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American Journal of Kidney Diseases :... Aug 2018Medicare's 2011 prospective payment system (PPS) was introduced to curb overuse of separately billable injectable drugs. After epoietin, intravenous (IV) vitamin D...
BACKGROUND & RATIONALE
Medicare's 2011 prospective payment system (PPS) was introduced to curb overuse of separately billable injectable drugs. After epoietin, intravenous (IV) vitamin D analogues are the biggest drug cost drivers in hemodialysis (HD) patients, but the association between PPS introduction and vitamin D therapy has been scarcely investigated.
STUDY DESIGN
Interrupted time-series analyses.
SETTING & PARTICIPANTS
Adult US HD patients represented in the US Renal Data System between 2008 and 2013.
EXPOSURES
PPS implementation.
OUTCOMES
The cumulative dose of IV vitamin D analogues (paricalcitol equivalents) per patient per calendar quarter in prevalent HD patients. The average starting dose of IV vitamin D analogues and quarterly rates of new vitamin D use (initiations/100 person-months) in incident HD patients within 90 days of beginning HD therapy.
ANALYTICAL APPROACH
Segmented linear regression models of the immediate change and slope change over time of vitamin D use after PPS implementation.
RESULTS
Among 359,600 prevalent HD patients, IV vitamin D analogues accounted for 99% of the total use, and this trend was unchanged over time. PPS resulted in an immediate 7% decline in the average dose of IV vitamin D analogues (average baseline dose = 186.5 μg per quarter; immediate change = -13.5 μg [P < 0.001]; slope change = 0.43 per quarter [P = 0.3]) and in the starting dose of IV vitamin D analogues in incident HD patients (average baseline starting dose = 5.22 μg; immediate change = -0.40 μg [P < 0.001]; slope change = -0.03 per quarter [P = 0.03]). The baseline rate of vitamin D therapy initiation among 99,970 incident HD patients was 44.9/100 person-months and decreased over time, even before PPS implementation (pre-PPS β = -0.46/100 person-months [P < 0.001]; slope change = -0.19/100 person-months [P = 0.2]). PPS implementation was associated with an immediate change in initiation levels (by -4.5/100 person-months; P < 0.001).
LIMITATIONS
Incident HD patients were restricted to those 65 years or older.
CONCLUSION
PPS implementation was associated with a 7% reduction in the average dose and starting dose of IV vitamin D analogues and a 10% reduction in the rate of vitamin D therapy initiation.
Topics: Aged; Cohort Studies; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Interrupted Time Series Analysis; Kidney Failure, Chronic; Male; Medicare; Middle Aged; Prospective Payment System; Renal Dialysis; United States; Vitamin D
PubMed: 29891194
DOI: 10.1053/j.ajkd.2018.03.027 -
Journal of Oral Microbiology 2024is a virulent microorganism associated with dental caries. This study aimed to investigate the antimicrobial effects of Cholecalciferol (D3) and Doxercalciferol (D2),...
BACKGROUND
is a virulent microorganism associated with dental caries. This study aimed to investigate the antimicrobial effects of Cholecalciferol (D3) and Doxercalciferol (D2), against and on glycosyltransferase gene expression.
METHODS
Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of D3 and D2 for were determined according to the Clinical Laboratory Standards Institute guidelines. The effect of the compounds on environmental pH in 1% w/v and 5% w/v sucrose broth cultures after 24 hours were assessed colorimetrically. Additionally, their impact on glycosyltransferases gene expression () in 5% w/v sucrose culture was evaluated using quantitative real-time PCR.
RESULTS
The MBCs of D3 and D2 were 83 µg/ml and 166 µg/ml respectively. Both compounds were effective in preventing the local pH drop <5.5 at ≥166 µg/ml in sucrose supplemented cultures. However, the compounds did not inhibit pH drop at MIC values. Notably, D2 upregulated expression significantly ( < 0.05) and downregulated and .
CONCLUSION
Vitamin D2 and D3 inhibited mediated pH drop in sucrose supplemented cultures and altered glycosyltransferase expression, suggesting potential therapeutic roles in dental caries prevention. Further research is needed to assess their full impact on survival under environmental stresses.
PubMed: 38550660
DOI: 10.1080/20002297.2024.2327758 -
Journal of Cellular Physiology Jan 2020Acute myeloid leukemia (AML) has a poor prognosis and requires new approaches for treatment. We have reported that a combination of vitamin D-based cell differentiation...
Acute myeloid leukemia (AML) has a poor prognosis and requires new approaches for treatment. We have reported that a combination of vitamin D-based cell differentiation agents (doxercalciferol/carnosic acid [D2/CA]) added following the cytotoxic drug arabinocytosine (AraC) increases AML cell death (CD), a model for improved therapy of this disease. Because AraC-induced CD is known to involve reactive oxygen species (ROS) generation, here we investigated if the modulation of cellular REDOX status plays a role in the enhancement of cell death (ECD) by D2/CA. Using thiol antioxidants, such as N-acetyl cysteine (NAC), we found a significant inhibition of ECD, yet this occurred in the absence of any detectable change in cellular ROS levels. In contrast, NAC reduced the vitamin D receptor (VDR) abundance and its signaling of ECD. Importantly, VDR knockdown and NAC similarly inhibited ECD without producing an additive effect. Thus, the proposed post-AraC therapy may be compromised by agents that reduce VDR levels in AML blasts.
Topics: Abietanes; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antioxidants; Apoptosis; Cell Line, Tumor; Cytarabine; Ergocalciferols; HL-60 Cells; Humans; Leukemia, Myeloid, Acute; RNA Interference; RNA, Small Interfering; Reactive Oxygen Species; Receptors, Calcitriol; U937 Cells; Vitamin D
PubMed: 31245853
DOI: 10.1002/jcp.28996 -
The Journal of Steroid Biochemistry and... Nov 2016Arabinocytosine (AraC, also known as cytarabine) is one of the mainstays of AML therapy, but like other DNA damaging therapeutic agents it is rarely curative by itself....
Arabinocytosine (AraC, also known as cytarabine) is one of the mainstays of AML therapy, but like other DNA damaging therapeutic agents it is rarely curative by itself. There is an emerging realization that the therapeutic outcomes may be improved by combining AraC with other compounds. Here we report that the addition of a differentiating agent combination immediately following AraC damage to AML blasts, selectively increases the cell kill. The experiments were performed using cultured cells from established cell lines of AML (HL60 and U937). The cells were exposed to 100nM AraC, a concentration which produced approximately 25-50% cell kill, followed by a combination of 100nM 1alpha-hydroxyvitamin D2 (1-D2) and 10μM carnosic acid (CA), which together can serve as a powerful differentiating agent combination for AML cells, but are not toxic alone. AraC-induced cell death, measured by annexin V/propidium iodide, was significantly (p<0.01) increased by the 1-D2/CA combination in both cell lines, but not by 1-D2 or CA alone. The enhancement of cell death occurred by both apoptosis and necrosis, was associated with increased DNA damage and with higher levels of DNA damage response (DDR) activated marker Chk1, but the expression of p27, a cell cycle inhibitor protein, was not enhanced by 1-D2/CA. The principal finding is that a vitamin D analog 1-D2 combined with a plant-derived antioxidant CA can markedly augment the cytotoxic action of AraC, an anti-leukemia therapeutic agent.
Topics: Abietanes; Annexin A5; Antimetabolites, Antineoplastic; Antioxidants; Apoptosis; Cell Cycle Checkpoints; Cell Cycle Proteins; Cell Differentiation; Comet Assay; Cytarabine; DNA Damage; Ergocalciferols; HL-60 Cells; Humans; Leukemia, Myeloid, Acute; Phosphorylation; Propidium; U937 Cells
PubMed: 26319201
DOI: 10.1016/j.jsbmb.2015.08.023 -
The Journal of Steroid Biochemistry and... Oct 2017Vitamin D has so far not fulfilled its early promise as an antineoplastic agent, in spite of compelling in vitro data. With the aim of bringing vitamin D or its...
Vitamin D has so far not fulfilled its early promise as an antineoplastic agent, in spite of compelling in vitro data. With the aim of bringing vitamin D or its derivatives (VDDs) effectively to the clinic, we developed a two-pronged approach. First, by adding the plant-derived Carnosic Acid (CA) to a vitamin D2 derivative Doxercalciferol we increased its differentiation potency without increasing it hypercalcemic properties. Second, we added these two agents together to AML cells already treated with Cytarabine (AraC), the standard drug for the treatment of patients with AML. We now report that BRAF, a part of the MAPK signaling pathway, is required for the optimally increased cell death in this system and acts upstream of BIM, the regulator of the caspase cascade that leads to cell death by apoptosis. It is proposed that this therapeutic regimen should be tested in a clinical trial.
Topics: Antineoplastic Agents; Apoptosis; Bcl-2-Like Protein 11; Cell Differentiation; Cell Line, Tumor; Cells, Cultured; Cytarabine; Gene Expression Regulation, Neoplastic; HL-60 Cells; Humans; Leukemia, Myeloid, Acute; Proto-Oncogene Proteins B-raf; Signal Transduction; Vitamin D
PubMed: 27637326
DOI: 10.1016/j.jsbmb.2016.09.009