ABSTRACT
BACKGROUND: Genetic tools to study gene function and the fate of cells in the anterior limb bud are very limited. RESULTS: We describe a transgenic mouse line expressing CreERT2 from the Aristaless-like 4 (Alx4) promoter that induces recombination in the anterior limb. Cre induction at embryonic day 8.5 revealed that Alx4-CreERT2 labeled cells using the mTmG Cre reporter contributed to anterior digits I to III as well as the radius of the forelimb. Cre activity is expanded further along the AP axis in the hindlimb than in the forelimb resulting in some Cre reporter cells contributing to digit IV. Induction at later time points labeled cells that become progressively restricted to more anterior digits and proximal structures. Comparison of Cre expression from the Alx4 promoter transgene with endogenous Alx4 expression reveals Cre expression is slightly expanded posteriorly relative to the endogenous Alx4 expression. Using Alx4-CreERT2 to induce loss of intraflagellar transport 88 (Ift88), a gene required for ciliogenesis, hedgehog signaling, and limb patterning, did not cause overt skeletal malformations. However, the efficiency of deletion, time needed for Ift88 protein turnover, and for cilia to regress may hinder using this approach to analyze cilia in the limb. Alx4-CreERT2 is also active in the mesonephros and nephric duct that contribute to the collecting tubules and ducts of the adult nephron. Embryonic activation of the Alx4-CreERT2 in the Ift88 conditional line results in cyst formation in the collecting tubules/ducts. CONCLUSION: Overall, the Alx4-CreERT2 line will be a new tool to assess cell fates and analyze gene function in the anterior limb, mesonephros, and nephric duct.
Subject(s)
Hedgehog Proteins , Transcription Factors , Animals , Extremities , Hedgehog Proteins/genetics , Homeodomain Proteins , Integrases/genetics , Integrases/metabolism , Mice , Mice, Transgenic , Transcription Factors/genetics , TransgenesABSTRACT
Background: The Medicare Current Beneficiary Survey (MCBS) limited-access data provides the unique opportunity to utilize administrative claims and adjusted survey data to investigate trends in utilization and medical expenditure across time. The adjusted survey data is a synthesized, matched version of the original survey data and claims. Researchers may choose adjusted survey data or original claims for cost evaluations according to their research purpose. However, limited research has examined methodological issues when estimating medical cost using different MCBS data sources. Objective: The study objective was to examine the reproducibility of individual-level medical cost using both MCBS data sources: adjusted survey and claims data. Methods: This serial cross-sectional study design analyzed 2006-2012 MCBS data. The sample included noninstitutionalized older Medicare beneficiaries (≥65 years old), with a cancer diagnosis and annually enrolled in Medicare Parts A, B, and D. The population was stratified by diabetes diagnosis. The primary outcome was annual medical cost. We investigated the discrepancies of medical cost estimated from the adjusted survey and original claims data. The agreement between cost estimates from the two sources in each year was determined using the Wilcoxon signed-rank test. Results: A total of 4918 eligible Medicare beneficiaries were included in this study, and 26% of beneficiaries also had diabetes (N = 1275). Significant disagreements in cost estimates between adjusted survey and claims data were present regardless of disease complexity (with or without diabetes). Significant disagreements in medical cost estimates were present in most years, except in 2010 (p = 0.467) and 2011 (p = 0.098), for beneficiaries with cancer and diabetes (p < 0.001 for all). Significant disagreements in medical cost estimates were present in all years for beneficiaries with cancer without diabetes (p < 0.001 for all). Conclusions: Based on discrepant cost estimates across data sources, researchers using MCBS to estimate costs should be cautious when using claims or adjusted survey data alone.
ABSTRACT
OBJECTIVES: Older adults are commonly affected by cancer and diabetes, and an investigation of the economic burden faced by these older adults remains a research gap. Therefore, the objective was to assess the economic burden of diabetes among Medicare beneficiaries with cancer by analyzing annual costs from administrative claims data. METHODS: We conducted a retrospective, serial cross-sectional study using the Medicare Current Beneficiary Survey (MCBS) from 2006 to 2012. Eligible beneficiaries must be currently or previously diagnosed with cancer (of any type), ≥65 years of age, non-institutionalized and continuously enrolled annually in Medicare Parts A, B and D. Diagnoses of cancer and diabetes were determined through self-report or claims. The primary outcome was the total economic burden of diabetes per capita annually, operationalized as the difference in total direct costs between cancer patients with and without diabetes. Simple linear regression was used to analyze trends of costs across the years. Multivariable regression estimated the effect of diabetes and covariates on total annual spending among beneficiaries with cancer from 2006-2012. KEY FINDINGS: From 2006 to 2012, 4918 beneficiaries included in MCBS had cancer, with over 25% (1275) also having diabetes. From 2006 to 2012, the mean economic burden of diabetes was $7815 per capita annually. After adjusting for covariates, beginning in 2006, diagnosis of diabetes significantly predicted higher total annual spending among cancer beneficiaries in 2007 [coefficient (SE) = 0.5768 (0.1918), P = 0.003], 2011 [coefficient (SE) = 0.4303 (0.1817), P = 0.018] and 2012 [coefficient (SE) = 0.3605 (0.1758), P = 0.040]. CONCLUSIONS: Medicare beneficiaries with cancer experienced a higher economic burden from concurrent diabetes.