Clinical Predictors of the Hypoglycemic Effect of Sodium-Glucose Co-transporter-2 Inhibitors in Hyperuricemic Patients: A Retrospective Descriptive Observational Study.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors decrease glycated hemoglobin (HbA1c) and prevent the progression of cardiovascular and kidney diseases. Because uric acid and electrolytes are physiologically similar to blood glucose in renal excretion, we assessed predictors for the hypoglycemic effect of SGLT2 inhibitor treatment by focusing on serum uric acid and serum electrolytes. We performed a retrospective descriptive observational study at the Tokyo Women's Medical University, Medical Center East, from June 2015 to July 2018. Patients who received treatment with any type of SGLT2 inhibitor were selected, which included a total of 165 patients. The response to SGLT2 inhibitors defined as changes in HbA1c after SGLT2 inhibitor treatment was the main outcome measure. Multiple linear regression analysis was used to assess predictors for the hypoglycemic effect by SGLT2 inhibitors. Among the 165 patients, SGLT2 inhibitor treatment decreased HbA1c from 8.2 to 7.6% after 12 weeks (p < 0.01). Multiple linear regression analysis revealed that predictors of early response to SGLT2 inhibitors were serum uric acid values (p = 0.014) and baseline HbA1c (p < 0.001). Furthermore, late response to SGLT2 inhibitors was associated with serum uric acid value (p = 0.047) and baseline HbA1c (p < 0.001). Serum uric acid did not vary during SGLT2 inhibitor treatment; specifically, the SGLT2 inhibitors did not reduce serum uric acid levels. There was no correlation between changes in serum uric acid and HbA1c (p = 0.13). Thus, this study showed that serum uric acid value is associated with the control of diabetes mellitus during SGLT2 inhibitor treatment. Further studies are required to validate these results.

Relationship between Recurrent Falls and Medication Use during Acute-Care Hospitalization: A Retrospective Descriptive Study.

Although recurrent falls during hospitalization lead to discharge to nursing homes, their association with medications has not been comprehensively assessed. We aimed to assess risk factors for recurrent falls focusing on medications during hospitalization in an acute-care setting. This retrospective descriptive study was conducted in Tokyo Women's Medical University, Medical Center East. Patients who experienced a fall during hospitalization were included and the incidence of recurrent falls was assessed during hospitalization. Multivariate logistic regression analysis was performed to assess the relationship between recurrent falls and medications and to calculate odds ratio and 95% confidence interval. Sensitivity analysis was performed on data stratified by sex or age. This study included 124 patients with an incidence of 20 (16%) recurrent falls. Multivariate logistic regression analysis revealed that selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants were associated with recurrent falls (odds ratio = 5.98, 95% confidence interval: 1.38-25.9, p = 0.02). Additionally, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants were significant risk factors for recurrent falls in women and those aged > 80 years. Selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants were associated with an increased risk of recurrent falls during hospitalization in an acute-care setting. Clinicians should pay attention to patients receiving selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants, especially women and aged > 80 years old.

NSAIDs may prevent EGFR-TKI-related skin rash in non-small cell lung cancer patients
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OBJECTIVES: Skin rash is a common adverse event induced by epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Here, we aimed to predict factors that reduce EGFR-TKI-related skin rash. MATERIALS AND METHODS: We conducted a single-center, retrospective study to predict factors that reduce skin rash in patients undergoing treatment for non-small cell lung cancer (NSCLC) with EGFR-TKIs using Cox proportional hazards model. RESULTS: Cox proportional hazard analysis revealed that coadministration of non-steroidal anti-inflammatory drug (NSAID) had protective effects against rash. Steroid coadministration showed a trend to being effective in reducing rash. CONCLUSION: NSAIDs may be useful in preventing EGFR-TKI-related skin rash.
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Induration at Injection or Infusion Site May Reduce Bioavailability of Parenteral Phenobarbital Administration.

BACKGROUND: Phenobarbital is well tolerated and effective for controlling agitation or preventing convulsion at the end of life. No information is available concerning parenteral bioavailability of phenobarbital when induration develops at the injection or infusion site. We investigated whether induration at injection or infusion site is related to phenobarbital bioavailability via parenteral routes of continuous subcutaneous infusion and intermittent subcutaneous or intramuscular injection. METHODS: A retrospective analysis was conducted on the medical data obtained from 18 patients who received chronic subcutaneous or intramuscular injections of phenobarbital for the prevention of convulsions and underwent plasma concentration monitoring of the drug. Patients whose concomitant medications were altered during the observation periods were excluded from the analysis. Comparisons were performed for concentration/dose (C/D) ratios obtained from patients with induration at injection or infusion sites (induration group, n = 6) and those without induration (noninduration group, n = 12). P < 0.05 was considered statistically significant. RESULTS: The induration group showed significantly reduced C/D ratio compared with the noninduration group [median (range): 0.131 (0.114-0.334) versus 0.219 (0.180-0.322) d/L, P < 0.05). Assuming that systemic clearance was constant in our patients, changes in the C/D ratio would have contributed to 40% (median) reduction in bioavailability of the drug from the injection or infusion site. CONCLUSIONS: Our data suggest that absolute bioavailability of phenobarbital may be reduced when induration develops at the injection or infusion site in patients treated parenterally by continuous subcutaneous infusion or intramuscular injection.

Eculizumab Dosing Intervals Longer than 17 Days May Be Associated with Greater Risk of Breakthrough Hemolysis in Patients with Paroxysmal Nocturnal Hemoglobinuria.

Eculizumab given bi-weekly is widely recommended for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). We undertook a retrospective analysis on the medical records of 763 dosings of 14 PNH patients to investigate whether a threshold would exist in dosing intervals associated with breakthrough hemolysis. We identified 12 events of breakthrough hemolysis in 4 patients. Multivariate logistic regression and receiver operating characteristics (ROC) analysis revealed a significant association between increased risk of breakthrough hemolysis and prolonged dosing intervals of 17 days or more and concomitant inflammation: odds ratios (OR) and 95% confidence intervals (CIs) were 1.6 (1.3-2.0, p<0.01) and 5.5 (1.3-22.8, p=0.02), respectively. ROC analysis showed that the best cut-off dosing interval discriminating breakthrough hemolysis was 16.5 days. We consider that eculizumab dosing intervals longer than 17 days may be associated with an increased risk for developing breakthrough hemolysis in patients with PNH.

Population pharmacokinetic and pharmacodynamic analyses of teicoplanin in Japanese patients with systemic MRSA infection.

BACKGROUND: Teicoplanin is a glycopeptide antibiotic used for the treatment of MRSA infection. An initial loading dose of 400 mg every 12 hours for three doses is the standard dosing regimen. This study aimed to assess whether this regimen was appropriate based on the pharmacokinetic/pharmacodynamic (PK/PD) analyses in Japanese patients. METHODS: We conducted a population pharmacokinetic (PPK) analysis of teicoplanin by NONMEM using serum drug concentrations obtained from 116 patients with MRSA infection. PD of the drug was analyzed by a model assuming that the variability of therapeutic responses (assessed by body temperature, serum C-reactive protein concentrations, and white blood cell counts) on the 3rd, 7th or 14th day of treatment is associated with the logarithm of serum unbound drug concentration (Cmax,unbound) divided by the MIC against MRSA (log[Cmax,unbound/MIC]). RESULTS: The final PPK model showed that creatinine clearance and serum albumin concentration were significant (p < 0.01) covariates of systemic clearance and peripheral volume of distribution of teicoplanin, respectively. The PD analyses indicated that log[Cmax,unbound/MIC] of 0.30 on Day 3 of teicoplanin therapy was the threshold for achieving successful clinical responses. Integrating the PK and PD data, we consider that the standard loading dose regimen would attain the threshold serum level within the initial 3 days in only less than 50% of the patients. CONCLUSION: We propose that an extended loading regimen (400 mg every 12 hours for the first 5 doses) would be a treatment option to maximize the therapeutic effects of teicoplanin in patients with systemic MRSA infection.

Effect of a comprehensive lifestyle modification program on the bone density of male heavy drinkers.

BACKGROUND: Heavy alcohol drinking is implicated in osteoporosis. Although abstinence is rapidly followed by a restoration of osteoblastic activity, little is known about the contributions of alcohol-related factors or the effectiveness of a lifestyle modification program (LMP) on bone density. METHODS: We conducted a study of 138 male alcoholic patients to investigate whether drinking history and concurrent factors were associated with the bone density of the calcaneus. A 2.5-months LMP in an institutionalized setting was completed by 20 of them, and its effect on bone density, serum parathyroid hormone (PTH), and 1.25-(OH)(2) vitamin D levels were assessed. RESULTS: The patients had a high prevalence of daytime drinking (93.5%), continuous drinking (84.1%), and current smoking (82.0%) with mean duration of alcohol abuse of 30.0 +/- 12.8 years. The patients had lower bone density than a reference control group (Z-scores: -0.45 +/- 1.02). Multiple stepwise regression analysis identified age, poor activities of daily living (ADL), continuous drinking, absence of liver cirrhosis, depression, and dementia as determinants of low bone density. The bone density of the 20 participants in the LMP improved 2.3% (p = 0.0003) with a more ameliorating effect on bone density than a conventional abstinence therapy (p = 0.014 for interventional effect). The upper normal range of PTH levels at baseline were significantly decreased, and 1.25-(OH)(2) vitamin D levels also had a trend toward decrease during the abstinence. CONCLUSIONS: Alcoholic patients may have many complications such as poor ADL and dementia, which are independently associated with decreased bone density. The results of this study support the idea that comprehensive approach to lifestyle factors to minimize risk of osteoporosis is the best way to improve bone density.

Anticholinergic and Sedative Drug Burden and Functional Recovery after Cerebrovascular Accident: A Retrospective Descriptive Study.

OBJECTIVES: Medications with anticholinergic or sedative effects induce impaired cognitive and physical performances. The aim of this study was to evaluate the associations of anticholinergic and sedative drug burden with recovery of physical function and activities of daily living in patients admitted to a Japanese rehabilitation hospital after cerebrovascular accidents. METHODS: We retrospectively reviewed the medical records of patients aged 18 years or older who had undergone the inpatient rehabilitation program for cerebrovascular disease in Nerima Ken-ikukai Hospital. Patients who did not complete the rehabilitation program because of acute unexpected changes of physical or psychological condition or the need for surgical procedures were excluded. The primary outcome was recovery of activities of daily living as measured by the motor and cognitive subscores of the Functional Independence Measure. The secondary outcome was recovery of physical function as assessed by the 10-m walk test and the Berg balance scale. Multiple Cox proportional hazard regression analyses were conducted to calculate hazard ratios with 95% confidence intervals for the outcome measures. RESULTS: Of 122 patients included in the study, 81 (66%) were exposed to anticholinergics and sedatives. Patients' age, body mass index, and average daily drug burden during hospitalization were independently associated with achieving the cutoff Functional Independence Measure-motor subscore. Patients' age and average daily drug burden during hospitalization were independently associated with achieving the Berg balance scale cut-off score. CONCLUSIONS: Our study of Japanese patients who were transferred from acute stroke care hospitals to a rehabilitation facility identified the drug burden of anticholinergics and sedatives as an independent factor associated with the time to recovery of activities of daily living and postural balance.

Reduced Clearance of Phenobarbital in Advanced Cancer Patients near the End of Life.

BACKGROUND AND OBJECTIVES: Little is known about the pharmacokinetics of phenobarbital in terminally ill cancer patients. We investigated whether phenobarbital clearance alters depending on the length of survival. METHODS: We retrospectively reviewed the clinical, laboratory, and therapeutic drug monitoring (TDM) records of patients who received parenteral or oral phenobarbital for 21 consecutive days or longer between 2000 and 2016. Patients were divided into non-cancer and cancer groups. Cancer patients were further stratified according to the survival interval after TDM: those who survived > 3 months were classified as long-surviving and the remainders short-surviving cancer patients. Phenobarbital clearance (CLPB) was calculated at steady state. Multiple comparisons of median CLPB were conducted among the three groups. RESULTS: Data were collected from 44 non-cancer patients and 34 cancer patients comprising 24 long-surviving and 10 short-surviving cancer patients. Among 10 short-surviving cancer patients, 4 had hepatic metastasis. Median CLPB (range) in short-surviving cancer patients [0.076 (0.057‒0.114) L/kg/day] was significantly (p < 0.05) lower than that in non-cancer patients [0.105 (0.060‒0.226) L/kg/day] and in long-surviving cancer patients [0.100 (0.082‒0.149) L/kg/day]. CONCLUSION: Terminally ill patients with advanced cancer may have reduced CLPB, thereby TDM is recommended for these patients particularly near the end of life.

[A Retrospective Evaluation of the Impact of Multi-disciplinary Approach for Improving the Quality of Anticoagulation Therapy in Ambulatory Patients with Non-valvular Atrial Fibrillation Receiving Warfarin].

While percent time within therapeutic range (%TTR) of international normalized ratio of prothrombin time (PT-INR) represents the quality of anticoagulation therapy with warfarin, it is often maintained less than 50% in patients with non-valvular atrial fibrillation (NVAF). We aimed to study if implementation of a multi-disciplinary ambulatory anticoagulation service (MAAS) may improve %TTR. Collaborating with cardiologists at Kanto Rosai Hospital, we conducted a MAAS for NVAF patients receiving warfarin from April 2013 to December 2015. Patients who agreed to utilize the service in addition to their appointments with cardiologists visited pharmacists to have counseling about diet, concomitant medications, and lifestyle. According to a protocol, pharmacists made dose adjustment proposals to cardiologists, if necessary. Upon approval by cardiologists, dose modifications were made. We retrospectively reviewed medical records of the patients who participated in the MAAS before and during the service. The study protocol was approved by the institutional review board. We identified 78 eligible patients (44 males and 34 females, aged 51 to 91 years). Their median %TTR increased significantly (p<0.05) from 57% during the pre-MAAS period to 77% during the MAAS period. In addition, the median percent time below therapeutic range (%TBTR) decreased significantly (p<0.05) from 35% during the baseline period to 11% during the MAAS period. The present study indicates that MAAS improves the quality of anticoagulation therapy with warfarin in ambulatory patients with NVAF. Further prospective, randomized studies with a greater number of patients are required to confirm the results of the present study.

Preventive effect of N-acetylcysteine on contrast-induced nephropathy following coronary angiography and angioplasty.

Contrast-induced nephropathy (CIN) is one of the serious side effects of contrast media. A few studies have suggested that N-acetylcysteine (NAC) is effective to prevent CIN, but the efficacy remains unclear in Japanese. Therefore, we retrospectively studied the preventive effect of NAC on CIN in Sakakibara Heart Institute. Patients who had been administered NAC for the purpose of preventing CIN before coronary intervention between February 2005 and November 2006 were included in the NAC group. In addition, age- and rate of diabetes mellitus-matched controls were randomly extracted. We retrieved and analyzed patient data including demographics, NAC dosage, and serum creatinine concentrations (Scr). NAC group (n=16) showed significantly higher baseline Scr (p<0.01) and a tendency toward a lower dose of contrast media (p=0.068) compared with controls (n=48). Since the occurrence of CIN was low, there was no significant difference in the proportion of CIN between the groups (NAC: 6%, controls: 4%). NAC group trended toward a decrease in Scr after the use of contrast media, while controls increased (-0.04+/-0.25 versus +0.03+/-0.36 mg/dl, p=0.096). The multivariate analysis showed that the dosage of NAC is inversely correlated with Scr independent of baseline Scr and dosage of contrast media. Despite higher baseline Scr (i.e., high-risk with CIN) in the NAC group, the real Scr value reflected a lower trend on average. In addition, this finding suggests that a larger dose of NAC results in a lower Scr value, we consider that the NAC dosage more likely prevented CIN.

[Approach to Practical Training in Basic Clinical Pharmacy for Third-Year Pharmacy Students: Literature Appraisal and Professional Writing].

　Training pharmacy students to become future clinical pharmacists is an important mission in the 6-year school of pharmacy curriculum in Japan. Since 2014, we have conducted an on-campus practical training program to develop basic skills in clinical pharmacy for third-year pharmacy students at Meiji Pharmaceutical University. This training program includes searching for and retrieving drug information; interpretation of laboratory findings, vital signs, and physical examinations; literature appraisal; and professional writing. These training sections are arranged in the above-mentioned order to facilitate effective understanding of each. In the literature appraisal section, each student group is assigned a report on a prospective controlled study of a given drug published in English and reads it critically according to the literature appraisal worksheet. Then the group writes a monograph on the drug described in the report based on the literature and other information. Thereafter, all students are reshuffled into new groups so that students who were assigned different drugs are placed together, in the so-called jigsaw learning method. Students then discuss which two or three drugs in a specific pharmacological class should be adopted in the hospital formulary according to the knowledge gained through this training program series. The themes were novel oral anticoagulants in the 2014 academic year, dipeptidyl peptidase 4 inhibitors in 2015, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors in 2016. Although there are some problems that need to be resolved in the future, this approach appears effective in helping students build drug information skills as a basic competence of clinical pharmacists.

Impact of relative dose intensity on bone marrow suppression induced by S-1: retrospective observational study.

BACKGROUND: S-1 (a combination of tegafur, gimeracil, and oteracil) is used to treat various cancers. Bone marrow suppression is a dose-limiting toxicity of S-1. The relationship between relative dose intensity (RDI) and bone marrow suppression has not been investigated. Hence, we aimed to elucidate the threshold for RDI to identify bone marrow suppression induced by S-1. METHODS: In this retrospective cohort study, patients who initiated S-1 treatment at Tokyo Women's Medical University, Medical Center East between June 2015 and June 2017 were included. Bone marrow suppression induced by S-1 was assessed using Common Terminology Criteria for Adverse Events version 4.0. The relationships between grade 3 or higher bone marrow suppression induced by S-1 and RDIs (i.e., 70, 75, and 80%) were investigated using the multivariate Cox proportional hazard model. RESULTS: We identified 143 patients in this study. The median RDI was 78.8%. Bone marrow suppression induced by S-1 developed in 19 (13.3%) patients. The multivariate Cox proportional hazard model revealed that grade ≥ 2 lymphocytopenia was associated with bone marrow suppression induced by S-1 regardless of the threshold for RDI. In addition, RDI > 75% [hazard ratio (HR) = 1.71, p < 0.05] and RDI > 80% (HR = 1.65, p < 0.05) were associated with bone marrow suppression induced by S-1. CONCLUSIONS: Reduced dose of S-1 still has the risk of developing bone marrow suppression. Clinicians should assess RDI to identify high risk patients with bone marrow suppression induced by S-1.

Meta-analysis of risk of malignancy with immunosuppressive drugs in inflammatory bowel disease.

BACKGROUND: There is a concern as to whether long-term administration of immunosuppressants in patients with inflammatory bowel disease (IBD) would increase the risk of malignancy. OBJECTIVE: To compare the risks of developing malignancy between patients with IBD treated with immunosuppressive agents and patients with IBD not receiving these agents. METHODS: A systematic literature review was conducted, and a meta-analysis was performed on data retrieved from cohort studies that followed patients with IBD who received immunosuppressive agents for more than a year and documented the incidence of newly developed malignancy. An electronic search was conducted using MEDLINE (1966-September 2006), the Cochrane Library (issue 3, 2006), and Japana Centra Revuo Medicina (1981-September 2006). Medical subject headings used in the searches were azathioprine, 6-mercaptopurine, cyclosporine, methotrexate, tacrolimus, inflammatory bowel disease, and neoplasms. We imposed no language limitation in the searches. Additionally, a manual search of reference listings from all articles retrieved from the electronic databases was performed. Using data obtained from control groups or population-based studies, the incidence of newly developed malignancy in patients with IBD treated with immunosuppressive agents was compared with that of patients with IBD who were not receiving immunosuppressive agents. Statistical analysis for the change in risk of developing malignancy was performed using the weighted mean difference (WMD) normalized to per person-year and its 95% confidence interval. RESULTS: Nine cohort studies met the inclusion criteria for this meta-analysis. Analysis of these studies showed no discernible difference (WMD -0.3 x 10(-3)/person-year; 95% CI -1.2 x 10(-3) to 0.7 x 10(-3)) in the incidence of any kind of malignancy in patients with IBD who received immunosuppressants compared with those who did not receive immunosuppressants. No significant difference in WMD was observed when the data from patients with either Crohn's disease (CD) or ulcerative colitis (UC) were analyzed separately. CONCLUSIONS: Our findings suggest that the administration of immunosuppressive agents in patients with either CD or UC probably does not confer a significantly increased risk of malignancy compared with patients with IBD who are not receiving these agents.

[Analysis of clinical factors that influence re-stenosis after percutaneous coronary stenting].

Evidence has recently been accumulating that a sirolimus-eluting stent (DES) is superior to a bare-metal stent (BMS) in preventing restenosis after percutaneous coronary intervention (PCI), and an increasing number of Japanese hospitals have been adopting DES. We conducted a retrospective study to identify clinical factors that influence the risk of restenosis after PCI, including stent types, by analyzing the data of 49 continuous patients who received PCI and follow-up coronary angiography in Hiratsuka City Hospital between March, 2004 and March, 2005. Age, sex, body mass index, smoking, complications, clinical diagnosis before PCI, the site and number of stenoses, implanted stent type (BMS or DES), the number of stents used, maximum inflating pressure and withdrawal of ticlopidine due to its adverse drug reactions were chosen as potential factors that may influence the risk of restenosis, and the correlation between these factors and restenosis was tested by Student's t-test or chi-square test. Coronary restenosis developed in 10 out of 49 patients, and factors having significant correlation with restenosis were age (73+/-7 in the restenosis group (R) and 64+/-12 in the non-restenosis group (N) (p<0.05)) and the type of stent (DES used in only one of 10 cases in R whereas in 24 of 39 in N (p<0.001)). Multivariate analysis showed older age (odds ratio (OR): 1.200 (95% CI: 1.038-2.823)) and the use of DES are independent predictors for restenosis (OR: 0.015 (95%CI: 0.001-0.249)). Our study further supports the efficacy of DES in PCI, but its long-term outcome is yet to be confirmed.

Safety of human papillomavirus vaccines in healthy young women: a meta-analysis of 24 controlled studies.

BACKGROUND: Human papillomavirus (HPV) vaccines have been shown to be effective for the eradication of HPV and prevention of cervical cancer. However, the number of women who receive HPV vaccinations has decreased over the last several years in Japan, due to concerns about adverse reactions associated with the vaccines. We evaluated the safety of three types of HPV vaccines separately in young women and the difference in the risk of adverse reactions between HPV and other vaccines by conducting a meta-analysis. METHODS: Primary literature was retrieved from MEDLINE, the Cochrane Central Register of Controlled Trials, and Japana Centra Revuo Medicina. Prospective controlled studies with participants consisting exclusively of healthy women who received bivalent, quadrivalent, or 9-valent HPV (2vHPV, 4vHPV or 9vHPV) vaccines were included. Primary safety outcome was the incidence of solicited local and systemic symptoms, and unsolicited symptoms. When two or more studies were found for the same analysis, a meta-analysis was applied. RESULTS: A total of 24 controlled studies from 22 articles were included in our study. Of the 24 studies, 16 were placebo-controlled and eight were active-controlled (different HPV vaccine or hepatitis vaccine). Average ages of the participants ranged from 12 to 37 years. A significantly higher incidence of solicited local symptoms was observed following injection of HPV vaccines (2vHPV and 4vHPV) compared to placebo, but there was no difference between HPV vaccines [risk ratio (RR) for 2vHPV: 1.25, 95% confidence interval (CI): 1.09 to 1.43, RR for 4vHPV: 1.16, 95% CI: 1.11 to 1.20]. The incidence of solicited systemic symptoms was not different between HPV vaccines and placebo (RR: 1.04, 95% CI: 0.99 to 1.09). The incidence of unsolicited symptoms was significantly higher for 2vHPV vaccine compared to placebo (RR: 1.28, 95% CI: 1.01 to 1.63), but was not significantly different between 2vHPV and hepatitis B vaccines. CONCLUSIONS: HPV vaccines had significantly higher risk of any injection site symptom compared to placebo or other vaccines (hepatitis A and B vaccines), and the incidence of solicited local symptoms was no difference between 2vHPV vaccination and 4vHPV vaccination. However, the most adverse reactions were transient.

Impact of Pharmacists' audit on improving the quality of prescription of dabigatran etexilate methanesulfonate: a retrospective study.

BACKGROUND: Appropriate prescription of dabigatran etexilate methanesulfonate (JAN) is more complicated than assumed, because there are totally 10 items of contraindications and instructions for dosage reduction depending on patients' characteristics. We aimed to study whether the routine audit of first-time prescriptions of dabigatran performed by pharmacists is effective in improving the quality of prescription. METHODS: A retrospective re-audit was performed on all the prescriptions of dabigatran issued at Kitahara International Hospital, Tokyo between March 2011 and February 2014, by evaluating the prescriptions rigorously against the approved prescribing information of the drug. The original routine audit of the prescriptions for inpatients was performed by hospital pharmacists using electronic medical records (EMR), whereas the audit for ambulant patients receiving external prescriptions was performed by community pharmacists using information obtained mainly by questioning patients. The frequencies of inappropriate prescriptions detected by the re-audit in the two groups were compared. RESULTS: Two hundred and twenty-eight patients (131 ambulant patients and 97 inpatients) were prescribed dabigatran for the first time during the study period. All patients met the approved indications. While 33% of the prescriptions for ambulant patients showed at least one violation of the approved usage, only 11% of the prescriptions for inpatients showed violations (p < 0.001). Two ambulant patients with creatinine clearance < 30 mL/min were dispensed dabigatran, whereas no such case was found among inpatients. A significantly greater proportion of ambulant patients aged ≥70 years showed violation of the instruction for dosage reduction compared to inpatients of the same age group (18 and 4%, respectively). CONCLUSION: The present study suggests that pharmacists may achieve better performance in auditing prescriptions of dabigatran when medical records are fully available than when information is available mainly by questioning patients. Further large-scale studies are required to clarify whether the audit of dabigatran prescriptions improves ultimate therapeutic outcomes or complications.

Consequences of Different Corticosteroids on Serum Potassium and Prostate-Specific Antigen in Patients Receiving Abiraterone for Castration-Resistant Prostate Cancer: A Retrospective Observational Study.

BACKGROUND: Abiraterone acetate is an androgen synthesis inhibitor approved for the treatment of castration-resistant prostate cancer (CRPC). Although co-administration of either prednisone or prednisolone at 10 mg/d has been recommended to reduce the risk of abiraterone-induced hyperaldosteronism (notably hypokalemia) and to give adjunctive pain relief effects, whether these glucocorticoids can be substituted by dexamethasone remains unknown. METHODS: We performed a retrospective review of medical records of patients who were given abiraterone for the treatment of CRPC with either prednisolone (ABI/PSL) 10 mg/d or dexamethasone (ABI/DEX) 0.5 or 1 mg/d between 2014 and 2017 in Juntendo University Nerima Hospital. Demographic and biochemical data including prostate-specific antigen (PSA) level were retrieved from the electronic medical records. RESULTS: Fifty-three eligible patients (27 in ABI/PSL group and 26 in ABI/DEX group) were extracted from the records. Both groups showed no significant changes in serum potassium level before and after starting treatment. In the ABI/PSL group, 12 patients (46%) showed elevations of PSA and 7 patients (27%) discontinued treatment within 3 months. In contrast, in the ABI/DEX group, only 6 patients (25%) showed elevations of PSA and 3 patients (13%, all were given dexamethasone 1 mg/d) discontinued treatment. CONCLUSIONS: Dexamethasone and prednisolone may be equally effective in preventing abiraterone-induced hypokalemia.

Population pharmacokinetic and pharmacodynamic analysis of a class IC antiarrhythmic, pilsicainide, in patients with cardiac arrhythmias.

Population pharmacokinetics (PK) of a sodium channel-blocking antiarrhythmic, pilsicainide, was studied using the nonlinear mixed-effects modeling technique in 91 patients with cardiac arrhythmias (80 suspected Brugada syndrome [BrS] and 11 with atrial fibrillation) who received an intravenous infusion of 10 mg of the drug. Population pharmacodynamic (PD) analysis was also performed using an effect compartment model. PD responses were assessed by changes in electrocardiogram (ECG) pattern (BrS-like elevation of ST-segment) and conduction parameters. The final PK model showed that gender (values were 50% lower in women than in men) and creatinine clearance were significant (P < .01) covariates of weight-normalized systemic clearance of pilsicainide. Patients who showed a BrS-like ECG pattern after the drug administration also showed a significantly (P < .01) greater prolongation in His-Purkinje conduction compared to the remaining patients. In conclusion, female gender, renal dysfunction, and the drug-induced BrS-like ECG morphology may be associated with augmented ECG responses to pilsicainide.

Influence of proton pump inhibitors and histamine H2 receptor antagonists on serum phosphorus level control by calcium carbonate in patients undergoing hemodialysis: a retrospective medical chart review.

BACKGROUND: Hyperphosphatemia is one of the common complications in patients undergoing hemodialysis. Although calcium carbonate (CaC) is often used to control serum inorganic phosphorus level in dialysis patients, co-administration of gastric acid reducers (ARs) may interfere with the phosphate binding effect of CaC. We performed a retrospective medical chart review to study whether ARs attenuate the hypophosphatemic effect of CaC in patients undergoing hemodialysis. METHODS: One hundred and eight chronic hemodialysis patients receiving either CaC alone or CaC concomitant with one of the ARs (proton pump inhibitors and histamine H2-receptor antagonists) were retrieved from the medical charts in Juntendo University Nerima Hospital. The patients were subdivided according to the interval between hemodialysis sessions (interdialysis interval of 48 or 72 h). A multivariate analysis was performed to identify clinical covariates associated with the variability of serum inorganic phosphorus levels. The study protocol was approved by the Institutional Review Board before the study was begun. RESULTS: Among patients on hemodialysis with a 72-h interdialysis interval, the magnitude of increase in serum inorganic phosphorus concentration in patients receiving CaC and AR was significantly greater than in those receiving CaC alone. While a similar trend was observed among patients with a 48-h interdialysis interval, the difference did not reach a significant level. A multivariate regression analysis revealed that concomitant administration of ARs with CaC and a longer interdialysis interval (72 h) were significantly and independently associated with the magnitude of increase in serum phosphorus concentration between dialysis sessions. No significant differences in albumin-corrected serum calcium concentrations and incidence of pathological fractures were observed between patients receiving CaC alone and those receiving CaC with ARs. CONCLUSIONS: Concomitant use of ARs with CaC may attenuate the hypophosphatemic effect of CaC in patients undergoing chronic hemodialysis. When hemodialysis patients require prescription of ARs for the prevention of upper gastrointestinal mucosal diseases (such as peptic ulcer), it may be prudent to choose a phosphate binder other than CaC.