Smoking Cessation Pharmacotherapy Utilization and Costs to a Medicaid Managed Care Plan.

BACKGROUND: Medicaid coverage for smoking cessation medications has expanded; however, little research has been conducted to evaluate patient-level changes in medication use over time and its associated economic impact on health plans. OBJECTIVE: The aim of this study was to characterize trends in smoking cessation medication utilization between 2006 and 2017 within a Medicaid population and estimate per-member per-month (PMPM) costs to the health plan. METHODS: This study was a retrospective longitudinal analysis conducted among adult members of a Medicaid managed care plan in California. Pharmacy claims data from January 1, 2006 to December 31, 2017 were analyzed to estimate utilization and cost of smoking cessation medications. Additionally, data from 3164 members who filled prescription(s) for cessation medication(s) in 2017 were evaluated to quantify quit attempts and use of combination therapy. For members who had been prescribed bupropion SR, varenicline, or the nicotine patch, the extent to which the durations of therapy were consistent with the manufacturers' recommended minimum duration of therapy were also assessed. RESULTS: The average PMPM expenditures for smoking cessation medications were approximately US$0.15 in 2017, compared with US$0.01-US$0.03 between 2006 and 2013. In 2017, a total of 3164 members initiated an estimated 3850 quit attempts, most commonly using the nicotine patch (57.5%) or varenicline (32.8%). Combination therapy accounted for 2.9% of quit attempts. The median therapy duration for the nicotine patch, varenicline, and bupropion SR was 28, 30, and 33 days, respectively, and for each of these medications, fewer than half of members filled prescriptions for the minimum recommended duration of therapy. CONCLUSIONS: Pharmacy claims data suggest that despite comprehensive coverage, most beneficiaries are underutilizing smoking cessation agents and are not completing the recommended treatment durations.

Interactions between antidepressants, sleep aids and selected breast cancer therapy.

Depression and insomnia are very significant pathologies in cancer patients as they contribute to the patient's overall cure and quality of life. Moreover, untreated depression and ongoing insomnia are associated with decreased immune responses and lower survival rates. With all disease states and especially with cancer, close attention to drug-drug interactions and the potential impact on the efficacy of therapy is paramount. One area of particular interest due to the lack of well-done clinical trials is drug-drug interaction(s) between antidepressants and cancer treatment. Pharmacokinetics of a certain drug allows for prediction of certain drug interactions based on chemical properties of the agents involved. If the agents depend on their metabolites for activity, active drug level will be decreased through this enzyme inhibition. In this paper, we looked at the cytochrome-P450 drug interactions between antidepressants and sleep aids with Selective Estrogen Receptor Modulators (SERM). Newer SERM metabolisms are less influenced by interactions with medications used to treat depression. However, tamoxifen metabolism could be severely altered by several antidepressants. This has direct consequences as patients on tamoxifen and antidepressant can have double the risk of relapse to cancer in two years. We discussed those interactions and made recommendations for clinical use.

Molecular effect of ethanol during neural differentiation of human embryonic stem cells in vitro.

Potential teratogenic effects of alcohol on fetal development have been documented. Especially studies have demonstrated deleterious effect of ethanol exposure on neuronal development in animal models and on the maintenance and differentiation of neuronal precursor cells derived from stem cells. To better understand molecular effect of alcohol on the process of neural differentiation, we have performed gene expression microarray analysis on human embryonic stem cells being directed to neural rosettes and neural precursor cells in the presence of ethanol treatment. Here we provide detailed experimental methods, analysis and information associated with our data deposited into Gene Expression Omnibus (GEO) under GSE56906. Our data provide scientific insight on potential molecular effects of fetal alcohol exposure on neural differentiation of early embryo development.

Gene expression signatures affected by alcohol-induced DNA methylomic deregulation in human embryonic stem cells.

Stem cells, especially human embryonic stem cells (hESCs), are useful models to study molecular mechanisms of human disorders that originate during gestation. Alcohol (ethanol, EtOH) consumption during pregnancy causes a variety of prenatal and postnatal disorders collectively referred to as fetal alcohol spectrum disorders (FASDs). To better understand the molecular events leading to FASDs, we performed a genome-wide analysis of EtOH's effects on the maintenance and differentiation of hESCs in culture. Gene Co-expression Network Analysis showed significant alterations in gene profiles of EtOH-treated differentiated or undifferentiated hESCs, particularly those associated with molecular pathways for metabolic processes, oxidative stress, and neuronal properties of stem cells. A genome-wide DNA methylome analysis revealed widespread EtOH-induced alterations with significant hypermethylation of many regions of chromosomes. Undifferentiated hESCs were more vulnerable to EtOH's effect than their differentiated counterparts, with methylation on the promoter regions of chromosomes 2, 16 and 18 in undifferentiated hESCs most affected by EtOH exposure. Combined transcriptomic and DNA methylomic analysis produced a list of differentiation-related genes dysregulated by EtOH-induced DNA methylation changes, which likely play a role in EtOH-induced decreases in hESC pluripotency. DNA sequence motif analysis of genes epigenetically altered by EtOH identified major motifs representing potential binding sites for transcription factors. These findings should help in deciphering the precise mechanisms of alcohol-induced teratogenesis.

Discovery of consensus gene signature and intermodular connectivity defining self-renewal of human embryonic stem cells.

Molecular markers defining self-renewing pluripotent embryonic stem cells (ESCs) have been identified by relative comparisons between undifferentiated and differentiated cells. Most of analysis has been done under a specific differentiation condition that may present significantly different molecular changes over others. Therefore, it is currently unclear if there are true consensus markers defining undifferentiated human ESCs (hESCs). To identify a set of key genes consistently altered during differentiation of hESCs regardless of differentiation conditions, we have performed microarray analysis on undifferentiated hESCs (H1 and H9) and differentiated EBs and validated our results using publicly available expression array datasets. We constructed consensus modules by Weighted Gene Coexpression Network Analysis and discovered novel markers that are consistently present in undifferentiated hESCs under various differentiation conditions. We have validated top markers (downregulated: LCK, KLKB1, and SLC7A3; upregulated: RhoJ, Zeb2, and Adam12) upon differentiation. Functional validation analysis of LCK in self-renewal of hESCs using LCK inhibitor or gene silencing with siLCK resulted in a loss of undifferentiation characteristics-morphological change, reduced alkaline phosphatase activity, and pluripotency gene expression, demonstrating a potential functional role of LCK in self-renewal of hESCs. We have designated hESC markers to interactive networks in the genome, identifying possible interacting partners and showing how new markers relate to each other. Furthermore, comparison of these datasets with available datasets from induced pluripotent stem cells (iPSCs) revealed that the level of these newly identified markers was correlated to the establishment of iPSCs, which may imply a potential role of these markers in gaining of cellular potency.