[Administration Period of Olanzapine as an Antiemetic Drug for Patients on FEC Therapy-A Survey].

Olanzapine(OLZ)is a multi-acting receptor-targeted antipsychotic drug approved in Japan in December 2017 for the treatment of anticancer drug-induced nausea and vomiting. However, the recommended doses and administration periods of OLZ in the literature and guidelines are varied. Reports on the efficacy and safety of OLZ combined with perioperative chemotherapy for breast cancer in Japanese patients are few. Moreover, the risk of nausea and vomiting during treatment with anticancer drugs in young and women patients remains to be high. In this study, we conducted an exploratory survey on the optimal duration of OLZ administration(days 1-4: 5 mg, before sleep)during perioperative breast cancer 5-fluorouracil, epirubicin, cyclophosphamide(FEC)therapy. We found that treatment with OLZ showed efficacy in improving nausea grade and maintaining relative dose intensity. Moreover, it could be used safely without interruption due to side effects, such as weight gain, elevation in blood glucose, somnolence, and insomnia. Prophylactic antiemetic therapy with OLZ administration (days 1-4: 5 mg)prior to sleep was effective in patients having FEC therapy-induced nausea and vomiting.

Visualization of cross-resistance between antimicrobial agents by asymmetric multidimensional scaling.

WHAT IS KNOWN AND OBJECTIVE: In our previous studies, we developed a cross-resistance rate (CRR) correlation diagram (CRR diagram) that visually captures the magnitude of CRRs between antimicrobials using scatter plots. We used asymmetric multidimensional scaling (MDS) to transform cross-resistance similarities between antimicrobials into a 2-dimensional map and attempted to visually express them. We also explored the antibiograms of Pseudomonas aeruginosa before and after the transfer to newly built hospitals, and we determined by the CRR diagram that the CRRs among ß-lactam antimicrobials other than carbapenems decreased substantially with the facility transfer. The present study tests whether the analysis of CRRs by asymmetric MDS can be used as new visual information that is easy for healthcare professionals to understand. METHOD: We tested the impact of changes in the nosocomial environment due to institutional transfers on CRRs among antimicrobials in asymmetric MDS, as well as contrasted the asymmetric MDS map and CRR diagram. RESULTS AND DISCUSSION: In the asymmetric MDS map, antimicrobial groups with the same mechanism of action were displayed close together, and antimicrobial groups with different mechanisms of action were displayed separately. The asymmetric MDS map drawn solely for antimicrobials belonging to the group with the same mechanism of action showed similarities to the CRR diagram. Also, the distance of each antimicrobial to other antimicrobials shown in the asymmetric MDS map was negatively correlated with the CRRs for them against that antimicrobial. WHAT IS NEW AND CONCLUSION: The asymmetric MDS map expresses the dissimilarity as distances between agents, and there are no meanings or units on the ordinate and abscissa axes of the output map. In contrast, the CRR diagram expresses the antimicrobials' resistance status as values, such as resistance rate and CRR. By analysing the CRRs in the asymmetric MDS, it is feasible to visually recognize cross-resistance similarities between antimicrobial groups as distances. The use of the asymmetric MDS combined with the CRR diagram allows us to visually understand the resistance and cross-resistance status of each antimicrobial agent as a 2-dimensional map, as well as to understand the trends and characteristics of the data by means of quantitative values.

Monitoring antimicrobial cross-resistance with cross-resistance rate correlation diagrams: Changes in antibiotic susceptibility of Pseudomonas aeruginosa due to hospital relocation.

WHAT IS KNOWN AND OBJECTIVE: Though most medical institutions calculate antimicrobial susceptibility and resistance rates of microbes isolated at their own facility as part of their efforts to promote the proper use of antibiotics, very few, if any, regularly monitor cross-resistance rates between antimicrobial agents. The authors have devised a tool in the form of a cross-resistance rate correlation diagram (CRR diagram) that allows easy identification of increases or decreases in, or changes in the pattern of, antimicrobial cross-resistance. The objective was to perform an analysis by CRR diagrams of the effect of relocation to a newly built facility on antimicrobial resistance and cross-resistance rates at a medical facility. METHODS: The Sakai City Medical Center relocated in July 2015 to a newly built facility located in a different primary medical care zone 3.5 km away. Based on the drug susceptibility test data compiled at the Sakai City Medical Center, resistance and cross-resistance rates of Pseudomonas aeruginosa before and after the relocation of the hospital facility were calculated, and the rates were assessed using CRR diagrams. RESULTS AND DISCUSSION: It was possible to confirm the effect of hospital relocation on antibiotic susceptibility of P aeruginosa in terms of changes in resistance and cross-resistance rates. The effect of the facility's relocation on cross-resistance rates was particularly notable with respect to ß-lactam antibiotics: cross-resistance rates among ß-lactams decreased substantially, represented as a large wedge-shaped change towards the origin on the CRR diagram. Rates of cross-resistance between classes of antibiotics with a different mechanism of antibiotic action changed little. WHAT IS NEW AND CONCLUSION: Including cross-resistance rates in the routine monitoring of resistance and susceptibility rates practiced by a medical institution can provide a comprehensive insight into the dynamics of bacterial flora in the facility. CRR diagrams, which allow visualization of the status and changes in cross-resistance, not only provide a new perspective for clinicians, but they also contribute to the proper use of antibiotics and serve as a tool in the education of healthcare professionals and students about antibiotic resistance.

Analysis of the predictive factors for a critical illness of COVID-19 during treatment － relationship between serum zinc level and critical illness of COVID-19.

OBJECTIVES: Because most severely ill patients with COVID-19 in our hospital showed zinc deficiency, we aimed to examine the relationship between the patient's serum zinc level and severe cases of COVID-19. METHODS: Serum zinc <70 µg/dL was defined as the criterion for hypozincemia, and patients continuously with serum zinc <70 µg/dL were classified in the hypozincemia cohort. To evaluate whether hypozincemia could be a predictive factor for a critical illness of COVID-19, we performed a multivariate analysis by employing logistic regression analysis. RESULTS: Prolonged hypozincemia was found to be a risk factor for a severe case of COVID-19. In evaluating the relationship between the serum zinc level and severity of patients with COVID-19 by multivariate logistic regression analysis, critical illness can be predicted through the sensitivity and false specificity of a ROC curve with an error rate of 10.3% and AUC of 94.2% by only two factors: serum zinc value (P = 0.020) and LDH value (P = 0.026). CONCLUSIONS: Proper management of the prediction results in this study can contribute to establishing and maintaining a safe medical system, taking the arrival of the second wave, and the spread of COVID-19 in the future into consideration.

Influence of analysis conditions for antimicrobial susceptibility test data on susceptibility rates.

BACKGROUND: To support effective antibiotic selection in empirical treatments, infection control interventions, and antimicrobial resistance containment strategies, many medical institutions collect antimicrobial susceptibility test data conducted at their facilities to prepare cumulative antibiograms. AIM: To evaluate how the setpoints of duplicate isolate removal period and data collection period affect the calculated susceptibility rates in antibiograms. METHODS: The Sakai City Medical Center is a regional core hospital for tertiary emergency medical care with 480 beds for general clinical care. In this study, all the Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae isolates collected at the Sakai City Medical Center Clinical Laboratory between July 2013 and December 2018 were subjected to antimicrobial susceptibility tests and the resulting data was analyzed. FINDINGS: The longer the duplicate isolate removal period, the fewer the isolates are available for every bacterial species. Differences in the length of the duplicate isolate removal period affected P. aeruginosa susceptibility rates to ß-lactam antibiotics by up to 10.8%. The setpoint of the data collection period affected the antimicrobial susceptibility rates by up to 7.3%. We found that a significant change in susceptibility could be missed depending on the setting of the data collection period, in preparing antibiogram of ß-lactam antibiotics for P. aeruginosa. CONCLUSIONS: When referring to antibiograms, medical professionals involved in infectious disease treatment should be aware that the parameter values, such as the duplicate isolate removal period and the data collection period, affect P. aeruginosa susceptibility rates especially to ß-lactam antibiotics. And antibiogram should be updated within the shortest time period that is practically possible, taking into account restrictions such as numbers of specimen.

Drug-induced lung disease adverse effect with Ledipasvir Acetonate/Sofosbuvir.

BACKGROUND: Interferon and ribavirin have been used as therapeutic agents for chronic hepatitis C infection or C-compensated cirrhosis in the conventional treatment. Hepatitis C virus (HCV) -specific direct-acting antiviral agents that directly inhibit the growth process of HCV have been approved since 2011. However, in the early post-marketing vigilance phase of ledipasvir acetonate/sofosbuvir (LDV/SOF), there were reports of interstitial lung disease in 4 out of 32,700 cases with death in 1 case; the onset mechanism is unknown. CASE PRESENTATION: Treatment for hepatitis C was deemed to be necessary, and the patient was referred to our hospital. Oral administration of LDV/SOF was started. On day 8 of administration, a fever of 38-39 °C and coughing were observed followed by the gradual appearance of shortness of breath. As there was no improvement, the patient visited her primary care physician on day 16 of administration and the patient was brought urgently to our hospital on the same day. Blood tests and imaging tests were conducted at our hospital on the day of emergency transport; inflammatory response markers showed abnormal values, and sialylated carbohydrate antigen Krebs von den Lungen-6 was within the normal value range at 303 U/mL. Because the possibility of infection was low based on results of imaging and bronchoalveolar lavage, drug-induced lung disease was suspected, LDV/SOF administration was discontinued, and steroid administration was started. Following steroid pulse therapy, treatment with oral prednisolone tablets was gradually tapered. The patient's symptoms were relieved and she was discharged. CONCLUSIONS: The patient's medication history in this case indicated that there were no drugs taken before or after administration of LDV/SOF until the adverse reaction occurred, and there were no supplements or dietary supplements taken. Therefore, LDV/SOF has been proposed as the cause of the suspected adverse effect. Pharmacists should try to collect adverse effect reports to identify adverse effects early.

[Eye Disorders Associated with S-1 Chemotherapy in Gastric Cancer Patients].

Eye disorders are one of the characteristic adverse events associated with S-1 chemotherapy. In this retrospective study, we investigated the frequency and outcome of eye disorders associated with S-1 chemotherapy in gastric cancer patients. This retrospective study included 75 advanced gastric cancer patients who received S-1 monotherapy between January 2014 and December 2015. We retrospectively evaluated the frequency, Grade, and treatment of eye disorders. Eye disorders were observed in 16 patients(21%). The median time of onset was 3(range, 1-8)months. Grade 2 watering eyes, eye discharge, and conjunctivitis were reported in 14, 8, and 4 patients, respectively. Artificial tears, fluorometholone eye-drops, and both of these treatments were used in 7, 1, and 8 patients, respectively. Ophthalmologic examination was performed for 3 patients. No delay or reduction of S-1 therapy was required for the eye disorders. Eye disorders associated with S-1 therapy in gastric cancer patients did not affect treatment if managed properly using eye drops.

[Examination of factors influencing continuity of S-1 adjuvant chemotherapy for gastric cancer patients].

After Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer(ACTS-GC), adjuvant chemotherapy with S-1 is a standard treatment for stage II or III gastric cancer patients. In this study, we retrospectively examined factors that influence the continuity of S-1 adjuvant chemotherapy. We analyzed the clinical documentation of 27 gastric cancer patients being treated with S-1 adjuvant chemotherapy. Patients who completed the treatment without reduction dose were classified into a complete group(n=14), and those for whom S-1 was discontinued or reduced due to adverse reactions were classified into a reduced/discontinuation group(n=13). First, we examined the background factors at baseline between these two groups. Univariate logistic regression analysis revealed that the operative procedure, leukocyte count, and serum creatinine level at baseline were identified as factors that influence the continuity of S-1 chemotherapy. Next, we investigated the hematological and nutritional conditions of these patients during the treatment period. The loss of body mass index(BMI)during the treatment period was remarkable in the reduced/discontinuation group regardless of the operative procedure. This result suggests that an early nutritional intervention might be important for gastric cancer patients undergoing S-1 adjuvant chemotherapy.

[Gastrojejunostomy followed by chemotherapy with S-1 in unresectable gastric cancer with pyloric stenosis].

We investigated the efficacy of gastrojejunostomy followed by S-1-based chemotherapy for unresectable gastric cancer with pyloric stenosis. We performed gastrojejunostomy and S-1-based chemotherapy in 14 unresectable gastric cancer patients with gastric outlet obstructions between April 2006 and June 2010. Although there were two complications after surgery, no treatment-related deaths were observed. The response rate of the S-1-based chemotherapy was 41.7%, and the median survival after surgery was 12.3 months. All patients were tolerating a regular diet and a significant improvement in oral intake lasted for at least 6 months. In conclusion, gastrojejunostomy followed by chemotherapy with S-1 appears to be an effective treatment modality for unresectable gastric cancer with pyloric stenosis. It enables us to practice S-1-based standard chemotherapy for advanced gastric cancer and improve the quality of life of patients.

[Examination of continuity of S-1 adjuvant chemotherapy for gastric cancer patients after gastrectomy].

Next to ACTS-GC (Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer), adjuvant chemotherapy with S-1 is the standard treatment for stage II or III gastric cancer patients.In this study, we retrospectively examined the continuity and adverse reaction of S-1 adjuvant chemotherapy in 30 gastric cancer patients who visited our hospital from 2007 to 2008, and compared them with those of patients treated with ACTS-GC. Whereas the persistent rate of S-1 adjuvant chemotherapy for one year in ACTS-GC was 65.8%, it was 86.7% in our hospital.The RP (Relative performance) value in cases who completed S-1 adjuvant therapy for one year in ACTS-GC and for one year in our hospital was 81.2% and 88.5%, respectively. Grade 3/4 adverse events in our hospital were leukopenia (3.3%), neutropenia (16.7%), and anorexia(6.7%). In conclusion, our hospital has shown a far greater continuity with S- 1 adjuvant chemotherapy than with ACTS-GC, a result suggesting that S-1 adjuvant chemotherapy is feasible in clinical practice.

[A case of paclitaxel-induced peripheral neuropathy successfully treated by H2-blocker, lafutidine].

We report a 75-year-old female gastric cancer patient with paclitaxel-induced peripheral neuropathy, which was successfully treated by the H2-blocker, lafutidine. From December 2007, she underwent second-line chemotherapy using paclitaxel (80 mg/m/2 day 1, 7, 14/28 days) for peritoneal dissemination which had been refractory to first-line chemotherapy using S-1 (80 mg/m / 2, day 1-28/42 days). After 2 courses, CT showed a complete response (CR) of the peritoneal dissemination. However, at the same time peripheral neuropathy appeared, which was aggravated to grade 3 at the 6th course. Beginning with the 7th course, we administered lafutidine (10 mg/day) for peripheral neuropathy, which recovered to grade 1 after 14 days of lafutidine administration. Lafutidine was administered until July 2008, when peripheral neuropathy kept grade 1 without lafutidine. After 9 courses, paclitaxel therapy failed because of general fatigue.

[A case of bleeding tendency due to warfarin in a patient treated with chemotherapy by S-1].

A 82-year-old male patient had suffered from a cancer of the papilla of Vater. After the operation, he received 4 courses of gemcitabine(GEM)adjuvant chemotherapy and warfarin(WF)administration because of thrombosis in the left internal jugular vein. Since the tumors re-grew, GEM was discontinued, and chemotherapy including S-1 and GEM was examined. However, the chemotherapy could not be continued because of edema in both lower legs and tassel midway in the 2nd course. Because of a bleeding tendency(non-measurable INR(international normalized ratio of prothrombin time)), WF administration was discontinued on the 11th day after S-1/GEM combined therapy was suspended. On the following day, although the INR value recovered to 1.7, it gradually worsened and the symptoms of pulmonary embolism developed on the 13th day. Then, INR was controlled by continuous infusion of heparin. Since the INR level decreased after that, in addition to heparin, re-medication of WF was performed. We tried to analyze the genotype of a patient, who had a tendency to bleed by coadministration of WF with S-1, in terms of hepatic cytochrome P-450(CYP)2C9 and vitamin K epoxide reductase complex subunit 1(VKORC1). We also measured the plasma concentration of S-and R-WF by HPLC after obtaining informed consent from the patient. We found that he is homozygous for CYP2C9 1/1 and for A/A of VKORC1(-1639G>A). The obtained data did not show the abnormalities of blood coagulation. Because the genotype of a patient with a tendency to bleed was a major type in a Japanese population, fine monitoring of INR is required in order to prevent side effects of blood coagulation by S-1 and WF coadministration, regardless of patient genotypes.

[Management of hand-foot syndrome in patient treated with capecitabine].

Capecitabine is one of the most effective oral regimens of chemotherapy against advanced or recurrent breast cancer. In addition, capecitabine could widely be used for treatment of colon cancer. It appears that more patients will be administered capecitabine because of its QOL benefits. However, Hand-Foot Syndrome(HFS)may appear to be about 50% of the patients who take this regimen. As a result, the patient's QOL is hindered and led to a reduction of the dosage or discontinuation of the treatment depending on the grade of adverse event. This time, we evaluated the efficacy of topical emollients, creams and vitamin B6 for prevention and reduction of HFS symptoms for patients who received capecitabine. We found the efficacy of preventative measures that the occurrence of HFS grade 1 or above could be decreased and delayed. We also noticed that these preventative measures appear to be decreased the occurrence of HFS grade 2 or above, which led to a reduction of dosage or discontinuation of the treatment. For continuation and completion of the treatment and securing of patient's QOL, the supportive measures are needed to control a variety of side effects, such as HFS and others, and a team care support is indispensable.