Creating and evaluating the score to assess overdose: the OD score.

BACKGROUND: During disasters (including epidemics such as coronavirus disease 2019), the capacity of emergency departments is exceeded, thereby hindering the administration of appropriate lifesaving measures. Furthermore, the number of overdose patients increases because of the stress overload during emergency situation. The fact that overdose patients are forced to be transported to medical facilities that do not typically treat them is becoming worrisome. Moreover, there is no definitive score for overdose. This study aimed to create a patient-specific scoring system to assess overdose. METHODS: This was a retrospective single-center study. The evidence-based OD score was evaluated on a scale of 0-15. Further, logistic analysis and receiver operating characteristic (ROC) curve analysis were performed to evaluate the score. RESULTS: Overall, 262 patients (including 118 overdose patients) receiving care at the intensive care unit of Japan's Teikyo University Hospital in 2021 were targeted. Regarding the total OD score, ROC analysis revealed a cutoff of 8 (area under the curve [AUC]: 0.99, 95% confidence interval [CI]: 0.980-0.997, sensitivity: 0.95, specificity: 0.95, p < 0.05), which was considered to indicate an overdose. Of the items evaluated in the OD score, the scenario at the location of the patient's discovery (adjusted odds ratio [AOR]: 16.8, 95% CI: 5.0-255.9, p = 0.002) and recent experience of mental anxiety (AOR: 55.7, 95% CI: 2.8-5399.5, p = 0.03) significantly predicted an overdose in multivariable logistic regression analysis. External validation revealed that the OD score could also identify overdose in patients treated in a cohort from 2022 (average cutoff: 8.6, average AUC: 1.0, p < 0.0001). CONCLUSIONS: The OD score could accurately assess overdose patients. Medical facilities that do not frequently address overdose patients will benefit from the use of this score.

Peptides Derived from Soybean ß-Conglycinin Induce the Migration of Human Peripheral Polymorphonuclear Leukocytes.

Food-derived peptides have various biological activities. When food proteins are ingested orally, they are digested into peptides by endogenous digestive enzymes and absorbed by the immune cell-rich intestinal tract. However, little is known about the effects of food-derived peptides on the motility of human immune cells. In this study, we aimed to understand the effects of peptides derived from a soybean protein ß-conglycinin on the motility of human peripheral polymorphonuclear leukocytes. We illustrated that MITL and MITLAIPVNKPGR, produced by digestion using in-vivo enzymes (trypsin and pancreatic elastase) of ß-conglycinin, induces the migration of dibutyryl cAMP (Bt2 cAMP)-differentiated human promyelocytic leukemia 60 (HL-60) cells and human polymorphonuclear leukocytes in a dose- and time-dependent manner. This migration was more pronounced in Bt2 cAMP-differentiated HL-60 cells; mRNA expression of formyl peptide receptor (FPR) 1 increased significantly than in all-trans-retinoic acid (ATRA)-differentiated HL-60 cells. This migration was inhibited by tert-butoxycarbonyl (Boc)-MLP, an inhibitor of FPR, and by pretreatment with pertussis toxin (PTX). However, the effect was weak when treated with WRW4, a selective inhibitor of the FPR2. We then demonstrated that MITLAIPVNKPGR induced intracellular calcium responses in human polymorphonuclear leukocytes and Bt2 cAMP-HL60 cells. Furthermore, pre-treatment by fMLP desensitized the calcium response of MITLAIPVNKPGR in these cells. From the above, MITLAIPVNKPGR and MITL derived from soybean ß-conglycinin induced polymorphonuclear leukocyte migration via the FPR1-dependent mechanism. We found chemotactic peptides to human polymorphonuclear leukocytes, which are the endogenous enzyme digests of soybean protein.

Anticholinergic Load Is Associated with Swallowing Dysfunction in Convalescent Older Patients after a Stroke.

This study aimed to establish whether anticholinergic load affects the swallowing function of geriatric stroke patients in convalescent stages, as no proven association between the anticholinergic load-based Anticholinergic Risk Scale and the swallowing dysfunction in Japanese patients was known. A retrospective cohort study was conducted on hospitalized older patients undergoing rehabilitation after stroke. The study outcomes included evaluating the patients at hospital discharge using the Functional Oral Intake Scale. To evaluate the effects of an increased anticholinergic load, we used a multivariate analysis to examine whether the change in the Anticholinergic Risk Scale during hospitalization was associated with the outcome. Of 542 enrolled patients, 345 (63.7%) presented with cerebral infarction, 148 (27.3%) with intracerebral hemorrhage, and 49 (9%) with subarachnoid hemorrhage. The change in the Anticholinergic Risk Scale was independently associated with the Functional Oral Intake Scale (ß = -0.118, p = 0.0164) at discharge. Among anticholinergics, the use of chlorpromazine, hydroxyzine, haloperidol, metoclopramide, risperidone, etc., increased significantly from admission to discharge. An increased anticholinergic load was associated with swallowing dysfunction in older patients undergoing stroke rehabilitation.

SLC23A3 is a renal hypoxanthine transporter.

LLC-PK1 renal cells show Na+-dependent and Na+-independent hypoxanthine uptake. While the latter is inhibited by adenine, neither are inhibited by xanthine. In rats, intestinal Na+-dependent hypoxanthine transporter Slc23a4 is not expressed in the kidney, and its action is inhibited by xanthine. This study aimed to clone Slc23a4-paralog SLC23A3 from the human kidney and investigate its hypoxanthine transport activity. We observed Na+-dependent 10 nM [3H]-hypoxanthine uptake in SLC23A3 RNA-injected Xenopus oocytes. Moreover, 100 µM xanthine did not inhibit Na+-independent 300 nM [3H]-hypoxanthine uptake, whereas 100 µM adenine did. These results confirm that SLC23A3 is a hypoxanthine transporter in the human kidney.

Evaluation of factors related to overdose in patients with impaired consciousness who are transported by emergency medical services: an age-specific research.

BACKGROUND: Drug overdose accounts for most of the admissions to the emergency department. Prescription drugs, most of which are psychotropic medications, are often misused for drug overdose. The purpose of this study was to investigate the association between overdose in patients transported with disorders of consciousness and psychotropic medications administered prior to transport, so as to enable quick differentiation of drug overdose patients from patients with disorders of consciousness. METHODS: We evaluated 222 patients transported to the Advanced Critical Care Center of Teikyo University Hospital due to disorders of consciousness. The patients were categorized into two groups: overdose group (n = 128) and control group with other disorders of consciousness (n = 94). Logistic regression models were used to assess the association between disorders of consciousness due to drug overdose and psychotropic drugs prescribed before emergency transportation based on sex and age. RESULTS: According to multivariate logistic regression analysis, only female sex (odds ratio [OR] 4.54, 95% confidence interval [CI] 2.43-8.05, P < 0.0001) was associated with overall overdose. Results from the univariate logistic regression analysis showed that in the group of patients aged 40-50 years, female sex (OR 4.36, 95% CI; 1.54-12.4, P = 0.006) and the use of psychotropic drugs (OR 5.05, 95% CI; 1.75-14.6, P = 0.003), benzodiazepines (OR 4.64, 95% CI; 1.61-13.4, P < 0.05), antidepressants (OR 11.4, 95% CI; 2.35-55.8, P = 0.003), and anticonvulsants (OR 4.46, 95% CI; 1.11-17.9, P = 0.035) were associated with overdose. According to multivariate logistic regression analysis, female sex (OR 4.44, 95% CI; 1.37-14.3, P = 0.013) and antidepressants (OR 7.95, 95% CI; 1.21-52.1, P = 0.031) were associated with overdose patients aged 40-50 years. CONCLUSIONS: As a reference in distinguishing overdose in women in their 40s and 50s who present with impaired consciousness, attention may need to be paid to the type of psychotropic drug used, especially antidepressants.

Polypharmacy and Malnutrition Management of Elderly Perioperative Patients with Cancer: A Systematic Review.

Malnutrition, which commonly occurs in perioperative patients with cancer, leads to decreased muscle mass, hypoalbuminemia, and edema, thereby increasing the patient's risk of various complications. Thus, the nutritional management of perioperative patients with cancer should be focused on to ensure that surgical treatment is safe and effective, postoperative complications are prevented, and mortality is reduced. Pathophysiological and drug-induced factors in elderly patients with cancer are associated with the risk of developing malnutrition. Pathophysiological factors include the effects of tumors, cachexia, and anorexia of aging. Metabolic changes, such as inflammation, excess catabolism, and anabolic resistance in patients with tumor-induced cancer alter the body's ability to use essential nutrients. Drug-induced factors include the side effects of anticancer drugs and polypharmacy. Drug-drug, drug-disease, drug-nutrient, and drug-food interactions can significantly affect the patient's nutritional status. Furthermore, malnutrition may affect pharmacokinetics and pharmacodynamics, potentiate drug effects, and cause side effects. This review outlines polypharmacy and malnutrition, the impact of malnutrition on drug efficacy, drug-nutrient and drug-food interactions, and intervention effects on polypharmacy or cancer cachexia in elderly perioperative patients with cancer.

Pharmacist medication instructions are associated with continued medication self-management in older adults: a retrospective observational study.

BACKGROUND: Various factors are related to self-management of medication. However, few reports comprehensively examine the factors related to patients, medication levels, and other factors related to the recuperative environment, such as family support. The aim of this study was to investigate factors affecting the continuation of medication self-management among hospitalized older adults receiving convalescent rehabilitation. METHODS: We conducted a retrospective observational study with 274 consecutive patients newly admitted to the convalescent rehabilitation wards at a single hospital in Japan between January 2017 and May 2018. Participants who were assessed for their ability to take their medication using the Japanese Regimen Adherence Capacity Tests, were deemed to be self-manageable, and were able to successfully continue to self-manage their medication from admission to discharge were categorized as the "continuation group," and those who were not able to continue were categorized as the "non-continuation group." We analyzed the groups' demographic data, laboratory data, and Functional Independence Measure. The primary outcome was the continuation of medication self-management from admission to discharge. RESULTS: After enrollment, 134 patients (median age 82 years; 62.7% women) were included in the final analysis. Some 60.4% of eligible patients were able to maintain medication self-management during their hospitalization. The multiple logistic regression analysis for the continuation of medication self-management during hospitalization after adjusting for confounding factors revealed that pharmacist medication instructions were independently and positively correlated with successful continuation of medication self-management (odds ratio: 1.378; 95% confidence interval 1.085-1.831; p = 0.0076). CONCLUSION: Successful continuation of medication self-management is associated with pharmacist medication instructions among hospitalized older adults undergoing rehabilitation. TRAIL REGISTRATION: The Ethics Committee's registration number is "TGE01216-066".

The impact of decreasing potentially inappropriate medications on activities of daily living in a convalescent rehabilitation setting.

Background Polypharmacy or potentially inappropriate medications negatively affect the functional recovery of rehabilitation. However, limited research exists regarding the effect of decreasing in potentially inappropriate medications use on functional improvement of rehabilitation in geriatric Japanese patients. Objective To elucidate whether decreasing PIM during hospitalization could be a predictor of rehabilitation outcomes among geriatric patients in a convalescent rehabilitation setting. Setting This study was conducted at the convalescent rehabilitation ward in the Hitachinaka General Hospital in Japan. Methods This retrospective observational cohort study included consecutive geriatric patients admitted at the convalescent rehabilitation ward between 2010 and 2018. Participants were divided based on presence or absence of decreasing in potentially inappropriate medications use during hospitalization. A multiple linear regression analysis was performed to analyze whether decreasing potentially inappropriate medications use during hospitalization could be a predictor of Functional Independence Measure-Motor at discharge. Main outcome measures The primary outcome was the Functional Independence Measure-Motor at discharge. Results In total, 569 participants (interquartile range 73-85 years; 33.6% men) were included in the present study. A multiple linear regression analysis of Functional Independence Measure-Motor at discharge, adjusting for confounding factors, revealed that decreasing in potentially inappropriate medications use was independently correlated with Functional Independence Measure-Motor at discharge. In particular, the use of first-generation antihistamines, antipsychotics, benzodiazepines, and non-steroidal anti-inflammatory drugs among potentially inappropriate medications decreased significantly during hospitalization. Conclusion Decreased potentially inappropriate medications use during hospitalization may be a predictor of improvement of rehabilitation outcomes in geriatric patients.

[Effectiveness of Topical NSAIDs in a Gastric Cancer Patient with Bone Metastasis Pain during Therapy with Opioids and Oral NSAIDs].

Cancer patients often suffer from severe pain related to bone metastasis. We encountered a patient in whom the addition of topical non-steroidal anti-inflammatory drugs (NSAIDs) for persistent pain related to bone metastasis during therapy with opioids and oral NSAIDs reduced pain, improving activities of daily living (ADL). Fentanyl patches, celecoxib, denosumab, and topical NSAIDs (loxoprofen tape, felbinac) were administered to a 72-year-old patient with gastric cancer and pain related to bone metastasis. Pain control was favorable, with a numerical rating scale (NRS) score of 2 and Japanese version Support Team Assessment Schedule (STAS-J) score of 1. Intervention by pharmacists for the use of topical NSAIDs decreased both the NRS and STAS-J scores to zero, improving ADL. The results suggest that topical NSAIDs relieve bone-metastasis-related pain, improving ADL. When bone-metastasis-related pain is localized, the prescription of topical NSAIDs should be considered, and positive intervention by pharmacists regarding their usage should be promoted.

Emergency intensive care unit pharmacist's intervention may reduce time to four-factor prothrombin complex concentrate administration: a retrospective study.

BACKGROUND: Four-factor prothrombin complex concentrate (4F-PCC) must be administered as soon as possible, and in our emergency intensive care unit (EICU), pharmacists are available on weekdays for consultation on expediting 4F-PCC administration. Although recent reports have described a reduction in time to 4F-PCC administration, few studies have addressed if this is because of EICU pharmacist's intervention, and there are no such studies in Japan. Therefore, we aimed to examine whether EICU pharmacist's intervention reduced time to 4F-PCC administration. METHODS: This single-center retrospective cohort study was conducted from December 2017 to May 2019. We enrolled patients who received 4F-PCC due to major bleeding or requirement of urgent surgical/invasive procedures (n = 10). Patients were divided into two groups, namely, the intervention group (n = 5), in which EICU pharmacists consulted on weekdays, and the nonintervention group (n = 5), in which an intervention was not possible because of the absence of the EICU pharmacist. RESULTS: The median time from patient presentation to the EICU to 4F-PCC administration (103 min vs. 111 min, p = 0.4) was similar between the two groups; however, the median time from 4F-PCC prescription ordering to administration was significantly shorter in the intervention group than in the nonintervention group (21 min vs. 60 min, p = 0.02). CONCLUSIONS: EICU pharmacist's intervention improves the process from 4F-PCC prescription to administration and can reduce time to 4F-PCC administration.

Utility and effectiveness of Symbicort® Turbuhaler® (oral inhalation containing budesonide and formoterol) in a patient with severe asthma after permanent tracheostomy.

BACKGROUND: The utility and effectiveness of inhalational asthma therapy in patients with a permanent tracheostomy has not been established. Previously, a few studies reported the use of nebulizer-type inhalers for treating these patients. Symbicort® Turbuhaler® (Symbicort) is an orally inhaled dry powder containing the corticosteroid budesonide and the bronchodilator formoterol. There are no reports describing the successful use of Symbicort in patients with a permanent tracheostomy. CASE PRESENTATION: We describe the case of a woman with poorly controlled severe asthma after a permanent tracheostomy. She had developed thyroid cancer with tracheal invasion for which right thyroid lobectomy and tracheal and esophageal resection were performed, with subsequent construction of a permanent tracheostomy. In our case, prior to surgery, asthma control had been improved by adding a bronchodilator-the long-acting muscarinic antagonist tiotropium-and the anti-IgE antibody agent omalizumab to single maintenance and reliever therapy (SMART) using Symbicort; surgery was then performed. After surgery, asthma control worsened as a result of a change from Symbicort to budesonide nebulizer and a tulobuterol patch. In order to resume SMART therapy, an In-Check® inspiratory flow meter was used to measure and assess whether the inspiratory flow rate was sufficient for a dry-powder inhaler. Inhalation guidance was provided. On inhalation with the tracheostomy closed at the same time, the inspiratory flow rate was 43 L/min at the maximum. This was judged to be sufficient for the effect of Symbicort, and thus the inhaler was changed to Symbicort. Asthma symptoms promptly improved, and the patient was subsequently discharged. CONCLUSIONS: The use of Symbicort resulted in improved asthma control in a patient with severe asthma following a permanent tracheostomy. Thus, it is suggested that inhalation powder could be an option for patients with permanent tracheostomy.

Dosing optimization of meropenem based on a pharmacokinetic analysis in patients receiving hemodiafiltration and an in vitro model.

The purpose of this study was to estimate the in vivo pharmacokinetics of meropenem during intermittent-infusion hemodiafiltration (I-HDF) and clarify its optimal dosage and dosing interval in patients receiving I-HDF. The clearance of meropenem by online hemodiafiltration (OL-HDF) and I-HDF was predicted using an in vitro system and assessed to establish whether the results obtained are applicable to clinical cases. In the in vivo study, the mean volume of distribution (Vd), non-I-HDF clearance (CLnon-I-HDF), and I-HDF clearance (CLI-HDF) were 15.80 ± 3.59 l, 1.05 ± 0.27 l/h, and 5.78 ± 1.03 l/h. Dosing regimens of 0.25 g once daily for a MIC of 8 µg/ml and of 0.5 g once daily for a MIC of 16 µg/ml achieved 40% T > MIC. In the in vitro and in vivo studies, observed CLHDF was similar to predictive CLHDF (= Cf/Cp × (QD + QSUB)). In conclusion, adjustments to the dose and interval of meropenem were developed based on the presumed susceptibility of pathogens to meropenem in patients receiving I-HDF. We suggest 0.5 g once daily as an appropriate regimen for empirical treatment.

Treatment sequence in castration-resistant prostate cancer: A retrospective study in the new anti-androgen era.

In recent years, abiraterone acetate (AA) and enzalutamide (EZL) have become available for the treatment of cancer. Prior clinical trials have demonstrated the benefits of these agents in males with castration-resistant prostate cancer (CRPC). The optimal sequencing of available therapies in the context of efficacy and known cross-resistance remains uncertain. Based on the mechanisms of action and accessible clinical data, AA and EZL may be indicated for the early stages of prostate cancer. Until clinical trials are conducted to determine the best treatment sequence, individualized therapy is required for each patient based on the clinicopathological characteristics. In the present study, 46 sequential patients (median age: 77, range 59-89; median serum PSA level: 56 ng/ml, range 1.5-3,211) with CRPC treated with EZL (160 mg/day) were retrospectively analyzed between June 2014 and July 2015 at the following institutions: Yamagata Prefectural Central Hospital (Yamagata, Japan); Yamagata Tokushukai Hospital (Yamagata, Japan); Ishinomaki Red Cross Hospital (Ishinomaki, Japan); Kan-etsu Hospital (Tsurugashima, Japan); Niigata Cancer Center Hospital (Niigata, Japan); Sakado Central Hospital (Sakado, Japan). A total of 18 patients were pre-treated with Docetaxel (DOC) and 28 patients were DOC-naïve. Once EZL therapy was initiated, increases in prostate specific antigen (PSA) levels were observed in 3/18 patients (17%) pre-treated with DOC and in 6/20 (30%) who were DOC-naïve. In total, 8/28 DOC-naïve patients were treated with AA without EZL. An increase in the PSA level was observed in only 1/8 (12%) cases following AA treatment in the DOC-naïve group. It was demonstrated that AA had a better efficacy in DOC-naïve patients. The efficacy of EZL was limited in AA-pre-treated patients following DOC administration.

Predictors of the therapeutic effect of sivelestat in patients with acute lung injury associated with systemic inflammatory response syndrome.

BACKGROUND: Sivelestat, a neutrophil elastase inhibitor, was previously approved in Japan for the treatment of acute lung injury associated with systemic inflammatory response syndrome. However, sivelestat produced inconsistent therapeutic benefits. This study aimed to identify factors predicting the therapeutic effects of sivelestat. METHODS: We enrolled 53 mechanically ventilated patients who received sivelestat. The patients were classified as effective (n = 28) if they were weaned from the ventilator within 28 days, or as ineffective groups (n = 25). Patient characteristics were compared between these groups and multivariate logistic regression analysis was used to identify predictive factors. A validation study was then conducted in sivelestat-free patients. RESULTS: A high red blood cell count and low hydrogen ion concentration were significantly associated with a higher ventilator weaning rate in patients receiving sivelestat. The validation study revealed that the hydrogen ion concentration value also significantly associated with ventilator weaning in patients who did not receive sivelestat. CONCLUSIONS: Although hydrogen ion concentration was inversely associated with the ventilator weaning rate, it did not predict sivelestat efficacy. This study indicated that acute lung injury patients with a high red blood cell count would derive the most benefit from sivelestat administration.

Evaluation of Thymidylate Synthase Expression in Prostate Cancer.

Thymidylate synthase (TS), a key enzyme in DNA synthesis, is over-expressed in a variety of cancer cells. 5-Fluorouracil, an anticancer agent clinically used against various cancers, including prostate cancer, inhibits DNA synthesis by binding TS. In this study, we investigated expression of TS in prostate cancer and its prognostic significance. Seventy-five prostatic tissue specimens were obtained from patients who had undergone prostate biopsy for diagnosis of prostate cancer. We analyzed the cancerous tissue specimens for TS expression using immunohistochemistry. TS expression was significantly increased in patients with bone metastasis. No relationship was found between expression of TS and the other clinicopathological findings. Because TS expression could be used as a prognostic parameter in patients with prostate cancer, an accurate prediction of prognosis might help to select patients for more intensive surgical, hormonal, or chemotherapeutic approaches, including 5-fluorouracil. Additional prospective studies are warranted to define the role of TS in selecting patients for adjuvant therapy for prostate cancer.

Remarkable response to neoadjuvant therapy with methotrexate, vinblastine, adriamycin, and Cisplatin for undifferentiated bladder carcinoma: a case report and literature review.

We report a case of primary undifferentiated bladder carcinoma, which revealed a remarkable response to methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) therapy. A 46-year-old Japanese woman presented at the hospital with the chief complaints of gross hematuria and pain during urination. Cystoscopy revealed a large smooth-surfaced tumor in the urinary bladder. The histopathological diagnosis was undifferentiated carcinoma. The patient then received 3 courses of MVAC over a 3-month period. Hydronephrosis disappeared after the first course, and the tumor shrank rapidly. After completion of the third MVAC course, radical cystectomy and ileal conduit surgery were performed. After 7 years, the patient has still had no recurrences or metastases. We retrospectively review the relative efficacy of the two popular chemotherapeutic regimens in the management of muscle-invasive bladder cancer in patients who had had radical cystectomy.

Efficacy of once or twice weekly administration of epoetin κ in patients receiving hemodialysis: A retrospective study.

Several clinically approved recombinant erythropoietin (rEPO) preparations, such as epoetin-ß, epoetin-δ and the epoetin-α derivative, darbepoetin-α, have been commercially produced. Since the expiration of patent protection, a number of novel rEPO biosimilars have been approved on the world market. In 2010, epoetin-κ, which is biosimilar to epoetin-α, was clinically approved. Epoetin-κ is a biopharmaceutical product that is based on serum-free media following master cell bank preparation. The present study analyzes the results obtained during a six-month observation period, in which the administration of epoetin-ß was switched to that of epoetin-κ. In a cohort of patients receiving chronic dialysis, who were clinically in a state of relative calm and were in control of their renal anemia, it was possible to sustain good control of the anemia by reducing the frequency of the epoetin-ß administration from the conventional and empirically determined three times a week to twice a week, and further to once a week. Furthermore, the good control was maintained upon changing from the administration of epoetin-ß to that of epoetin-κ. Moreover, three months subsequent to this switch, the degree of instability observed among the patients had decreased. Despite the fact that the situation following the changeover requires further investigation, it may be concluded that the results obtained in this study are indicative of the clinical equivalence and efficacy of epoetin-κ.

Proposal of a pharmacokinetically optimized dosage regimen of antibiotics in patients receiving continuous hemodiafiltration.

The aim of the study was to quantitatively predict the clearance of three antibiotics, amikacin, vancomycin, and teicoplanin, during continuous hemodiafiltration (CHDF) and to propose their optimal dosage in patients receiving CHDF. For this goal, in vitro CHDF experiments with a polyacrylonitrile (PAN) membrane were first performed using these antibiotics, and then the clearances were compared with in vivo CHDF situations determined in 16 critically ill patients. The in vitro CHDF clearances were described as the product of the outflow rate of a drain (Q(outflow)) and the drug unbound fraction in artificial plasma, indicating that drug adsorption to the PAN membrane has minor effect on drug clearance in our settings. The observed in vivo clearances also agreed very well with the predicted values, with a product of Q(outflow) and plasma unbound fraction, when residual creatinine clearance (CL(CR)) was taken into account (within a range of 0.67- to 1.5-fold for 15 of 16 patients). Based on these results, a nomogram of the optimized dosages of amikacin, vancomycin, and teicoplanin was proposed, and it was evident that Q(outflow) and residual CL(CR) are major determinants of the dosage and dosing interval for these antibiotics. Although the applicability needs to be confirmed with another type of membrane or higher Q(outflow), our nomogram can help determine the dosage setting in critically ill patients receiving CHDF.

Development and evaluation of pharmaceutical services in the ICU/CCU by medical staffs.

Questionnaires were sent out to the staffs (13 physicians, 52 nurses and 5 medical engineers) of the ICU/CCU at the University of Tokyo Hospital, to evaluate pharmaceutical services by analyzing problems in the services offered. Four components of pharmaceutical services were evaluated: inventory control of drugs, check of drug usage and doses, mixing of injections, and offering drug information. Almost all responses from medical staffs evaluated pharmaceutical services overall as "good". The high response rate (96%) from the nursing staff was attributed to the fact that they were familiar with the pharmacist's role with drug inventory, and mixing injections, when nursing was not available for these tasks. Although 50% of physicians rated the pharmaceutical services of providing drug information as "good", this value was lower than responses on other items of the questionnaires, which suggests some dissatisfaction. The occurrences of drug information obtained by passive offering (121 subjects) was 4 times as common as drug information obtained by active offering (30 subjects). From this finding, and comments on the questionnaires from physicians, it suggests that physicians require more drug information for dosage regimens, and prefer the drug information to be provided more actively. Further, an important comment from physicians and nurses was that the services of pharmacists are not available on all shifts/all days of the week to provide consultation for drug information and mixing of injections. Although having a pharmacist available daily around the clock is desirable and ideal to the medical team, the number of pharmacists under the present system cannot support this. As a solution, we think that it is crucial that pharmacists educate medical staff when they are present to in order to optimize therapy and patient care over time.