Pharmaceutical interventions are sometimes ineffective in patients who take dietary supplements (DS) because the medical staff providing the treatment are not aware that the patient is taking DS. This study was performed to analyze pharmaceutical interventions administered to inpatients taking DS. The pharmaceutical interventions were chosen by the pharmacists in charge of each ward with the support of a nutritional representative・supplement adviser. Then, we tried to develop a systematic pharmaceutical management strategy for patients who were taking DS based on this analysis. This study examined 32 interventions (involving 28 patients including 3 patients who were treated multiple times), and 20 patients (63%) who stopped taking DS during the study period. The most serious issues that arose during the interventions included DS-drug interactions (6, 19%), issues associated with perioperative management (6, 19%), direct DS-induced damage (including suspected cases) (5, 16%), and conditions that required immediate attention (5, 16%). We found that by examining the patients' characteristics including their disease status and any medications that they were taking we were able to avoid drug treatment failure. This indicates that it is necessary for pharmacists to be aware of patients' use of DS. We developed a systematic “pharmaceutical management algorithm” based on our analysis of the above-mentioned pharmaceutical interventions. We consider that this algorithm will aid the selection of pharmaceutical management strategies by pharmacists．In future, we will improve the practicality and efficacy of the algorithm based on feedback from clinical pharmacists.
We retrospectively evaluated the clinical outcomes of pharmaceutical interventions relating to outpatient chemotherapy and estimated their associated economic impact between August 2014 and August 2015. We developed a novel pharmaceutical system, involving JPY1,164,000 allocated to a total of 582 patients. There were 117 proposals for pharmaceutical interventions, 106 (90.6%) of which were accepted by physicians. The number of proposals for supportive therapy was 56, 29 (51.8%) of which significantly decreased the grade of chemotherapy-induced adverse events compared to before pharmaceutical interventions (P < 0.001). The number of reductions in grade 1, 2, and 3 events was 14, 11 and 4, respectively. In this study, the potential economic costs associated with reduction of grade 1, 2 and 3 chemotherapy-induced adverse events were calculated as JPY112,000, JPY112,000, and JPY2,140,000, respectively, based on the costs paid by the Adverse Drug Reaction Relief System of the Pharmaceuticals and Medical Devices Agency. According to this cost calculation, we estimated that the total cost saving associated with the clinical outcomes of pharmaceutical interventions was JPY11,360,000. This is the first study to estimate the economic impact associated with the clinical outcomes of pharmaceutical interventions for outpatient chemotherapy. These results suggest that pharmaceutical interventions contribute to the quality and safety of outpatient chemotherapy by decreasing chemotherapy-induced adverse events.
We investigated the effects of plasticizers and polymers on the physical properties and drug dissolution capabilities of films containing a high drug dosage of in order to find formulations that would be easy for patients to swallow. In this study, acetaminophen (AA) was used as the model drug, and glycerin (GL) and polyethylene glycol 400 (PEG) were used as plasticizers. Carboxy methylcellulose sodium (CMC) and hydroxypropyl methylcellulose (HPMC) were used as polymers. Adding GL decreased the strength and tended to increase the elasticity of films made with either polymer. Adding PEG changed the characteristics of each polymer film differently. For CMC films, strength increased and elasticity did not change. In HPMC films, strength did not change, and elasticity increased. The level of adhesiveness can effect proper swallowing. Adding GL increased adhesiveness for CMC film only, while adding PEG increased adhesiveness in both polymers. In GL containing films, a relationship was observed between adhesiveness and elasticity, as elasticity seems to be a good indicator of adhesiveness. However, in films containing PEG, there was no consistent relationship, therefore both characteristics may require separate evaluation. Drug dissolution from all films was almost 100% after 30 minutes, and was not influenced by the plasticizers. For preparing AA films for drug administration purposes, we suggest that GL is suitable for CMC and PEG is suitable for HPMC. GL seems to be useful as a plasticizer because it has a moderate effect on both polymer matrices.
Massive bleeding induced by disintegration of breast cancer tumors for 4 yrs (88 yrs-old lady) was treated by applying Mohs' paste (75g/45mL of Zinc complex). This huge site healed quickly and the healing effects were sustained for 48 days. Based on this clinical evidence, the hemostatic mechanism of Mohs' paste was evaluated using the hind limb ischemia model in mice. Unilateral hind limb ischemia was induced in 6 week-old male C57BL/6JJmsSlc mice by resecting the right femoral and saphenous arteries. Mice were painted once a day with Mohs' paste containing 0, 37.5, 50 and 62.5g/45mL of zinc after the surgery. Hind limb blood perfusion was measured by using a laser Doppler perfusion imaging system (moorLDI2-Ⅱλ : S/N 5489). To identify capillaries, the thigh muscles were harvested on Day 1 to make a tissue section and immunostained for CD31. One day after painting of Mohs' paste, blood flow suppression to the ischemic leg was significantly enhanced in a dose dependent manner. Furthermore, anti-CD31 immunostaining revealed that Mohs' paste decreased capillary density in the ischemic muscle. The results of both the clinical and animal studies suggest that Mohs' paste suppressed angiogenesis due to the acute effects of aggregated protein and the sustained effects of decreases of CD31.
Employee job satisfaction is strategically important to hospital organizations. However, current job satisfaction in Japanese hospital pharmacists has not been clarified. To examine the job satisfaction of hospital pharmacists, we conducted a questionnaire survey on 194 hospital pharmacists at eight hospitals in Kitakyushu-Chikuho, Fukuoka district.The job satisfaction instrument, which is structured on 12 job satisfaction facets and global job satisfaction, developed by the American Society of Health-System Pharmacists was used, and each satisfaction item was evaluated using a 5-point Likert scale. A total of 154 responses were used for analysis. As a result, more than half of the hospital pharmacists reported being highly satisfied (defined as score of 4 or 5) in terms of global job satisfaction. In the multiple regression analysis with all of the facet scores as independent variables and global job satisfaction as the dependent variable, the four most important job satisfaction facets associated with global job satisfaction were Management (t-statistic 3.91), Community (3.05), Pay (2.61), and Staffing (-3.80). In the logistic regression analysis with respondent characteristics as independent variables and highly satisfied measure as the dependent variable, hospital bedsize, gender and pharmacy specialist/certified pharmacist were most often significantly associated with being highly satisfied with a job satisfaction facet.These findings may provide useful information to improve job satisfaction in Japanese hospital pharmacists.
Cisplatin (CDDP) is a key drug in hepatic arterial infusion therapy for hepatocellular carcinoma. Anaphylactic symptoms appear sometimes after multiple CDDP infusions. This study is a retrospective analysis of patients exhibiting CDDP-related hypersensitivity reactions, including anaphylactic symptoms, in order to elucidate risk factors. Of the 240 patients who received CDDP infusion therapy at our hospital from April 2009 to March 2014, 16 (6.67%) exhibited allergic reactions; 13 of these patients exhibited anaphylactic symptoms. Factors significantly associated with anaphylactic symptoms were male ratio, cumulative CDDP dose, and number of CDDP administrations. Logistic regression analysis detected the number of administrations as a risk factor for allergic reactions. Allergic reactions occurred after a median of 7 CDDP administrations, a finding consistent with reported values for intravenous administration of CDDP. Finally, we found that more than 20% of patients exhibit allergic reactions after 6 or more CDDP administrations, suggesting the need for caution in the treatment of these patients.
Fosphenytoin (FOS) is a phosphate ester prodrug developed as an alternative to intravenous phenytoin for acute treatment of seizures. Although both FOS and phenobarbital (PB) are used for status epilepticus as second-line drugs, there is no data on their comparative efficacy and safety. We retrospectively analyzed data from children treated with FOS or PB for convulsive status epilepticus and acute exacerbation of seizures. Our aim was to compare the efficacy and safety of intravenous FOS with those of intravenous PB for convulsive status epilepticus and acute exacerbation of seizures. Seventy-seven children were included in the study: 54 received FOS, and 23 received PB. The primary end point was recurrence of seizures and drug-related adverse events. The response rate, defined as no recurrence of seizures within 24 hours after termination of seizure, was 92% (50/54) and 95% (22/23) in FOS group and in PB group, respectively. Adverse events occurred in 27% (15/54) of patients in FOS group and in 95% (22/23) of patients in PB group (P < 0.01). Although no serious adverse events occurred in patients in both FOS group and PB group, the incidence of both sedation and disturbance of consciousness were significantly higher in PB group than FOS group. From these results, FOS is recommended as second-line drugs for status epilepticus and acute exacerbation of seizures. However, the optimal serum concentration achievement rate was significantly lower in FOS group than PB group. To maintain optimal serum phenytoin levels (10 - 20 µg/mL), higher doses of FOS might be required.
Pemetrexed plus carboplatin chemotherapy has shown efficacy as a first-line treatment for advanced non-small cell lung cancer. However, severe neutropenia has often been reported as a serious adverse effect after the administration of this combination chemotherapy. Various risk factors associated with severe neutropenia induced by pemetrexed plus carboplatin chemotherapy have not yet been clarified. To clarify the risk factors associated with induced severe neutropenia by pemetrexed plus carboplatin, we retrospectively reviewed the records of 42 patients who had received first-line treatment with this combination chemotherapy at Yamato Municipal Hospital between April 2011 and May 2015. Of the 42 patients, 11 (26.2％) developed grade 3 or 4 neutropenia. Multiple logistic regression analysis showed that the creatinine clearance rate (CCr) of between 45 and 66 mL/min [odds rate: 11.00, 95% confidence interval (CI): 1.26-95.94, P = 0.030] and the co-administration of proton pump inhibitors (PPIs) [odds rate: 9.16, 95% CI: 1.02-82.48, P = 0.048] were significantly related to severe neutropenia in patients treated with pemetrexed plus carboplatin chemotherapy after adjustment with use of non-steroidal anti-inflammatory drugs and body surface area. Therefore, patients with moderately impaired renal function (45 mL/min ≤ CCr < 66 mL/min) or co-administration of PPIs may be risk factors for the development of neutropenia induced by pemetrexed plus carboplatin chemotherapy.
In an intensive care unit (ICU), diverse types of injectable drugs are administrated as continuous infusions according to the condition of the patient. Since incompatibilities of injectable drugs can result in loss of efficacy of medications, it is important that pharmacists quickly recommend appropriate administration routes and provide information on compatibility. In this study, we developed a compatibility chart of frequently used continuous infusions in ICU and evaluated its usefulness. The compatibility chart contained information on trade name, pH, pharmaceutical characteristics, and compatibility with other continuous infusions, for 35 injections. Compatibility determinations were based on information in package inserts, interview forms, and other publications. To evaluate the usefulness of the compatibility chart, we administered a questionnaire survey to 67 nurses and 29 physicians working in ICU. The response rate of nurses and physicians was 100% and 65.5%, respectively. Among the questionees, 91.0% of nurses and 36.8% of physicians had used the compatibility chart. Of the questionees who used the chart, 86.9% of nurses and all physicians rated it as “very useful” or “useful.” Many nurses found that use of the compatibility chart shortened the investigation time of compatibility. Furthermore, this chart provided the pharmacists with quick access to compatibility information. These results show that the compatibility chart for injections was useful in preventing injection incompatibilities in ICU.
Herpes zoster (HZ) is a common viral infection in patients who receive bortezomib, therefore, the prophylactic administration of anti-viral drugs (AVDs) for HZ is recommended. However, the optimum dosage of AVDs for prophylaxis of HZ is unknown. The aim of this study was to evaluate the status of AVDs usage for prophylaxis of HZ and the effect of AVDs for prevention of HZ. We retrospectively analyzed the risk factors of HZ in patients with multiple myeloma, who were treated with bortezomib at nine hospitals in Japan between December 2006 and June 2010, and researched methods of prophylaxis. Of the 113 patients identified, 25 patients developed HZ. The median duration of development of HZ from initiation of bortezomib therapy was 29 days. Twenty-seven patients received AVDs orally for prophylaxis of HZ during bortezomib therapy; 17 patients received 200 mg acyclovir per day, 7 received 400 mg acyclovir per day, 2 received 500 mg valacyclovir per day and 1 received another dosage. One of these 27 prophylactic patients developed HZ; this patient received 200mg acyclovir per day. We analyzed the risk factors for HZ by use of multiple analyses, but could not identify significant risk factors with the exception of the prophylactic administration of AVDs (Odds ratio: 10.544, P = 0.025). Patients with multiple myeloma treated with bortezomib should receive prophylactic administration of AVD for HZ, however 1 patient developed HZ in support of low-dose acyclovir. A prospective trial to determine the optimum dosage of AVDs is required.
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