Kouichi Tanabe

Relationship between Carnitine Pharmacokinetics and Fatigue in Patients Treated with Cisplatin-Containing Chemotherapy

Background: Approximately 70% of the patients who receive chemotherapy suffer from fatigue, which lowers their quality of life and also has a negative influence on therapeutic efficacy. Previous studies have suggested a relationship between blood carnitine levels and fatigue. We conducted a prospective observational study to examine the relationship between carnitine pharmacokinetics and chemotherapy-induced fatigue in patients receiving cancer chemotherapy regimens that include cisplatin. Patients and Methods: 11 patients receiving chemotherapy including cisplatin (60-80 mg/m2) were included in the study. We performed 24-h urine collections and took blood samples on day 1 (before the initiation of chemotherapy) and days 2, 3, 4, and 8 in order to measure the carnitine concentrations in the serum and urine. These were compared with measures of self-reported fatigue. The primary endpoint was the change in self-reported fatigue subscales from baseline to day 8. Results: Urinary carnitine concentrations differed significantly on days 2 and 3 (p = 0.003). The Functional Assessment of Chronic Illness Therapy-Fatigue scale version 4A score on day 8 indicated significantly higher levels of fatigue as compared to day 1 (p = 0.013). Conclusion: This study suggests that there is an association between urinary carnitine levels and self-reported fatigue.

A novel predictive factor for the onset time of docetaxel-induced onychopathy: a multicenter retrospective study.

BackgroundTaxanes are known to cause onychopathy. Previous studies have reported the relationship between onychopathy and paclitaxel dosing intervals and cumulative doses. However, there are no studies of the predictive factors for docetaxel-induced nail changes. The present study used the drug accumulation rate (mg/m2/day) as a novel indicator and evaluated its usefulness for the prediction of onychopathy.MethodsFrom January 2008 to December 2009, we examined patients who received docetaxel at the Toyama University Hospital and Tonami General Hospital to determine the time to onset of onychopathy, the accumulation rate, and the cumulative dose. We then divided the study subjects into two groups, and used Receiver Operating Characteristic (ROC) analysis to calculate a cut-off value. We evaluated both indicators as predictive factors for onychopathy using the log-rank test and Cox proportional hazards model.ResultsNinety-five patients were included in the present study. The results of the log-rank test sub-analysis revealed that the median number of days until onychopathy onset was significantly shorter in patients with an accumulation rate greater than the cut-off (P = 0.009), and in those with a cumulative dose below the cut-off (P < 0.001). The hazard ratios for the accumulation rate and cumulative dose, evaluated using Cox proportional hazards regression analysis, were 1.44 (P = 0.036) and 0.99 (P < 0.001), respectively.ConclusionsThe results of the present study indicated that the drug accumulation rate influenced the time to onset of docetaxel-induced onychopathy.Trial registrationThis study is not applicable for trial registration due to retrospective chart review without intervention.

Evaluation of A Novel Information-Sharing Instrument for Home-Based Palliative Care: A Feasibility Study.

Aim: To examine the feasibility and usefulness of a novel region-based pathway: the Regional Referral Clinical Pathway for Home-Based Palliative Care. Method: This was a feasibility study to evaluate the frequency of variances and the perceived usefulness of pathway using in-depth interviews. All patients with cancer referred to the palliative care team between 2011 and 2013 and received home care services were enrolled. Result: A total of 44 patients were analyzed, and pathway was completed in all the patients. The target outcome was achieved in 61.4% while some variances occurred in 54.5%. Nine categories were identified as the usefulness of the pathway, such as reviewing and sharing information and promoting communication, education, motivation, and relationships. Conclusion: This novel pathway is feasible and seems to be useful.

Exploring Risk Factors that Contribute to the Onset of Ritodrine-Associated Serious Adverse Drug Reactions

Background: Ritodrine is a drug used for threatened premature labor. The severe adverse drug reactions associated with ritodrine are known to be pneumonedema, leukopenia, and rhabdomyolysis, but there have been few investigations on the risk factors. We performed a case-control study and selected case reports as a case group and healthy pregnant women in clinical practice as a control group. Methods: We extracted the onsets of pneumonedema, leukopenia, and rhabdomyolysis associated with ritodrine from case reports in Japan as a case group. We selected healthy pregnant women with ritodrine administration in clinical practice as a control group. We investigated their age, medical history; Pregnancy Induced Hypertension (PIH), multiple pregnancies, concomitant drugs administered, and maximum rate of ritodrine infusion, and examined the association with those factors with the onset of adverse drug reactions by logistic regression analysis. Results: The results of the case group showed: pneumonedema (28 cases); leukopenia (25 cases); rhabdomyolysis (21 cases). The risk factors significantly associated with pneumonedema are a medical history of the cardiovascular system, PIH, multiple pregnancy, and concomitant treatment with steroids, which all match with the precautions in ritodrine’s package insert. The factors associated with leukopenia are its administration longer than 7 days and the concomitant treatment with Mg. The factors associated with rhabdomyolysis are multiple pregnancies and a concomitant treatment with Mg. Conclusion: Risk factors for the onset of pneumonedema match the descriptions in the ritodrine package insert, and can be explained by pharmacological actions. Thus, this study could elucidate the risk factors for rare adverse drug reactions limited to pregnant women. The onsets of leukopenia and rhabdomyolysis were caused by physiological changes by pregnancy and its progression of disease state and ritodrine’s pharmacological action, and were suggested the possibility of risk factors.

Usefulness of a Collaborative Home Visit Program Between Hospital and Visiting Nurses

This study aimed to provide a basis for appropriate home care for cancer patients by clarifying the usefulness of home visits in a collaboration program between visiting and certified hospital nurses. This was a mixed-methods study. (1) A quantitative study was conducted, involving all patients referred to the palliative care team, and (2) a questionnaire survey was conducted, involving 40 visiting nurses. In the study (1), the subjects were all patients who were referred to a palliative care team before (October 2010 to March 2012; control group) and after (April 2012 to September 2013; collaborative home visit group) the initiation of collaborative home visits. After the patients underwent observation through December 2013, their data from charts, as of January 2014, were obtained. The proportion of home deaths increased by 3.8%, from 58.3% (n = 14) to 62.1% (n = 18), after the initiation of collaborative home visits; this increase was not significant (P = .78). However, in the survey (2), visiting nurses’ sense of difficulty in providing palliative home care was significantly reduced in comparison between those with and without experience of such visits (P = .013). Visiting nurses’ reduced sense of difficulty in providing palliative home care after collaboration during home visits suggests the usefulness of such collaboration for them. This program may contribute to increases in the proportion of home deaths by increasing the numbers of nurses newly engaged in palliative home care.

Stability of octreotide acetate decreases in a sodium bisulfate concentration-dependent manner: compatibility study with morphine and metoclopramide injections

Purpose Sodium bisulfate is known to affect the stability of octreotide. However, the critical concentration of sodium bisulfate is not known. Therefore, we assessed the critical concentration of sodium bisulfate needed to preserve the stability of octreotide using actual drugs containing sodium bisulfate. Methods Although morphine and metoclopramide preparations are considered to be compatible with octreotide, some of their products are known to contain sodium bisulfate. Thus, octreotide was mixed with preparations of sodium bisulfate solutions at serial concentrations and morphine and metoclopramide preparations containing sodium bisulfate, and octreotide stability was then evaluated using high performance liquid chromatography. Results Octreotide concentrations decreased significantly at a sodium bisulfate concentration of 0.1 mg/mL or higher after 10 days when octreotide was mixed with sodium bisulfate solutions at various concentrations. A significant decrease in octreotide concentrations also occurred when it was mixed with morphine and metoclopramide preparations containing sodium bisulfate and stored for 10 days; however, slight decreases were observed in the mixture with both preparations and were within the clinically acceptable range for morphine preparations. Conclusions These results indicate that the residual rate of octreotide decreases with time in a sodium bisulfate concentration-dependent manner when octreotide was mixed with morphine or metoclopramide. However, this incompatibility may be clinically acceptable when the final sodium bisulfate concentration is lower than 0.1 mg/mL and the mixed solution is used within 7 days.