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Item Association of Cannabis Use With Nausea and Vomiting of Pregnancy(Wolters Kluwer, 2022) Metz, Torri D.; Allshouse, Amanda A.; McMillin, Gwendolyn A.; Silver, Robert M.; Smid, Marcela C.; Haas, David M.; Simhan, Hyagriv N.; Saade, George R.; Grobman, William A.; Parry, Samuel; Chung, Judith H.; Jarlenski, Marian P.; Obstetrics and Gynecology, School of MedicineOur objective was to evaluate whether cannabis use was associated with nausea and vomiting in early pregnancy. Participants from nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be) enrolled from October 2010 through September 2013 with a PUQE (Pregnancy-Unique Quantification of Emesis) questionnaire and an available stored urine sample from the first study visit (median gestational age 12 weeks) were included. Cannabis exposure was ascertained by urine immunoassay for 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH); positive results were confirmed with liquid chromatography tandem mass spectrometry. The primary outcome was moderate-to-severe nausea by the PUQE score. Overall, 9,250 participants were included, and 5.8% (95% CI 5.4-6.3%) had detectable urine THC-COOH. In adjusted analyses, higher THC-COOH levels were associated with greater odds of moderate-to-severe nausea (20.7% in the group with THC-COOH detected vs 15.5% in the group with THC-COOH not detected, adjusted odds ratio 1.6, 95% CI 1.1-2.2 for a 500 ng/mg Cr THC-COOH increment).Item Genetic and Modifiable Risk Factors Contributing to Cisplatin-Induced Toxicities(American Association for Cancer Research, 2019-02-15) Trendowski, Matthew R.; El Charif, Omar; Dinh, Paul C. Jr.; Travis, Lois B.; Dolan, M.; Medicine, School of MedicineEffective administration of traditional cytotoxic chemotherapy is often limited by off-target toxicities. This clinical dilemma is epitomized by cisplatin, a platinating agent that has potent antineoplastic activity due to its affinity for DNA and other intracellular nucleophiles. Despite its efficacy against many adult-onset and pediatric malignancies, cisplatin elicits multiple off-target toxicities that can not only severely impact a patient’s quality of life, but also lead to dose reductions or the selection of alternative therapies that can ultimately affect outcomes. Without an effective therapeutic measure by which to successfully mitigate many of these symptoms, there have been attempts to identify a priori those individuals who are more susceptible to developing these sequelae through studies of genetic and nongenetic risk factors. Older age is associated with cisplatin induced ototoxicity, neurotoxicity and nephrotoxicity. Traditional genome-wide association studies have identified single nucleotide polymorphisms in ACYP2 and WFS1 associated with cisplatin-induced hearing loss. However, validating associations between specific genotypes and cisplatin-induced toxicities with enough stringency to warrant clinical application remains challenging. This review summarizes the current state of knowledge with regard to specific adverse sequelae following cisplatin-based therapy with a focus on ototoxicity, neurotoxicity, nephrotoxicity, myelosuppression and nausea/emesis. We discuss variables (genetic and nongenetic) contributing to these detrimental toxicities, and currently available means to prevent or treat their occurrence.Item Management of Chemotherapy Induced Nausea and Vomiting in Patients on Multiday Cisplatin Based Combination Chemotherapy(Hindawi, 2015-09) Ranganath, Praveen; Einhorn, Lawrence; Albany, Costantine; Medicine, School of MedicineIntroduction of cisplatin based chemotherapy has revolutionized the treatment of germ cell tumors. A common side effect of multiday cisplatin chemotherapy is severe nausea and vomiting. Considerable progress has been made in the control of these side effects since the introduction of cisplatin based chemotherapy in the 1970s. Germ cell tumor which is a model for a curable neoplasm has also turned into an excellent testing ground to develop effective strategies to prevent chemotherapy induced nausea and vomiting (CINV) in multiday cisplatin based regimens. The use of combination of a 5-hydroxytryptamine (HT)3 receptor antagonist, a neurokinin-1 (NK1) antagonist, and dexamethasone has greatly improved our ability to prevent and control acute and delayed CINV. Mechanism and pattern of CINV with multiday chemotherapy may differ from those in single day chemotherapy and therefore efficacy of antiemetic drugs as observed in single day chemotherapy may not be applicable. There are only few randomized clinical trials with special emphasis on multiday chemotherapy. Further studies are essential to determine the efficacy, optimal dose, and duration of the newer agents and combinations in multiday cisplatin based chemotherapy.Item Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting(Massachusetts Medical Society, 2016-07-14) Navari, Rudolph M.; Qin, Rui; Ruddy, Kathryn J.; Liu, Heshan; Powell, Steven F.; Bajaj, Madhuri; Dietrich, Leah; Biggs, David; Lafky, Jacqueline M.; Loprinzi, Charles L.; Department of Medicine, IU School of MedicineBACKGROUND We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy. METHODS In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3–receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide–doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point. RESULTS In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P = 0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P = 0.002), and the overall 120-hour period (37% vs. 22%, P = 0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P = 0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2. CONCLUSIONS Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.)Item Olanzapine for the Treatment of Advanced Cancer–Related Chronic Nausea and/or Vomiting(American Medical Association, 2020-06) Navari, Rudolph M.; Pywell, Cameron M.; Le-Rademacher, Jennifer G.; White, Patrick; Dodge, Andrew B.; Albany, Costantine; Loprinzi, Charles L.; Medicine, School of MedicineImportance: Nausea and vomiting, unrelated to chemotherapy, can be substantial symptoms in patients with advanced cancer. Objective: To evaluate the utility of olanzapine for treating chronic nausea/vomiting, unrelated to chemotherapy, in patients with advanced cancer. Design, setting, and participants: This study is a double-line, placebo-controlled, randomized clinical trial conducted from July 2017 through April 2019, with analysis conducted in 2019. Eligible participants were outpatients with advanced cancer who had persistent nausea/vomiting without having had chemotherapy or radiotherapy in the prior 14 days. Chronic nausea was present for at least 1 week (worst daily nausea numeric rating scores needed to be greater than 3 on a 0-10 scale). Interventions: Patients received olanzapine (5 mg) or a placebo, orally, daily for 7 days. Main outcomes and measures: Patient-reported outcomes were used for study end points. Data were collected at baseline and daily for 7 more days. The primary study end point (the change in nausea numeric rating scores from baseline to the last treatment day) and the study hypothesis were both identified prior to data collection. Results: A total of 30 patients (15 per arm) were enrolled; these included 16 women and 14 men who had a mean (range) age of 63 (39-79) years. Baseline median nausea scores, in all patients, were 9 out of 10 (range, 8-10). After 1 day and 1 week, the median nausea scores in the placebo arm were 9 out of 10 (range, 8-10) on both days, compared with the olanzapine arm scores of 2 out of 10 (range, 2-3) after day 1 and 1 out of 10 (range, 0-3) after 1 week. After 1 week of treatment, the reduction in nausea scores in the olanzapine arm was 8 points (95% CI, 7-8) higher than that of the placebo arm. The primary 2-sided end point P value was <.001. Correspondingly, patients in the olanzapine arm reported less emesis, less use of other antiemetic drugs, better appetite, less sedation, less fatigue, and better well-being. One patient, on the placebo, stopped treatment early owing to lack of perceived benefit. No patients receiving olanzapine reported excess sedation or any other adverse event. Conclusions and relevance: Olanzapine, at 5 mg/d, appeared to be effective in controlling nausea and emesis and in improving other symptoms and quality-of-life parameters in the study population. Trial registration: ClinicalTrials.gov Identifier: NCT03137121.Item Pain and Nausea Intensity, Social Function, and Psychological Well-Being among Women with Metastatic Breast Cancer(Sage, 2022-11-01) Senkpeil, Ryan R.; Olson, Julie S.; Fortune, Erica E.; Zaleta, Alexandra K.; Engineering Technology, Purdue School of Engineering and TechnologyAdvances in diagnostics and therapeutics have improved prognosis for metastatic breast cancer (MBC). Yet, treatment and disease burden-including experiences of pain and nausea-present practical and emotional challenges. To better support patients and enhance quality of life, deeper understanding of the pathways linking physical and psychological health is needed. To this end, we examined associations of pain and nausea with depression and anxiety among women with MBC. In doing so, we highlighted social function as a potentially important mechanism in this relationship. This observational, cross-sectional study included 148 predominantly non-Hispanic White, highly educated women living with MBC. Multivariate regression models demonstrated that more intense pain and nausea were significantly associated with higher levels of depression and anxiety (p < .001). Causal mediation analyses confirmed significant indirect effects whereby decreases in social function associated with pain and nausea contributed to depression and anxiety. Thus, our findings illustrate decreased social function as one pathway through which pain and nausea contribute to escalation of depression and anxiety. Our results, therefore, underscore the importance of supporting social function among women with MBC to potentially reduce psychological sequelae of pain and nausea.