Integrated multi-omics analyses and functional validation reveal TTK as a novel EMT activator for endometrial cancer.

BACKGROUND: Cancer-testis antigens (CTAs) are often expressed in tumor and testicular tissues but not in other normal tissues. To date, there has been no comprehensive study of the expression and clinical significance of CTA genes associated with endometrial cancer (EC) development. Additionally, the clinical relevance, biological role, and molecular mechanisms of the CTA gene TTK protein kinase (TTK) in EC are yet to be fully understood. METHODS: Using bioinformatics methods, we comprehensively investigated the genomic, transcriptomic, and epigenetic changes associated with aberrant TTK overexpression in EC samples from the TCGA database. We further investigated the mechanisms of the lower survival associated with TTK dysregulation using single-cell data of EC samples from the GEO database. Cell functional assays were used to confirm the biological roles of TTK in EC cells. RESULTS: We identified 80 CTA genes that were more abundant in EC than in normal tissues, and high expression of TTK was significantly linked with lower survival in EC patients. Furthermore, ROC analysis revealed that TTK could accurately distinguish stage I EC tissues from benign endometrial samples, suggesting that TTK has the potential to be a biomarker for early EC detection. We found TTK overexpression was more prevalent in EC patients with high-grade, advanced tumors, serous carcinoma, and TP53 alterations. Furthermore, in EC tissue, TTK expression showed a strong positive correlation with EMT-related genes. With single-cell transcriptome data, we identified a proliferative cell subpopulation with high expression of TTK and known epithelial-mesenchymal transition (EMT)-related genes and transcription factors. When proliferative cells were grouped according to TTK expression levels, the overexpressed genes in the TTKhigh group were shown to be functionally involved in the control of chemoresistance. Utilizing shRNA to repress TTK expression in EC cells resulted in substantial decreases in cell proliferation, invasion, EMT, and chemoresistance. Further research identified microRNA-21 (miR-21) as a key downstream regulator of TTK-induced EMT and chemoresistance. Finally, the TTK inhibitor AZ3146 was effective in reducing EC cell growth and invasion and enhancing the apoptosis of EC cells generated by paclitaxel. CONCLUSION: Our findings establish the clinical significance of TTK as a new biomarker for EC and an as-yet-unknown carcinogenic function. This present study proposes that the therapeutic targeting of TTK might provide a viable approach for the treatment of EC.

L1CAM Predicts Adverse Outcomes in Patients with Endometrial Cancer Undergoing Full Lymphadenectomy and Adjuvant Chemotherapy.

BACKGROUND: L1 cell adhesion molecule (L1CAM) has been established as an important predictor of poor survival of early-stage endometrial cancer patients. We investigated whether L1CAM remains a significant predictor of poor survival of patients with advanced-stage endometrial cancer undergoing extensive surgical staging and adjuvant chemotherapy. METHODS: We prepared tissue microarray (TMA) from surgical tissue specimens of 161 endometrial cancer patients who underwent full lymphadenectomy combined with adjuvant chemotherapy for patients at risk for recurrence, and evaluated expression of L1CAM using immunohistochemistry. The correlation between L1CAM positivity and clinicopathological factors and the prognostic significance of L1CAM expression was investigated. RESULTS: Among 161 cases who had a follow-up duration of over 3 years, 48 cases (29.8%) showed positive staining for L1CAM. L1CAM positivity was significantly correlated with non-endometrioid histology (p < 0.0001), vascular invasion (p = 0.0157), and positive cytology (p = 0.005), and was a significant predictor of poor survival among advanced-stage patients, but not early-stage patients in our cohort. L1CAM-positive patients showed a higher recurrence rate and frequency of distant failure than L1CAM-negative patients. Multivariate analysis revealed that para-aortic lymph node metastasis (PANM) and L1CAM positivity were independent predictors of poor survival. Overall survival can be stratified into three groups by the combination of PANM and L1CAM positivity. CONCLUSION: L1CAM is an independent predictor of poor survival in endometrial cancer patients undergoing full lymphadenectomy and adjuvant chemotherapy, thus indicating that L1CAM can be clinically used as a biomarker to identify those patients at increased risk of recurrence.

Four versus six chemotherapy cycles in endometrial carcinoma with a high risk of recurrence: a retrospective study.

OBJECTIVE: This study compared the survival outcomes and the incidence of chemotherapy-related adverse events in endometrial cancer patients who received four and six cycles of adjuvant chemotherapy to examine the optimal number of adjuvant chemotherapy cycles. METHODS: A total of 112 patients with endometrial cancer with a high risk of recurrence were retrospectively enrolled; 46 patients received four cycles and 66 received six cycles of adjuvant chemotherapy. Between-group differences of overall survival, disease-free survival, hematological and non-hematological toxicities were analyzed. Baseline patient's background differences were assessed with inverse probability of treatment weighting using propensity score. RESULTS: Overall and disease-free survivals between the two groups were not significantly different. Paclitaxel + carboplatin, every 3-4 weeks was the most frequently used chemotherapy regimen in both groups. Patients in the six-cycle chemotherapy group developed neutropenia G4 or febrile neutropenia more frequently than those in the four-cycle group; odds ratio (95% confidence interval) is 4.07 (1.51-10.96). Peripheral sensory neuropathy was the most frequently observed non-hematological toxicity; the incidence of peripheral sensory neuropathy was not significantly different between four- and six-cycle chemotherapy group, P = 0.832. The result was same in the subgroup analysis in patients who received TC regimen, P = 0.455. CONCLUSION: This study implies a possible benefit of fewer cycles of adjuvant chemotherapy in endometrial cancer patients with a high risk of recurrence because of the lower incidence of hematological toxicities without impairing survival outcomes.

Tailored radical hysterectomy for locally advanced cervical cancer.

OBJECTIVE: The survival and prognostic factors for locally advanced cervical cancer treated with nerve-sparing Okabayashi-Kobayashi radical hysterectomy have not been elucidated. We aimed to evaluate the oncological outcomes of those patients after radical hysterectomy with adjuvant chemotherapy. METHODS: This retrospective cohort study was conducted from January 2002 to December 2011. Treatment was conducted at a single tertiary center in northern Japan. We used the Okabayashi-Kobayashi radical hysterectomy with lymphadenectomy. We applied unilateral nerve preservation for stage IIA/IIB cancer if there was a one-sided extension of the disease outside the cervix. Indication for adjuvant therapy was based on Sedlis criteria. High-risk was defined as evidence of lymph node metastasis, pathological parametrial invasion, and a positive/close surgical margin. The choice of adjuvant therapy was chemotherapy which consisted of paclitaxel and cisplatin. RESULTS: The study included 76 early-stage IB1 (≤4 cm) and IIA1 cervical cancer and 45 locally advanced stage IB2 (>4 cm), IIA2, and IIB disease treated consecutively. The median follow-up was 106 (range: 6-203) months. There were 18 (15%) patients with recurrence, with five of 76 in the early-stage (7%) and 13 of 45 in the locally advanced disease (29%) (P<0.001). For locally advanced cervical cancer, pT classification (P<0.001), lymph node metastasis (P=0.007), and histology (P=0.05) were associated with locoregional recurrence. The five-year locoregional recurrence rate in the locally advanced disease was 20% and 5% in the early-stage disease (P=0.01). The five-year disease-free survival in the locally advanced cervical cancer was 71% and 93% in the early-stage disease (P<0.001). The overall survival in locally advanced disease depended on the adeno-type histology and lymph node metastasis. CONCLUSION: The tailored use of nerve-sparing Okabayashi-Kobayashi radical hysterectomy with adjuvant chemotherapy based on tumor histology and lymph node metastasis may be a possible option as a treatment of locally advanced cervical cancer in selected patients.

Appendicular muscle mass and exercise/sports participation history in young Japanese women.

Background: It remains unclear how past exercise habits can affect the skeletal muscle mass in adulthood in Japanese populations. Aim: The purpose of the present investigation was to examine the association of appendicular muscle mass (AMM) and skeletal muscle mass index (SMI) with the history of exercise and/or physical activity participation in Japanese women. Subjects and methods: One hundred and twenty females, aged between 18 and 28 years old, participated in the present investigation. Using a dual-energy X-ray absorptiometry scanner, the appendicular lean soft tissue, which is considered as a measure of AMM, was evaluated. Skeletal muscle mass index (SMI) was also assessed. Furthermore, all subjects answered a physical activity questionnaire. Results: Exercise habits at 7 years of age or older positively affected the AMM and SMI. The results of the multiple regression analysis showed that exercise history at 16-18 years of age as well as the current status of exercise and/or physical activity participation was a significant predictor of SMI and AMM. Conclusions: These results indicate that not only the past history of participation in physical and/or sports activities but also the current status of daily physical activity and sports activity play an important role in maintaining appropriate SMI and AMM in young women.

Pulmonary Apical Opacities on Thin-Section Computed Tomography: Relationship to Primary Spontaneous Pneumothorax in Young Male Patients and Corresponding Histopathologic Findings.

OBJECTIVE: The purpose of this study was to test the hypothesis that apical opacities on computed tomography (CT) are related to occurrence of primary spontaneous pneumothorax (PSP) in young male patients. METHODS: We compared the frequency of apical opacities on thin-section CT between 70 male patients with PSP (PSP group) and 74 male patients without a history of PSP (non-PSP group). We also evaluated histopathologic findings of 39 specimens from 37 surgical cases in the PSP group. RESULTS: Apical opacities were significantly more frequent in the PSP group than in the non-PSP group (right side, P = 0.01; left side, P = 0.005). Histopathologically, subpleural band-like alveolar collapse was seen in 35 specimens (89.7%), which was always accompanied by fibroelastosis and fibroblastic foci. CONCLUSIONS: Apical opacities on CT were significantly associated with PSP in young male patients. These apical opacities histopathologically correspond to fibrotic pleural thickening with subpleural alveolar collapse.

Surveillance of protocol deviations in Japanese oncology registration trials: a single institute experience.

Background The contents and requirements of study protocols vary depending upon each clinical registration trial. This study aims to describe details of protocol deviations in Japanese oncology registration trials. Methods We reviewed deviation reports that were discussed by the Institutional Review Board between 2010 and 2015. Results A total of 499 clinical trials were performed, from which 967 deviations were reported. In the initial 3 years, 445 deviations occurred in 535 ongoing trials, while 522 deviations occurred in 876 trials in the subsequent 3 years. The frequency of deviations related to visit, examination, treatment, and others was 189 (19.5%), 446 (46.1%), 275 (28.4%), and 57 (5.9%), respectively. Serious deviations were common at the time of registration of trials and during treatment. The deviations were attributable to the institution (n = 520), subject (n = 93), sponsor (n = 28), schedule management (n = 162), disease condition (n = 95), and others (n = 69). Conclusion This study showed the number and detail responsible factors of protocol deviations. Our findings support to distinguish between the measures to reduce the serious deviations and to reduce the overall number of deviations.

Pemetrexed-related interstitial lung disease reported from post marketing surveillance (malignant pleural mesothelioma/non-small cell lung cancer).

BACKGROUND: Interstitial lung disease (ILD) is important drug related toxicity because it commonly forced to discontinue the treatment. METHODS: To characterize the prevalence and patterns of pemetrexed induced ILD, an independent ILD advisory board composed of external experts performed reassessment of ILD in two post marketing surveillance (PMS) studies for malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC). RESULTS: ILD incidences were originally 1.6% and 2.6% in 903 MPM and 683 NSCLC patients in safety analyses, respectively. Based on the reassessment by the board, the incidence was 1.1% MPM and 1.8% NSCLC. Common possible risk factors of ILD in MPM and NSCLC patients were male gender, 60 years or older age, and pre-existing ILD. Asbestosis in MPM, and smoking history in NSCLC are also considered as risk, respectively. In terms of computed tomography (CT) pattern, 7 of 10 cases in MPM patients had acute interstitial pneumonia pattern, which four were fatal. Eight of the 12 NSCLC patients had diffuse grand glass opacity, which all had recovered. Onset of ILD in MPM varied between the first and the fifth courses of pemetrexed treatment, and the latest onset was 48 days after the last administration. For NSCLC, it was between the second and the ninth course, 7 and 56 days after the last administration. CONCLUSIONS: The risk of pemetrexed-related ILD is similar level as other anti-cancer drugs under clinical settings. Careful observations continuously during and at least for 2 months after the last administration of pemetrexed are advised.

Do all patients in the phase I oncology trials need to be hospitalized? Domestic but outstanding issues for globalization of drug development in Japan.

INTRODUCTION: Most trials investigating new drugs around the world, including phase I trials, are conducted in outpatient clinics. However, in Japan, regulatory authority requirements and traditional domestic guidelines often require hospitalization of phase I study participants. PATIENTS AND METHODS: Patients participating in single-agent phase I clinical trials at National Cancer Center Hospital between December 1996 and August 2014 were monitored. Toxicity requiring hospitalization is defined as toxicity that needs intensive treatment. Study designs were classified into three types: first-in-human (FIH) study, dose-escalation study (conventional dose-escalation study to determine maximum tolerated dose (MTD) in Japanese patients), and dose-finding study (to assess safety and pharmacokinetic profiles up to the MTD previously determined in the West). RESULTS: A total of 945 patients who participated in a variety of single-agent phase I clinical trials between December 1996 and August 2014 were included in this study. Patients participated in one of three study types: dose-escalation (n = 582, 62%), first-in-human (n = 129, 14%), or dose-finding (n = 234, 25%). A total of 76 study drugs were evaluated as part of this pool of phase I studies. Subdivided by mechanism of action, 20 (26%) were cytotoxic, 50 (66%) were molecularly targeted, and 6 (8%) were immune checkpoint inhibitor. Thirty-six patients (3.8%) had severe toxicities requiring hospitalization during the first cycle. The overall number of toxicities requiring hospitalization and/or grade 4 toxicities during any cycle was 5.0%. CONCLUSIONS: The frequency of severe toxicity that needs to be hospitalized was unexpectedly low. The data did not demonstrate the need for hospitalization in the phase I trials, suggesting that phase I trials in Japan could be conducted in outpatient settings.

[RISK OF TUBERCULOSIS INFECTION AND DISEASE AMONG JAPANESE FEMALE NURSES AND MALE DOCTORS IN RECENT YEARS].

[Objectives and Materials] Based on the tuber- culosis (TB) surveillance database, the incidence rates of TB infection and active disease among healthcare workers were observed for female nurses and male doctors in 2010 in comparison with those of the general population. [Results] The relative risk (RR) of active TB among female nurses aged 20-69 years was 4.86 (95% confidence interval: 4.31-5.45) for 2010, which has increased from 2.30 observed in 1987-1997. The RR was highest for nurses aged 20-29 years at 8.84 and declined with age until 3.60 for those aged 50-59 years that was still significantly higher than 1. For male doctors the RR was significantly higher than 1 only for those aged 39 years or younger. The rates of those who were -indicated for treatment of latent TB infection (LTBI) were clearly higher among healthcare workers; for female nurses the RR was 32.7 (95% CI: 30.5-35.0), ranging from the highest level of 62.8 among those aged 20-29 years down to 11.6 for those aged 60-69 years. For male doctors also, the RR was high at 9.7 (7.9- 11.7) for 20-69 years, ranging from 14.5 for those aged 20- 29 years down to 5.3 for those aged 60-69 years. [Discussion] TB cases of nurses and doctors were more likely to be detected by the active case finding measures such as periodic screening and contact investigations than cases in the general population, which indicates the current effort of addressing the occupational exposure in the healthcare set- tings. The high level of risk of TB disease as Iwell as LTBI among healthcare professions and its possibly increasing trend as. seen in female nurses warrants further strengthening of monitoring of the problem and overall countermeasures in their workplaces.

[Calcium and bone metabolism across women's life stages. Treatment for the malignant tumors in women and bone calcium metabolism.]

In the malignant tumors in women, uterine cervical cancer, endometrial cancer, ovarian cancer, and breast cancer are representative diseases. The cancer treatment is classified roughly into an operation, medical treatment, and radiation therapy and has an extremely big influence on ovarian function. With the improvement in survival of cancer patients, the importance of the health care for the cancer survivors increases. It is necessary to prevent the onset of the osteoporotic fractures to maintain QOL. This paper describes the action that the malignant tumors of the women affect bone metabolism mainly from the viewpoint of ovarian function.

A Comparative Study of Self-Efficacy for Social Participation of People with Mental Illness in Japan and China.

Self-efficacy for social participation (SESP) of people with mental illness was examined in urban areas of Japan and China. The subjects were 266 people (140 Japanese, 126 Chinese) with mental illness who were living in their local community. Our SESP scale (SESP27) and the Rosenberg Self-Esteem Scale, Norbeck Social Support Questionnaire (NSSQ), Sense of Coherence measure (SOC13), General Health Questionnaire (GHQ12), and a self-administered questionnaire related to living conditions were used for data collection. Data were analyzed descriptively, correlations between scales were examined, and multiple regression analysis was performed by country. The results showed that annual income was related to SESP in Japan and China. Therefore, improvement of welfare and employment support for economic independence is likely to improve SESP of people with mental illness in both countries. In addition, SESP in people with mental illness is affected by self-esteem in Japan, and coping skills such as improvement of life functions in China. Thus, SESP is affected differently by the social, cultural and institutional characteristics of each country.

[Viewpoint: Skill Certifications for Japanese Medical Technologists].

With the development of medicine, the field of clinical laboratory medicine evolves rapidly, and it will be more specialized in the near future. Medical technologists are required to hone their skills and knowledge, in order to keep up with the evolution. In recent years, board certifications by several medical societies are considered to indicate the skills of medical technologists. The number of board-certified medical technologists in populated areas such as Tokyo, Kanagawa, Osaka, and Fukuoka is greater than in less populated areas such as Kyusyu and Tohoku. The rate of certified medical technologists among prefectures is the highest in Mie (10.1%), followed by Nagasaki (8.8%). Tokyo, Ishikawa, Kyoto, and Osaka have acquisition rates greater than 7%. In contrast, prefectures of Miyazaki, Kumamoto, Yamanashi, and Akita have low acquisition rates of less than 4%. Being certified is not only an opportunity for personal career advancement, but also a chance to improve the laboratory. More technologists are being certified in our laboratory, and we are encouraging a future increase in their number. However, there are some problems to be overcome. Assignment of competent staff and long-term and premeditated rotation are considered to be important for staff to find the work rewarding, and the laboratory to be trusted by physicians.

Distribution of lymph node metastasis sites in endometrial cancer undergoing systematic pelvic and para-aortic lymphadenectomy: a proposal of optimal lymphadenectomy for future clinical trials.

PURPOSE: The aim of this study was to demonstrate the precise mapping of lymph node metastasis (LNM) sites in endometrial cancer. METHODS: A total of 266 patients who underwent primary radical surgery including systematic pelvic and para-aortic lymphadenectomy for endometrial cancer from 1993 to 2010 were enrolled in this study. We removed lymph nodes from the femoral ring to the para-aortic node up to the level of renal veins. We analyzed the distribution of positive-node sites according to their anatomical location. RESULTS: Overall, 42 of 266 patients (15.8 %) showed LNM. The median number of nodes harvested was 62.5 (range 40-119) in pelvic nodes (PLN), and 20 (range 3-47) in para-aortic nodes (PAN). Among 42 cases with positive-nodes, 16 cases (38.1 %) showed positive PLN alone, 7 cases (16.7 %) in PAN alone, and 19 cases (45.2 %) in both PLN and PAN. The most prevalent site of positive-nodes was PAN (9.8 %) followed by obturator nodes (9.4 %), internal iliac nodes (7.1 %), and common iliac nodes (5.6 %). Six of 19 cases (31.6 %) of positive PAN above the inferior mesenteric artery (IMA) showed negative PAN below IMA. Metastasis to the deep inguinal nodes was found to be extremely rare (0.38 %). Single-site LNM was the most frequently observed in obturator nodes, followed by PAN above IMA. CONCLUSION: Routine resection of deep inguinal nodes is not recommended, whereas para-aortic lymphadenectomy should be extended up to the level of renal veins for endometrial cancer.

[Analysis on workload for hospital DOTS service].

BACKGROUND AND OBJECTIVE: A directly observed treatment short course (DOTS) trial was launched in Japan in the late 1990s and targeted patients with social depression at urban areas. Based on these findings, the Ministry of Health, Labour and Welfare established the Japanese DOTS Strategy in 2003, which is a comprehensive support service ensuring the adherence of tuberculosis patients to drug administration. DOTS services are initially provided at the hospital to patients with infectious tuberculosis who are hospitalized according to the Infectious Diseases Control Law. After being discharged from the hospital, the patients are referred to a public health center. However, a survey conducted in 2008 indicated that all the patients do not receive appropriate DOTS services at some hospitals. In the present study, we aimed to evaluate the protocols and workload of DOTS at hospitals that are actively involved in tuberculosis medical practice, including DOTS, to assess whether the hospital DOTS services were adequate. METHOD: We reviewed a series of articles on hospital DOTS from a Japanese journal on nursing for tuberculosis patients and identified 25 activities regarding the hospital DOTS service. These 25 items were then classified into 3 categories: health education to patients, support for adherence, and coordination with the health center. In total, 20 hospitals that had > 20 authorized tuberculosis beds were selected--while considering the geographical balance, schedule of this survey, etc.--from 33 hospitals where an ex-trainee of the tuberculosis control expert training program in the Research Institute of Tuberculosis (RIT) was working and 20 hospitals that had collaborated with our previous survey on tuberculosis medical facilities. All the staff associated with the DOTS service were asked to record the total working time as well as the time spent for each activity. The data were collected and analyzed at the RIT. RESULT: The working times for each activity of the DOTS service for nurses, pharmacists, ward clerks, head nurses, and doctors were 100, 90, 87, 86, and 63 min, respectively. For other professions, including medical social workers, nursing aids, nutritionists, and physical therapists, the working times for each activity of the DOTS service were 31, 18, 10, and 8 min, respectively. The professionals who spent a longer time on health education, support for patient adherence, and coordination with the health center were pharmacists, doctors, and head nurses; nurses, pharmacists, and doctors; and head nurses, doctors, and ward clerks, respectively. DISCUSSION: Aging of tuberculosis patients was associated with problems on adherence in many patients, including patients who were not suited for a standard regimen, patients whose activity of daily life had deteriorated due to senile dementia, patients with diabetes mellitus, etc. Smoking cessation and mental care for cases of multi-drug resistant disease are new challenges in tuberculosis patient care. The present study clearly indicated that activities including patient education, support for patient adherence, and coordination with the health center--essential components of the hospital DOTS service according to the Japanese DOTS Strategy--were performed by a team of professionals including doctors, nurses, pharmacists, medical social workers, etc., depending on the features and roles that they serve and the needs of each patient. For good practice of hospital DOTS, it is essential to not only provide DOTS, but also effectively provide individual or group health education and coordinate with health centers, thus aiming towards a better community DOTS service after patient discharge.

[Safety and effectiveness of pemetrexed in patients with non-small cell lung cancer in Japan - analysis of post-marketing surveillance].

The safety and effectiveness of pemetrexed(PEM)in patients with non-small cell lung cancer(NSCLC)were reviewed using data from post-marketing surveillance. Among 699 patients registered from June 2009 to May 2010, 683 patients were analyzed(343, first-line therapy: 340, second-line therapy or beyond). Patient backgrounds were as follows: median age=65 years(16.1%B75 years old); 64.7% male; 91.9% performance status 0-1; 83.2% Stage IV; 99.0% non-squamous cell cancer. Also, 86% of the first-line and 20% of the second-line cohort were receiving a concomitant anti-cancer drug(mostly platinum agents). The incidence rate of adverse drug reactions(ADR)was 76.7%, including serious cases(18.0%). The most common ADRs were decreased white blood cell count(26.8%), decreased neutrophil count(25.3%), anemia(19.2%), decreased platelet count(17.0%), and nausea(23.0%). The incidence of interstitial lung disease, which is a concern during chemotherapy, was 2.6%. Peripheral neuropathy and alopecia, events influencing a patient's quality of life, were less than 1%. The estimated median survival time was 23.2 months[95%CI: 19.8 months-not calculable]in the first-line cohort, and 11.8 months[95% CI: 10.5-13.7 months]in the B second-line cohort. The surveillance results showed no apparent difference in total ADRs in this current study compared to the safety profile established in clinical trials previously conducted in Japan and overseas. These results demonstrate the safety and effectiveness of PEM treatment for NSCLC patients in daily clinical settings.

Lack of information on gender differences in the package inserts of prescription drugs in Japan.

The package inserts of prescription drugs provide essential information for the proper administration of pharmacotherapy. The incidence of adverse reactions for several drugs is known to be higher in women than in men. However, no studies have examined whether information on gender differences is included in Japanese package inserts. Therefore, this study investigated information on gender differences in the package inserts of Japanese prescription drugs, using the drug information database JAMES provided by the Medical Information System Development Center and the Japan Pharmaceutical Information Center. Non-proprietary names of prescription drugs were yielded 1,679 in Japan. Of the 1,679 ingredients in package inserts of prescription drugs, 76 (4.5%) included information on gender differences. The number of inserts that contained information on gender differences in the "DOSAGE AND ADMINISTRATION," "ADVERSE REACTIONS," and "PHARMACOKINETICS" sections was 3, 16, and 62, respectively. Furthermore, in the "ADVERSE REACTIONS" section, 15 of the 16 inserts mentioned a higher frequency of adverse reactions in women compared with men. Importantly, most of the inserts with information on gender differences in the "PHARMACOKINETICS" section mentioned a higher area under the curve for women than for men. Most of the package inserts of prescription drugs with information on gender differences provide useful information aimed at preventing risks in women. However, there is an extreme lack of information on gender differences in the package inserts of prescription drugs in Japan, and we consider enhancing information on gender difference as an urgent issue.

Barriers and misconceptions hindering reduction of intestinal schistosomiasis in Mbita Sub-County, Western Kenya.

BACKGROUND: Community and individual participation are crucial for the success of schistosomiasis control. The World Health Organization (WHO) has highlighted the importance of enhanced sanitation, health education, and Mass Drug Administration (MDA) in the fight against schistosomiasis. These approaches rely on the knowledge and practices of the community to be successful; however, where the community knowledge is low and inappropriate, it hinders intervention efforts. Hence, it is essential to identify barriers and misconceptions related to awareness of schistosomiasis, sources of infection, mode of transmission, symptoms, and control measures. METHODS: This was a mixed-method cross-sectional study involving 1200 pre-school children randomly selected and examined for Schistosoma mansoni infection using the Kato-Katz technique. All parents/guardians of selected children were enrolled for a pre-tested questionnaire survey, while 42 were engaged in focus group discussions (FGDs). The level of knowledge and awareness among parents/guardians about schistosomiasis was evaluated in relation to the infection status of their pre-school children. RESULTS: Among pre-school children, the prevalence of intestinal schistosomiasis was 45.1% (95% CI 41.7-48.5). A majority of parents/guardians (85.5%) had heard about schistosomiasis, and this awareness was associated with the participant's level of education (OR = 0.16, 95% CI 0.08, 0.34). In addition, a positive association was observed between higher educational attainment and knowledge of the causative agent (OR = 0.69, 95% CI 0.49, 0.96). Low education level was significantly associated with limited knowledge of transmission through lake water contact (OR = 0.71, 95% CI 0.52, 0.97) and infection from the lake (OR = 0.33, 95% CI 0.19, 0.57). Notably, parents/guardians who have heard of schistosomiasis could not recognize symptoms of S. mansoni infection, such as abdominal pain (91.8%, 815/888) and blood in the stool (85.1%, 756/888). Surprisingly, 49.8% (442/888) incorrectly identified hematuria (blood in urine), a key sign of S. haematobium, but not S. mansoni, in an endemic area for S. mansoni infection. The majority (82.6%, 734/888) of parents/guardians were unaware that dams are potential infection sites, despite 53.9% (479/888) of their pre-school-aged children testing positive for schistosome infection. CONCLUSIONS: Despite the high level of awareness of intestinal schistosomiasis in the study area, we identified a low level of knowledge regarding its causes, modes of transmission, signs and symptoms and potential sites of transmission within the community. This study emphasizes the need for targeted educational interventions to address the misconceptions and knowledge gaps surrounding intestinal schistosomiasis through tailored community-based programs.

Safety and effectiveness of gemcitabine in 855 patients with pancreatic cancer under Japanese clinical practice based on post-marketing surveillance in Japan.

OBJECTIVE: When gemcitabine was approved as an anti-cancer drug, there were limited data for Japanese patients treated with gemcitabine. Generally, advanced or metastatic pancreatic cancer patients experience poor prognosis and suffer from debilitating disease-related symptoms. Reports and information on gemcitabine use within a large patient pool will be beneficial to aid physicians. Therefore, this post-marketing surveillance was conducted as a non-interventional, observational study on the use of gemcitabine in a clinical practice setting in Japan. METHODS: Patients had no previous treatment with gemcitabine and were diagnosed with pancreatic cancer by an attending physician. Patients were registered between May 2001 and December 2003 in Japan. The patients were treated with gemcitabine. Data such as patient background, treatment details, adverse events, tumor response, serum CA19-9 levels and drug-related symptom improvement were assessed. RESULTS: Of the 890 patients registered for the study, 855 were included in the analysis of gemcitabine for safety. Four hundred and forty-three (51.9%) patients reported drug-related adverse events, with 97 patients (11.4%) experiencing serious adverse events. The incidence of interstitial lung disease was 0.7% (six patients). Six hundred patients were evaluated for tumor response. The overall response rate was 6.0% and the disease control rate was 54.0%. CA19-9 decreased in 63.6% of the 335 evaluable patients, with a ≥75% decrease seen in 19.4% of the total group. Drug-related symptom improvement was observed in 27.0% of the 686 evaluable patients. CONCLUSIONS: This large-scale surveillance could confirm the safety of gemcitabine for Japanese pancreatic cancer patients as well as elucidate the efficacy profile, measured by drug-related symptom improvement, for Japanese pancreatic cancer patients.

[Development and application of microbiology data monitoring system (Akita-ReNICS) for networking hospitals in Akita Prefecture].

Networking among regional hospitals recently became required for infection control activities in Japan. In Akita prefecture, we developed a microbiology data warehouse for networking hospital laboratories in 2010. Designated users can easily obtain microbiology data and compare it with other participating hospitals using this system. For example, users are able to compare the MRSA/MSSA ratio in Staphylococcus aureus with other participating hospitals in Akita-ReNICS. The effectiveness and assignment of this system were shown by a questionnaire administrated in 2013. In this paper, we clarify the current state and assignment of Akita-ReNICS and consider its effective application for better infection control activities.