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  • 1
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    Impact of pharmacy interventions on pain management in an oncology palliative medicine (PM) outpatient clinic.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 31_suppl ( 2017-11-01), p. 119-119
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 31_suppl ( 2017-11-01), p. 119-119
    Abstract: 119 Background: PM can improve the quality of life and survival for cancer patients (pts); however, the demand for PM challenges providers with delayed follow ups resulting in less than one-third of pts achieving significant pain improvement between clinic visits. Engaging pharmacists in the provision of PM may help improve pain management in cancer pts. Methods: Adult cancer pts starting a new pain regimen or requiring changes to an existing regimen at baseline were referred for pharmacy follow up in 3-7 days (assessment #1). The pharmacist evaluated each pt using the Edmonton Symptom Assessment Scale and recommended changes to the referring PM provider, prompting a 2 nd follow up in 3-7 days (assessment #2). If no changes were required, pts continued therapy and returned for the final clinic visit (day 28 +/- 7). The primary endpoint was the proportion of pts achieving significant pain improvement (≥ 2-point decrease in pain score on a scale of 0-10) from baseline to final visit, which was compared to historical controls using Fisher’s Exact test. Changes in pain severity from baseline to final visit were compared using Generalized McNemar’s test, and descriptive statistics were used to describe characteristics at assessment #1. Results: Of 102 pts evaluable for the primary endpoint, 76% had stage IV disease, 58% were female, and median age was 57 yrs. Significantly more pts achieved pain improvement from baseline to final visit compared to historical controls (49% v 30%; P 〈 0.001). Changes in pain severity from baseline to final visit are described in the table. At assessment #1, 70% of pts required an intervention, primarily due to uncontrolled pain (72%), side effects (26%), and/or lack of response to non-pain medications (22%). The most common types of interventions were dose adjustments (62%), education (36%), and/or adding a new medication (30%). Over 90% of recommendations were accepted by the referring PM provider. The median time of assessment was 15 mins. Conclusions: Routine inclusion of pharmacists in the outpatient PM interdisciplinary team improves the effectiveness of pain management. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.31_suppl.119
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Effect of durable hematocrit control and minimal thrombotic risk in real-world polycythemia vera patients treated with ruxolitinib.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e19080-e19080
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e19080-e19080
    Abstract: e19080 Background: Polycythemia Vera (PV) is a myeloproliferative neoplasm characterized by unregulated red blood cell production. Most patients (pts) harbor a JAK2 mutation and must have erythrocytosis or elevated red cell mass for diagnosis (DX). Pts are at increased risk of thrombosis. Current treatments include aspirin, therapeutic phlebotomy (TP), and cytoreductive therapy such as hydroxyurea (HU). In 2014, based on the RESPONSE study, ruxolitinib (rux), a selective JAK inhibitor, was approved for second line treatment after intolerance or inadequate response to HU. A recent real-world analysis of rux in PV showed durable hematocrit (HCT) control and decreased need for TP (Coltoff 2020). Despite emerging clinical reports, real-world data on HCT control, dose adjustment, and thrombotic risk with rux are extremely limited. Methods: A retrospective chart review from three centers was performed to evaluate PV pts treated with rux between Dec 2014 and Dec 2019. Pts age 〈 18 at rux start, who received rux through investigational studies, and/or who had myelofibrosis were excluded. Data cutoff was May 30, 2022. Results: 69 patients were identified. Median time from PV DX to rux start was 4.4 yrs (range 0.1 to 40.2), and median follow-up from start of rux was 3.3 yrs (range 0.1 to 6.3). Pt characteristics: 37 (54%) Male, 59 pts (86%) White, 4 (6%) Black, and 64 (93%) Non-Hispanic. The most common reasons for starting rux were HU intolerance (46%), uncontrolled platelet count (28%), and symptom burden (19%). Median time on rux was 2.4 yrs (range 0.1 to 6.3); 43 pts (62%) remained on rux at data cutoff. A total of 6 pts (9%) received less than 3 months of rux before discontinuation, 8 pts (12%) received less than 6 months of rux. 41% pts (27/66), did not have HCT control (HCT 〈 45%) within 1 month prior to rux start. Of evaluable pts, HCT control rates at 3 and 6 months were 88% (52/59) and 89% (47/53) respectively. Phlebotomy frequency in the 3-month periods before and after rux start were known for 48 pts; 21 (44%) experienced a decrease in phlebotomies within 3 months after initiation of rux, 20 (42%) remained stable, and 7 (16%) saw an increase (ranging from +1 to +3). Twelve pts (17%) required dose reductions/suspensions due to cytopenias. One pt experienced an acute pulmonary embolism while on rux (4.4 yrs after rux initiation). The pt was diagnosed with T cell lymphoma while on rux and the thrombotic event was attributed to lymphoma. This pt achieved HCT control on rux at 3 and 6 months. No arterial thromboses were observed. Conclusions: In this real-world analysis, rux was highly effective in controlling HCT in the vast majority of PV pts by 3 and 6 months. PV pts treated with rux rarely developed thrombosis. Rux was well tolerated, and few patients required dose reduction or discontinuation. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.e19080
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Diffuse reflectance infrared spectrometry of powdered coals
    Elsevier BV ; 1982
    In:  Fuel Vol. 61, No. 6 ( 1982-6), p. 529-536
    Details
    In: Fuel, Elsevier BV, Vol. 61, No. 6 ( 1982-6), p. 529-536
    Type of Medium: Online Resource
    ISSN: 0016-2361
    URL: Article
    DOI: 10.1016/0016-2361(82)90175-2
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1982
    detail.hit.zdb_id: 1483656-7
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  • 4
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    Potentially actionable pharmacogenetic variants and symptom control medications in oncology
    Springer Science and Business Media LLC ; 2021
    In:  Supportive Care in Cancer Vol. 29, No. 10 ( 2021-10), p. 5927-5934
    Details
    In: Supportive Care in Cancer, Springer Science and Business Media LLC, Vol. 29, No. 10 ( 2021-10), p. 5927-5934
    Type of Medium: Online Resource
    ISSN: 0941-4355 , 1433-7339
    URL: Article
    DOI: 10.1007/s00520-021-06170-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1463166-0
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  • 5
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    Optimization of Voriconazole Therapy for the Treatment of Invasive Fungal Infections in Adults
    Wiley ; 2018
    In:  Clinical Pharmacology & Therapeutics Vol. 104, No. 5 ( 2018-11), p. 957-965
    Details
    In: Clinical Pharmacology & Therapeutics, Wiley, Vol. 104, No. 5 ( 2018-11), p. 957-965
    Abstract: Therapeutic concentrations of voriconazole in invasive fungal infections (IFIs) are ensured using a drug monitoring approach, which relies on attainment of steady‐state pharmacokinetics. For voriconazole, time to reach steady state can vary from 5–7 days, not optimal for critically ill patients. We developed a population pharmacokinetic/pharmacodynamic model‐based approach to predict doses that can maximize the net benefit (probability of efficacy‐probability of adverse events) and ensure therapeutic concentrations, early on during treatment. The label‐recommended 200 mg voriconazole dose resulted in attainment of targeted concentrations in ≥80% patients in the case of Candida spp . infections, as compared to only 40–50% patients, with net benefit ranging from 5.8–61.8%, in the case of Aspergillus spp . infections. Voriconazole doses of 300–600 mg were found to maximize the net benefit up to 51–66.7%, depending on the clinical phenotype (due to CYP2C19 status and pantoprazole use) of the patient and type of Aspergillus infection.
    Type of Medium: Online Resource
    ISSN: 0009-9236 , 1532-6535
    URL: Issue
    URL: Article
    DOI: 10.1002/cpt.2018.104.issue-5
    DOI: 10.1002/cpt.1012
    RVK:
    XA 36900
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2040184-X
    SSG: 15,3
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  • 6
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    Genome‐wide Association Study Identified Chromosome 8 Locus Associated with Medication‐Related Osteonecrosis of the Jaw
    Wiley ; 2021
    In:  Clinical Pharmacology & Therapeutics Vol. 110, No. 6 ( 2021-12), p. 1558-1569
    Details
    In: Clinical Pharmacology & Therapeutics, Wiley, Vol. 110, No. 6 ( 2021-12), p. 1558-1569
    Abstract: Medication‐related osteonecrosis of the jaw (MRONJ) is a rare but serious drug‐related adverse event. To identify pharmacogenomic markers of MRONJ associated with bisphosphonate therapy, we conducted a genomewide association study (GWAS) meta‐analysis followed by functional analysis of 5,008 individuals of European ancestry treated with bisphosphonates, which includes the largest number of MRONJ cases to date (444 cases and 4,564 controls). Discovery GWAS was performed in randomly selected 70% of the patients with cancer and replication GWAS was performed in the remaining 30% of the patients with cancer treated with intravenous bisphosphonates followed by meta‐analysis of all 3,639 patients with cancer. GWAS was also performed in 1,369 patients with osteoporosis treated with oral bisphosphonates. The lead single‐nucleotide polymorphism (SNP), rs2736308 on chromosome 8, was associated with an increased risk of MRONJ with an odds ratio (OR) of 2.71 and 95% confidence interval (CI) of 1.90–3.86 ( P  = 3.57*10 −8 ) in the meta‐analysis of patients with cancer. This SNP was validated in the MRONJ GWAS in patients with osteoporosis (OR: 2.82, 95% CI: 1.55–4.09, P  = 6.84*10 −4 ). The meta‐analysis combining patients with cancer and patients with osteoporosis yielded the same lead SNP rs2736308 on chromosome 8 as the top SNP (OR: 2.74, 95% CI: 2.09–3.39, P  = 9.65*10 −11 ). This locus is associated with regulation of the BLK , CTSB , and FDFT1 genes, which had been associated with bone mineral density. FDFT1 encodes a membrane‐associated enzyme, which is implicated in the bisphosphonate pathway. This study provides insights into the potential mechanism of MRONJ.
    Type of Medium: Online Resource
    ISSN: 0009-9236 , 1532-6535
    URL: Issue
    URL: Article
    DOI: 10.1002/cpt.v110.6
    DOI: 10.1002/cpt.2397
    RVK:
    XA 36900
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2040184-X
    SSG: 15,3
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  • 7
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    Review of Opioid Pharmacogenetics and Considerations for Pain Management
    Wiley ; 2017
    In:  Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy Vol. 37, No. 9 ( 2017-09), p. 1105-1121
    Details
    In: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, Wiley, Vol. 37, No. 9 ( 2017-09), p. 1105-1121
    Abstract: Opioid analgesics are the standards of care for the treatment of moderate to severe nociceptive pain, particularly in the setting of cancer and surgery. Their analgesic properties mainly emanate from stimulation of the μ receptors, which are encoded by the OPRM1 gene. Hepatic metabolism represents the major route of elimination, which, for some opioids, namely codeine and tramadol, is necessary for their bioactivation into more potent analgesics. The highly polymorphic nature of the genes coding for phase I and phase II enzymes (pharmacokinetics genes) that are involved in the metabolism and bioactivation of opioids suggests a potential interindividual variation in their disposition and, most likely, response. In fact, such an association has been substantiated in several pharmacokinetic studies described in this review, in which drug exposure and/or metabolism differed significantly based on the presence of polymorphisms in these pharmacokinetics genes. Furthermore, in some studies, the observed variability in drug exposure translated into differences in the incidence of opioid‐related adverse effects, particularly nausea, vomiting, constipation, and respiratory depression. Although the influence of polymorphisms in pharmacokinetics genes, as well as pharmacodynamics genes ( OPRM1 and COMT ) on response to opioids has been a subject of intense research, the results have been somehow conflicting, with some evidence insinuating for a potential role for OPRM1 . The Clinical Pharmacogenetics Implementation Consortium guidelines provide CYP2D6 ‐guided therapeutic recommendations to individualize treatment with tramadol and codeine. However, implementation guidelines for other opioids, which are more commonly used in real‐world settings for pain management, are currently lacking. Hence, further studies are warranted to bridge this gap in our knowledge base and ultimately ascertain the role of pharmacogenetic markers as predictors of response to opioid analgesics.
    Type of Medium: Online Resource
    ISSN: 0277-0008 , 1875-9114
    URL: Issue
    URL: Article
    DOI: 10.1002/phar.2017.37.issue-9
    DOI: 10.1002/phar.1986
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2061167-5
    SSG: 15,3
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  • 8
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    Genetic Predictors of Ibrutinib-Related Cardiovascular Side Effects in Patients with Chronic Lymphocytic Leukemia
    American Association for Cancer Research (AACR) ; 2023
    In:  Clinical Cancer Research ( 2023-09-22)
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), ( 2023-09-22)
    Abstract: Purpose: Patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib are at risk of developing cardiovascular side effects (CVSEs). The molecular determinants of CVSEs have not been fully elucidated. We interrogated genetic polymorphisms in the Bruton Tyrosine Kinase (BTK) signaling pathway for their association with ibrutinib-related CVSEs. Experimental Design: We conducted a retrospective/prospective observational pharmacogenetic study of 50 patients with newly diagnosed or relapsed CLL who received ibrutinib at a starting daily dose of 420 mg for at least six months. CVSEs, primarily atrial fibrillation and hypertension, occurred in ten patients (20%), of whom four discontinued therapy. DNA was isolated from buccal swabs of all 50 patients and genotyped for 40 single nucleotide polymorphisms in GATA4, SGK1, KCNQ1, KCNA4, NPPA, and SCN5A using a customized next generation sequencing panel. Univariate and multivariate logistic regression analysis were performed to determine genetic and clinical factors associated with the incidence of ibrutinib-related CVSEs. Results: GATA4 rs804280 AA (P =.043), KCNQ1 rs163182 GG (P =.036) and KCNQ1 rs2237895 AA (P =.023) genotypes were univariately associated with ibrutinib-related CVSEs. Based on multivariate analysis, a high genetic risk score, defined as the presence of at least two of these genotypes, was associated with 11.5-fold increased odds of CVSEs (P =.019; 95% CI, 1.79-119.73). Conclusions: Our findings suggest possible genetic determinants of ibrutinib-related CVSEs in CLL. If replicated in a larger study, pre-treatment pharmacogenetic testing for GATA4 and KCNQ1 polymorphisms may be a useful clinical tool for personalizing treatment selection for CLL and/or instituting early risk-mitigation strategies.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-23-0421
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 9
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    Supportive care medications (SCMs) and pharmacogenomics (PGx) relevance in 6,985 cancer patients (pts) undergoing distress screening.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 11592-11592
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 11592-11592
    Abstract: 11592 Background: SCMs are prescribed based on symptom burden, but response is variable, possibly due to PGx. We investigated the association between symptom burden, SCM prescribing, and frequency of SCMs with PGx evidence. Methods: Cancer pts ≥ 18 years old and completing electronic distress screening within 90 days of intake between 1/1/2017-12/31/2017 were included. Anxiety was measured using Generalized Anxiety Disorder 2-item (0-6) and depression using Patient Health Questionnaire-2 (0-6). Fatigue, nausea, neuropathy, pain and sleep were measured on a 0-10 scale. SCM prescribing within 90 days of intake was documented. Logistic regression compared symptom scores and SCM prescribing. Receiver Operating Characteristics analysis estimated sensitivity/specificity. Optimal symptom thresholds were selected according to Youden’s J statistic. SCMs with PGx evidence level A or B (according to Clinical Pharmacogenetics Implementation Consortium) were summarized. Results: Of 6985 pts, 65% were female, 75% Caucasian, 20% African American and median age was 60. 49% reported ≥ 1 severe symptom, which correlated with SCM prescribing (p 〈 0.001). 3208 (46%) were prescribed SCM(s), mainly for pain (69%) or nausea (46%). Of these, 2759 (86%) received ≥ 1 SCM with PGx evidence and 2695 (84%) received a SCM metabolized by CYP2D6 - hydrocodone (47%), ondansetron (41%), and oxycodone (28%). Based on reported CYP2D6 allele frequencies conferring altered metabolism (~20%), 539 of the 2695 pts may have altered drug response. Threshold scores for each symptom are summarized in the table. Fatigue and nausea were not associated with SCM prescribing. Conclusions: Symptom burden is high in cancer pts and correlates with SCM prescribing. Many SCMs have PGx evidence, suggesting preemptive testing, particularly for CYP2D6, may have broad applicability in this population.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.11592
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 10
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    Fluconazole vs. voriconazole prophylaxis for prevention of invasive fungal infections post haploidentical stem cell transplant.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e19504-e19504
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e19504-e19504
    Abstract: e19504 Background: IFIs are one of the most detrimental complications of profound and prolonged neutropenia post-allogeneic SCT. Prophylaxis with broad spectrum azole antifungals has become standard of care given favorable outcomes associated with their use in this setting. Nonetheless, the choice of antifungal agent varies between institutions due to absence of consensus guidelines in patients undergoing haploidentical SCT. Methods: Non-interventional retrospective study seeking to compare efficacy of fluconazole vs. voriconazole for prevention of IFI post haploidentical SCT for hematologic malignancies. SCT databases at two academic insitutions (one uses fluconazole and other uses voriconazole) were queried to identify patients who underwent allogeneic SCT from April 2012 until March 2018, and received prophlaxis with either voriconazole (group I) or fluconazole (group II). Patients with intent to start prophylaxis with fluconazole or voriconazole were included, even if antifungal agent was changed later. Primary endpoint was cumulative incidence of breakthrough IFIs (based on MSG criteria) on day +100 and +180. Fisher exact test was used to compare rates of breakthrough IFIs between two cohorts. Secondary endpoint was overal survival (OS). Kaplan Meiers analysis was performed to compare OS on day +180 and 1-year post SCT. Results: The cohort included 141 patients (group I: 75 and group II: 66). Percentage of patients who underwent transplant for leukemia was higher in group I compared to group II (77.3% vs. 56.1%, p 〈 0.001). A haploidentical SCT was performed in 62.7% of patients in group I compared to 100% in group II (p 〈 0.001). All patients received non-myeloablative conditioning. There was no statistically significant difference in rates of IFIs between two groups on day +100 (0% in I vs. 4.5% in II, p = 0.9) and +180 (1.4% vs. 4.6%, p = 0.2). A significant difference in OS was noted on day +180 and at 1-year in univariate analysis (Table). Conclusions: Our findings suggest that prophylactic use of either voriconazole or fluconazole after haploidentical SCT is associated with low rates of IFIs. However, survival data favored voriconazole over fluconazole. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e19504
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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