The high-cost,type 2 diabetes mellitus patient: an analysis of managed care administrative data

Background

Type 2 diabetes mellitus (T2DM) affects 25.8 million individuals in the United States and exerts a substantial economic burden on patients, health care systems, and society. Few studies have categorized costs and resource use at the patient level. The goals of this study were to assess predictors of being a high-cost (HC) patient and compare HC T2DM patients with not high-cost (NHC) T2DM patients.

Methods

Using managed care administrative claims data, patients with two or more T2DM diagnoses between 2005 and 2010 were selected. Patients were followed for 1 year after their first observed T2DM diagnosis; patients not continuously enrolled during this period were excluded from the study. Study measures included annual health care expenditures by component (i.e., inpatient, outpatient, pharmacy, total). Patients accruing total costs in the top 10% of the overall cost distribution (i.e., patients with costs > $20,528) were classified as HC a priori; all other patients were considered NHC. To assess predictors of being HC, a logistic regression model was estimated, accounting for demographics; underlying comorbidity burden (using the Charlson Comorbidity Index [CCI] score); diagnoses of renal impairment, obesity, or hypertension; and receipt of insulin, oral antidiabetics only, or no antidiabetics.

Results

A total of 1,720,041 patients met the inclusion criteria; 172,004 were HC. The mean (SD) CCI score for HC patients was 4.3 (3.0) versus 2.1 (1.7) for NHC patients. Mean (SD; upper 95% confidence interval-lower 95% confidence interval) annual per-patient costs were $56,468 ($65,604; $56,778-$56,157) among HC patients and $4,674 ($4,504; $4,695-$4,652) among NHC patients. Inpatient care and pharmacy costs were higher for HC patients than for NHC patients. The strongest predictor of being an HC patient was having a CCI score of 2 or greater (odds ratio [OR] = 4.896), followed by a diagnosis of obesity (OR = 2.106), renal impairment (OR = 2.368), and insulin use (OR = 2.098).

Conclusions

High-cost T2DM patients accrue approximately $52,000 more in total annual health care costs than not high-cost T2DM patients. Patients were significantly more likely to be high-cost if they had comorbid conditions, a diagnosis of obesity, or used insulin.     

Rationale and Roadmap for Developing Panels of Hotspot Cancer Driver Gene Mutations as Biomarkers of Cancer Risk

Cancer driver mutations (CDMs) are necessary and causal for carcinogenesis and have advantages as reporters of carcinogenic risk. However, little progress has been made toward developing measurements of CDMs as biomarkers for use in cancer risk assessment. Impediments for using a CDM-based metric to inform cancer risk include the complexity and stochastic nature of carcinogenesis, technical difficulty in quantifying low-frequency CDMs, and lack of established relationships between cancer driver mutant fractions and tumor incidence. Through literature review and database analyses, this review identifies the most promising targets to investigate as biomarkers of cancer risk. Mutational hotspots were discerned within the 20 most mutated genes across the 10 deadliest cancers. Forty genes were identified that encompass 108 mutational hotspot codons overrepresented in the COSMIC database; 424 different mutations within these hotspot codons account for approximately 63,000 tumors and their prevalence across tumor types is described. The review summarizes literature on the prevalence of CDMs in normal tissues and suggests such mutations are direct and indirect substrates for chemical carcinogenesis, which occurs in a spatially stochastic manner. Evidence that hotspot CDMs (hCDMs) frequently occur as tumor subpopulations is presented, indicating COSMIC data may underestimate mutation prevalence. Analyses of online databases show that genes containing hCDMs are enriched in functions related to intercellular communication. In its totality, the review provides a roadmap for the development of tissue-specific, CDM-based biomarkers of carcinogenic potential, comprised of batteries of hCDMs and can be measured by error-correct next-generation sequencing. Environ. Mol. Mutagen. 61:152–175, 2020. Published 2019. This article is a U.S. Government work and is in the public domain in the USA. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.     

Conventional type 1 dendritic cells induce TH1, TH1-like follicular helper T cells and regulatory T cells after antigen boost via DEC205 receptor

Conventional dendritic cells (cDCs) are specialized in antigen presentation. In the mouse spleen, cDCs are classified in cDC1s and cDC2s, and express DEC205 and DCIR2 endocytic receptors, respectively. Monoclonal antibodies (mAbs) αDEC205 (αDEC) and αDCIR2 have been fused to different antigens to deliver them to cDC1s or cDC2s. We immunized mice with αDEC and αDCIR2 fused to an antigen using Poly(I:C) as adjuvant. The initial immune response was analyzed from days 3 to 6 after the immunization. We also studied the influence of a booster dose. Our results showed that antigen targeting to cDC1s promoted a pro-inflammatory T_H1 cell response. Antigen targeting to cDC2s induced T_FH cells, GCs, and plasma cell differentiation. After boost, antigen targeting to cDC1s improved the T_H1 cell response and induced T_H1-like T_FH cells that led to an increase in specific antibody titers and IgG class switch. Additionally, a population of regulatory T cells was also observed. Antigen targeting to cDC2s did not improve the specific antibody response after boost. Our results add new information on the immune response induced after the administration of a booster dose with αDEC and αDCIR2 fusion mAbs. These results may be useful for vaccine design using recombinant mAbs.     

Functional correlations of axial muscle fiber type proportions in the waterfall-climbing Hawaiian stream fish Sicyopterus stimpsoni

Assessing the factors that contribute to successful locomotor performance can provide critical insight into how animals survive in challenging habitats. Locomotion is powered by muscles, so that differences in the relative proportions of red (slow-oxidative) vs. white (fast-glycolytic) fibers can have significant implications for locomotor performance. We compared the relative proportions of axial red muscle fibers between groups of juveniles of the amphidromous gobiid fish, Sicyopterus stimpsoni, from the Hawaiian Islands. Juveniles of this species migrate from the ocean into freshwater streams, navigating through a gauntlet of predators that require rapid escape responses, before reaching waterfalls which must be climbed (using a slow, inching behavior) to reach adult breeding habitats. We found that fish from Kaua'i have a smaller proportion of red fibers in their tail muscles than fish from Hawai'i, matching expectations based on the longer pre-waterfall stream reaches of Kaua'i that could increase exposure to predators, making reduction of red muscle and increases in white muscle advantageous. However, no difference in red muscle proportions was identified between fish that were either successful or unsuccessful in scaling model waterfalls during laboratory climbing trials, suggesting that proportions of red muscle are near a localized fitness peak among Hawaiian individuals.     

Outcomes beyond hospital discharge in infants and children with viral meningitis: A systematic review

Viruses are the commonest cause of childhood meningitis, but outcomes beyond hospital discharge are poorly described. We undertook a systematic literature review of long‐term outcomes following paediatric viral meningitis. A search was carried out using MEDLINE, Embase, and Cochrane Review for studies from 1 January 1990 to 31 December 2018. Studies were included where specific outcome measures were available beyond hospital discharge for children <16 years old with viral meningitis. In total, 3588 papers were identified of which 14 were eligible for inclusion. Four studies reported outcomes in children with nonenterovirus 71 meningitis. A US study of 16 cases demonstrated subtle language difficulties at 3‐year follow‐up in infants in contrast to an Australian study, which revealed no impairment in language. A Fijian study showed that two out of eight cases had sensorineural hearing loss compared with none in a UK cohort of 668 infants. Three studies evaluated outcomes of enterovirus 71 meningitis in China and Taiwan, two showed cases recovered without sequelae, while one demonstrated an increased risk of attention deficit hyperactivity disorder. Two studies including 141 cases of human parechovirus revealed no evidence of neurodevelopmental sequelae. Conversely, an Australian study demonstrated neurodevelopmental sequelae in 11 out of 77 infants with parechovirus meningitis. Most studies identified in this review demonstrated a high proportion of good clinical outcomes following viral meningitis. However, the data are limited, so robustly conducted neurodevelopmental studies are warranted to inform the evidence‐based management of viral meningitis beyond hospital discharge.     

IFNL cytokines do not modulate human or murine NK cell functions

The interferon-lambda (IFNL) cytokines have been shown to be important in HCV infection with SNPs in the IFNL3 gene associated with both natural and treatment induced viral clearance. We have recently shown that rs1299860 (an IFNL3 associated SNP) and an NK cell gene, KIR2DS3, synergised to increase the odds of chronic infection in a homogenous cohort of Irish women infected with HCV. To characterise a biological basis for the genetic synergy, we investigated for any evidence that IFNL cytokines regulate NK cell functions. Using a range of functional responses, we did not find any evidence of NK cell activation by IFNL3, IFNL1 or IFNL2 cytokines. Similar results were found using human and murine NK cells. In addition, and in contrast to our preliminary study, we did not find any evidence that IFNL cytokines inhibited NK cell cytokine production; thus, the biological basis for the genetic synergy remains to be discovered.