The presence of multiple NS5A RASs is associated with the outcome of sofosbuvir and ledipasvir therapy in NS5A inhibitor-naïve patients with chronic HCV genotype 1b infection in a real-world cohort.

It is unclear whether multiple nonstructural (NS) 5A resistance-associated substitutions (RASs) correlate with the outcome of sofosbuvir (SOF) and ledipasvir (LDV) therapy. We investigated the effects of multiple NS5A RASs in NS5A inhibitor-naïve patients with chronic hepatitis C virus genotype 1b infection treated with SOF/LDV. In 313 patients treated with SOF/LDV, we assessed the effects of multiple NS5A RASs on the sustained virological response (SVR). RASs at L28, R30, L31, Q54, P58, Q62, A92, and Y93 in the NS5A region were examined by direct sequencing. The prevalence of RASs was as follows: 2.6% at L28, 8.7% at R30, 6.1% at L31, 48.7% at Q54, 9.9% at P58, 9.9% at Q62, 5.1% at A92, 13.8% at Y93, and 19.2% at L31 or Y93. A total of 133 patients had no RASs. SVR was achieved in 98.7% of the patients. SVR rates significantly differed between patients with and without the L31 or Y93 RAS (93.0% [53/57] vs 100% [250/250], P = .0011). In addition, among patients with the L31 or Y93 RAS, 29.8%, 45.6% and 24.6% had one, two and three or more NS5A RASs, respectively. The SVR rate was significantly lower in patients with the L31 or Y93 RAS with more than three NS5A RASs compared to those with fewer than three NS5A RASs (71.4% [10/14] vs 100% [43/43], P = .0025). Although the prevalence of multiple NS5A RASs at baseline was low in NS5A inhibitor-naïve patients, the presence of multiple NS5A RASs was associated with the effectiveness of SOF/LDV therapy.

Sorafenib plus hepatic arterial infusion chemotherapy with cisplatin versus sorafenib for advanced hepatocellular carcinoma: randomized phase II trial.

BACKGROUND: Sorafenib (Sor) is acknowledged as a standard therapy for advanced hepatocellular carcinoma (HCC). This trial was conducted to evaluate the effect of addition of hepatic arterial infusion chemotherapy with cisplatin (SorCDDP) to Sor for the treatment of advanced HCC. PATIENTS AND METHODS: We conducted a multicenter open-labeled randomized phase II trial in chemo-naïve patients with advanced HCC with Child-Pugh scores of 5-7. Eligible patients were randomly assigned 2:1 to receive SorCDDP (sorafenib: 400 mg bid; cisplatin: 65 mg/m2, day 1, every 4-6 weeks) or Sor (400 mg bid). The primary end point was overall survival. RESULTS: A total of 108 patients were randomized (Sor, n = 42; SorCDDP, n = 66). The median survival in the Sor and SorCDDP arms were 8.7 and 10.6 months, respectively [stratified hazard ratio (95% confidence interval), 0.60 (0.38-0.96), P = 0.031]. The median time to progression and the response rate were, respectively, 2.8 months and 7.3% in the Sor arm and 3.1 months and 21.7% in the SorCDDP arm. The adverse events were more frequent in the SorCDDP arm than in the Sor arm, but well-tolerated. CONCLUSION: SorCDDP yielded favorable overall survival when compared with Sor in patients with advanced HCC. CLINICAL TRIAL REGISTRATION: UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703.

Triple-marker PCR assay of sentinel lymph node as a prognostic factor in melanoma.

BACKGROUND: Metastasis of sentinel lymph node (SLN) is generally evaluated on histopathological examination and controversy still exists over the usefulness of PCR assay of SLN. OBJECTIVE: To investigate the prognostic value of triple-marker PCR assay of SLN. METHODS: A total of 165 patients with primary cutaneous melanoma who underwent SLN biopsy were included. Clinical and histopathological data were retrieved from each patient's file and triple-marker PCR assay (tyrosinase, GP-100 and MART-1) was performed on the SLN as well as routine histopathological evaluation. PCR positivity was defined as the expression of all three PCR markers. To evaluate melanoma-specific survival (MSS) and disease-free survival (DFS), we used the Kaplan-Meier method and the log-rank test. Multivariate analyses using the Cox proportional hazards regression model were also performed. RESULTS: Sentinel lymph nodes were identified in all 165 patients: 61 patients (37.0%) were male and 104 (63.0%) were female, with a mean age of 60.2 years. Of the 165 melanomas, 81 (49.1%) were acral lentiginous melanomas. Compared with the patients with PCR positivity (1-2 markers) or PCR negativity, patients with PCR positivity (3 markers) had significantly poor MSS (5-year survival rate, 58.7% vs. 84.4%; P < 0.0001) and DFS (5-year survival rate, 25.0% vs. 83.9%; P < 0.0001), with median follow-up of 42 months for MSS and 38 months for DFS. These survival rates of patients with PCR positivity (3 markers) were lower than those of patients with histopathologically positive SLN. In multivariate analysis, PCR positivity (3 markers) was an independent prognostic factor for both MSS (hazard ratio [HR], 2.81; 95% confidence interval [CI], 1.07-7.33; P = 0.035) and DFS (HR, 2.48; 95% CI, 1.08-5.69; P = 0.032). CONCLUSIONS: The expression of three PCR markers was a significant prognostic factor for both MSS and DFS and might be closely correlated to a dismal prognosis.

Expression of milk fat globule epidermal growth factor-VIII may be an indicator of poor prognosis in malignant melanoma.

BACKGROUND: Milk fat globule epidermal growth factor-VIII (MFG-E8) is a secreted protein that binds phosphatidylserine and promotes apoptotic cell ingestion by phagocytes, mediating the immune tolerance and maintenance of homeostasis. A recent study has shown that MFG-E8 expression in human melanoma is increased with tumour progression; however, the effect of its expression on patient survival has not yet been clarified. OBJECTIVE: To analyse MFG-E8 expression in melanoma, and to determine whether it can serve as a marker for diagnosis, tumour progression and/or prognosis. METHODS: MFG-E8 expression was examined by immunohistochemistry in 60 primary melanomas, 22 metastatic lesions and 30 benign naevi. The following clinicopathological variables were evaluated: age, gender, histological type, tumour site, Breslow thickness, Clark's level, the presence or absence of ulceration and tumour-infiltrating lymphocytes, and survival periods. Statistical analyses were performed to assess associations and melanoma-specific survival. RESULTS: MFG-E8 expression was significantly higher in primary and metastatic melanoma than in naevus. Furthermore, it increased according to tumour progression and metastasis. Patients with MFG-E8 expression in primary tumours had significantly shorter survival periods than those without MFG-E8 expression. Univariate and multivariate analyses revealed that MFG-E8 expression was a statistically significant and independent prognostic factor. CONCLUSION: MFG-E8 expression may serve as a tumour progression marker and can predict an unfavourable prognosis in patients with melanoma.

Applicability of both dentist and patient perceptions of dentists' explanations to the evaluation of dentist-patient communication.

OBJECTIVES: Very little is known about dentist-patient communicative behaviours in actual practice. This study evaluated dentist and patient perceptions of dentist-patient communication and patient outcome. PARTICIPANTS: The subjects were 171 dentist-patient pairs in Kitakyushu, Japan. RESEARCH DESIGN: Dentists and patients answered the same questionnaire items using the same response categories to evaluate dentist-patient communication. Based on the scores of patient and dentist perceptions with respect to dentist-patient communication, patient-dentist pairs were categorised into one of 3 groups. Data analyses used one-way ANOVA, multiple linear regression analysis, and multiple logistic regression analysis. RESULTS: We found that, with respect to dentist-patient communication, patients in the 'patient better' group (i.e., the patient's evaluation was more positive than the dentist's evaluation) were more likely to have a positive outcome (e.g., 'improvement of health and fear,' 'satisfaction with care') than those in the other two groups. Patients in the 'doctor better' group (i.e., the dentist's evaluation was the more positive) were more likely to have a negative outcome than those in the other two groups. CONCLUSIONS: A positive patient outcome is more likely when the patient's evaluation is better than a dentist's evaluation with respect to dentist-patient communicative behaviours. The method based on patient and dentist perceptions with respect to dentist-patient communication might be effective in evaluating dentist-patient communication.

Effects of weather variability on infectious gastroenteritis.

Although multiple combinations of weather variability may contribute to an increased incidence of infectious gastrointestinal disease, few studies have investigated the association between weather variability and cases of infectious gastroenteritis. We acquired data for infectious gastroenteritis cases and weather variability in Fukuoka, Japan, from 1999 to 2007 and used time-series analysis to assess the effects of weather variability on infectious gastroenteritis cases, adjusting for confounding factors. In total, 422,176 infectious gastroenteritis cases were reported during the 9-year study period. The weekly number of infectious gastroenteritis cases increased by 7.7% (95% CI 4.6-10.8) for every 1 degrees C increase in the average temperature and by 2.3% (95% CI 1.4-3.1) for every 1% decrease in relative humidity. From 1999 to 2007, infectious gastroenteritis cases increased significantly with increased average temperature and decreased relative humidity in Fukuoka, Japan.

Impact of weather factors on Mycoplasma pneumoniae pneumonia.

BACKGROUND: Although multiple combinations of weather factors may contribute to an increased incidence of Mycoplasma pneumoniae pneumonia, few studies have investigated the association between weather factors and cases of M pneumoniae pneumonia. METHODS: Data on cases of M pneumoniae pneumonia and weather factors in Fukuoka, Japan from 1999 to 2007 were obtained and time-series analysis was used to assess the effects of weather variables on M pneumoniae pneumonia cases, adjusting for confounding factors. A total of 13 056 M pneumoniae pneumonia cases were reported during the 9-year study period, of which 12 234 (93.7%) were under 15 years of age. RESULTS: The weekly number of M pneumoniae pneumonia cases increased by 16.9% (95% CI 11.3% to 22.8%) for every 1 degrees C increase in the average temperature and by 4.1% (95% CI 2.7% to 5.5%) for every 1% increase in relative humidity. CONCLUSIONS: From 1999 to 2007, cases of M pneumoniae pneumonia increased significantly with increased average temperature and relative humidity in Fukuoka, Japan.

Stand structure and woody species diversity in relation to stand stratification in a subtropical evergreen broadleaf forest, Okinawa Island.

Stand structure and woody species diversity in a subtropical evergreen broadleaf forest grown in a silicate habitat, Okinawa Island, have been investigated on the basis of stand stratification. The forest stand consisted of four layers. The floristic composition of the top and the lower three layers was only slightly similar, although approximately one-third of the species were common to them. Mean tree weight decreased from the top toward the bottom layer whereas tree density increased from the top downward. This trend resembled the mean weight-density trajectory of self-thinning plant populations. The relationship between mean tree height and tree density for the upper two layers supported Yamakura's quasi -1/2 power law of tree height. The values of the Shannon-Wiener index, H', and the equitability index, J', tended to increase from the top layer downward except for the bottom layer. The values of H' and J' were, respectively, 4.83 bit and 0.82 for trees taller than 0.10 m. The lower layers contained many species of smaller height. High species diversity of the forest depended on small trees in the lower layers. Conservation of small trees in the lower layers, especially the bottom layer, is indispensable for sound maintenance of Okinawan evergreen broadleaf forests.

The number of steps taken by flight attendants during international long-haul flights.

BACKGROUND: Previous studies have revealed that female cabin attendants on long flights are most likely to have health problems. Since health problems can be related to workload and work stress and since the number of steps taken by an employee during a work shift can be an objective measure of the work load of cabin attendants, it is necessary to evaluate the predictors of the number of steps. METHODS: We used pedometers worn by 118 female flight attendants to study the number of steps during flights and its predictors during long international flights. RESULTS: The mean number of steps during 636.53 (SD = 129.11 )-minute flights was 10,742.85 (SD = 3,547.17). The crude number of steps per minute was 16.88, and the adjusted number of steps per minute was 14.04. Flight length and the number of sleeping hours worked (i.e., between midnight and 6:00 am) were significant predictors of the number of steps. CONCLUSION: Although it is implied that flight duration and night flight increase the work load of flight attendants, we need to consider psychological aspects to evaluate the overall effects of their jobs on work stress and health.

Rate of health insurance reimbursement and adherence to anti-hypertensive treatment among Japanese patients.

BACKGROUND: Although several studies have reported the effects of free medical care on compliance in patients with hypertension, no study has reported the effects of an economic incentive, such as subsidized medical costs, on compliance with medication protocol, in patients with hypertension. The unique characteristics of the Japanese health insurance system provide for a 10% decrease in the subsidy for medication immediately on retirement (approximately 60 years of age) for insured patients, and a 100% subsidy for insured patients who are 70 years of age or older. We examined the association between level of health insurance coverage and follow-up rate of medical treatment among Japanese patients with hypertension. METHODS: The subjects, from throughout Japan, were patients with hypertension (n=1236). The study was conducted in 1991. The odds of completing a 1-year treatment in relation to the rate of health insurance reimbursement were calculated using multiple logistic regression analysis. RESULTS: We found the following. (1) Compared with the base group, the odds of completing a 1-year treatment increased to 2.62 or 2.51 in the group whose reimbursement rate was 100%. (2) Compared with the base group, the odds of completing a 1-year treatment was no larger than 1 in the group whose reimbursement rate had been 100% for more than 6 years ('76-'). (3) Compared with the base level, the odds of completing a 1-year treatment increased to 1-1.81 in the group whose liability decreased to 80%. CONCLUSION: Although the results imply that even a small economic incentive might be effective in securing a patient's compliance with anti-hypertensive medical treatment, the effect appear limited in both duration and magnitude.

[Growth analysis on the competition-density effect in Cunninghamia lanceolata stands].

The competition-density (C-D) effect in Cunninghamia lanceolata stands was analyzed by using the reciprocal equation 1/omega = A rho + B, where omega and rho represent mean stem volume and density, respectively, the C-D curve given by the reciprocal equation on logarithmic coordinates shifted upward with time. With the increase of physical time t the biological time tau defined as the integral of lambda (t), the growth coefficient in general logistic growth curve, tended to increase to the maximum. The coefficients A and B included in the reciprocal equation were calculated at each growth stage. With increasing tau, the coefficient A increased abruptly up to a maximum value, and then tended to decrease gradually to a constant level, whereas the coefficient B decreased exponentially, and tended to close to zero. The coefficient of growth lambda (t) decreased with increasing stand age.

A signal detection approach to the combined effects of work stressors on alcohol consumption.

OBJECTIVE: To test the relationship between work stress and alcohol consumption and the efficacy of signal detection analysis in a work stress-alcohol consumption study. METHOD: The study was part of a Work Site Health Project, which included a stress reduction program, at a manufacturing company in Osaka, Japan. The study design was a cross-sectional survey. The participants were Japanese male whitecollar workers (N = 457; 30 to 50 years old) in the head administrative office of a large manufacturing company. Measurements consisted of demographic variables of the workers (age, marital status, manner of living and Type A personality), work stress measures, working hours and alcohol consumption. RESULTS: Of eight independent variables, six significant predictors of heavy alcohol consumption were identified in the first signal detection analysis. Of these six variables, job demand and skill discretion were work-stress-related measures. In the second multiple regression analysis, skill discretion and job demand were significant predictors of alcohol consumption among the workers in two of the seven subgroups categorized by the first signal detection analysis. CONCLUSIONS: It was revealed that work stress did relate to alcohol consumption. However, the effect of the work stress upon alcohol consumption was limited to specific types of workers with multiple specific attributes. It was also inferred that the signal detection approach is an effective approach to the work stress alcohol consumption relationship.

Work stressors, drinking with colleagues after work, and job satisfaction among white-collar workers in Japan.

Although previous studies have examined the buffering effects of social support and coping style on the relationship between stress and alcohol consumption, they have typically relied on analysis of variance (ANOVA) or regression analysis. In addition, few studies have examined the potential stress-buffering effects of drinking with coworkers after work on the relationship between job stress and job dissatisfaction. In the present study, using a signal detection analysis, we evaluated the interactions of drinking with coworkers after work and work-stressor variables among Japanese white-collar workers (n = 397) in 1997. The analysis was performed for two groups of subjects divided based on their status in the company. This was necessary because in Japan the obligations to drink socially increase with one's rising status in the company. In both the "staff members and lower-level managers" and "middle-level and higher-level managers' groups, an interaction between work-stressor variables and drinking variables was observed. The findings imply that drinking with coworkers after work ameliorated the sense of job dissatisfaction, but only among those subjects who already had lower levels of work stressors. For subjects with high levels of work stressors, attitudes toward drinking with coworkers were unrelated to job satisfaction levels.

Work stressors and alcohol consumption among white-collar workers: a signal detection approach.

OBJECTIVE: Previous findings regarding the relationship between work stress and alcohol consumption are inconsistent and inconclusive. One of the primary reasons for the inconsistency of the findings is that simple models, such as multiple regression analysis or analysis of variance (ANOVA), have been conventionally adopted in studies examining the relationship between work stressors and alcohol consumption. Since higher order interactions of multiple work stressors, which lead to heavy alcohol consumption, might not be fully uncovered within the framework of a multiple regression analysis or ANOVA, another approach to exploring the interactions of work stressors is presented in this study. METHOD: A signal detection analysis method was used to evaluate higher order interactions of work stress variables and to obtain basic information on 465 Japanese male white-collar workers. RESULTS: Of 11 work stressor or work position variables, four significant predictors of heavy alcohol consumption were identified. CONCLUSIONS: Two procedures were successfully performed in this study: (1) evaluating several higher order interactions of work stressors associated with heavy alcohol consumption, and (2) obtaining basic information to permit dividing the subjects into subgroups for further analysis using models and independent variables unique to each subgroup.

[Cost of medication for influenza infected elderly inpatients].

Influenza vaccine is recommended for the elderly, a high-risk group for influenza infection. Unlike in many developed countries, the rate of influenza vaccination is extremely low in Japan. One of the primary reasons for this low level of vaccination use may be insufficient study on the cost-effectiveness of influenza vaccination in Japan. We determined the cost of medical tests and medications for inpatients with influenza in a referred hospital. We compared the medical costs by (1) level of daily life activity, (2) presence of pneumonia, and (3) living/dead status, 9 months after the infection. In addition, we set up a control group of patients for comparison of their medical costs to those of the influenza patients. Mean costs were 37,279 (+/- 26,784) yen for patients, and 2,361 (+/- 4,893) yen for controls. Mean costs were 32,424 (+/- 30,935) yen for inpatients without limitations to activity, 44,075 (+/- 20,937) yen for bed-bound inpatients, 44,614 (+/- 28,609) yen for inpatients with pneumonia, 27,009 (+/- 22,783) yen for inpatients without pneumonia, 57,624 (+/- 21,041) yen for inpatients who died within 9 months of the onset of influenza, and 16,934 (+/- 11,920) yen for inpatients who were alive 9 month after influenza infection.

Chromosome 11q13 and atopic asthma.

Asthma is a complex syndrome in which bronchial inflammation and smooth muscle hyperactivity lead to labile airflow obstruction. The commonest form of asthma is that due to atopy, which is an immune disorder where production of IgE to inhaled antigens leads to bronchial mucosal inflammation. The ultimate origins of asthma are interactive environmental and genetic factors. The genetics is acknowledged to be heterogeneous, and one chromosomal region of interest and controversy has been 11q13. To clarify the nature of the chromosome 11q13 effect in atopy and asthma, we conducted a genetic association study in subjects with marked atopic asthma and matched controls, which incorporated the study of 13 genetic variants over a distance of 10-12 cM and which took account of detailed immune and clinical phenotyping. Association with high IgE levels was limited to the interval flanked by D11S1335 and CD20 in a 0.8-Mb interval and was greatest for variants of Fc epsilonRIbeta and HTm4; these variants also associated with asthma (recurrent wheeze with labile airflow obstruction and need for regular inhaler treatment). At the more telomeric marker, D11S480, variants associated with asthma, but not with high IgE levels. The data might support the possibility of multiple loci relevant to atopic asthma on chromosome 11q13.