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The objective of this study is to verify the validity of a hyper grid type (double grid model) computational model, for calculating flood flows with inundations. Nowadays, detailed information of the bathymetry is available due to improved measurement techniques, such as LP data. However, the number of grid cells used in the computation is limited because of the limitation of computational infrastructures. A double grid approach based on the model proposed by Volp et. al.(2013) is employed to overcome this problem.This model directly uses the high resolution topographic data though the discretization of the governing equations are made on coarser grid. The computational results showed that the present numerical model can compute the large scale flood phenomena efficiently and accurately.

Prescribing direct oral anticoagulants (DOACs) with off-label dosage and administration is discouraged due to concerns about their effectiveness and safety. Consequently, our hospital pharmacist established a formulary with physicians for oral anticoagulants. Our study aimed to assess the adherence to this formulary by investigating the rate of appropriate DOAC prescribing. We included patients who were newly prescribed or continued on DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) at our hospital. We calculated the percentage of patients prescribed the correct dosage and administration according to the package insert and compared this across three time periods: pre-intervention (period A; April-September 2019), post-intervention phase 1 (period B; August 2021-January 2022), and post-intervention phase 2 (period C; November 2022-April 2023). We also examined the number of inquiries and consultation requests made by hospital pharmacists regarding DOAC dosage and administration. A total of 782 patients were surveyed (191 in period A, 263 in period B, and 328 in period C). The appropriate prescribing rates for DOACs were 79.1% in period A, 84.4% in period B, and 86.6% in period C. The proportion of cases where hospital pharmacists questioned or consulted doctors about DOAC dosage and administration was 3.7% in period A, 6.1% in period B, and 10.1% in period C. These findings indicate that active intervention by hospital pharmacists using the formulary regarding oral anticoagulant formularies may promote appropriate DOAC use.

Background: In-hospital therapeutic drug monitoring (TDM) requires a suitable quantification method for target drugs from the viewpoint of precision, throughput, and testing costs. We previously developed a practical HPLC-UV platform for quantification of serum levels of various drugs. In this report, the platform was effectively applied to the quantification of patient serum levels of five different drugs by clinical professionals in our hospital during their daily work., Methods: The residual sera of patients receiving carbamazepine (CBZ), phenytoin (PHT), lamotrigine (LTG), vancomycin (VCM), or voriconazole (VRCZ) were used in the present clinical study. The quantification method for each drug consisted of rapid solid-phase extraction (SPE) of each drug in the patient serum, followed by optimized HPLC-UV analysis of the drug in the SPE eluate. Furthermore, patient serum levels of PHT, CBZ, and VCM were also measured by ligand-binding assay using a cobas ® analyzer in our hospital, and those of LTG and VRCZ were measured by HPLC-MS/MS at an outsourced provider. Passing-Bablok regression analysis and Bland-Altman analysis were employed to analyze the agreement of drug levels in patient sera, which was separately quantified using two different methods-our HPLC-UV platform and the cobas analyzer, or HPLC-UV and HPLC-MS/MS., Results: All analytical conditions of the present method using our HPLC-UV platform were well optimized for each target drug quantification in the patient's serum, and the quantification method for each drug was fully validated for accuracy, precision and reproducibility. Furthermore, Passing-Bablok regression analysis and Bland-Altman analysis revealed that patient serum levels of PHT, CBZ, and VCM quantified by our HPLC-UV platform were closely correlated with those quantified by the cobas ® analyzer, and the levels of LTG and VRCZ quantified by our HPLC-UV platform were also correlated with those quantified by HPLC-MS/MS., Conclusions: Our HPLC-UV platform can be performed without requiring special analytical techniques. This platform is expected to be used for the measurement of blood levels of multiple drugs for in-hospital routine TDM., (© 2023. The Author(s).)

Introduction: Measurement of blood Favipiravir (FPV) levels and accumulation of data in COVID-19 patients are critical for assessing FPV efficacy and safety. We performed a retrospective study based on measurements of blood levels of FPV and related factors in COVID-19 patients admitted to our hospital. Furthermore, we also investigated the association between blood FPV levels and uric acid level alterations before and after FPV administration., Methods: We enrolled 27 COVID-19 patients who had received FPV treatment at Hokushin General Hospital from April 1 to December 31, 2020. Age, gender, COVID-19 severity, presence of comorbidities, and laboratory data for each subject were investigated to identify factors that correlate with blood FPV levels. Uric acid levels were measured before and after FPV administration and a difference between the levels (i.e., a change of uric acid level) was evaluated., Results: When a significant univariate variable was input by the stepwise method and a combination of variables that maintained statistical superiority was searched, serum ferritin was the only factor that independently affected blood FPV level. Furthermore, in the high-FPV group (20 μg/mL or more), a significant increase in uric acid levels was observed after FPV administration. The increment value was significantly larger than that in the low-FPV group (less than 20 μg/mL)., Conclusions: Ferritin level was an important independent factor inversely affecting blood FPV level. Furthermore, a high blood FPV level induced the elevation of uric acid levels in COVID-19 treatment., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

An in-hospital rapid method for quantifying the serum level of favipiravir (FPV) in the pharmacological treatment of COVID-19 was developed by an appropriate combination of a solid-phase extraction treatment and a reversed-phase HPLC/UV detection system. The quantification method was well-validated and applied to measuring the serum FPV level in a clinical practice at a general hospital that accepts COVID-19 patients. Furthermore, an analysis of data from our preliminary interaction analysis revealed, for the first time, that FPV selectively forms complexes with ferric (Fe 3+ ) and cupric (Cu 2+ ) ions.

Chronic heart failure (CHF) is a critical disease in the aging population. Conventional therapy in hospitals cannot cure elderly patients with CHF at the end of life. Patients and their families experience anxiety and need comfortable care at home or in a nursing facility. To improve chronic cardiovascular disease management, we developed a simplified but integrated clinical pathway to facilitate medical and nursing care teamwork in the local community. Our institution is a central hospital in the North Shinshu district, which has an approximate population of 100000. We developed a pathway for both clinical program and information provision between our hospital and neighboring clinics. A hospital team evaluates and shares patient information with a homecare medical team every 6 months using the medical staff pathway. To maintain the efficacy and security of pharmacotherapy, a hospital clinical pharmacist reviews the prescriptions and prepares a drug profile book to share drug information between patients and all medical staff. These efforts have resulted in preventing adverse effects of drugs and reduced the cost of medications. Physical activity evaluation and nutrient guidance are also useful for patients to maintain their personal lifestyles. We initiated use of the pathway from 2009 and have followed up over 500 patients since then. We have also established a community partnership council to promote face-to-face communication among multiple categories of institutions and government agencies. Members of the council collaborate to help patients with cardiovascular disease to manage their own lives at home.

A high-throughput method for determining the octanol/water partition coefficient (P(o/w)) of a large variety of compounds exhibiting a wide range in hydrophobicity was established. The method combines a simple shake-flask method with a novel two-phase solvent system comprising an acetonitrile-phosphate buffer (0.1 M, pH 7.4)-1-octanol (25:25:4, v/v/v; AN system). The AN system partition coefficients (K(AN)) of 51 standard compounds for which log P(o/w) (at pH 7.4; log D) values had been reported were determined by single two-phase partitioning in test tubes, followed by measurement of the solute concentration in both phases using an automatic flow injection-ultraviolet detection system. The log K(AN) values were closely related to reported log D values, and the relationship could be expressed by the following linear regression equation: log D=2.8630 log K(AN) -0.1497(n=51). The relationship reveals that log D values (+8 to -8) for a large variety of highly hydrophobic and/or hydrophilic compounds can be estimated indirectly from the narrow range of log K(AN) values (+3 to -3) determined using the present method. Furthermore, log K(AN) values for highly polar compounds for which no log D values have been reported, such as amino acids, peptides, proteins, nucleosides, and nucleotides, can be estimated using the present method. The wide-ranging log D values (+5.9 to -7.5) of these molecules were estimated for the first time from their log K(AN) values and the above regression equation., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Cyclophosphamide and vincristine are known to be the chemotherapeutic agents most frequently associated with hyponatremia. Here, we report the case of a 69-year-old man with non-Hodgkin's lymphoma who developed severe hyponatremia during chemotherapy. The Japanese man was diagnosed with diffuse large B-cell lymphoma, and underwent chemotherapy treatment with THP-COP (cyclophosphamide, pirarubicin, vincristine, and prednisolone). In the first course of chemotherapy, he developed hyponatremia (nadir 109 mEq/L) and his urinary N-acetyl-β-D-glucosaminidase (NAG) level had increased. After the second courses of chemotherapy with rituximab, pirarubicin, and prednisolone, without cyclophosphamide and vincristine, he had developed light hyponatremia (nadir 130 mEq/L). However, after the third and fourth courses of chemotherapy with rituximab, pirarubicin, prednisolone, and cyclophosphamide, he had developed a medium level of hyponatremia (nadir 124-125 mEq/L) and his NAG level had increased further. The possible mechanism of this phenomenon is due to renal tubular damage by cyclophosphamide. We conclude that extra caution is necessary if a patient develops severe hyponatremia following chemotherapeutic treatment with cyclophosphamide and vincristine.

A 53-year-old woman ingested about 300 mL of 95% methanol. After immediate ethanol antagonist therapy and hemodialysis, she recovered completely. Few days later, the plasma concentration of methanol and formate was measured. A gas chromatography was used for the plasma methanol concentration measurement, and a colorimetric method was used for plasma formate concentration measurement (Formate Colorimetric Assay Kit; BioVision, California, USA). Patient's plasma methanol concentration before hemodialysis was 676.9 mg/dL and plasma formate concentration was 16.9 mg/dL. By removing blood methanol and formate using hemodialysis before formate accumulations in the body, the patient was discharged without any sequelae. We were able to obtain correlation between a gas chromatography and colorimetric method without gas chromatography-mass spectrometry, with good correlation coefficients. The sensitivity was sufficient for analyzing blood sample. Monitoring formate concentration is useful in determining the treatment and evaluating the prognosis of methanol poisoning. We suggest that this colorimetric method is useful in a facility with no access to a gas chromatography in order to measure a plasma formate concentration.

Highly hydrophilic volatile organic/aqueous two-phase solvent systems containing an organic salt such as, acetonitrile/800 mM and 1200 mM ammonium acetate (1 : 1, v/v) were efficiently utilized for high-speed counter-current chromatography (HSCCC) to separate hydrophilic compounds. The retention of the upper and the lower stationary phases in the column of the cross-axis coil planet centrifuge (CCC instrument) was studied by changing the flow-rate of the mobile phase (1.0-3.0 ml/min). Using the acetonitrile/800 mM ammonium acetate two-phase solvent system, the stationary phase was retained at 46.3% relative to the total column capacity of 65 ml by the reversed-phase elution mode at a flow-rate of 1.0 ml/min. The best retention of the stationary upper phase of 51.5% was obtained by the solvent system of the acetonitrile/1200 mM ammonium acetate at the above flow-rate. With the acetonitrile/800 mM ammonium acetate system the base line separation of adenine and adenosine monophosphate (AMP) detected by evaporative light scattering detector (ELSD) and UV was achieved with lower phase mobile at a flow-rate of 1.0 ml/min within 70 min.

Inflammatory pseudotumor (IPT) is a benign tumorous lesion of unknown cause, which is composed of fibrous tissue with infiltration of plasma cells and lymphocytes. A 57-year-old male with gastritis was indicated to have hepatic dysfunction during observation of the course of gastritis at a nearby hospital. He was referred to our facility to undergo detailed examinations. When he visited our hospital for the initial examination, he had no subjective symptoms. His past medical history was unremarkable. There were no distinct abnormalities on the medical examination. Blood tests revealed a white blood cell count of 10400 / L, CRP of 0.29 mg/dl, AST of 31 IU/L, ALT of 46 IU/L, ALP of 583 IU/L and -GTP of 408 IU/L, showing a mild inflammatory reaction and elevated hepatobiliary enzymes. Abdominal ultrasonographic examination revealed a tumor mass approximately 4 cm in diameter in a lateral hepatic segment. The margin and center of the mass were hypoechoic and iso- to hyperechoic, respectively, and the inside of the mass was non-homogeneous. Needle biopsy revealed only inflammatory findings with no indications of malignancy. Since computed tomography (CT) of the abdomen, done 4 months after detection of the tumor mass, revealed the mass to have increased to approximately 6 cm in diameter, excision biopsy was considered. The CT taken 2 months later revealed the mass to have regressed to approximately 2 cm in diameter, but excision of the lateral hepatic segment was undertaken at the patient's request. As a result, the diagnosis of IPT of the liver was confirmed. Imaging findings of hepatic IPT are variable and specific findings are lacking. Since the rate of correct diagnosis with needle biopsy is also low, IPT of the liver is often very difficult to differentiate from malignant tumors. On the other hand, since it may show spontaneous regression, indications for surgery must be assessed very carefully.

The patient was a 66-year-old woman who underwent upper gastrointestinal endoscopy as part of a detailed examination because of loss of appetite and anemia, and type 2 gastric cancer was detected on the greater curvature in the pyloric area. Abdominal ultrasonography and CT revealed lymph node enlargement around the pyloric area and multiple liver metastases in both lobes of the liver. Curative resection was judged to be impossible, and oral S-1 therapy was started. However, no efficacy was observed even after the completion of three courses, and especially because of the rapid increase in the size of the liver metastases, treatment was switched to combination therapy consisting of a continuous hepatic artery infusion of 5-FU+Leucovorin (day 1-7) and weekly PTX for 3 consecutive weeks (day 8, 15, 22) followed by a 1-week rest. The tumor marker levels decreased rapidly, and at the end of 4 courses marked regression of the primary tumor and lymph node metastases as well as of the metastatic foci in the liver was observed. Adverse events have been mild, and at present, 6 months after the switch in treatment, good QOL has been maintained, and treatment is continuing. This method appears to be an effective treatment strategy for unresectable advanced gastric cancer complicated by liver metastasis.

Gastrointestinal stromal tumors (GISTs) in the small intestine are relatively rare. We present a case of GIST arising from the small intestine, which could be resected under laparoscopic assistance. A 60-year-old male visited another hospital due to massive anal bleeding. Blood examination showed severe anemia. Although anemia improved after conservative treatment, the bleeding site was not identified and he was referred to our hospital for close examination. Abdominal CT showed a well-defined mass with homogeneous internal density in the left upper abdomen. On abdominal angiography, selective enhancement of the second jejunal artery revealed a tumor stain. Due to suspected GIST in the small intestine, laparoscopic-assisted resection of the jejunum was performed. Histopathological examination demonstrated low-grade malignant GIST. The laparoscopic procedure is considered to be useful as minimally invasive surgery for diagnosis and treatment of selected cases with GISTs in the small intestine.

We performed D2 low anterior resection in a patient with stage I rectal cancer [pathological diagnosis: proper muscle (pm) invasion, n0, lymphatic invasion (ly), (-); venous invasion (v), (-); anal margin, (-)]. The tumor recurred at the anastomotic site approximately one year later and was treated with Miles' operation [pm, n0, ly (+); v (-); deep border of the primary tumor (-)]. The tumor marker CEA increased to 50.4 ng/ml at four months after surgery and pelvic local recurrence was detected. Since then, the patient has been receiving chemoradiotherapy on an out-patient basis. Cytokeratin immunostaining of all the lymph nodes collected during the two operations showed clusters of occult neoplastic cells (ONCs) in the perinodal fat around the nodes harvested at the first operation. These findings suggest that the risk of local recurrence of rectal cancer is increased even in stage I disease if ONCs are found in the perinodal fat. Further studies are required to examine the relationship between local recurrence and extranodal ONCs in patients with primary rectal cancer.

The gene of an intracellular D(-)-3-hydroxybutyrate oligomer hydrolase (i3HBOH) was cloned and sequenced from a poly(3-hydroxybutyrate) (PHB)-degrading bacterium, Acidovorax sp. strain SA1. The i3HBOH gene has 876 nucleotides corresponding to the deduced sequence of 292 amino acids. In this amino acid sequence, the general lipase box sequence (G-X(1)-S-X(2)-G) was found, whose serine residue was determined to the active sites serine by site-directed mutagenesis. An i3HBOH was purified to electrophoretical homogeneity from SA1. The molecular mass of the purified enzyme was estimated to be 32 kDa by SDS-PAGE. The N-terminal amino acid sequence of the purified enzyme corresponded to the deduced N-terminal amino acid sequence in the cloned i3HBOH gene. This is the first cloning and sequencing of an intracellular D(-)-3-hydroxybutyrate oligomer hydrolase gene to date.