Clinical impact of monitoring frequency per day as a prospective audit and feedback strategy for patients receiving antimicrobial agents by injection.

BACKGROUND: Implementation of antimicrobial stewardship programmes improve antimicrobial therapies and thus result in better patient outcomes and safety. The impact of prospective audit and feedback (PAF) is likely dependent on how frequently it is conducted, and how quickly after antibiotic prescription it is initiated. To our knowledge, however, no report has yet investigated the impact of an increase in monitoring frequency per day on PAF strategy. Here, we evaluated the clinical impact of an increase in monitoring frequency per day as a PAF strategy in patients receiving antimicrobial injections. METHODS: We conducted a single-centre, retrospective observational pre-post study to evaluate the impact of increasing the frequency of monitoring from once daily (once daily review group) to twice daily (twice daily review group). Time to intervention and clinical outcomes were compared before and after implementation of twice daily review. RESULTS: Time to intervention for inappropriate antimicrobial therapy was significantly shorter in the twice daily review group than the once daily review group (5.1 ± 6.1 hours vs 29.9 ± 21.5 hours, HR: 4.53, 95% CI: 2.90-7.07, P < .001). The twice daily review group had a significantly lower rate of clinical failure (16.2% vs 38.3%, P = .004) and hepatotoxicity (4.1% vs 15.0%, P = .035) than the once daily review group. CONCLUSIONS: An increase in monitoring frequency from once daily to twice daily significantly shortened the time to intervention for inappropriate antimicrobial therapy, with a concomitant reduction in clinical failure and hepatotoxicity.

Anorexia, pain and peripheral neuropathy are associated with a decrease in quality of life in patients with advanced pancreatic cancer receiving outpatient chemotherapy - a retrospective observational study.

BACKGROUND: Cancer chemotherapy usually improves clinical outcomes in patients with advanced pancreatic cancer (APC), but can also cause moderate-to-severe adverse events (AEs). We investigated the relationship between moderate-to-severe AEs and quality of life (QOL) in patients with APC who received outpatient chemotherapy. METHODS: We recruited APC patients who received outpatient chemotherapy in Gifu University Hospital between September 2017 and December 2018. Adverse events related to chemotherapy were assessed by a pharmacist collaborating with a physician using common terminology criteria for AEs (CTCAE) ver 4.0, and QOL of patients was self-assessed by patients using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L Japanese edition 2). Associations between the EQ-5D-5L utility value and serious AEs were assessed using proportional odds logistic regression. RESULTS: A total of 59 patients who received 475 chemotherapy cycles were included. The proportional odds logistic regression indicated that grade ≥ 2 anorexia, pain and peripheral neuropathy were significantly correlated with a decreased EQ-5D-5L utility value. Pharmaceutical intervention for these AEs significantly improved the patients' EQ-5D-5L utility value. CONCLUSIONS: Anorexia, pain and peripheral neuropathy were significantly associated with a decrease in QOL. It is assumed that appropriate pharmaceutical intervention with particular emphasis on these AEs can improve the QOL of pancreatic cancer patients receiving outpatient chemotherapy.

Albumin-bilirubin score for predicting neuropsychiatric symptoms in patients receiving ifosfamide-based chemotherapy.

WHAT IS KNOWN AND OBJECTIVE: Ifosfamide, an alkylating agent, is widely used in the treatment of malignant diseases. However, these treatments are often limited due to the incidence of neuropsychiatric symptoms such as delirium, seizures, hallucinations and agitation. In this study, we examined risk factors for neuropsychiatric symptoms in patients receiving ifosfamide-based chemotherapy. METHODS: The study cases were patients with cancer receiving ifosfamide-based chemotherapy between April 2007 and March 2018. Risk analysis for ifosfamide-related neuropsychiatric symptoms was determined by time-dependent Cox proportional hazard regression analysis. RESULTS AND DISCUSSION: Of 183 eligible patients, 32 patients (17.5%) experienced ifosfamide-related neuropsychiatric symptoms. Time-dependent Cox proportional hazard model showed that the albumin-bilirubin (ALBI) score was significantly correlated with the incidence of ifosfamide-related neuropsychiatric symptoms (hazard ratio [HR] =1.45, 95% confidence interval [CI] = 1.05-2.01, p = 0.025). Additionally, there were correlations between the predicted risk of neuropsychiatric symptoms and ifosfamide-dose per cycle (HR =0.51, 95% CI = 0.27-0.94, p = 0.030) and creatinine clearance (Ccr) (HR = 0.53, 95% CI = 0.28-1.00, p = 0.050). In contrast, neither serum albumin nor total bilirubin was a significant risk factor for neuropsychiatric symptoms. WHAT IS NEW AND CONCLUSION: These findings indicate that ALBI score may be a useful biomarker for predicting neuropsychiatric symptoms in patients receiving ifosfamide-based chemotherapy.

Real-world data of the association between quality of life using the EuroQol 5 Dimension 5 Level utility value and adverse events for outpatient cancer chemotherapy.

BACKGROUND: Outpatient cancer chemotherapy may lead to improved quality of life (QOL) by allowing treatment to continue without impairing the social lives of patients compared with hospitalization. However, the occurrence of serious adverse events may cause a decline in QOL. We investigated the relationship between outpatient chemotherapy-induced adverse events and QOL. METHODS: A single-center retrospective descriptive study was conducted in patients who received outpatient chemotherapy at Gifu University Hospital (Gifu, Japan) between September 2017 and December 2018. The utility values of QOL, type and severity of adverse events, type of cancer, chemotherapy regimen, and other patient demographics were analyzed. Adverse events were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. QOL was evaluated using the Japanese version of the EuroQol 5 Dimension 5 Level (EQ-5D-5L). Associations between the EQ-5D-5L utility value and serious adverse events were assessed using adjusted (age and sex) odds ratios obtained with a proportional odds logistic regression model. RESULTS: Data from 1008 patients who received 4695 chemotherapy cycles were analyzed. According to proportional odds logistic regression, the adverse events that significantly correlated with a decreased EQ-5D-5L utility value were malaise, edema of the limbs, peripheral neuropathy, pruritus, and dry skin. Based on the proportional odds logistic analysis, neither cancer type nor anticancer drugs were significantly correlated with the EQ-5D-5L utility value in patients who received chemotherapy. Pharmaceutical care for peripheral neuropathy significantly improved patients' EQ-5D-5L utility value from 0.747 to 0.776 (P < 0.01). CONCLUSIONS: Adverse events (i.e., peripheral neuropathy, malaise, and edema of the limbs) are significantly correlated with a decrease in QOL, regardless of the type of cancer or anticancer drugs used. Pharmaceutical care provided by pharmacists in collaboration with physicians may improve QOL.

Clinical efficacy of osimertinib for a patient with ileus due to peritoneal carcinomatosis.

We report a patient of stage IV lung adenocarcinoma who developed ileus due to peritoneal carcinomatosis. We placed an ileus tube and started an oral intake of osimertinib. Within one month, the tumor had shrunk, and the ileus was controlled.

Optimal dose of sunitinib for long-term treatment in Japanese patients with renal cell carcinoma.

BACKGROUND/AIM: Sunitinib is used for the treatment of metastatic renal cell carcinoma (mRCC). Asian patients, including Japanese, tend not to tolerate long-term sunitinib therapy of 50 mg p.o. once daily for 4 weeks, followed by 2 week off treatment due to severe adverse events at this dosage level. The aim of this retrospective study was to investigate the optimal dose of sunitinib for long-term continuation in Asian patients with mRCC. PATIENTS AND METHODS: The study cases were 50 patients with mRCC who were treated with sunitinib between June 2008 and December 2017. Risk analysis for "unacceptable" adverse events (depending on the physician, ranging from grade 2 to ≥ grade 3) leading to discontinuation of sunitinib was determined by time-dependent Cox proportional hazard regression analysis. RESULTS: A total of 54 unacceptable adverse events leading to discontinuation occurred. Multivariable analysis indicated that a sunitinib dose of ≤ 37.5 mg/day significantly reduced the risk of discontinuation due to adverse events in comparison with 50 mg/day [hazard ratio (HR) 0.08, 95% confidence interval (CI) 0.03-0.21, p < 0.001). The progression-free survival (PFS) with a sunitinib dose ≤ 37.5 mg/day was longer than that associated with a dose of 50 mg/day, albeit not to a statistically significant degree (120 days for ≤ 37.5 mg/day vs 41 days for 50 mg/day, HR 0.39, 95% CI 0.10-1.44, p = 0.157). CONCLUSION: Our findings suggest that the optimal dose of sunitinib for Asian, including Japanese, patients with mRCC is ≤ 37.5 mg/day.

Effects of pharmacokinetics-related genetic polymorphisms on the side effect profile of afatinib in patients with non-small cell lung cancer.

OBJECTIVES: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) represent the first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer. Afatinib is a second-generation EGFR-TKI with excellent therapeutic effects. However, severe diarrhea and skin disorders are observed at high frequencies, often leading to treatment interruption because of low quality of life (QOL). The relationship between individual variations and the onset of these side effects remains to be elucidated. This study aimed to reveal the association among these side effects, pharmacokinetics, and related genetic polymorphisms. MATERIALS AND METHODS: In total, 33 patients were recruited between July 2014 and June 2017. Afatinib plasma concentrations were measured at day 9 when the concentrations reached a steady state (early phase) and when the prescription dose was stable for more than 1 month (stable phase). We analyzed single nucleotide polymorphisms in the genes ATP-binding cassette sub-family B member 1 (ABCB1), ABCG2, and flavin-containing monooxygenase 3. RESULTS: The incidences of both diarrhea and acneiform eruption were greater than 80%. Afatinib plasma concentration and the severity of diarrhea in the early phase were correlated. Pharmacokinetics-related genetic polymorphisms influenced the severity of diarrhea. Particularly, the afatinib plasma concentration was higher and diarrhea was more severe in patients carrying the A allele of ABCG2 C421A. Onset of side effects, genetic polymorphisms, and diarrhea in the maintenance phase or acneiform eruption in the early or maintenance phases were not correlated. The severity of diarrhea is influenced by drug plasma concentrations in the early phase and genetic polymorphisms related to afatinib pharmacokinetics. CONCLUSION: Particular genetic polymorphisms can be screened before afatinib administration and the dose adapted to individual patients can be controlled, leading to reduced side effects, improved QOL, and better patient compliance to maintain the therapeutic effects.

High total bilirubin level is a significant risk factor for severe neutropenia in patients receiving irinotecan-based chemotherapy.

Irinotecan is effective for the treatment of metastatic colorectal cancer (mCRC) and advanced pancreatic cancer (aPC). However, these treatments are often limited due to the incidence of severe neutropenia. We identified risk factors for severe neutropenia in patients with mCRC or aPC, receiving irinotecan-based chemotherapy regimens. The study selected 104 patients (mCRC: 53 and aPC: 51) who received irinotecan-based chemotherapy between January 2014 and May 2018 and who were included in the present study. The initial dose of irinotecan was 150 mg/m2 in all patients, and patients with a lower initial dose of irinotecan were excluded. Severe neutropenia (grade ≥ 3) occurred in 56 patients (53.8%). Multivariable Cox proportional hazards analysis indicated that modified FOLFIRINOX (mFOLFIRINOX) and serum total bilirubin (T-Bil) were significant risk factors for severe neutropenia. Moreover, with receiver-operating characteristic (ROC) curve analysis, the cutoff for T-Bil was found to be 0.7 mg/dL. Among patients treated with mFOLFIRINOX therapy, the incidence of severe neutropenia was significantly higher in patients with high level of T-Bil (> 0.7 mg/dL) than in those without it (93.8% vs 55.0%, P = 0.006). A chemotherapy regimen (modified FOLFIRINOX therapy) and T-Bil > 0.7 mg/dL were significant risk factors for severe neutropenia in patients receiving 150 mg/m2 irinotecan.

Evaluation and Comparison of Daiokanzoto and Lubiprostone for Constipation: A Retrospective Cohort Study.

Daiokanzoto (DKT) and lubiprostone (LPS) are drugs used for constipation, but few studies have compared them. This study examined the effectiveness, adverse events, and medical economic efficiency of DKT and LPS for constipation. Patients who received DKT (DKT group) and those who received LPS (LPS group) during admission to Ogaki Municipal Hospital between November 2012 and May 2016 were enrolled. Drug efficacy was evaluated based on the median value of bowel movement frequency over 1 week before and after drug administration, and their safety was evaluated by the presence or absence of diarrhea, abdominal pain, nausea, and vomiting. To assess medical economic efficiency, drug costs for constipation per week were calculated. The median values (quartile ranges) of bowel movement frequency at 1 week after drug administration were 8.5 (6.0-12.0) in the DKT group and 5 (3.0-7.0) in the LPS group, which was significantly different (p < 0.01). Diarrhea occurred significantly less often in the DKT group (4 cases) than in the LPS group (17 cases) (p < 0.01). The median cost of drugs administered for constipation for 1 week was significantly lower in the DKT group (631 [quartile range, 513-653] yen) than in the LPS group (1431 [1135-2344] yen) (p < 0.01). DKT had a higher immediate effect on constipation and was associated with more frequent bowel movement and fewer adverse events of diarrhea than LPS, suggesting that it may be effective and safe for treating constipation, and DKT is inexpensive.

Single-centre retrospective observational study comparing trough blood concentration and safety of teicoplanin formulations.

Teicoplanin formulations are marketed as antibiotic mixtures with several compounds that share the same core structure. Recent studies conducted in vitro have reported differences in the composition ratio of different teicoplanin products. In this retrospective study, we examined the trough blood concentration of the originator brand and a generic teicoplanin product. Target patients were retrospectively assigned to the originator (Targocid) or generic group. The groups were matched 1:1 using propensity scores. The initial trough blood concentration analysis identified 44 matches. In both groups, the median dosing day for the first measurements was 4, respectively. The initial trough blood concentration of the originator group was significantly higher (mean ± SD, 16.3 ± 4.5 mg/L) than that of the generic group (12.8 ± 4.7 mg/L; 95% CI, -5.4 to -1.6). A significant difference was observed in the frequency of serum creatinine elevation in the study of the frequency of adverse events using Common Terminology Criteria for Adverse Events (originator group, 41.9% vs generic group, 20.9%). In cases where discontinuation was necessary due to side effects, there were three patients in the originator group and one patient in the generic group. This study found that trough blood concentration differed between formulations. Therefore, correction might be necessary while monitoring drug concentration in the blood. Trough blood concentrations are used as surrogate markers for efficacy and safety, so further studies on differences in efficacy and safety between formulations are required.

Clinical impact of matrix-assisted laser desorption ionization-time of flight mass spectrometry combined with antimicrobial stewardship interventions in patients with bloodstream infections in a Japanese tertiary hospital.

BACKGROUND: Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has the potential to permit early organism identification and optimization of antibiotic therapy. However, MALDI-TOF MS combined with antimicrobial stewardship is available at only a limited number of institutions. Here, we evaluated the clinical impact of implementing MALDI-TOF MS combined with antimicrobial stewardship intervention in patients with bloodstream infections. METHODS: We conducted a single-centre, prospective cohort study to evaluate the clinical impact of implementing MALDI-TOF MS combined with antimicrobial stewardship intervention in patients with bloodstream infections. Processes and clinical outcomes in patients with bloodstream infections were compared before and after implementation of MALDI-TOF MS. RESULTS: Compared with the conventional identification method, MALDI-TOF MS combined with antimicrobial stewardship intervention significantly decreased the time to organism identification (48.6 ± 46.0 hours vs 78.1 ± 38.9 hours, P < 0.001), effective antimicrobial therapy (12.9 ± 19.0 hours vs 26.2 ± 44.8 hours, P < 0.001) and optimal antimicrobial therapy (53.3 ± 55.0 hours vs 91.7 ± 88.7 hours, P < 0.001. Moreover, the rate of clinical failure (14.0% vs 33.3%, P < 0.001) and incidence of adverse events (7.5% vs 23.9%, P < 0.001) was lower in the MALDI-TOF MS group than in the conventional identification group. A multivariate Cox proportional hazard analysis indicated that implementation of MALDI-TOF MS was a protective factor against clinical failure in patients with bloodstream infections (hazard ratio, 0.61; 95% confidence interval, 0.38-0.99; P = 0.047). CONCLUSIONS: Implementation of the MALDI-TOF MS combined with antimicrobial stewardship intervention facilitated early optimization of antimicrobial therapy with a remarkable concomitant reduction in clinical failure and adverse events in patients with bloodstream infections.

Rapid attainment of target trough concentrations of tacrolimus for early improvement of clinical symptoms in patients with ulcerative colitis.

WHAT IS KNOWN AND OBJECTIVE: The target trough concentration of tacrolimus for ulcerative colitis is recommended to be 10-15 ng/mL in the initial two weeks and 5-10 ng/mL in the later phase. However, the effectiveness of rapid attainment of these target trough concentrations of tacrolimus in patients with ulcerative colitis is still unclear. In the present study, we evaluated the clinical efficacy and safety of rapid attainment of target trough concentrations of tacrolimus in patients with ulcerative colitis. METHODS: A prospective cohort was conducted at Gifu University Hospital in Gifu, Japan. Hospitalized patients who received tacrolimus for the treatment of ulcerative colitis between April 2009 and March 2017 were enrolled. Since June 2011, the initial loading dose of tacrolimus increased from 0.05 to 0.1-0.2 mg/kg/d, and the maintenance dose to achieve the target trough concentration was determined to be 12.5 ng/mL by proportional calculation with measured blood concentration. The period required to attain target trough concentration and the clinical efficacy before and after dosage modification was compared. RESULTS: The initial dose after dosage modification was significantly increased compared to that before dosage modification (0.10 [0.04-0.22], median [range] mg/kg/d vs 0.05 [0.03-0.05] mg/kg/d, P < 0.001). The period required to attain a target trough concentration over 10 ng/mL was significantly shortened by dosage modification (6 [4-14] days before dosage modification vs 4.5 [2-8] days after modification, P = 0.048). Further, stool frequency score was significantly improved after dosage modification, without affecting the incidence of adverse events. WHAT IS NEW AND CONCLUSION: Our findings suggest that rapid attainment of the target trough concentration of tacrolimus improves clinical symptoms in patients with ulcerative colitis.

Clinical outcome of pharmacist-led prospective audit with intervention and feedback after expansion from patients using specific antibiotics to those using whole injectable antibiotics.

Prospective audit with intervention and feedback (PAF) and preauthorisation of antimicrobials are core strategies for antimicrobial stewardship (AS). PAF participants were expanded from patients using specific antibiotics to those using whole injectable antibiotics to evaluate clinical outcome. From January 2016 to December 2016, PAF was performed in patients using specific antibiotics (period 1) and from January 2017 to December 2017, PAF was performed in patients using whole injectable antibiotics (period 2). PAF was implemented for 5 days every week by pharmacists involved in infectious diseases chemotherapy. In total, 11,571 and 11,103 patients used antibiotic injections during periods 1 and 2, respectively. No significant difference in mortality within 30 days from the initial use of injection antibiotics was observed. The average duration of hospitalisation was significantly shorter during period 2 among patients using antibiotics; however, this was not significantly different from that of patients not receiving antibiotics. The average duration of therapy for intravenous antibiotics was significantly shorter during period 2 than during period 1. The ratio of methicillin-resistant Staphylococcus aureus (MRSA) to S. aureus was significantly low during period 2. The duration of intravenous antibiotic therapy for Escherichia coli bacteraemia during period 2 decreased significantly. De-escalation and appropriate antimicrobial treatment rates at specific doses during period 2 increased significantly. Expansion of patients eligible for PAF from patients using specific antibiotics to patients using whole injectable antibiotics shortened hospital stays, suppressed drug resistance, and promoted the appropriate use of antibiotics.

Influence of renal dysfunction on dose reduction and virologic efficacy of regimens combining ribavirin and all-oral direct acting antivirals in patients with chronic hepatitis C virus infection.

AIM: Several interferon (IFN)-free, all-oral regimens with direct acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection also include ribavirin (RBV). We investigated the influence of renal dysfunction on virologic efficacy and adverse effects in 189 patients with HCV genotype 2 infection who received combination RBV-DAA regimens. METHODS: The incidence of RBV-induced anemia, RBV dose reduction, and virologic efficacy were compared according to baseline renal function as defined by the estimated glomerular filtration rate (eGFR). RESULTS: Patients with renal dysfunction (eGFR = 30-59 mL/min/1.73 m2 ) had higher rate of RBV dose reduction and more marked decreases in hemoglobin levels. These findings were more pronounced in patients with the ITPA CC genotype, who are more sensitive to RBV-induced anemia. Although there were no statistically significant differences in sustained virologic response (SVR) rates according to renal function overall (P = 0.1650), the SVR rate was significantly lower in patients who required RBV dose reduction than in those who did not (P < 0.0001). CONCLUSIONS: Baseline renal dysfunction could unfavorably affect the outcomes of RBV-DAA in patients with chronic HCV infection due to the increased risk of RBV dose reduction, even in the era of IFN-free DAA regimens.

Effect of high-flow high-volume-intermittent hemodiafiltration on metformin-associated lactic acidosis with circulatory failure: a case report.

BACKGROUND: Metformin-associated lactic acidosis is a well-known life-threatening complication of metformin. We here report the case of a patient who developed metformin-associated lactic acidosis without organ manifestations, due to the simultaneous ingestion of an overdose of metformin and alcohol, and who recovered with high-flow high-volume intermittent hemodiafiltration. CASE PRESENTATION: A 44-year-old Asian woman with type 2 diabetes attempted suicide by ingesting 10 tablets of metformin 500 mg and drinking approximately 600 mL of Japanese sake containing 15% alcohol. She was transferred to our emergency department because of disturbed consciousness. Continuous intravenous administration of noradrenalin (0.13 µg/kg per minute) was given because she was in shock. Laboratory findings included a lactate level of 119 mg/dL (13.2 mmol/L), bicarbonate of 14.5 mmol/L, and serum metformin concentration of 1138 ng/mL. She was diagnosed as having metformin-associated lactic acidosis worsened by alcohol. After 4560 mL of bicarbonate ringer (Na+ 135 mEq/L, K+ 4 mEq/L, Cl- 113 mEq/L, HCO3- 25 mEq/L) was administered, high-flow high-volume intermittent hemodiafiltration. (dialysate flow rate: 500 mL/min, substitution flow rate: 3.6 L/h) was carried out for 6 h to treat metabolic acidosis and remove lactic acid and metformin. Consequently, serum metformin concentration decreased to 136 ng/mL and noradrenalin administration became unnecessary to maintain normal vital signs. On hospital day 12, she was moved to the psychiatry ward. CONCLUSIONS: HFHV-iHDF may be able to remove metformin and lactic acid efficiently and may improve the condition of hemodynamically unstable patients with metformin-associated lactic acidosis.

Changes in the quality of medicines during storage under LED lighting and consideration of countermeasures.

BACKGROUND: In recent years, the popularity of LED lighting has rapidly increased, owing to its many advantages, including economic benefits. We examined the change in the quality of drugs during storage under LED and fluorescent lighting and found that some medicines exhibited a different degree of color change depending on the light source. The purpose of this study was to investigate the effects of different plastic storage bags on the color change over time when various medicines were stored under LED and fluorescent lighting conditions. METHODS: Photostability tests were conducted on several types of target drugs. Subsequently, subjective evaluation by ten evaluators and objective evaluation by image analysis software were carried out regarding color change. RESULTS: A similar change in color tone was observed after all types of illumination. Subjective evaluation by 10 evaluators revealed that "change in color tone" occurred in the order of bulb-color LED lighting < daylight-color LED lighting < fluorescent lighting, regardless of the type of plastic bags. A similar tendency was observed also in objective evaluation. In this study, it was considered that a brown light-shielding plastic bag was more effective than a normal plastic bag for the prevention of the color change of medicines stored under LED lighting. CONCLUSIONS: The above results suggested that the most appropriate combination of plastic bag and light source for medicine storage was a brown light-shielding plastic bag and bulb-color LED lighting.

Efficacy and Safety of Daikenchuto for Constipation and Dose-Dependent Differences in Clinical Effects.

BACKGROUND: Daikenchuto (DKT) is a Kampo medicine used for the treatment of constipation. In this study, we evaluated the effectiveness of DKT against constipation. PATIENTS AND METHODS: Thirty-three patients administered DKT for constipation were selected and divided into low-dose (7.5 g DKT; n = 22) and high-dose (15 g DKT; n = 11) groups. We retrospectively evaluated weekly defaecation frequency, side effects, and clinical laboratory data. RESULTS: Median defaecation frequencies after DKT administration (5, 5.5, 5, and 8 for the first, second, third, and fourth weeks, resp.) were significantly higher than that before DKT administration (2) in all 33 cases (P < 0.01). One case (3%) of watery stool, one case of loose stools (3%), and no cases of abdominal pain (0%) were observed. Median defaecation frequencies in the high-dose group (7 and 9) were significantly higher than those in the low-dose group (4 and 3) in the first (P = 0.0133) and second (P = 0.0101) weeks, respectively. There was no significant change in clinical laboratory values. CONCLUSION: We suggest that DKT increases defaecation frequency and is safe for treating constipation.

Evaluation of treatment outcomes of patients with MRSA bacteremia following antimicrobial stewardship programs with pharmacist intervention.

BACKGROUND: Methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) is associated with high mortality and implementing an appropriate antimicrobial stewardship (AS) program with treatment intervention is essential. The aim of this study was to evaluate the impact of AS with pharmacist intervention on patients with MRSA-B. METHODS: Patients who were diagnosed with MRSA-B between January 2012 and April 2013 were defined as the pre-intervention group, while those diagnosed between May 2013 and December 2015 were defined as the intervention group (ie, AS with pharmacist intervention). The factors affecting bundle compliance rates and mortality were analysed. RESULT: The pre-intervention group comprised 43 patients and the intervention group comprised 51 patients. Bundle compliance rates were estimated as follows in the intervention group: an increase was observed in the appropriate duration of therapy (from 44.8% to 72.1%, P = .027), incidences of the early use of anti-MRSA drugs (from 62.3% to 82.4%, P = .038), and the number of negative follow-up blood cultures (from 40.0% to 80.0%, P < .001), and a decrease was observed for 30-day mortality (from 41.8% to 21.6%, P = .044) and hospital mortality (from 58.1% to 27.5%, P = .003). In multivariate analysis, the intervention group was independent of 30-day mortality and hospital mortality risk reduction factors (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.12-0.86, and OR, 0.20; 95% CI, 0.07-0.53). CONCLUSIONS: AS programs with pharmacist intervention improve mortality in patients with MRSA-B.

Control of Nausea and Vomiting in Patients Receiving Anthracycline/Cyclophosphamide Chemotherapy for Breast Cancer.

BACKGROUND/AIM: Chemotherapy-induced nausea and vomiting (CINV) is one of most distressing adverse events during cancer chemotherapy. In breast cancer patients receiving anthracycline and cyclophosphamide (AC) chemotherapy, CINV is poorly controlled. PATIENTS AND METHODS: The prevalence of guideline-consistent antiemetic medication and control of CINV were investigated retrospectively in breast cancer patients receiving the first cycle of AC chemotherapy. Risks for CINV were analyzed by the multivariate logistic regression analysis. The effect of olanzapine added to the standard antiemetic medication on the incidence of CINV was subsequently evaluated in separate patients who received the first cycle of AC chemotherapy. RESULTS: Although the guideline-consistent antiemetic medication was performed in all subjects, the control rate of nausea (32%), but not vomiting (78%) was low. Risk analysis indicated that age younger than 55-year-old was a significant factor that reduces the control of both nausea and vomiting. Olanzapine (5 mg/day for 5 days), when added to the standard three-drug antiemetic medication, significantly improved the control of nausea and complete response. CONCLUSION: CINV was poorly controlled in breast cancer patients receiving AC chemotherapy, in which age younger than 55-year-old was a significant risk for both nausea and vomiting. Olanzapine was effective for improvement of the control of CINV associated with AC chemotherapy. Therefore, care should be taken to prevent CINV in young patients receiving AC chemotherapy by adding olanzapine to the standard three-drug antiemetic medication.

Beneficial effects of a gait used while wearing a kimono to decrease the knee adduction moment in healthy adults.

The knee adduction moment (KAM) relates to medial knee osteoarthritis (OA). Several gait modifications to reduce the KAM for the prevention of knee OA have been studied. Most of the modifications, however, involve voluntary changes in leg alignment. Here we investigated the biomechanical effects for reducing the KAM of a walking style with a small trunk rotation and arm swing gait, which is a natural walking style used while wearing a kimono (Nanba walk) that shifts the ground reaction force toward the stance leg (reduced lever arm). Twenty-nine healthy adults (21.5 ± 0.6 years) participated in the present study. A three-dimensional analysis system with 10 cameras and 1 force plate was used to obtain the KAM and other biomechanical data. Surface electromyography (EMG) of the hip and trunk muscles (internal obliquus abdominal muscle: IO, external obliquus abdominal muscle: EO, multifidus muscle: MF, and gluteus medius muscle: Gmed) was also assessed, and integrated EMG (iEMG) of the four muscles was assessed in the first and second halves of the stance phase. The 1st and 2nd peak KAMs were significantly decreased during Nanba walking (0.40±0.09 and 0.37±0.13 Nm/kg) compared with normal walking (0.45±0.09 and 0.45±0.13 Nm/kg; P = 0.002, P<0.001, respectively). The lever arm lengths at the 1st and 2nd peak KAMs were also significantly decreased during Nanba walking compared with normal walking (p = 0.023 and p<0.001, respectively). The iEMGs of IO, EO and Gmed muscles during the first half, and the iEMGs of EO and GM during the second half of the stance phase were significantly increased during Nanba walking compared with normal walking. The Nanba gait modification could be a useful strategy for reducing the KAM with high activation of the trunk and hip joint muscles for the prevention and/or treatment of medial knee OA.