[Risk Factors for Anti-PD1 Antibody-Induced Skin Eruptions].

Skin complication caused by anti-programmed cell death-1(PD1)antibody is a typical immune-related adverse event. We designed this study to clarify the correlation between risk factors(patient's background and laboratory data)and skin toxicity( rash and eruption, excluding itch)after administration of either nivolumab or pembrolizumab. From February 2016 to January 2018, we evaluated the clinical outcomes of 54 patients who were administered anti-PD1 antibody. The patients were divided into 2 groups: 9 patients with skin eruption caused by anti-PD1 antibody(skin eruption group)and 45 patients without skin eruption caused by anti-PD1 antibody(non-skin eruption group). Univariate analysis revealed a significant difference in eosinophil counts in both the groups before anti-PD1 antibody administration(>300/µL)(p=0.020). Factors with p<0.2 in the univariate analysis and 4 factors, age(<65 years of age), sex(male), allergy(+), and pembrolizumab, likely to be related to the appearance of skin eruption, were examined by multivariate analysis. Consequently, eosinophil count before anti-PD1 antibody administration(>300/µL)was identified as a risk factor (odds ratio: 9.530, 95% confidence interval: 1.260-71.80). In conclusion, we suggest that cases with an increased eosinophil count before anti-PD1 antibody administration(>300/µL)may be associated with the appearance of skin eruption.

[Construction and Evaluation of a New Support System for Prescription Inspection of Anticancer Drug Injection Preparation via Quality Control].

Using electronic medical charts at the department of pharmacy of Gifu Municipal Hospital, we constructed a new support system for the prescription inspection of anticancer drug injection preparation via quality control. The system comprises: (1)a "regimen inspection sheet" that can be easily used to check the regimen and clinical laboratory data of patients before the administration of anticancer drugs and(2)an "instruction sheet confirming implementation" that can conveniently confirm the latest clinical laboratory data used to decide the administration of anticancer drugs. Using this system, the safety of anticancer drug administration and work efficiency may be improved.

Medical and economic factors influencing generic drug use in the Japanese public health system: Influencing factors in different populations.

Factors influencing generic drug use must be considered when new drug policies are established and initiatives are implemented to promote generic drug use. This study was conducted to elucidate medical and economic factors that influence generic drug use in the Japanese public health system by evaluating the degree of generic drug use via a multivariate analysis. We conducted a retrospective study of medications administered to inpatients at Gifu Municipal Hospital (Japan) from November 1 to 14, 2014. Details of inpatients (age, sex, and type of medical insurance) and the drugs administered (prescribing institution, dispensing pharmacy, price, and class) were assessed. A total of 1409 drugs (original, 639; generic, 770) were analyzed. Multivariate analysis showed significant differences in out-of-pocket medical fees [odds ratio (OR), 0.595], drugs prescribed at Gifu Municipal Hospital (OR, 1.811), drugs prepared at a health insurance pharmacy (OR, 1.541), drugs containing the same active substances as in the generic drugs used at Gifu Municipal Hospital (OR, 3.712), and drugs costing ≥30 yen and containing the same active substance/having the same specifications (OR, 0.516). Drugs prescribed at a large key hospital in the community with high adoption rates of generic drugs, drugs containing the same active substances as the generic drugs adopted by the hospital, and drugs prepared at health insurance pharmacies contributed to a more frequent use of generic drugs. By contrast, out-of-pocket medical fees and being prescribed expensive drugs contributed to the less frequent use of generic drugs.

[Predictors of Nivolumab-Induced Skin Reactions].

Skin reactions to nivolumab are typical immune-related adverse events. We investigated the relation between patient background and test values before nivolumab administration and skin reactions. From February 2016 to February 2017, we evaluated the clinical outcomes of 21 patients who were administered nivolumab. Patients were divided into 2 groups: 3 cases of skin reactions to nivolumab(skin reaction group)and 18 cases without skin reactions to nivolumab(non-skin reaction group). In the skin reaction group, the numbers of eosinophils and basophils before nivolumab administration were significantly higher than those in the non-skin reaction group(p=0.0015 and p=0.0075, respectively). It was suggested that the numbers of eosinophils or basophils before nivolumab administration might be associated with the appearance of skin reactions.

Establishing an Indicator of Hypokalemia in Patients Receiving Anti-Epidermal Growth Factor Receptor Antibodies.

Risk factors for hypokalemia were analyzed in patients who received anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR MoAbs) at Gifu Municipal Hospital between February 2010 and March 2013. Subjects were 51 patients (27 men and 24 women) with the median age (interquartile range) of 66 (63-72) years. The study period started from the initiation of anti-EGFR MoAbs administration and ended 4 weeks after administration was completed. Patients were categorized into the side effect group if both minimum serum potassium (Min S-K) grade and b grade (pre-treatment S-K grade-Min S-K grade) were B1; otherwise, they were placed into the no side effect group. Univariate analysis for factors to prevent the side effect identified the "concomitant use of hyperkalemia-inducing drugs" to be statistically significant (p=0.010). Multivariate analysis was conducted on factors with a p value of <0.25 in the univariate analysis and on "concomitant use of hyperkalemia-inducing drugs," which was likely to clinically affect S-K decrease, although its p value was >0.25. It showed that "concomitant use of hyperkalemia-inducing drugs" was a significant risk-prevention factor (odds ratio: 0.138, 95% confidence interval[CI]: 0.033-0.581, p=0.007). In conclusion, "concomitant use of hyperkalemia-inducing drugs" is a factor associated with preventing hypokalemia accompanying anti-EGFR MoAbs administration.

The Establishment of Indicators of Thrombocytopenia in Patients Receiving Lenalidomide Therapy.

The onset of thrombocytopenia and related factors was analyzed in patients with multiple myeloma (MM) who were receiving lenalidomide (Len) therapy at the Department of Hematology, Gifu Municipal Hospital between July 2010 and March 2014. We included 28 MM patients (18 males and 10 females) with a median age of 70.5 (range: 55-84) years. The patients were examined from the start of Len therapy until treatment discontinuation, prolongation, or dose reduction. A significant correlation was observed between platelet (Plt) count prior to the start of Len therapy (pre-treatment Plt) and the difference between pre-treatment Plt and the minimum Plt up to the point in time of treatment discontinuation, prolongation, or dosage reduction (min-Plt) (r=0.674, p<0.001). Univariate analysis revealed that factors causing thrombocytopenia of grade 2or above as a side-effect showed a significant difference when the Plt count was below the lower limit of the normal value (<14.0×10(4)/µL)(p=0.011). Factors with p<0.25 in the univariate analysis and daily dosage of Len were examined by multivariate analysis; thus, a Plt count below the lower limit of the normal value was identified as a factor (odds ratio: 15.12, 95% confidence interval [CI]: 1.712-133.5, p=0.015). In conclusion, we suggest that a Plt count below the lower limit of the normal value prior to the start of Len therapy is a prognostic factor for thrombocytopenia as a side-effect of Len therapy.

[A female chronic myeloid leukemia patient who gave birth after stopping imatinib intentionally but who maintained a major molecular response with interferon].

Imatinib was administrated to a 38-year-old woman with chronic myeloid leukemia(CML). A major molecular response (MMR)(≤5 copies/0.5 µgRNA in Amp-CML detected using the transcription mediated amplification/hybridization protection assay(TMA/HPA)method)was achieved in 18 months. She maintained MMR for 10 months, and wished to become pregnant. Imatinib was stopped intentionally because she wished to plan a pregnancy, but we prescribed interferon alpha (IFN-a)due to the likelihood of the CML recurring after pregnancy. The nausea caused by IFN-a was improved by administrating it during the night, and she gave birth to a healthy baby by a normal delivery, whilst maintaining MMR. In this case, IFN-a treatment gave good clinical results, the patient's prognosis was improved, and she could maintain a good quality of life. We consider this to be an informative example of IFN-a therapy for CML during pregnancy.

[Analysis of factors influencing the occurrence of infusion reaction after initial treatment with rituximab].

We investigated factors influencing the occurrence of infusion reactions after initial treatment with rituximab. We included patients who were administered rituximab for the treatment of B-cell non-Hodgkin's lymphoma at the Gifu Municipal Hospital Hematology from February 2010 to March 2013. Fifty-one patients were included; their median age was 72(44-87)years, and 31 were men and 20 were women. We defined the index of infusion reaction as the maximal change in body temperature within 24 hours from the administration of rituximab and evaluated the correlation with change in body temperature and each factor, and differences of change in body temperature between the upper and lower groups divided by standard value of each factor by using the t test without correspondence. The "2,000 U/mL or less group"of soluble interleukin-2 receptor(sIL- 2R)levels and the "over 2,000 U/mL group"showed significant different(p=0.014). The "double value or less group"of a standard value(211 IU/L)and "over double value group"showed significantly different lactate dehydrogenase(LDH)levels (p=0.017). The "lower limit or less group"of the standard value(men: 13 g/dL, women: 12 g/dL)and the "over lower limit group"showed significantly different hemoglobin(Hb)levels(p=0.020). In conclusion, the levels of sIL-2R, LDH, and Hb may predict the occurrence of infusion reaction after the initial administration of rituximab in patients with B-cell non-Hodgkin's lymphoma.

The adoption of generic drugs by a hospital: effects on drug dispensation among community pharmacies.

BACKGROUND: The objective of the current study is to elucidate the effect that the adoption of generic drugs by a large hospital has on the dispensation of generic drugs by community pharmacies. We evaluated the percentage of generic drugs dispensed by pharmacies and the cost of drugs dispensed before and after the adoption of generic drugs by a large hospital. METHODS: Participants comprised patients who were admitted to Gifu Municipal Hospital prior to its adoption of generic drugs (November 1, 2013 to November 14, 2013) and after its adoption (November 1, 2014 to November 14, 2014) and who utilized generic drugs dispensed by pharmacies. RESULTS: Results indicated that the pre-adoption dispensation rate of generic drugs by pharmacies was 48.3% (477/926 drugs), while the post-adoption rate was 57.7% (604/1046 drugs), indicating an increase of 9.4 points (P < 0.001). Furthermore, an investigation into the price paid for generic drugs as a percentage of the total price paid for all drugs indicated the following: the pre-adoption percentage was 23.5% (9756/41,461 yen), and the post-adoption percentage was 34.1% (19,221/56,438 yen), indicating an increase of 10.6 points (P < 0.001). CONCLUSIONS: The results of this study revealed that the adoption of generic drugs by a hospital may promote the use of generic drugs by pharmacies and lead to reduced medical costs as well.