Primary Care Requirements for Pharmacists-Clinical Reasoning Education at Schools of Pharmaceutical Sciences.

For appropriate primary care practice corresponding to the various symptoms of a patient, team medicine on that combines the expertise of physicians and other medical staff has been recommended in recent years. It results in (1) higher quality of medical care, (2) lower burden on the physician, (3) better medical safety, and (4) reduced medical expenses. In order to promote team medicine through inter-professional collaboration, the responsibilities of the medical staff need to be reviewed to expand their respective roles. The Ministry of Health, Labour and Welfare designated nine specific medical acts by pharmacists in 2010. Some acts require clinical reasoning (medical interview and physical assessment) in order to manage side effects in patients undergoing drug therapy. The new curriculum introduced in 2015 includes primary care education for pharmacists who see patients before they are seen by a physician. Because such patients are usually seen by the pharmacist on a walk-in basis, medical interview and inspection education is especially important in this situation. However, there is incongruity in the physical assessment education of prospective pharmacists among schools of pharmaceutical sciences in recent years, which tends to focus primarily on vital signs. Moreover, there is currently no consensus among physicians on the optimum range of procedures performed by a pharmacist before the patient is seen by a physician. In this presentation, the practice of primary care by pharmacists is discussed from the following perspectives: (1) target symptoms and patients, (2) clinical reasoning education at pharmaceutical schools, and (3) future issues.

Group A Streptococcus pharyngitis outbreak among university students in a judo club.

We report on an outbreak of Group A Streptococcus (GAS) pharyngitis among university students in a judo club. Eventually, 14 of total 23 club members developed acute pharyngitis clinically. In a span of 15 days in April 2013, 12 students visited our hospital complaining of sore throat and high fever. All were men with a median age of 19.5 years (interquartile range, 18-21). The rapid streptococcal antigen test was positive in 3 of 4 patients (75%) without previous antibiotic treatment, and in 2 of 8 patients (25%) with previous antibiotic treatment. The definitive diagnosis of GAS pharyngitis was made by either a positive RADT or positive throat culture of GAS when patients had more than 2 findings from the Centor scoring system in this study. 5 students received the definitive diagnosis. The throat culture results showed that 1 out of 9 asymptomatic students was GAS-positive. The outbreak might have occurred by person-to-person contact while living in a dormitory and during judo training, which is a highly close-contact sport. However, there was also the possibility of oral transmission by the shared use of water bottles, although the culture from 1 bottle was negative. Some students continued to participate in the judo club activities after the onset of sore throat or fever. Healthcare professionals, teachers, and coaches should be aware of the potential outbreaks of infectious diseases among university students engaged in athletic activities. Furthermore, it is important to educate athletes about infectious diseases.

Preferences of Japanese rheumatoid arthritis patients in treatment decision-making.

OBJECTIVES: We investigated the decision-making preferences of rheumatoid arthritis (RA) patients using two different scales: the Decision Making Preference Scale (DMPS) and the modified Control Preference Scale (CPS). In addition, we evaluated the factors associated with patients' preferences for decision-making. METHODS: A cross-sectional study was performed using a self-administered anonymous questionnaire between October and December 2010 on 406 RA outpatients who consecutively visited 3 hospitals in Japan. The following variables were investigated: (1) DMPS, which is a subscale of the Autonomy Preference Index, composed of six items; patients responded on a 5-point Likert scale. (2) The modified CPS, in which patients were asked to choose one actual and one desired role in decision-making from among three options (passive role, collaborative role, and active role). (3) Sociodemographic data and RA-specific characteristics. Multivariate analyses were used to assess the relationship between patients' preferences and selected variables. RESULTS: The response rate was 58.6 %. There were few patients who wished to make their own decisions when they were hospitalized or illness became worse. However, the majority of patients desired to collaborate with the doctor in making treatment decisions according to the results of modified CPS. The results of modified CPS were significantly associated with the total scores of DMPS. Multivariate analysis demonstrated they younger age and not-housewife were associated with high scores of DMPS. CONCLUSIONS: Patient preferences in decision-making vary at RA outpatient clinic. Physicians need to assess decision-making preferences on an individual basis.

Can we determine depressive conditions on the basis of somatic symptoms? A cross-sectional study of depressive conditions among Japanese patients at a university hospital general medicine clinic.

OBJECTIVE: We evaluated the relationship between somatic symptoms and depressive conditions among patients visiting the general medicine clinic of a university hospital. METHODS: We distributed interview forms to 332 consecutive patients who visited our clinic for the first time between March and July 2011. Somatic symptoms were rated using a symptom checklist, and depressive conditions were evaluated using the Zung Self-Rating Depression Scale (SDS). We categorized and compared 2 groups of patients: patients with an SDS score of more than 48 (depressive group) and patients with an SDS score of less than 48 (non-depressive group). RESULTS: A total of 284 (85.5%) patients returned the forms. The SDS scores were obtained from the forms of 182 patients (64.1%). The average age of these 182 patients was 46.5±18.04 years. The mean number of checked symptoms was 4.3±3.03, and the most common symptom was general fatigue (n=106; 58.2%). The number of checked symptoms in the survey was higher in the depressive group patients than in the non-depressive group patients. Multiple logistic regression analysis indicated that general fatigue, headache, and sleeping problems were significant dependent variables which were related to depressive conditions. We defined these 3 symptoms as depression-related somatic symptoms (DRSS). On a receiver-operating characteristic curve, the optimal cutoff scores were 2 of 3 DRSS and 4 of 20 somatic symptoms. CONCLUSION: General physicians should consider possible depressive conditions when patients have 2 or more DRSS or 4 or more somatic symptoms.

Irinotecan hydrochloride (CPT-11) in dialysis patients with gastrointestinal cancer.

We investigated changes in drug disposition and toxicities with CPT-11 in 15 dialysis patients with gastrointestinal cancers to clarify whether CPT-11 could be administered safely in such patients. For comparison, the same parameters were also investigated in 10 cancer patients not undergoing dialysis. Items investigated included (1) plasma concentrations of SN-38, SN-38G and CPT-11 at 0, 1, 12, 24, 36, 48 and 72 h after administration, together with a comparison of mean AUC values for 3 dose levels of CPT-11 (50, 60 and 70 mg/m2) in dialysis patients and controls; and (2) occurrence of adverse events. Several findings emerged from this study: (1) No significant difference was observed in the AUC for SN-38 or CPT-11 between the dialysis and control groups; (2) The AUC for SN-38G at each dose was significantly higher in dialysis patients; and (3) Grade 1-4 leucopenia was observed in 11 of the dialysis patients. One patient developed grade 4 leucopenia and died due to sepsis. Anorexia, diarrhea, nausea, alopecia and interstitial pneumonia occurred in 6 dialysis patients. We found changes in drug dispositions of CPT-11, SN-38 and SN-38G in dialysis patients, suggesting that hepatic excretion, especially that of SN-38G, was increased. No significant difference in occurrence of adverse events was observed between the 2 groups. This indicates that CPT-11 can be administered safely in patients on dialysis.

Influence of bacterial superantigen TSST-1 against the anti-proliferative efficacy of immunosuppressive drugs and interleukin 2 production in peripheral blood mononuclear cells of hemodialysis patients and healthy subjects.

We investigated the influence of bacterial superantigen on the efficacies of immunosuppressive drugs on the blastogenesis of peripheral-blood mononuclear cells of 27 hemodialysis patients awaiting renal transplantation. The IC(50) values for prednisolone, methylprednisolone, cyclosporine, and tacrolimus evaluated in the superantigen-stimulated cells were significantly higher than those evaluated in concanavalin A-stimulated cells (p = 0.0002-0.018). Interleukin-2 amounts produced from superantigen-stimulated cells were significantly larger than those from concanavalin A-stimulated cells (p = 0.0363). These results suggest that superantigen attenuates the suppressive efficacies of glucocorticoids and calcineurin inhibitors by stimulating lymphocytes of hemodialysis patients awaiting transplantation to overproduce interleukin-2.

Evidence of different pharmacokinetics including relationship among AUC, peak, and trough levels between cyclosporine and tacrolimus in renal transplant recipients using new pharmacokinetic parameter--why cyclosporine is monitored by C(2) level and tacrolimus by trough level--.

The clinical efficacy of calcineurin inhibitors administered to renal transplant patients is considered to be a strong function of the area under the concentration time curve (AUC). Interestingly, monitoring timings of blood concentrations for two similar calcineurin inhibitors, cyclosporine (CYA; Neoral) and tacrolimus (TAC; Prograf) are different. Namely, CYA blood concentration is usually monitored at 2 h after administration (C(2)) substituted for peak concentration (C(p)) and TAC at trough concentration (C(t)). In the literature, data describing such characteristics of CYA and TAC have been presented in the past. However, each of these patient groups had different backgrounds. We have attempted to examine the behavior of blood concentration curves simultaneously for both CYA and TAC by establishing controlled groups of renal transplant patients with similar clinical backgrounds. Furthermore, we have analyzed the correlation with C(p) and C(t) versus AUC implementing area under the trough level (AUTL), or area above the trough level (AATL) as new pharmacokinetic parameters, such that C(2) for CYA and C(t) for TAC have been verified using controlled clinical data. We have also found distinct differences in the pharmacokinetics between CYA and TAC with the relationships between AUC, C(p), and C(t).

Intramesocolic diverticular perforation of the sigmoid colon diagnosed by detecting air collection in anterior pararenal space on computed tomography: report of a case.

A 64-year-old woman was admitted to our hospital with lower abdominal pain. Routine laboratory values were unremarkable except for the white blood cell count (15,000/micro litter) and the C-reactive protein (CRP) value (22.5 mg/dl). A Computed tomography (CT) scan revealed air collection in the middle of the anterior pararenal space. One day later, CT revealed air collection in the anterior pararenal space spread to the right side and abscess in the sigmoid mesentery. Because an intramesocolic perforation of the sigmoid colon was suspected, an emergency operation was performed. Abscess formation was recognized in the sigmoid mesentery, and sigmoidectomy including the contaminated mesentery and Hartmann.s procedure were performed. The perforation was 3 cm in diameter, and some diverticula were present in the vicinity of the perforated site. The specimen microscopically revealed perforation at the edge of the diverticulum in association with sudden disruption of the proper muscle layer. Based on pathological findings, intramesocolic diverticular perforation of the sigmoid colon was diagnosed. The present case is a very rare condition. However, it was possible to make a diagnosis preoperatively by detecting air collection in the anterior pararenal space on CT scan. If a sigmoid perforation occurs between the leaves of the mesocolon, air extends into the root of the sigmoid mesocolon and within the anterior pararenal space.

Study of interleukin-6 in the spread of colorectal cancer: the diagnostic significance of IL-6.

We investigated the diagnostic significance of IL-6 for lymph node metastasis and/or hepatic metastasis from colorectal cancer in 65 patients and evaluated the contributions of 8 factors (IL-6, HGF, IL-1beta, TNF-alpha, TGF-beta1, ELAM-1, ICAM-1, VCAM-1) toward Dukes.s classification of 53 patients. We also examined IL-6 expression in tumor tissue. From the receiver operating characteristic (ROC) curve analysis, an optimal cutoff value of 5.8 pg/ml was determined to classify lymph node and/or hepatic metastasis, and that of 6.3 pg/ml was determined to classify hepatic metastasis. These values indicated sensitivities of 55.0% and 71.4%, and specifi cities of 100% and 88.6%, respectively. IL-6, HGF, and ELAM-1 were very useful for distinguishing among Dukes.s A/B group, C group, and D group. In all cases with high IL-6 values (more than 25.0 pg/ml), immunohistochemical staining was positive for IL-6 in the cytoplasm of cancer cells. IL-6 is strongly suspected to be involved in lymph node and/or hepatic metastasis by promoting it through HGF, and serum IL-6 value (pg/ml) would be useful diagnostically to estimate whether or not there is a high risk of lymph node and/or hepatic metastasis.

Clinical significance of interleukin-6 (IL-6) in the spread of gastric cancer: role of IL-6 as a prognostic factor.

BACKGROUND: It is becoming clear that various cytokines are associated with the spread of cancer cells. The purpose of this study was to compare interleukin (IL)-6 levels in patients with gastric cancer to elucidate the role of IL-6 in predicting the spread of tumors. METHODS: In 60 patients, we assessed the correlation of serum IL-6 (pg/ml) with stage, histological findings, hepatic metastasis, and related factors (hepatocyte growth factor [HGF], IL-1beta, tumor necrosis factor [TNF]-alpha, and transforming growth factor [TGF]-beta1). We also investigated the diagnostic significance of the IL-6 level for advanced gastric cancer and lymph node metastasis, as well as the association between IL-6 elevation and outcome. Finally, we examined the expression of IL-6 in tumor tissue. RESULTS: Significant relationships were seen between serum IL-6 and stage, depth of tumor invasion (pT), lymphatic invasion (ly), venons invasion (v)*, lymph node metastasis (pN), hepatic metastasis (cH), and HGF (P < 0.01; *P < 0.05). With regard to the diagnostic significance of the IL-6 level for advanced gastric cancer and lymph node metastasis, when the cutoff value of IL-6 was set at 1.97 pg/ml, the sensitivity was 81.8% and 87.5%; specificity was 66.7% and 58.3%; and accuracy was 77.1% and 72.9%, respectively. The 1- and 3-year cumulative survival rates for patients with an IL-6 value of more than 1.97 pg/ml (69.0% and 43.4%, respectively) were significantly lower than those for patients with an IL-6 value of 1.97 pg/ml or less (94.4% and 87.2%, respectively; P < 0.05). Immunohistochemical staining was positive for IL-6 in the cytoplasm of cancer cells. CONCLUSION: We suspect that IL-6 is involved in cancer invasion and lymph node and/or hepatic metastasis. Our results indicate that IL-6 could be used as a prognostic factor for survival.