Search

Purpose: The effect of pharmacist intervention on blood sugar control in diabetic outpatients in a pharmacist-managed clinic was studied by focusing on the re-elevation of the glycated hemoglobin (A1c) level defined as a continuous variable. Methods : A retrospective chart review was performed at the Mizushima Kyodo Hospital from April 2014 to March 2016. Of the 221 diabetic outpatients who were provided guidance by nurses and nutritional managers, 62 further consulted the pharmacist-managed clinic. The remaining 159 patients were enrolled in a nonintervention group. Finally, the data of 115 patients with A1c level of ≥7.5% and A1c re-elevation were extracted. Intergroup comparison was performed between the pharmacist intervention (n = 26) and nonintervention (n = 89) groups. In both the groups, the starting point (baseline) was the time when the A1c level of ≥7.5% was observed. Subsequent monitoring was performed once in every 3 months. The average cumulative level of A1c re-elevation (CARE) was compared between groups. Patients with A1c level of ≥8.0% and A1c level between 7.5% and 8.0%, and male and female patients were also compared. Furthermore, the number of days until the re-elevation of the A1c level from the baseline was also compared. Results : The CARE values were 0.89 ± 0.86% and 1.51 ± 1.25% in the pharmacist intervention and nonintervention groups, respectively, showing a significant difference ( P = .0195). There were no significant differences between patients with A1c level of ≥8.0% and A1c level between 7.5% and 8.0%, or between males and females. The number of days until the re-elevation of A1c level from the baseline also showed no significant difference. Conclusion: Pharmacist intervention for diabetic outpatients in pharmacist-managed clinics significantly suppressed CARE when compared with effects of no intervention, and this could be useful for preventing the exacerbation of diabetes., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Objective: We conducted a retrospective study based on composite endpoints for treatment failure to evaluate the effect of pharmacist-led VCM initial dose planning for Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia patients., Methods: A retrospective cohort study was performed between pharmacist intervention and non-intervention groups. In this study, four types of failure were defined as the composite endpoint. When any one of the following failures occurred: 1) Death within 30 days from the start of VCM therapy, 2) Positive blood culture 7 days after the start of VCM therapy, 3) Change of VCM to another anti-MRSA agent, and 4) Development of nephrotoxicity, we considered that VCM treatment had failed. Survival time analysis was conducted with the Kaplan-Meier method and Cox's proportional hazard model that included seven predefined parameters: pharmacist intervention, age, sex, weight, baseline VCM trough concentration, Charlson Comorbidity Index (CCI), and Pitt Bacteremia score (PBS). The effect of pharmacist intervention was studied as the survival probability estimated from the period of time from the start of VCM administration to the earliest failure., Results: The survival rate at 30 days after starting VCM therapy, at the end of follow-up, was 53.1 and 82.1% in the non-intervention and intervention groups, respectively. A significant survival time prolongation was noted in the intervention group (p = 0.011, log rank test). Among the seven parameters, only pharmacist intervention was significantly different and its hazard ratio was 0.26 (p = 0.014). The survival probability of the intervention group was higher than that of the non-intervention group for the time to each failure. In subgroup analyses, a significant difference was noted in male patients between the intervention and non-intervention groups (p = 0.005). Age was categorized into those under and over 65 years old. For those over 65 years old, a significant difference was shown between the groups (p = 0.018)., Conclusion: To our knowledge, this is the first study to evaluate the failure of VCM treatment based on the composite endpoint. Pharmacist intervention through the initial VCM dose planning could maintain a balance between the efficacy and safety of VCM treatment and might avoid treatment failure for patients with MRSA bacteremia. Further investigations with large sample sizes are required to confirm our findings., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To evaluate the impact of pharmacist interventions on preventing nephrotoxicity from vancomycin., Methods: A pre- to postpharmacist intervention study was performed in the Tsuyama Central Hospital. 508 Patients admitted from May 2007 to May 2012 served as the non-pharmacist intervention group, while 102 patients admitted from June 2012 to November 2013 formed the pharmacist intervention group. Pharmacist interventions were mainly performed for the initial dosage planning, controlling vancomycin prescriptions, and real-time monitoring of medical records before routine therapeutic drug monitoring. The non- and pharmacist intervention groups were compared to evaluate the outcomes of pharmacist interventions., Results: By pharmacist interventions, initial trough concentration of vancomycin promptly tightened within the 10 - 20 μg/mL therapeutic trough concentration range (p < 0.001), and reaching an ineffective or risky trough concentration was avoided. Also, the mean vancomycin trough concentrations of patients with and without nephrotoxicity were 23.9 and 13.9 μg/mL, respectively. Furthermore, by multivariate logistic regression analysis, significant increased risks of nephrotoxicity in baseline creatinine clearance, and 15 - 20 and over 20 μg/mL of initial vancomycin trough concentration were observed. Significant decreased risk of nephrotoxicity was gender (male). Although pharmacist intervention showed a trend of 45% decrease in the incidence of nephrotoxicity, there was no significant difference between the pharmacist intervention and non-intervention groups., Conclusion: Pharmacist intervention may have an impact on vancomycin therapy from the standpoint of balancing a higher vancomycin trough concentration with risk of nephrotoxicity.

Our study aimed to find more effective protective agents against mucosa toxicity induced by methotrexate and 5-fluorouracil. We focused on the relationship between oral mucositis and keratinocyte injury and examined methotrexate and 5-fluorouracil-induced cytotoxicity in normal human epidermal keratinocyte cell lines. Cell viability and superoxide radical activity were measured based on converting WST-1 (4-[3-(4-indophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzen disulfonate) to a water-soluble formazan dye. DNA synthesis by 5-bromo-2'-deoxyuridine incorporation was measured as an indirect parameter of cell proliferation. Allopurinol and amifostine were used as the radical scavengers. l-glutamine was used as a mucosa-protective agent. A cyclooxygenase inhibitor interrupting the production of hydroxyl radicals in the arachidonic acid cascade was also examined. 5-fluorouracil and methotrexate caused cytotoxicity due to the activation of intracellular superoxide radicals specifically on normal human epidermal keratinocytes. From the electron spin resonance study, it was found that allopurinol was a superoxide radical scavenger, while amifostine was hydroxyl radical scavenger. Allopurinol showed no effect on the cytotoxicity due to 5-fluorouracil and methotrexate. The cell injury induced by methotrexate was restored by amifostine. However, the cell injury induced by 5-fluorouracil was markedly recovered by a selective cyclooxygenase-1 inhibitor compared to amifostine. It was suggested that amifostine and cyclooxygenase-1 inhibitor could be useful protective agents against methotrexate and 5-fluorouracil chemotherapeutic toxicity. Additionally, this in vitro cell injury model using normal human epidermal keratinocytes may be useful for understanding the pathophysiology of oral mucositis induced by chemotherapeutic agents.

A simple liquid chromatography (LC) method was developed for determination of the therapeutic level of mizoribine in human plasma. After precipitation of plasma proteins with 6% perchloric acid, mizoribine was determined by LC with spectophotometric detection. The peak height for mizoribine was linearly related to its concentrations, which ranged from 0.09 to 3.13 microg/mL. Therefore, the limit of quantitation was considered to be 0.09 microg/mL. The accuracy was 104.96-107.37%. The intra- and interday relative standard deviation values were in the range of 1.10-3.25%. The detection limit was 0.025 microg/mL, defined as a signal-to-noise ratio of 3. The plasma concentrations of mizoribine were not related to the dosage. Because mizoribine was mainly excreted in the urine, the plasma concentrations of mizoribine might be affected by a change in renal function. Therefore, the mizoribine concentration in blood should be monitored and the dosage adjusted, depending on the condition of renal function. It was suggested that the present method may be applied well in the therapeutic drug monitoring for mizoribine.

Therapeutic drug monitoring of anti-inflammatory drugs is necessary for the identification of the agents that cause toxic events and for the decision on the treatment for intoxication. Recently, capillary electrophoresis (CE) has been developed for the simple and rapid analyses of a variety of chemical agents. Micellar electrokinetic chromatography (MEKC) can separate acidic, neutral and basic anti-inflammatory drugs in serum. Furthermore, serum samples are directly applied to the CE system without any pretreatments, and some anti-inflammatory drugs can be separated from serum albumin in the MEKC analysis. On the other hand, capillary zone electrophoresis (CZE) enables us to determine a few microg/mL levels of acidic anti-inflammatory drugs with simple running buffer and stacking technique. A rapid and simultaneous determination of several analgesic anti-inflammatory agents, including ibuprofen, acetaminophen, indomethacin, and salicylic acid in human serum has been developed by using CZE. Therefore, the CZE and MEKC analysis may become a potentially useful alternative to high-performance liquid chromatography (HPLC) and fluorescence polarization immunoassay (FPIA) for therapeutic drug monitoring, particularly in serum of patients suffering from intoxication by overdosage of nonsteroidal anti-inflammatory agents.

A capillary electrophoretic method for the simultaneous determination of sulfamethoxazole and trimethoprim in plasma was developed. Sulfamethoxazole and trimethoprim extracted from human plasma with ethyl acetate were analyzed at 20 kV and 25 degrees C using 15 mm phosphate buffer (pH 6.2) as the electrolyte. The detection was by UV at 220 nm. The run time was 8.0 min and the limit of quantification was 10.00 microg/mL for sulfamethoxazole and 2.00 microg/mL for trimethoprim. The recovery was >99% for both compounds. This method enabled the detection of sulfamethoxazole and trimethoprim in plasma of patients after oral ingestion of their combined formulation. The present simple and rapid method is applicable to drug monitoring in immunocompromised patients who are taking the combined formulation of these compounds for the treatment or prophylaxis of Pneumocystis carinii pneumonia., (Copyright 2004 John Wiley & Sons, Ltd.)

A simple high-performance liquid chromatographic method was developed for the simultaneous determination of the therapeutic levels of acyclovir and ganciclovir in human plasma. After precipitation of plasma proteins with 6% perchloric acid, acyclovir and ganciclovir were simultaneously determined by reversed-phase chromatography with spectophotometric detection at 254 nm. The peak heights for acyclovir and ganciclovir were linearly related to their concentrations ranging from 0.063 to 2.080 micro g/mL. The recovery was 100.48-102.84% for acyclovir and 99.26-103.07% for ganciclovir. The intra- and inter-day relative standard deviation values were in the range 0.186-8.703% for acyclovir and 0.137-6.424% for ganciclovir. The detection limits for both compounds were 0.01 micro g/mL determined as the signal-to-noise ratio of 3. The present method is applicable to therapeutic monitoring during antiviral medication., (Copyright 2003 John Wiley & Sons, Ltd.)

A rapid and simultaneous determination of several analgesic antiinflammatory agents--ibuprofen, acetaminophen, indomethacin, and salicylic acid--in human serum was developed by using capillary zone electrophoresis (CZE) coupled with diode-array ultraviolet detection. After precipitation of serum protein with acetonitrile containing 3-isobutyl-1-methylxanthine as the internal standard, an aliquot of deproteinized samples was applied directly to the CZE system. It enabled us to measure all of these four agents within 6 min, and there were no peaks interfering with the assay of these agents or 3-isobutyl-1-methylxanthine. Both the separation and quantification of these agents in human serum were reproducible after repeated analysis within a day or day-to-day analysis. In addition, there was a good correlation for each drug (r = 0.997-0.999) between the values in serum determined by CZE analysis and those measured either by high-performance liquid chromatography with ultraviolet detection (ibuprofen and indomethacin) or by fluorescence polarization immunoassay (acetaminophen and salicylic acid). Therefore, the present CZE analysis could provide a simple, rapid, and efficient method for the identification as well as monitoring of analgesic antiinflammatory agents, particularly in serum of patients suffering from intoxication by overdosage of these agents.

Objective: To report a case of elevated blood tacrolimus concentration after application of topical tacrolimus ointment in an erythrodermic patient., Case Summary: A 44-year-old man developed generalized erythroderma and itching due to infection with human T-cell lymphotropic virus. Despite application of strong glucocorticosteroid ointments, the symptoms and area of erythroderma were not alleviated. Daily topical application of tacrolimus 0.1% ointment was added and therapeutic drug monitoring was started. The dose and applied area of tacrolimus were gradually increased from 2.5 to 12.5 g/d and from 10% to 90% of body surface area, respectively. Because the trough concentration of tacrolimus in whole blood increased from 7.5 ng/mL on treatment day 9 to 15.4 ng/mL on day 13, the dose was reduced to 10 g/d. However, the concentration further elevated to 16.5 ng/mL. Therefore, the applied area was reduced to 20% of body surface area, and the tacrolimus concentration decreased gradually thereafter. Although the transient increase of blood tacrolimus concentration was observed on day 23, treatment with 20% applied area and 5 g/d were maintained., Discussion: Topically applied tacrolimus was substantially absorbed with the expansion of its applied area and dose. Increased tacrolimus concentrations may have a tendency to depend on the increase of the percent of body surface area per dose. Our findings showing the elevation of blood tacrolimus concentration after application of the ointment to a large area of the body suggest that the applied area should be as narrow as possible in a barrier-disrupted condition such as erythroderma. However, the safety of tacrolimus ointment has not been established in patients with generalized erythroderma., Conclusions: Tacrolimus concentrations in whole blood should be carefully monitored to prevent nephrotoxicity. Based on the results of that monitoring, the application area and dose of tacrolimus ointment should be closely adjusted, especially in generalized erythrodermic cases.

The effects of a variety of fibrates on the cell viability were examined in human embryonal rhabdomyosarcoma cells (HRMSC). Five fibrates, including fenofibrate, clofibrate, gemfibrozil, bezafibrate and ciprofibrate, all concentration-dependently reduced the cell viability determined by the mitochondrial enzyme activity. The cell injury occurred time-dependently and was marked at 24-48 h. The toxic action of fibrates was specific to HRMSC, since bezafibrate did not induce any marked changes in the viability of human microvascular endothelial cells or arterial smooth muscle cells. Synergistic cell injury was observed after a combined treatment with bezafibrate and simvastatin, although simvastatin alone reduced the cell viability. The cell injury was characterized by a typical nuclear damage, as evidenced by Hoechst 33342 staining and deoxynucleotidyl transferase dUTP nick-end label-positive staining. Similar cell-specific injury was induced by 8(S)-hydroxyeicosatetraenoic acid, a potent peroxisome proliferator-activated receptor alpha (PPARalpha) agonist. Consistent with these data, a marked expression for PPARalpha mRNA was observed in HRMSC but not in the endothelial or smooth muscle cells. Therefore, it is suggested that fibrates cause a cell-specific injury in HRMSC via activation of PPARalpha. Moreover, our present cell injury model using HRMSC may be useful for elucidating the mechanisms of clinical rhabdomyolysis induced by lipid-lowering agents.

In the present study, the effects of systemic injection of radiographic contrast media (RCM) on vascular permeability was examined in various tissues of rats and the involvement of mast cell histamine in the RCM-induced vascular hyperpermeability subsequently determined. Both ionic (amidotrizoate) and non-ionic RCM (iohexol) enhanced vascular permeability specifically in lungs, as assessed by the extravasation of Evans blue (EB) dye. Another ionic RCM, ioxaglate, also markedly increased pulmonary vascular permeability and decreased pulmonary histamine content, whereby the extent of the reduction correlated well with the vascular hyperpermeability. Depletion of mast cells by prior treatment with compound 48/80 markedly attenuated the ioxaglate-induced enhancement of EB extravasation. The ioxaglate-increased extravasation was also inhibited by the mast cell stabilizer sodium cromoglicate and histamine H(1) and H(2) receptor antagonists. In isolated rat pulmonary mast cells, ioxaglate induced the concentration-dependent release of beta-hexosaminidase, an index of mast cell degranulation. The present findings thus show clearly that RCM causes the degradation of pulmonary mast cells and the resultant release of histamine that in turn increases vascular permeability by stimulating histamine H(1) and H(2) receptors.

Objective: To determine if there is a significant difference in the national certification examination scores, and in comments received from clinical faculty, between PBL and pre-PBL groups., Design: Retrospective analyses of national certification examination scores and clinical faculty evaluation files., Participants: Medical technology students at the University of Hawaii., Main Outcome Measures: Means of a national certification examination scores of PBL and pre-PBL groups are statistically compared. Types of clinical faculty comments are rank-ordered and compared between the two groups., Results: PBL group did significantly better in the Urinalysis section of the national certification examination. Pre-PBL group received more "Quiet but got better" comments from clinical faculty., Conclusion: PBL can affect student outcomes in both national certification exams and perception by clinical faculty.

Objective: To describe the steps taken by the Hawaii Society for Clinical Laboratory Science, an affiliate of the American Society for Clinical Laboratory Science, to inform local laboratory professionals of current trends and to prepare for the future., Results: A Strategic Planning workshop was conducted at the 1997 Hawaii Society for Clinical Laboratory Science Annual Meeting where participants reviewed the essential (but non-traditional) functions of clinical laboratory scientists, and described current realities, identified forces and players affecting the changes, and envisioned the future of our profession., Conclusion: As the way health care is provided changes in response to economics and advances in technology, the role of clinical laboratory scientists needs to be redefined. The Hawaii Society for Clinical Laboratory Science continues to provide timely support for members, and plans to work collaboratively with the local chapter of the Clinical Laboratory Managers' Association to advance clinical laboratory science to an appropriate place in the health care community.

Seven hours after suicidal ingestion of about 21 g of boric acid, a 26-year-old female admitted to our hospital in a state of slightly impaired consciousness, with frequent vomiting, shivering, fever and skin flush. Immediately, gastric lavage, followed by administration of activated charcoal and laxative (MgSO4), was performed. In order to ensure her urination, fluid infusion therapy was conducted with the aid of diuretics (furosemide). Since the serum concentrations of boric acid was very high, hemodialysis was carried out twice during the first 39 h. She responded well to the above mentioned treatment and was discharged 12 d post-admission without any sequelae. The concentrations of boric acid in serum and urine were measured in appropriate intervals with our modified Miyamoto's method, and the pharmacokinetics of boric acid were analyzed. The concentration of boric acid in serum and urine at the beginning of treatment was 465 micrograms/ml and 3.40 mg/ml, respectively. The half-life of boric acid in serum was 13.46 h, whereas it was shortened to 3.76 h during hemodialysis. The total body clearance was 0.99 l/h, while it increased to 3.53 l/h by hemodialysis. The additional removal of boric acid by hemodialysis was estimated to be about 5 g. It was concluded that the hemodialysis was very useful in the treatment of boric acid poisoning, because it accelerated the elimination of boric acid about four times faster than with conventional treatment.

The seroprevalence of hepatitis B surface antigen (HBsAg) by gender and age and of human T-lymphotropic virus type I (HTLV-I), and their concomitant carriage was examined among blood donors at the Kitakyushu Red Cross Blood Centre in the fiscal year of 1988. The positive rates of HBsAg among males were consistently higher than those of females; the peaks were detected in male donors aged 30-39 years and in females aged 40-49 years. Declining seropositive rates in individuals aged 50 years or over were observed for both genders. Self-selection due to chronic HBV infection may partly account for such tendencies. On the other hand, the prevalence rates of anti-HTLV-I antibodies among males were uniformly lower than those of females, which must be attributable to male-to-female transmission of HTLV-I via sexual contact. Elevated positive rates in proportion to age were noted for both genders, which may be explained in part by birth cohort effect. The seropositive rates of HBsAg among HTLV-1 carriers were not statistically different from those of non-HTLV-I carriers. Conversely, the prevalence of antibodies to HTLV-I was unrelated to the status of seropositivity of HBsAg.

We examined mortality from adult T-cell leukemia/lymphoma (ATL/ATLL) and other diseases alleged to be associated with human T-lymphotropic virus type I (HTLV-I) among anti-HTLV-I antibody-positive blood donors in Kyushu, Japan. During 1984-87, a total of 3,991 blood donors aged 40 years or over were followed from the date of donation to the date of death or the end of the study. Crude mortality rates from ATL (with 95 percent confidence intervals) were 68 per 100,000 (13-202) for males and 36 per 100,000 (3-132) for females. The rates were underestimated by approximately 50 percent because of self-selection and short observation periods. Neither death rates from other cancers nor death rates from all cancers were elevated.

The efficacy of both the emetic syrup prepared in the previous report and the United States Pharmacopoeia (USP) ipecac syrup concerning the prevention of drug absorption was investigated in 4 beagle dogs using a randomized and cross-over design. In order to control the intragastric pH of the beagle dogs, the administration of pentagastrin or hydrochloric acid (HCl)-glycine buffer (pH 1.5) was tested. The intragastric pH changed from 7.2 to 1.8 with the intramuscular administration of pentagastrin, but the primary emesis occurred more slowly. On the other hand, the HCl-glycine buffer (pH 1.5) gave the appropriate emesis. Therefore, the HCl-glycine buffer (pH 1.5) was used to control the intragastric pH of the beagle dogs. Acetaminophen (AcA), salicylic acid (SA) and kanamycin (KM) as markers were administered orally after conditioning the intragastric pH at 1.5. The emetic syrup or the USP ipecac syrup was then administered. The recovery rate of AcA and KM from vomit was 42-65%. The emetic syrup and the USP ipecac syrup significantly reduced the absorption of AcA from the calculation of pharmacokinetic parameters compared to the control syrup. It was observed that the absorption of cephaeline (CP) in the emetic syrup was less than that of CP in the USP ipecac syrup.

Callus and adventitious roots were induced on leaf segments from shoot culture of Cephaelis ipecacuanha A. Richard on Murashige-Skoog medium containing 2,4-dichlorophenoxyacetic acid, indole-3-acetic acid, 1-naphthaleneacetic acid and kinetin. The contents of emetic alkaloids in calli, roots and root suspension cultures were quantified by HPLC. Roots cultured in solid and liquid Murashige-Skoog media yielded emetine and cephaeline. The amount of the two alkaloids in the root suspension culture was very similar to that of roots from ipecac mother plant grown in a greenhouse. In contrast, calli subcultured on Murashige-Skoog media containing combinations of 2,4-dichlorophenoxyacetic acid and kinetin produced only trace amounts of emetic alkaloids.

Shoot cultures of Cephaelis ipecacuanha A. Richard were established by using shoot tips as initial explants. Multiple shoots were obtained from node segments upon culture on B5 medium supplemented with NAA-BA (0.01-3, 5 mg/l). These shoots were rooted on B5 and 1/2 MS media containing IAA or NAA, and the regenerated plants were transferred to soil and grown in a greenhouse. The emetic alkaloids of the regenerated plants, mother plants and leaves of shoot cultures were analyzed by TLC and HPLC. Seven months of growth under greenhouse condition, the contents of the emetic alkaloids in the regenerated plants were comparable to those of the mother plants.