugs and outcomes. Results A total of 3195 GLP-1ra stable users was identified in 2011-2014. 1893, 1829, and 1367 GLP-1ra stable users were 1:1 matched to DPP-4i, SU and insulin users, respectively. Compared to DPP-4i, SU and insulin, the use of GLP-1ra was associated with a lower risk of composite CVD events [hazard ratio (95% confidence interval) 0.73 (0.57–0.96), 0.76 (0.57–1.00), and 0.81 (0.62–1.07), respectively]. Subgroup analyses revealed that GLP-1ra versus DPP-4i yielded a greater cardiovascular benefit in those without established CVD versus those with established CVD. Conclusions This comparison study extends the supporting evidence for the cardiovascular safety of GLP-1ra to a broad spectrum of real-world T2D patients using GLP-1ra.http://deepblue.lib.umich.edu/bitstream/2027.42/173662/1/12933_2020_Article_1053.pd