Objective: Combination therapy with glecaprevir and pibrentasvir (G/P) has been shown to provide a sustained virologic response (SVR) rate of >97% in patients with chronic hepatitis C virus (HCV) infection in the first published real-world Japanese data. However, a recently published study showed that the treatment was often discontinued in patients ≥75 years old, resulting in low SVR in intention-to-treat (ITT) analysis. Thus, our aim was to evaluate real-world data for G/P therapy in patients ≥75 years of age, the population density of which is high in “rural” regions.Patients and Methods: We conducted a multicenter study to assess the efficacy and safety of G/P therapy for chronic HCV infection, in the North Kanto area in Japan.Results: Of the 308 patients enrolled, 294 (95.5%) completed the treatment according to the protocol. In ITT and per-protocol analyses, the overall SVR12 rate was 97.1% and 99.7%, respectively. The old-aged patients group consisted of 59 participants, 56 of whom (94.9%) completed the scheduled protocol. Although old-aged patients tended to have non-SVR factors such as liver cirrhosis, history of HCC, and prior DAA therapies, the SVR12 rates in old-aged patients were 98.3% and 100% in the ITT and PP analyses, respectively. Of 308 patients enrolled, adverse events were observed in 74 patients (24.0%), with grade ≥3 events in 8 patients (2.6%). There was no significant difference in any grade and grade ≥3 adverse events between the old-aged group and the rest of the study participants. Only one patient discontinued the treatment because of adverse events.Conclusion: G/P therapy is effective and safe for old-aged patients.

Major bleeding associated with sagittal split ramus osteotomy (SSRO) involves vessels such as the inferior alveolar, facial, and maxillary arteries and veins, and the retromandibular vein (RMV). The present study aimed to clarify and classify the three-dimensional variations in RMV position and course direction in relation to the mandible. Specimens comprised a total of 15 scientific cadavers, and the relationship between RMV and the mandible lateral and posterior views was observed.We identified 3 patterns on the lateral view, the mean distance between the RMV and the posterior border of the ramus was 3.9 mm at the height of the lingula. A total of five course patterns were identified on the posterior view. In no course pattern, the RMV inferior to the lingula was lateral to its position superior to the lingual. The present findings suggest that it may be possible to predict correlations with intraoperative bleeding risk. Further study is planned using contrast computed tomography in patients with jaw deformity for skeletal classification.

Objective: The development of hepatocellular carcinoma (HCC) is not uncommon in patients who achieve eradication of the hepatitis C virus through direct-acting antiviral (DAA) treatment. The aim of this study was to identify the patients at high risk for novel HCC development after a sustained virologic response (SVR) by DAA treatment.Patients and Methods: A total of 518 patients with no history of HCC treatment and who achieved SVR by DAA treatment were evaluated retrospectively. The correlations between HCC development and the patients’ characteristics were evaluated. For patients who underwent gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) or dynamic contrast-enhanced computed tomography, the relationship between the imaging findings and subsequent HCC development was also assessed.Results: HCC developed newly in 22 patients, and the 1-year and 3-year cumulative HCC rates were 2.0% and 8.5%, respectively. In multivariate analysis, a FIB-4 index >4.0 and a post-treatment α-fetoprotein >4.0 ng/ml were significant risk factors for HCC. In 26 of 118 patients who underwent an MRI before DAA treatment, a non-hypervascular hypo-intense nodule was seen in the hepatobiliary phase, and in 6 of 182 patients who underwent a CT, a non-hypervascular hypo-enhanced nodule was seen in the delayed phase. The sensitivity and specificity of the MRI-positive findings for the subsequent development of HCC were 0.92 and 0.87, respectively, and those of the CT were 0.40 and 0.99, respectively. In multivariate analysis of patients who underwent an MRI, a non-hypervascular hypo-intense nodule was the only factor that was significantly related to HCC development (HR 32.4, p = 0.001).Conclusion: Gd-EOB-DTPA-enhanced MRI was found to be reliable for risk evaluation of subsequent HCC development in patients after SVR by DAA treatment. Patients with a non-hypervascular hypo-intense nodule need more careful observation for incident HCC.

OBJECTIVE: To analyze patient characteristics of cancer rehabilitation and outcomes at our hospital. METHODS: This retrospective study analyzed 580 patients, who underwent cancer rehabilitation at our hospital and rehabilitation outcome after therapy were investigated. The relationship between the initial Barthel index and discharge outcomes was investigated, with a special focus on cancer patients with bone metastasis. The Barthel index and performance status (Eastern Cooperative Oncology Group) before and after rehabilitation were analyzed, and threshold value of home discharge was calculated from a receiver operating characteristic curve (ROC). General criteria for home discharge from our hospital included independence in performing basic activities of daily living such as bathing, feeding, and toileting or availability of home support from a family member/caregiver. RESULTS: The outcomes after rehabilitation among all the patients were as follows: discharge home 59%, death 13%, and others 27%. Statistical differences were observed between the initial and final values of the Barthel index in patients with bone metastasis, who could be discharged home (p=0.012). ROC analysis of the initial Barthel index for predicting home discharge revealed a threshold value of 60, sensitivity of 0.76, and specificity of 0.72. CONCLUSION: The patients with bone metastasis had a lower rate of home discharge and a higher rate of mortality than all the study patients who underwent cancer rehabilitation at our hospital. It is proposed that at the time of initiation of rehabilitation for patients with bone metastasis, an initial Barthel index lower than 60 might predict a worse outcome than home discharge.
Activities of Daily Living ; Asian Continental Ancestry Group* ; Baths ; Humans ; Mortality ; Neoplasm Metastasis* ; Rehabilitation ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity ; Treatment Outcome

Objectives: We developed versions 2 and 3 of the Biological Prognostic Score (BPS) for advanced cancer patients and confirmed the prediction accuracy. Methods: We conducted a parametric survival analysis using blood test data, performance status (PS), clinical symptoms, age, sex, and cancer type as variables for advanced cancer patients who completed or suspended cancer treatment, in the development of BPS2 and BPS3. We then prospectively compared the accuracy between BPS2/BPS3 and the Palliative Prognostic Index (PPI). Results: We developed the BPS2 and BPS3 based on the data from 589 patients in a development cohort. While the former version was calculated based on the cholinesterase, blood urea nitrogen, and white blood cell counts, the latter was calculated based on the BPS2, ECOG PS and edema. For 206 patients in a validation cohort, the overall accuracy in prediction of survival for 3 and 6 weeks using the BPS2 and BPS3 were significantly higher than those for the PPI. Conclusion: The usefulness of BPS2 and BPS3 was suggested.

Levetiracetam (LEV), a relatively new antiepileptic drug, is now frequently used for treating partial or generalized seizures. Among the adverse effects of LEV, rhabdomyolysis is rare. We describe here a case of LEV-induced rhabdomyolysis in a 26-year-old woman. The patient’s seizures had been controlled with carbamazepine and phenobarbital for the previous 7 years. However, LEV was initiated at the age of 26 years because her seizures control deteriorated with seizures occurring monthly. She experienced lower limb weakness with a high level of creatine kinase 15 days after starting LEV. When LEV was discontinued, her creatine kinase levels decreased and her symptoms gradually improved. This case provide another example of rhabdomyolysis during the early phase of LEV treatment.
Rhabdomyolysis

The effectiveness of the Kampo medicine shakuyakukanzoto extract for patients with muscle cramp is well known, but recently side effects related to pseudoaldosteronism have also been reported. To avoid this issue, Kampo medicines without Glycyrrhizae Radix are needed for treatment of muscle cramp. We investigated the therapeutic effect of shimotsuto extract, which has traditionally been used to treat anemia, in 26 patients (mean age : 70.7 ± 12.1 years) with muscle cramp. Improvement of the symptom was noted in 18 patients (69%), with no change in 8 patients (31%). The abdominal muscle tension of the former patients was significantly lower than the latter. Here, the cases of four representative patients in whom muscle cramp was improved by shimotsuto are described. The response rate to shimotsuto was similar to that of shakuyakukanzoto. Our results suggest that shimotsuto extract is a suitable alternative to shakuyakukanzoto for treatment of muscle cramp in older non-robust type patients not in need of emergency care.

Objective: To develop and confirm the validity of a Biological Prognostic Score using only blood test results for prediction of prognosis in patients with advanced cancer. Methods: We conducted parametric survival time analysis using blood test results, age, sex, and primary diagnosis as independent variables, and event of death as a dependent variable, among patients in a palliative care unit (a development cohort). We then developed the Biological Prognostic Score (BPS). Thereafter, we confirmed the accuracy of the BPS and the Palliative Prognostic Index (PPI) prospectively among patients, who withdrew or withheld further curative or life-prolonging therapies, in other facilities (a validation cohort). Results: We developed the BPS, which consists of cholinesterase, blood urea nitrogen, and total iron-binding capacity, from 122 patients in a development cohort. We then examined 195 patients in a validation cohort and found that the area under the receiver operating characteristic curve for 1-9 week survival prediction was BPS=0.76-0.86 and PPI=0.69-0.73. Discussion: Our results suggest that the BPS was valid. It will be necessary to perform further examinations in multiple facilities and to explore more generalized parameters that could replace total iron-binding capacity in our BPS.

OBJECTIVES: We conducted multi-directional language development tests as a part of the Research on Sensory and Communicative Disorders (RSVD) in Japan. This report discusses findings as well as factors that led to better results in children with severe-profound hearing loss. METHODS: We evaluated multiple language development tests in 33 Japanese children with cochlear implants (32 patients) and hearing aid (1 patient), including 1) Test for question and answer interaction development, 2) Word fluency test, 3) Japanese version of the Peabody picture vocabulary test-revised, 4) The standardized comprehension test of abstract words, 5) The screening test of reading and writing for Japanese primary school children, 6) The syntactic processing test of aphasia, 7) Criterion-referenced testing (CRT) for Japanese language and mathematics, 8) Pervasive development disorders ASJ rating scales, and 9) Raven's colored progressive matrices. Furthermore, we investigated the factors believed to account for the better performances in these tests. The first group, group A, consisted of 14 children with higher scores in all tests than the national average for children with hearing difficulty. The second group, group B, included 19 children that scored below the national average in any of the tests. RESULTS: Overall, the results show that 76.2% of the scores obtained by the children in these tests exceeded the national average scores of children with hearing difficulty. The children who finished above average on all tests had undergone a longer period of regular habilitation in our rehabilitation center, had their implants earlier in life, were exposed to more auditory verbal/oral communication in their education at affiliated institutions, and were more likely to have been integrated in a regular kindergarten before moving on to elementary school. CONCLUSION: In this study, we suggest that taking the above four factors into consideration will have an affect on the language development of children with severe-profound hearing loss.
Aphasia ; Asian Continental Ancestry Group ; Child ; Child Development Disorders, Pervasive ; Cochlear Implants ; Communication Disorders ; Comprehension ; Hearing ; Hearing Aids ; Hearing Loss ; Humans ; Japan ; Language Development ; Mass Screening ; Mathematics ; Rehabilitation Centers ; Vocabulary ; Weights and Measures ; Writing

  In Japan, few health care professionals have a basic understanding（core competency）of the design of clinical research and statistical analysis. We developed a blended distance–learning program comprising face–to–face lectures with e–learning for busy health care professionals who work in the clinical settings to achieve core competency in clinical research. The purpose of this study was to examine the educational effects of this program.
1）Four months after the end of the program, 64％ of the participants had started to conduct clinical research.
2）This program may increase the number of research colleagues that can discuss clinical research.
3）This program could enhance the confidence（self–efficacy）of health care professionals in clinical research.