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Background: Excessive tension at the anastomosis contributes to anastomotic leakage (AL) in low anterior resection (LAR). However, the specific tension has not been measured. We assessed whether "Bridging," characterized by the proximal colon resembling a suspension bridge above the pelvic floor, is a significant risk factor for AL following LAR for rectal cancer. Methods: This retrospective study reviewed the medical records and laparoscopic videos of 102 patients who underwent laparoscopic LAR using the double stapling technique at Yachiyo Hospital between January 2014 and December 2023. Patients were classified based on whether they had Bridging (tight or sagging) or were in a Resting state of the proximal colon, and the association between Bridging and AL was examined. Results: AL occurred in 31.3% of the Tight Bridging group, 20% of the Sagging Bridging group, and 2.2% of the Resting group (P = 0.002). The incidence of AL was significantly higher in patients with Bridging than in those without (23.2% vs. 2.2%, P = 0.003). Multivariate analysis revealed that Bridging is an independent risk factor for AL (odds ratio = 6.97; 95% confidence interval: 1.45–33.6; P = 0.016). Conclusions: The presence of Bridging is a significant risk factor for AL following LAR for rectal cancer, suggesting the need for implementing preventive measures in patients with this condition. [ABSTRACT FROM AUTHOR]

Background: The optimal approach for the safe implementation and education of robotic pancreaticoduodenectomy (RPD) remains unclear. Prolonged operation time may cause surgeon fatigue and result in perioperative complications. To solve this issue, our department adopted task division by the console surgeon turnover between resection and reconstruction in 2022. Methods: This study retrospectively investigated consecutive patients who underwent RPD from November 2009 (initial introduction of RPD) to December 2023. The analysis excluded patients who underwent concomitant resection of other organs. The cases performed by a single console surgeon (single approach) were compared with those performed by two or more console surgeons (multiple approach). Results: This study analyzed 85 consecutive RPD cases, including 51 with the single approach and 34 with the multiple approach. The operation time was significantly shorter (832 vs. 618 min, p < 0.001), and the postoperative major complication was less frequent (45% vs. 12%, p = 0.003) in the multiple approach group, although less experienced surgeons performed the multiple approach (number of RPD experiences: 19 cases vs. 5 cases, p < 0.001). The console surgeon turnover between the resection and reconstruction resulted in a safe pancreatojejunostomy performed by the less experienced surgeon (number of pancreatic reconstruction experiences: 6.5 vs. 14 cases, p = 0.010). Surgeons who started RPD with a multiple approach observed a reduction in surgical time and a lower incidence of complications earlier than those who started with a single approach. Conclusion: Task division during the early introduction phase of RPD using the multiple approach demonstrated potential contributions to improved surgical outcomes and enhanced educational benefits. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia has been reported to be associated with short-term outcomes after gastric endoscopic submucosal dissection (ESD). The "strength, assistance with walking, rising from a chair, climbing stairs, and falls" (SARC-F) questionnaire has been widely used as a screening tool for sarcopenia; however, SARC-F combined with body mass index and age (SARC-F+EBM) has recently been reported to be more useful than SARC-F alone. This study aimed to investigate the association between sarcopenia, measured using SARC-F+EBM, and short-term outcomes after gastric ESD. Methods: Patients who underwent gastric ESD at our institution between May 2020 and June 2023 were included, and their medical records were reviewed retrospectively. A SARC-F+EBM score ≥ 12 indicated sarcopenia. We evaluated the incidence of adverse events and the length of hospital stay in the sarcopenia and non-sarcopenia groups. Results: Overall, 263 patients (64 and 199 in the sarcopenia and non-sarcopenia groups, respectively) were investigated. The incidence of adverse events with a Common Terminology Criteria for Adverse Events grade ≥ 3 was not significantly different between the sarcopenia and non-sarcopenia groups (6.2% vs. 8.5%, p = 0.791). The proportion of patients with an extended hospital stay (≥ 10 days) was significantly higher in the sarcopenia group than that in the non-sarcopenia group (12.5% [8/64] vs. 3.5% [7/199], p = 0.012). Multivariate analysis showed that sarcopenia and lesions that present technical difficulty in ESD were independent risk factors for extended hospital stays (≥ 10 days). Of the eight cases having extended hospital stays in the sarcopenia group, four were due to the management after gastric ESD, three were due to family circumstances, and one was due to decreased activities of daily living. Conclusions: Sarcopenia is not a predictor of adverse events associated with gastric ESD. However, patients with sarcopenia may be hospitalized for longer owing to non-ESD-related factors. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is the fifth most prevalent malignancy globally and the fourth major contributor to cancer-related mortality. The comparative effectiveness of robotic gastrectomy (RG) versus laparoscopic gastrectomy (LG) at different stages of gastric cancer is unclear regarding surgical and survival outcomes. We compared surgical and survival outcomes between RG and LG in early-stage (cStage I) and advanced (cStage II/III) gastric cancers to elucidate the difference in the efficacy of RG across various stages of gastric cancer. Methods: We identified 299 patients (LG, 170; RG, 129) with cStage II/III disease and 569 (LG, 455; RG, 114) with cStage I disease who underwent either LG or RG. Following propensity score matching for RG and LG, 118 pairs were selected for cStage II/II and 113 pairs for cStage I. Surgical and survival outcomes of LG and RG were separately compared for cStage II/III and cStage I. Results: In cStage II/III, RG showed significantly fewer intra-abdominal complications of Clavien–Dindo (C.D.) Grade ≥ III in the RG group than in the LG group (LG = 8.5 vs. RG = 1.7%, P = 0.033). Multivariate analysis identified LG as an independent risk factor for intra-abdominal complications of C.D. Grade ≥ III (OR 5.69, 95% CI 1.17–27.70, P = 0.031). However, in cStage I, no difference in surgical outcomes between LG and RG was observed. No differences were observed in survival outcomes between LG and RG in both cStage I or cStage II/III. Conclusions: The real benefit of RG was demonstrated in surgical outcomes, especially for advanced-stage gastric cancer. [ABSTRACT FROM AUTHOR]

Background: The Medical Information Database Network (MID-NET®) in Japan is a vast repository providing an essential pharmacovigilance tool. Gastrointestinal perforation (GIP) is a critical adverse drug event, yet no well-established GIP identification algorithm exists in MID-NET®. Methods: This study evaluated 12 identification algorithms by combining ICD-10 codes with GIP therapeutic procedures. Two sites contributed 200 inpatients with GIP-suggestive ICD-10 codes (100 inpatients each), while a third site contributed 165 inpatients with GIP-suggestive ICD-10 codes and antimicrobial prescriptions. The positive predictive values (PPVs) of the algorithms were determined, and the relative sensitivity (rSn) among the 165 inpatients at the third institution was evaluated. Results: A trade-off between PPV and rSn was observed. For instance, ICD-10 code-based definitions yielded PPVs of 59.5%, whereas ICD-10 codes with CT scan and antimicrobial information gave PPVs of 56.0% and an rSn of 97.0%, and ICD-10 codes with CT scan and antimicrobial information as well as three types of operation codes produced PPVs of 84.2% and an rSn of 24.2%. The same algorithms produced statistically significant differences in PPVs among the three institutions. Combining diagnostic and procedure codes improved the PPVs. The algorithm combining ICD-10 codes with CT scan and antimicrobial information and 80 different operation codes offered the optimal balance (PPV: 61.6%, rSn: 92.4%). Conclusion: This study developed valuable GIP identification algorithms for MID-NET®, revealing the trade-offs between accuracy and sensitivity. The algorithm with the most reasonable balance was determined. These findings enhance pharmacovigilance efforts and facilitate further research to optimize adverse event detection algorithms. [ABSTRACT FROM AUTHOR]

Background: Intracorporeal mechanical gastrogastrostomy (IMG) techniques have recently been developed and their short-term safety was presented in their initial evaluation. However, whether they are comparable to extracorporeal hand-sewing gastrogastrostomy (EHG) remains unclear. The aim of the study is to establish the safety of IMG in totally laparoscopic pylorus-preserving gastrectomy (TLPPG) compared to EHG in laparoscopy-assisted pylorus-preserving gastrectomy (LAPPG). Methods: We retrospectively analyzed the short-term outcomes of patients with middle-third early gastric cancer who underwent LAPPG or TLPPG between 2005 and 2022. The primary objective of this study was to evaluate the non-inferiority of IMG to EHG in terms of safety, with the primary endpoint being the risk difference in anastomosis-related complications (ARCs). The sample size required to achieve a statistical power of 80% for the non-inferiority test was 971 with a one-sided alpha level of 5% and non-inferiority of 5%. Results: The analysis included a total of 1,021 patients who underwent LAPPG or TLPPG during the study period. Among them, 488 patients underwent EHG, while 533 underwent IMG. The incidences of ARCs were 11.3% and 11.4% in EHG and IMG, respectively. The observed difference in incidence was 0.0017 (90% confidence interval − 0.0313 to 0.0345), which statistically demonstrated the non-inferiority of IMG to EHG in the incidence of ARCs. Among other complications, the incidence of wound infection in IMG was lower than that in EHG. Conclusion: IMG is safe regarding ARCs compared with EHG. These results will encourage surgeons to introduce IMG for patients with early middle gastric cancer. [ABSTRACT FROM AUTHOR]

Background: In the recent years, a high risk of developmental delay not only in very low birth weight infants and late preterm infants but also in early term infants (37–38 weeks) have increasingly been reported. However, in Japan, there are virtually no studies regarding the development delays in early term infants. Methods: This study used the data from the Japan Environment and Children's Study (JECS), a birth cohort study conducted in Japan. Data were selected for analysis from the records of 104,065 fetal records. The risk of neurodevelopmental delays at 6 months and 12 months after birth was evaluated using multivariate analysis for infants of various gestational ages, using the 40th week of pregnancy as a reference value. Neurodevelopment was evaluated at 6 months and 12 months after birth using the Ages and Stages Questionnaires, Japanese translation (J-ASQ-3). Results: The proportion of infants born at a gestational age of 37 to 38 weeks who did not reach the J-ASQ-3 score cutoff value was significantly higher in all areas at both 6 months and 12 months after birth, when compared to that of infants born at 40 weeks. The odds ratio decreased at 12 months after birth compared to that at 6 months after birth. Conclusion: Early term infants in Japan are at an increased risk of neurodevelopmental delay at 12 months after birth. Significance: What's known on this subject: Early term infants with gestational ages of 37 to 38 weeks and not only premature babies may be at an increased risk of developmental delay. What this study adds: This study was conducted using data from a birth cohort of 104,065 fetal records. Early term infants had an increased risk of developmental delay at 6 months, and while the risk decreased by 12 months after birth, it was still high. [ABSTRACT FROM AUTHOR]

Background: Stoma prolapse (SP) is a common stoma-related complication, particularly in loop colostomies. This study aimed to investigate potential risk factors for SP development after laparoscopic loop colostomy. Methods: In total, data from 140 patients who underwent laparoscopic loop colostomy were analyzed between September 2016 and March 2022. Risk factors for SP were investigated retrospectively. Results: The median follow-up duration after colostomy was 12.5 months, and SP occurred in 33 (23.6%) patients. Multivariate analysis showed that being overweight (body mass index ≥ 25; odds ratio [OR], 8.69; 95% confidential interval [CI], 1.61–46.72; p = 0.012) and having a thin rectus abdominis penetration of the stoma (< 8.9 mm; OR, 8.22; 95% CI, 2.50–27.05; p < 0.001) were independent risk factors for SP. Other patient characteristics and surgical factors associated with stoma construction were unrelated to SP development. Conclusions: Being overweight and the route penetrating the thinner rectus abdominis during stoma construction was associated with a significantly higher incidence of SP after laparoscopic loop colostomy. Selecting a construction site that penetrates the thicker rectus abdominis muscle may be crucial for preventing SP. [ABSTRACT FROM AUTHOR]

Background and aims: Conversion to laparotomy is among the serious intraoperative complications and carries an increased risk of postoperative complications. In this cohort study, we investigated whether or not the Endoscopic Surgical Skill Qualification System (ESSQS) affects the conversion rate among patients undergoing laparoscopic surgery for rectal cancer. Methods: We performed a retrospective secondary analysis of data collected from patients undergoing laparoscopic surgery for cStage II and III rectal cancer from 2014 to 2016 across 56 institutions affiliated with the Japan Society of Laparoscopic Colorectal Surgery. Data from the original EnSSURE study were analyzed to investigate risk factors for conversion to laparotomy by performing univariate and multivariate analyses based on the reason for conversion. Results: Data were collected for 3,168 cases, including 65 (2.1%) involving conversion to laparotomy. Indicated conversion accounted for 27 cases (0.9%), while technical conversion accounted for 35 cases (1.1%). The multivariate analysis identified the following independent risk factors for indicated conversion to laparotomy: tumor diameter [mm] (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.01–1.05, p = 0.0002), combined resection of adjacent organs [+/−] (OR 7.92, 95% CI 3.14–19.97, p < 0.0001), and surgical participation of an ESSQS-certified physician [−/+] (OR 4.46, 95% CI 2.01–9.90, p = 0.0002). The multivariate analysis identified the following risk factors for technical conversion to laparotomy: registered case number of institution (OR 0.99, 95% CI 0.99–1.00, p = 0.0029), institution type [non-university/university hospital] (OR 3.52, 95% CI 1.54–8.04, p = 0.0028), combined resection of adjacent organs [+/−] (OR 5.96, 95% CI 2.15–16.53, p = 0.0006), and surgical participation of an ESSQS-certified physician [−/+] (OR 6.26, 95% CI 3.01–13.05, p < 0.0001). Conclusions: Participation of ESSQS-certified physicians may reduce the risk of both indicated and technical conversion. Referral to specialized institutions, such as high-volume centers and university hospitals, especially for patients exhibiting relevant background risk factors, may reduce the risk of conversion to laparotomy and lead to better outcomes for patients. Trial Registration: This study was registered with the Japanese Clinical Trials Registry as UMIN000040645. [ABSTRACT FROM AUTHOR]

Aim: The lifestyle habits of young people are often associated with that of middle-aged and older adults, and intervention from a young age is important for the prevention of lifestyle-related diseases. Hypertension is a lifestyle-related disease, and an increasing number of patients are suffering from it. Therefore, in this study, we investigated the factors that cause fluctuations in blood pressure in university students. Subject and methods: The survey was conducted from 2011 to 2019 and included 14,720 male and 6,039 female university students. The questionnaire included items such as age, sex, weight control orientation, and lifestyle habits. Height, weight, and systolic and diastolic blood pressures were measured. Body mass indices (BMI) were calculated, and the participants were classified as underweight, normal body type, or obese. In addition, abnormal blood pressure (ABP) was defined as systolic/diastolic blood pressure above 120 and/or 80 mmHg. Results: A multivariate logistic regression analysis revealed that ABP was significantly associated with snacking (odds ratio, 95% confidence interval 0.68, 0.52–0.90) in males with underweight; sleep duration ≥ 6 h (1.10, 1.02–1.19), snacking (0.84, 0.75–0.96), and weight decreasing orientation (1.22, 1.12–1.32) in males with normal body types; exercise habits (0.75, 0.56–1.00) in females with normal body types. Conclusion: The present study revealed different risk factors by body type associated with ABP in Japanese university students. In particular, weight loss orientation in a standard-bodied male may be a risk factor for ABP. Our study suggests that interventions by body type may prevent lifestyle-related diseases. [ABSTRACT FROM AUTHOR]

Background: Muscle weakness is associated with adverse clinical outcomes including disability and mortality. We report demographic, anthropometric and lifestyle correlates of grip strength in UK and Japanese population-based cohorts. Aim: To report prevalence of low grip strength according to 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) and 2019 Asian Working Group for Sarcopenia (AWGS 2019) thresholds and to consider correlates of grip strength in Eastern and Western populations. Methods: UK (1572 men; 1415 women) and Japanese (519 men; 1027 women) participants were recruited from two cohorts harmonised by consensus. Muscle strength was measured by grip strength dynamometry. Potential correlates of grip strength were examined using sex-stratified linear regression; univariate correlates (p < 0.05) were included in mutually adjusted models. Results: Mean (SD) age was 66.2 (2.8) and 65.8 (12.3) in UK and Japanese cohorts, respectively. Prevalence of low grip strength was higher in Japanese participants (EWGSOP2 5.4% versus 2.4%, AWGS 2019 9.0% versus 3.7%). In both cohorts and sexes, univariate correlates of lower grip strength were older age, shorter height, not consuming alcohol, leaving education earlier and greater comorbidity. Apart from older age and shorter height, the only factors related to lower grip strength in mutually adjusted analyses were greater comorbidity among UK participants (kg difference in grip strength (95%CI) per additional comorbidity − 0.60(− 0.98, − 0.21) among men and − 0.50(− 0.86, − 0.13) among women) and not consuming alcohol among Japanese men (− 1.33(− 2.51, − 0.15)). Discussion: Correlates of muscle strength were similar in both cohorts. Conclusions: A global approach to age-related muscle weakness prevention may be appropriate. [ABSTRACT FROM AUTHOR]

Background: Programmed death-ligand 1 (PD-L1) inhibitor plus platinum–etoposide chemotherapy is used as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC), regardless of age. Objective: We examined the role of the Geriatric 8 (G8) screening tool for evaluating treatment outcomes in patients with ES-SCLC treated with PD-L1 inhibitor plus platinum–etoposide chemotherapy as first-line therapy. Patients and Methods: Between September 2019 and October 2021, we prospectively evaluated patients with ES-SCLC treated with immunochemotherapy at ten institutions in Japan. The G8 score was assessed before treatment initiation. Results: We evaluated 44 patients with ES-SCLC. Patients with G8 score > 11 had longer overall survival (OS) than those with G8 score ≤ 11 (not reached versus 8.3 months; log-rank test, p = 0.005). In univariate and multivariate analyses, G8 score > 11 [hazard ratio (HR) 0.34; 95% confidence interval (CI) 0.15–0.75; p = 0.008 and HR 0.34; 95% CI 0.14–0.82; p = 0.02, respectively) and performance status (PS) of 2 (HR 5.42; 95% CI 2.08–14.2; p < 0.001 and HR 6.94; 95% CI 2.25–21.4; p < 0.001, respectively) were independent prognostic factors for OS. Among patients with good PS (0 or 1), the OS in patients with G8 score > 11 was significantly longer than that in patients with G8 score ≤ 11 (not reached versus 12.3 months; log-rank test, p = 0.02). Conclusions: G8 score evaluation before treatment initiation was useful as a prognostic factor for ES-SCLC patients who received PD-L1 inhibitors and platinum–etoposide chemotherapy, even with good PS. [ABSTRACT FROM AUTHOR]

Background: Age-related differences in the limited range of motion of the lower extremities and their relationship with low back pain in juvenile athletes have not been well assessed. This study investigated the relationship between low back pain and limited range of motion of the hip and knee in young baseball players during the baseball season. Results: Participants comprised 1215 baseball players (216 pitchers, 999 fielders) aged 6–16 years who underwent medical checkups (self-completed questionnaire and physical examination). Of the 1215 players, 255 (21.0%) experienced seasonal low back pain requiring rest during the previous year. The prevalence of low back pain and a positive Thomas test, straight-leg-raising test, and heel-to-buttock test increased with age. Univariate analysis revealed that a positive heel-to-buttock test in both the throwing and non-throwing arm sides in the 11–12 age group and a positive Thomas test in the throwing arm side in the 13–14 age group were associated with seasonal low back pain (P = 0.0051, P = 0.021, and P = 0.048, respectively). Multivariate analysis, adjusted for factors associated with low back pain, showed significant associations between the positive heel-to-buttock test (odds ratio 1.75, 95% confidence interval 1.11–2.79; P = 0.016) and low back pain in players aged 11–14 years. Conclusions: A positive heel-to-buttock test is potentially associated with low back pain among juvenile baseball players. Particular attention should be paid to the limited range of motion of the knee joint and tightness of the quadriceps femoris muscle among baseball players with low back pain aged 11–14 years. [ABSTRACT FROM AUTHOR]

The COVID-19 outbreak affected the daily lives of individuals with Down syndrome, who were considered to have a higher risk of severe infection. While several studies have reported mental health issues in children and/or parents in the general population, no study has focused on people with Down syndrome and their caregivers. This study investigated the disinfection behaviors of individuals with Down syndrome and their caregivers' stress. A cross-sectional retrospective survey was conducted in October 2020. Caregivers of children and adults with Down syndrome were administered questionnaires including measures for practiced disinfection behavior in children, caregiver's child-related stress, and psychological distress. About half of the respondents' children practiced hand hygiene and mask-wearing behaviors, while physical distancing was performed less frequently. Habitual practices in physical distancing are affected by intellectual function. Logistic regression showed that caregivers' stress was associated with the irritability of individuals with the disorder (adjusted odds ratio [OR] = 8.44, 95% confidence interval [CI] 1.69–42.09) and the burden of infection-prevention behaviors for people with Down syndrome (adjusted OR = 4.26, 95% CI 1.88–9.65). This study showed the characteristics of disinfection behaviors in individuals with Down syndrome and associated factors for serious caregiver stress. [ABSTRACT FROM AUTHOR]

Objectives: A high rate of preterm birth has been reported in Okinawa Prefecture, the southernmost island prefecture of Japan. Hence, this study aimed to identify the risk factors for preterm birth in this prefecture. Methods: This retrospective study included data from January 2013 to December 2019 from three facilities in Okinawa Prefecture. Of 13,468 cases of preterm birth at ≥ 22 weeks of gestation, 11,868 were included in this study. Stillbirth and multiparity cases were excluded. First, we compared the overall preterm and full-term birth groups by categorizing the patient background, obstetric, and fetal risk factors. Further, we categorized preterm births into three groups (22–27, 28–33, and 34–36 weeks of gestation) and examined patient background factors to identify potential risk factors for the occurrence of preterm birth in each group. Results: Preterm births accounted for 21.2% (2,521 cases) of all cases, with the rates of 2.6% (317 cases), 6.7% (800 cases), and 11.8% (1,404 cases) at 22–27, 28–33, and 34–36 weeks of gestation, respectively. To prevent preterm birth in Okinawa Prefecture, the present study specifically focused on patient background characteristics. In the multinomial logistic regression, the risk factors for preterm birth at 22–27 weeks of gestation were previous preterm birth (P < 0.0001) and lower age (P = 0.026); at 28–33 weeks of gestation, the risk factors were previous preterm birth (P < 0.0001) and history of cervical conization (P = 0.009); and at 34–36 weeks of gestation, only previous preterm birth (P < 0.0001) was a risk factor. Conclusions for practice: Previous preterm birth, younger age, and history of cervical conization were risk factors for Preterm birth in Okinawa. To reduce premature births in Okinawa Prefecture, it is important to pick up women with these risk factors and provide them with appropriate guidance and education on an ongoing basis. Significance: What is already known about this subject? Previous studies have shown that smoking and short stature increase the rate of preterm birth in Okinawa Prefecture. What does this study add? Previous preterm birth, younger age, and history of cervical conization were risk factors for preterm birth in Okinawa Prefecture. [ABSTRACT FROM AUTHOR]

Postpartum depression (PPD) is as a major public health issue and clinical priority worldwide. This study aimed to investigate the association between pre-pregnancy sleep duration and PPD. A multicenter retrospective study was conducted using clinical data of women who delivered at term between 2014 and 2018 at 12 maternity care hospitals in Japan. A total of 15,314 women were stratified into five groups according to their pre-pregnancy sleep duration: < 6, 6–7, 7–8, 8–9, and ≥ 9 h. Univariate and multivariate regression analyses were conducted to determine whether pre-pregnancy sleep duration affects the Edinburgh Postnatal Depression Scale (EPDS) scores at 1 month postpartum. We also evaluated whether the risk for PPD differs between primipara and multipara women classified according to pre-pregnancy sleep duration. The adjusted odds ratio for high EPDS scores (≥ 9) among women who slept for < 6 h and 6–7 h was 2.08 (95% confidence interval [CI]: 1.60–2.70) and 1.41 (95% CI: 1.18–1.68), respectively, relative to that in women with 7–8 h of sleep as the reference group. A 1-h increase in sleep duration was associated with an approximately 14% reduction in the risk for high EPDS scores. The association between short sleep duration and high EPDS scores was more remarkable in multipara women than in primipara women. Short pre-pregnancy sleep duration is associated with high EPDS scores, and this association is more significant in multipara women than in primipara women. Our findings emphasize the importance of collecting information on pre-pregnancy sleep duration to identify women at a high risk for PPD. [ABSTRACT FROM AUTHOR]

Purpose: Deep white matter lesions (DWMLs), T2 high-intensity areas in the subcortical white matter on magnetic resonance imaging (MRI), are a clinical phenotype of cerebral small vessel disease. Factors such as age and hypertension have been reported to significantly contribute to the presence and severity of DWMLs in cross-sectional studies. We herein report a 10-year longitudinal study on DWMLs in elderly Japanese subjects to reveal the clinical variables contributing to the progression of DWMLs. Methods: A total of 469 Japanese subjects were invited to participate in the study. Of the participants at baseline, 259 subjects completed the revisit MRI study 10 years later. In those 259 subjects, we evaluated the correlation between the progression of DWMLs and clinical variables, such as the gender, age, and overt vascular risk factors. To clarify the role of hypertension, 200 subjects with grade 1 DWMLs at baseline were categorized into three groups according to their status of hypertension and its treatment. Results: Of the 200 subjects with grade 1 DWMLs, 47 subjects (23.5%) showed progression of DWMLs (progression group). In the progression group, the percentage of subjects with hypertension and the systolic blood pressure values were higher than in the non-progression group. In addition, subjects ≥ 60 years old at baseline tended to show deterioration of DWMLs in the group with hypertension without antihypertensive treatment. Conclusion: The results of this 10-year longitudinal study imply a positive correlation between long-standing hypertension and the progression of DWMLs. [ABSTRACT FROM AUTHOR]

Objective: To measure the medial opening gap and examine a technique for preserving the tibial posterior slope (TPS) in open-wedge high tibial osteotomy (OWHTO) using computer-simulated three-dimensional (3D) surgery. Materials and methods: This study included 24 symptomatic knees from 20 patients (7 men and 13 women; mean age, 67.9 years; range 54–89 years). Digital imaging and communications from computed tomography examination were applied to a 3D picture software program, and several anatomical landmarks were registered. Then, computer simulation of OWHTO as a virtual surgery was performed: the correction angle was decided to make the femorotibial angle 170°, and the TPS did not differ between pre- and postplanification. The distance between the proximal and distal cortices of the medial tibia was measured at three points, which were the anterior (AD), posterior (PD), and longest (LD) distance sites in the sagittal plane, using the 3D view, and the ratios of AD/PD and AD/LD were measured. The anteromedial opening gap was compared to the posteromedial gap and the longest distance gap at the osteotomy site. Spearman's rank correlation coefficient test was used in statistical analysis. Results: Mean AD/PD was 0.740 ± 0.051 (range 0.651–0.850), and mean AD/LD was 0.652 ± 0.040 (range 0.571–0.768). The correction angle was not associated with the values of both AD/PD and AD/LD. Conclusions: Difference in AD/PD and AD/LD between each patient was regarded as a significant variation. Therefore, preoperative planification with 3D computer simulation to measure AD/PD and AD/LD may be helpful to avoid a significant increase in TPS. [ABSTRACT FROM AUTHOR]

Introduction: Many environmental factors are related to the development of asthma. However, the key factors of childhood asthma onset have not been sufficiently elucidated. Further, low-weight births have increased in Japan. The aim of this study was to examine the risk factors for the incidence of childhood asthma and to evaluate whether these risk factors differ according to birth weight in Japan. Methods: We used the National Longitudinal Survey from 2001 to 2010. Multiple logistic regression analyses were conducted to determine the effects of gender, birth weight, single vs. multiple births, birth order, nutrition, keeping pets in the home, place of residence, annual household income, and parent ages, smoking behaviors, and educational backgrounds on asthma-related hospital visits. Results: Overall, 45,060 children were analyzed. The rate of cumulative hospital visits until age 10 was 18.9%. Birth weight < 2500 g (adjusted odds ratio [AOR] = 1.14, 95% confidence interval [CI] 1.03–1.26), being a boy (AOR = 1.27, 95% CI 1.21–1.33), having older siblings (AOR = 1.07, 95% CI 1.02–1.14), parental smoking behavior, mother's age, and low household income (AOR = 1.17, 95% CI 1.10–1.24) were associated with asthma-related hospital visits. Discussion: Parental smoking behavior is a key risk factor for the development of asthma. Among low birth weight infants, being a boy, having older siblings, and father's smoking behavior were predictive factors for the development of asthma. However, low birth weight was not associated with the development of asthma after 6 years of age. [ABSTRACT FROM AUTHOR]

Background: Reducing non-completion of quality-of-life assessment in clinical trials is an important challenge in obtaining accurate data and unbiased interpretation of patients' quality-of-life for each regimen. We evaluated the effect of changing our questionnaire distribution procedure in a multicenter phase II/III trial on the response rate to a quality-of-life questionnaire. Methods: In the trial, we distributed 1767 questionnaires and 1045 were returned. We adopted a regression discontinuing design and estimated the change in response rate between pre-intervention (quality-of-life questionnaires were sent to each center soon after patient registration) and post-intervention (a set of tailored questionnaires was sent just before the first quality-of-life assessment). Results: The post-intervention response rate was higher (odds ratio = 1.62) than the pre-intervention response rate. Conclusions: A simple logistic intervention reduced the non-completion of QOL assessment in this case, suggesting that a simple change can contribute to improving clinical trial accomplishment. [ABSTRACT FROM AUTHOR]

Introduction: This post hoc subanalysis of the randomized Japanese Primary Prevention Project investigated whether once-daily low-dose aspirin versus no aspirin reduced the risk of cardiovascular events (CVEs) in patients aged ≥ 70 years with atherosclerotic risk factors. Methods: Patients aged < 70 years (young-old) or ≥ 70 years (old) with hypertension, dyslipidemia, or diabetes participated between 2005 and 2007. Patients were randomized 1:1 to receive 100 mg enteric-coated aspirin once daily or no aspirin plus standard of care. The primary outcome was a composite of death from cardiovascular causes plus nonfatal stroke and nonfatal myocardial infarction. The secondary outcome was a composite of the primary outcome plus transient ischemic attack, angina pectoris, and arteriosclerotic disease requiring medical or surgical intervention. Old (n = 7971) and young-old (n = 6493) patients were followed up for a median 5.02 years. Results: Aspirin did not reduce the risk of primary (hazard ratio [HR] 0.92 [95% confidence interval {CI} 0.74–1.16]; P = 0.50) or secondary (0.85 [0.70–1.04]; P = 0.11) outcomes in patients aged ≥ 70 years. In old men with high-density lipoprotein < 40 mg/dL, treatment with low-dose aspirin was associated with a reduction in the incidence of the primary endpoint compared with the group not receiving aspirin (10/260 vs 22/250; HR 0.44 [95% CI 0.20–0.93]; P = 0.03). This subgroup was also found to contain significant larger proportions of patients with elevated body mass index, patients with diabetes mellitus, and smokers (P < 0.001). Old patients also showed differences in bleeding outcomes. Serious extracranial hemorrhage requiring transfusion or hospitalization occurred significantly more frequently in the aspirin-treated group than in the non–aspirin-treated group (35 [0.88%] vs 18 [0.45%]; HR 1.96 [1.11–3.46]; P = 0.020). Gastrointestinal hemorrhage occurred significantly more frequently in the aspirin-treated group than the non–aspirin-treated group (63 [1.58%] vs 18 [0.45%]; relative risk [RR] 3.5 [2.08–5.90]; P < 0.0001). Cerebral hemorrhage (intracranial hemorrhage) tended to occur more frequently in the aspirin-treated group than the non–aspirin-treated group (22 [0.55%] vs 11 [0.28%]; RR 2.01 [0.97–4.14]; P = 0.058). Cerebral hemorrhage occurred significantly more frequently in old patients than in young-old patients (33 [0.41%] vs 10 [0.15%]; HR 2.7 [1.34–5.53]; P = 0.0055). Gastrointestinal hemorrhage occurred in a slightly higher proportion of old patients compared with young-old patients (81 [1.02%] vs 53 [0.82%]; RR 1.2 [0.88–1.76]; P = 0.21). Discussion/Conclusions: Aspirin did not reduce the risk of the primary or secondary outcomes in old patients. Aspirin treatment may have reduced CVEs within a high CVE risk elderly population subgroup. Aspirin treatment in such a group requires caution, because of the increased risk of intracranial hemorrhage, severe extracranial hemorrhage requiring hospitalization or transfusion, and gastrointestinal bleeding in old patients receiving aspirin therapy. Clinical Trial Registration: The study is registered at ClinicalTrials.gov [NCT00225849]. [ABSTRACT FROM AUTHOR]

Background: With an increase in the complexity and cost of clinical trials and the advances in information technology, monitoring guidance issued by regulatory authorities recommends risk-adapted monitoring. To introduce the monitoring method for investigator-initiated investigational new drug (IND) trials using unapproved anticancer drugs, we performed exploratory retrospective analyses to identify risk factors for data quality. Methods: To select investigator-initiated IND trials using unapproved anticancer drugs, we set the trial selection criteria. Data collection was performed by using audit trails and monitoring reports. Collected data were analyzed by univariate and multivariate analyses to identify the independent risk factors related to error. Results: By trial selection criteria, 5 investigator-initiated IND trials using unapproved anticancer drugs were selected. The error rates of the total data, critical data, and noncritical data were 7.4%, 9.7%, and 5.9%, respectively. There was no difference between clinical research core hospitals certified by the Ministry of Health, Labour and Welfare and other hospitals in univariate analysis (odds ratio [OR], 1.00; 99% confidence interval [CI], 0.96-1.05; P = .9179). As the main independent risk factors related to error, critical data in the importance of data (OR, 1.28; 99% CI, 1.24-1.33; P < .0001) and groups with ≤3 patients after registration (OR, 1.12; 99% CI, 1.10-1.15; P < .0001) were significantly related to errors in multivariate analysis. Conclusions: The results of this research suggest that the feasibility of risk-based monitoring and sampling source data verification was indicated for noncritical data and patients after the third case. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy-induced neutropenia (CIN) is a common side effect of chemotherapy and an important dose-limiting factor. However, an association between CIN development and longer survival was recently reported in several solid cancers. In the present study, we aimed to assess whether CIN could be a prognostic factor and clarify other prognostic factors for patients with metastatic pancreatic cancer. Methods: We retrospectively analyzed the medical records of 84 patients who received gemcitabine monotherapy as first-line chemotherapy for metastatic pancreatic cancer to assess whether CIN could be a prognostic factor. Potential prognostic factors of survival were examined by univariate and multivariate analyses using the log-rank test and Cox proportional hazard model, respectively. Results: Median survival time was 170 days [95% confidence interval (CI), 147-193] in patients without CIN (grade 0), 301 days (95% CI, 152-450) in patients with grade 1-2 CIN, and 406 days (95% CI, 271-541) in patients with grade 3 CIN. The multivariate analysis revealed that a pretreatment C-reactive protein level of <0.50 mg/dL [hazard ratio (HR), 0.534; 95% CI, 0.323-0.758, P = 0.015] and grade 3 CIN (HR, 0.447; 95% CI, 0.228-0.875, P = 0.019) were independent favorable prognostic factors in patients with metastatic pancreatic cancer treated with gemcitabine. Conclusions: Neutropenia during chemotherapy was associated with increased survival of patients with metastatic pancreatic cancer. Monitoring of CIN could be used to predict treatment responsiveness. [ABSTRACT FROM AUTHOR]

Background: Cystatin C (Cys-C) is a more sensitive marker of renal function than creatinine (Cre) in pediatric and adult populations. However, the reference values of serum Cys-C for estimating glomerular filtration rates (eGFRs) in premature infants during the first year of life have not been sufficiently studied. Methods: In this prospective study, 481 blood samples were collected from 261 preterm infants with uncomplicated clinical courses during their first year of life. Infants were divided into three groups according to gestational age at birth: 27-30 weeks, 31-33 weeks, and 34-36 weeks. Serum Cys-C and Cre levels were measured at 6-30 days, 3-5 months, 7-9 months, and 12-14 months after birth and the eGFR was calculated using two previously published equations. Results: The median serum Cys-C levels were 1.776, 1.248, 1.037, and 0.960 mg/L at the first, second, third, and fourth measurement time-point, respectively, with the value significantly decreasing with age up to 12-14 months. Cys-C levels were independent of gestational age and gender. In contrast to Cys-C, serum Cre values declined rapidly up to 3-5 months, then remained constant up to 12-14 months. Using the Cys-C-based equation, the eGFR significantly increased with increasing age until approximately 1 year after birth; however, no such trend was noted using the equation based on Cys-C + Cre. Conclusions: Reference ranges for Cys-C in premature infants decline gradually over the first year after birth. Cys-C appears to be a more reliable marker than Cre for estimating GFR in preterm infants. [ABSTRACT FROM AUTHOR]

Purpose: Few epidemiological studies have assessed the relationship between the traditional Japanese dietary pattern and longitudinal changes in cardiovascular disease risk factors among Japanese people. We designed a 3-year longitudinal study of 980 subjects living in Japan to evaluate how the Japanese dietary pattern is related to longitudinal changes in well-recognized risk factors for cardiovascular disease among apparently healthy Japanese adults. Methods: Dietary consumption was assessed via a validated food frequency questionnaire. Principal component analysis was used to derive three major dietary patterns-'Japanese,' 'sweets-fruits-cooked wheaten food,' and 'Izakaya (Japanese Pub)' from 39 food groups. Results: After adjustment for potential confounders, the mean (95 % confidence interval) for the change per year in diastolic blood pressure for men, systolic blood pressure, and diastolic blood pressure for women related to the 'Japanese' dietary pattern factor score tertiles were 0.89 (0.10, 1.68), 2.25 (0.19, 4.31), and 0.75 (−1.00, 2.50) for the lowest tertile, 0.77 (−0.02, 1.56), 1.01 (−1.13, 3.15), and 0.44 (−1.38, 2.26) for the middle tertile and − 0.04 (−0.81, 0.72), −0.48 (−2.52, 1.56), and −0.77 (−2.51, 0.96) for the highest tertile (trend P value = 0.03, <0.01, and 0.04, respectively). A significant detrimental relationship was found between the 'Izakaya (Japanese Pub)' pattern factor score tertiles and the longitudinal change in serum triglyceride concentration only in men (trend P value = 0.02). Conclusions: Greater adherence to a traditional Japanese diet was independently related to a decreased change every year in diastolic blood pressure in men and women and in systolic blood pressure in women over a 3-year follow-up period. The findings suggest that the 'Japanese' dietary pattern appeared to be related to a fall in blood pressure, which might have a beneficial effect on cardiovascular disease. A randomized trial is required to clarify the underlying mechanism. [ABSTRACT FROM AUTHOR]

To determine the best discriminative items for identifying young children with autism spectrum disorders (ASD), we conducted a secondary analysis using longitudinal cohort data that included the Japanese version of the 23-item modified checklist for autism in toddlers (M-CHAT-JV). M-CHAT-JV data at 18 months of age and diagnostic information evaluated at age 3 or later from 1851 Japanese children was used to isolate six highly discriminative items. Using data from two different community samples (n = 1851, n = 665) these items were shown to have comparable psychometric values with those of the full version. Our results suggest that these items might work as a short form screener for early identification of ASD in primary care settings where there are time constraints on screening. [ABSTRACT FROM AUTHOR]

Purpose: To examine the relation of work type with health-related quality of life (HRQoL) in healthy workers.Methods: We cross-sectionally examined 4427 (3605 men and 822 women) healthy workers in Japan, aged 19-69 years. We assessed HRQoL based on scores for five scales of the SF-36. Multiple regression was applied to examine the relation of work type (nighttime, shift, day to night, and daytime) with the five HRQoL norm-based scores, lower scores of which indicate poorer health status, adjusted for confounding factors, including sleeping duration.Results: Shiftwork was inversely related to role physical [regression estimate (β) = -2.12, 95 % confidence intervals (CI) -2.94, -1.30, P < 0.001], general health (β = -1.37, 95 % CI -2.01, -0.72, P < 0.001), role emotional (β = -1.24, 95% CI -1.98, -0.50, P < 0.001), and mental health (β = -1.31, 95% CI -2.01, -0.63, P < 0.001) independent of confounding factors, but not to vitality. Day-to-nighttime work was inversely related to all the five HRQoL subscales (Ps 0.012 to <0.001).Conclusion: Shiftwork was significantly inversely related to four out of the five HRQoL, except for vitality, and day-to-nighttime work was significantly inversely related to all five HRQoL, independent of demographic and lifestyle factors. [ABSTRACT FROM AUTHOR]

Study design:This is a cross-sectional study.Objectives:The objective of this study was to ascertain the essential items mediating adequate dietary intake based on the Japanese Food Guide in common among the transtheoretical model (TTM), self-efficacy (SE) and outcome expectancy (OE).Setting:Members of the organization Spinal Injuries Japan.Methods:We posted a questionnaire survey to 2731 community-dwelling Japanese adults with spinal cord injury (SCI), and responses from 841 individuals were analyzed. Food intake was assessed as the frequency scores of 10 food items eaten in a daily diet in Japan. The correlations between the frequency scores of food intake and TTM, SE and OE were determined by binominal logistic regression analysis.Results:The frequency scores of food intake were significantly associated with 'To eat vegetable dishes (dishes made mainly from vegetables or potatoes) not less than twice a day', 'To eat green/yellow vegetables not less than twice a day', 'To eat dairy products not less than once a day' and 'To eat fruits not less than once a day' in TTM. 'To eat vegetable dishes (dishes made mainly from vegetables or potatoes) not less than twice a day', 'To eat dairy products not less than once a day' and 'To eat fruits not less than once a day' were significantly associated with the frequency scores of food intake in SE. In OE, no differences were shown.Conclusion:This study finds that vegetable dishes, dairy products and fruits are the key items mediating adequate dietary intake. Dietary guidelines promoting the intake of these dishes for SCI individuals are needed. [ABSTRACT FROM AUTHOR]

The article focuses on the predictors for a high trough apixaban level in older patients with atrial fibrillation prescribed with reduced dose of the drug based on an analysis of a registry of patients in Japan. The analysis discovered the relation between reduced dose and bleeding that required hospitalization. Among the independent predictors are female gender, creatinine clearance and heart failure. Also noted is the anti-Xa assay needs of patients with three or more risk factors.

Purpose: The medial branch of the posterior ramus of the lumbar spinal nerve is well known to be innervated independently and to end in the multifidus muscle without anastomosis. This prospective cohort study aimed to determine the diagnostic specificity and sensitivity of multifidus muscle denervation (MMD) by needle electromyography (N-EMG) for lumbar foraminal and lateral exit-zone stenosis (LF/LEZS).Methods: We enrolled 61 consecutive patients experiencing unilateral dysesthesia and/or leg pain in the L4 or L5 regions with suspicious LF/LEZS. The Japanese Orthopedic Association (JOA) score, Visual Analog Scale (VAS) for leg pain, and N-EMG were examined. In this study protocol, all patients received at least 3 months of conservative therapy. Surgery was performed on patients who experienced less than 50% VAS pain relief compared with their initial score after confirming the responsible level by lumbar nerve root block. The specificity of N-EMG was the proportion of patients who improved with conservative therapies (non-surgery) after 3 months. The sensitivity of N-EMG was the proportion of patients who improved with surgical therapies (surgery) after more than 12 months.Results: Twenty-three patients underwent surgery. The initial lower JOA, positive Kemp test and motor weakness were significantly higher in the surgery group. The MMD by N-EMG indicated that 34 of 38 patients were negative in the non-surgery group. In the surgery group, 21 of 23 patients were positive. The diagnostic sensitivity and specificity were 91.3 and 92.1%, respectively.Conclusions: Needle electromyography is a simple and available additional method for the diagnosis of LF/LEZS. [ABSTRACT FROM AUTHOR]

Background In the international, phase III, randomized, double-blind CORRECT trial, regorafenib significantly prolonged overall survival (OS) versus placebo in patients with metastatic colorectal cancer (mCRC) that had progressed on all standard therapies. This post hoc analysis evaluated the efficacy and safety of regorafenib in Japanese and non-Japanese subpopulations in the CORRECT trial. Methods Patients were randomized 2 : 1 to regorafenib 160 mg once daily or placebo for weeks 1-3 of each 4-week cycle. The primary endpoint was OS. Outcomes were assessed using descriptive statistics. Results One hundred Japanese and 660 non-Japanese patients were randomized to regorafenib ( n = 67 and n = 438) or placebo ( n = 33 and n = 222). Regorafenib had a consistent OS benefit in the Japanese and non-Japanese subpopulations, with hazard ratios of 0.81 (95 % confidence interval [CI] 0.43-1.51) and 0.77 (95 % CI 0.62-0.94), respectively. Regorafenib-associated hand-foot skin reaction, hypertension, proteinuria, thrombocytopenia, and lipase elevations occurred more frequently in the Japanese subpopulation than in the non-Japanese subpopulation, but were generally manageable. Conclusion Regorafenib appears to have comparable efficacy in Japanese and non-Japanese subpopulations, with a manageable adverse-event profile, suggesting that this agent could potentially become a standard of care in patients with mCRC. [ABSTRACT FROM AUTHOR]

Objectives: To examine the effect of a dietary supplement containing bilberry extract (BE) on eye fatigue induced by acute video display terminal (VDT) loads. Design and setting: A prospective, randomized, double-blind, placebo-controlled study was performed from August 2012 to February 2013 in the Medical Corporation Jico-kai Yagi Hospital, and the Shinyokohama Shinoharaguchi Orthopedic Surgery and Dermatology Clinic, in Japan. Participants: Two hundred eighty-one office workers aged 20-40 years that used VDTs were screened by critical flicker fusion (CFF) and near point accommodation (NPA). Intervention: The participants were randomized to either a BE (480 mg/day) or placebo (vehicle) group, and took allocated capsule, daily, for 8 weeks. Measurements: The CFF, NPA, contrast visual acuity, functional visual acuity, keratoconjunctival epithelial damage, and fluorescein tear film break-up time were examined, and 18 subjective symptoms of eye fatigue were evaluated by questionnaire. Adverse events were reported via medical interviews. Data were collected both before and after VDT load at baseline, and 4, and 8 weeks after daily supplementation with either BE or placebo. Results: Of 281 participants screened, 88 having relatively lower levels of CFF and NPA were enrolled in the study. Of these, 37 control and 43 BE group subjects completed the study. The VDT load-induced reduction in CFF was alleviated after 8 weeks of BE supplementation (95% confidence interval, 0.10-1.60; p=0.023), in contrast to placebo supplementation, while NPA variation was not. Of the subjective symptoms of eye fatigue, VDT load-induced ocular fatigue sensation, ocular pain, eye heaviness, uncomfortable sensation, and foreign body sensation were mitigated more in the BE group than in the control group, at week 8 (p<0.05). There were no severe adverse events in either group. Conclusions: BE supplementation improved some of the objective and subjective parameters of eye fatigue induced by VDT loads. [ABSTRACT FROM AUTHOR]

Purpose: Coffee and green tea consumption may be associated with circulating adipokines, but data are inconsistent, scarce or lacking. We examined the association of coffee and green tea consumption with serum adiponectin, leptin, visfatin, resistin and plasminogen activator inhibitor-1 (PAI-1) among a Japanese working population. Methods: The authors analyzed data ( n = 509) from a cross-sectional survey among Japanese workers aged 20-68 years. Serum adipokines were measured using a Luminex suspension bead-based multiplexed array. Coffee and green tea consumption was assessed using a validated diet history questionnaire, and caffeine consumption from these beverages was estimated. Multiple regression analysis was performed with adjustment for potential confounding variables. Results: Coffee consumption was significantly, inversely associated with leptin and PAI-1 ( P for trend = 0.007 and 0.02, respectively); compared with subjects consuming <1 cup per day, those consuming ≥4 cups per day had 13 and 10 % lower means of leptin and PAI-1, respectively. Similar associations were observed for caffeine consumption ( P for trend = 0.02 for both leptin and PAI-1). Additionally, we noted a significant positive association between coffee consumption and adiponectin in men ( P for trend = 0.046), but not in women ( P for trend = 0.43, P for interaction = 0.11). Moreover, there was a positive association between coffee consumption and resistin in current male smokers ( P for trend = 0.01), but not in male non-smokers ( P for trend = 0.35, P for interaction = 0.11). Green tea consumption was not associated with any adipokine. Conclusions: Higher consumption of coffee and caffeine but not green tea was associated with lower serum levels of leptin and PAI-1 in Japanese adults. [ABSTRACT FROM AUTHOR]

Summary: Serum sclerostin levels could be closely associated with serum phosphate and fibroblast growth factor-23 levels in hemodialysis patients with low intact parathyroid hormone (PTH) levels. Further study is required to indicate whether these close associations are present in patients with spontaneously low PTH levels without any vitamin D treatment. Introduction: Intact parathyroid hormone (iPTH) is involved in the interaction between sclerostin and phosphate/fibroblast growth factor-23 (FGF23) in animal models. However, their relationship in patients on hemodialysis (HD) is unclear. Methods: Data of 102 HD patients were collected regarding clinical and laboratory parameters and mineral bone disorder medications. The patients were divided into subgroups according to the iPTH level (A, <70 pg/mL; B, 70-150 pg/mL; C, 150-300 pg/mL; and D, ≥300 pg/mL). Results: The sclerostin level was significantly and positively correlated with phosphate and log of FGF23 levels in subgroups A, B, and combined A and B. Multiple linear regression analysis in the combined A and B subgroup revealed that male sex ( t = 3.24, P = 0.01; 95 % confidence interval [CI] 11.78 to 50.43) and phosphate level ( t = 2.13, P = 0.04; 95 % CI, 1.08 to 36.91) were independent factors for serum sclerostin level. The log of serum FGF23 level ( t = 1.90, P = 0.06, 95 % CI −1.85 to 63.50) appeared to be an important factor for serum sclerostin level. The frequency of patients using vitamin D treatment was not significantly different among subgroups A (93.1 %), B (88.0 %), C (85.2 %), and D (90.5 %). Conclusion: Serum sclerostin levels were associated with serum phosphate and FGF23 levels in patients with low iPTH levels. Further study is required to indicate whether these close associations are present in patients with spontaneously low iPTH levels without vitamin D treatment. [ABSTRACT FROM AUTHOR]

Summary: A 12-month extension phase of DIRECT in Japanese subjects with osteoporosis showed that total 3 years of denosumab treatment in Japanese postmenopausal women and men with osteoporosis was associated with low fracture rates, persistent bone turnover marker (BTM) reductions, continuous bone mineral density (BMD) increases, and a favorable overall benefit/risk profile. Introduction: The DIRECT trial demonstrated that 2 years of treatment with denosumab 60 mg subcutaneously every 6 months significantly reduced the incidence of vertebral fracture compared to placebo in Japanese postmenopausal women and men with osteoporosis. The purpose of this study is to evaluate the efficacy and safety of denosumab treatment for up to 3 years. Methods: This study includes a 2-year randomized, double-blind, placebo-controlled phase and a 1-year open-label extension phase in which all subjects received denosumab. The data correspond to 3 years of denosumab treatment in subjects who received denosumab (long-term group) and 1 year of denosumab treatment in subjects who received placebo (cross-over group) in the double-blind phase. Results: Eight hundred and ten subjects who completed the double-blind phase enrolled into the extension phase, and 775 subjects completed the study. All subjects received denosumab with daily supplements of calcium and vitamin D. The cumulative 36-month incidences of new or worsening vertebral fractures and new vertebral fractures were 3.8 and 2.5 %, respectively, in the long-term group. In this group, the BMD continued to increase, and the reduction in BTMs was maintained. In the cross-over group, comparable BMD increases and BTMs reductions to those of in their first year of the long-term group were confirmed. Adverse events did not show a notable increase with long-term denosumab administration. One event of osteonecrosis of the jaw occurred in the cross-over group. Conclusions: Three-year denosumab treatment in Japanese subjects with osteoporosis showed a favorable benefit/risk profile. [ABSTRACT FROM AUTHOR]

Background: In times of disaster, public servants face multiple burdens as they engage in a demanding and stressful disaster-response work while managing their own needs caused by the disaster. Purpose: We investigated the effects of work-related factors on the mental health of prefectural public servants working in the area devastated by the Great East Japan Earthquake to identify some ideas for organizational work modifications to protect their mental health. Methods: Two months after the earthquake, Miyagi prefecture conducted a self-administered health survey of prefectural public servants and obtained 4,331 (82.8 %) valid responses. We investigated relationships between mental health distress (defined as K6 ≥ 13) and work-related variables (i.e., job type, overwork, and working environment) stratified by level of earthquake damage experienced. Results: The proportion of participants with mental health distress was 3.0 % in the group that experienced less damage and 5.9 % in the group that experienced severe damage. In the group that experienced less damage, working >100 h of overtime per month (adjusted odds ratio [OR], 2.06; 95 % confidence interval [CI], 1.11-3.82) and poor workplace communication (adjusted OR, 10.96; 95 % CI, 6.63-18.09) increased the risk of mental health distress. In the group that experienced severe damage, handling residents' complaints (adjusted OR, 4.79; 95 % CI, 1.55-14.82) and poor workplace communication (adjusted OR, 9.14; 95 % CI, 3.34-24.97) increased the risk, whereas involvement in disaster-related work (adjusted OR, 0.39; 95 % CI, 0.18-0.86) decreased the risk. Conclusions: Workers who have experienced less disaster-related damage might benefit from working fewer overtime hours, and those who have experienced severe damage might benefit from avoiding contact with residents and engaging in disaster-related work. Facilitating workplace communication appeared important for both groups of workers. [ABSTRACT FROM AUTHOR]

Background: Although the Oxford classification of IgA nephropathy appears valid, we found crescents were significantly related to renal outcome in our cohort, whereas segmental glomerulosclerosis (S) was not. The timing of renal biopsy may significantly affect the variables in the Oxford classification. Method: The relationship between biopsy timing and pathological variables (mesangial hypercellularity score [M], endocapillary hypercellularity [E], S, tubular atrophy/interstitial fibrosis [T], crescents, and global glomerulosclerosis [G]) was analyzed retrospectively in 250 children with IgA nephropathy. Results: The median time from disease onset to renal biopsy was 5.1 months (interquartile range, 2.7-15.4). M (ρ = −0.26, P < 0.0001), E (ρ = −0.34, P < 0.0001), and crescents (ρ = −0.14, P = 0.023) showed significant negative correlations, and S (ρ = 0.15, P = 0.018) and G (ρ = 0.25, P < 0.0001) showed significant positive correlations with time to biopsy (Spearman test). M, E, and crescents differed significantly in renal biopsies obtained before and after 3 years from onset (Wilcoxon test). Most crescents (92.9 %) were cellular/fibrocellular and were acute lesions. As crescents formed early after disease onset and decreased over time, they may be prognostic for acute phase, but not for chronic phase disease. Conclusions: Renal biopsy timing may alter the significance of variables used in the Oxford classification. [ABSTRACT FROM AUTHOR]

Summary: Patients with rheumatoid arthritis showed greater response to 18-month administration of daily teriparatide especially in the increase of bone formation markers at 1 month and femoral neck bone mineral density at 18 months compared to postmenopausal osteoporosis patients. Introduction: The aim of this study was to evaluate the effects of 18-month administration of daily teriparatide (TPTD) in osteoporosis patients with rheumatoid arthritis (RA) by comparing that of postmenopausal osteoporosis patients (Porosis). Methods: The effects of TPTD were examined between RA ( n = 70; age 68.4 years; disease activity score assessing 28 joints with CRP [DAS28-CRP] 2.8; rheumatoid factor [RF] positivity 75.5 %) with 77.1 % of prior bisphosphonate (BP), 84.3 % of oral prednisolone (PSL) (4.4 mg/day at baseline), 25.7 % of biologics, and Porosis ( n = 62; age 71.3 years) with 77.4 % of prior BP. Results: Femoral neck (FN) bone mineral density (BMD) increase at 18 months was significantly greater in RA compared to Porosis (4.7 vs. 0.7 %, P = 0.038), whereas it was 9.7 versus 7.9 % ( P = 0.736) in the lumbar spine (LS). The increase of bone formation markers (bone alkaline phosphatase [bone ALP] and N-terminal type I procollagen propeptide [PINP]) at 1 month were all significantly greater in RA compared to Porosis. A multivariate logistic regression analysis revealed that the significant indicator of 18-month BMD increase in RA was a 3-month increase of under-carboxylated osteocalcin (ucOC) for LS ( β = 0.446, P = 0.005) and baseline ucOC for FN ( β = 0.554, P = 0.001), in which both showed significant negative correlation with baseline PSL dose. Conclusions: RA showed greater response to daily TPTD administration, especially in the increase of bone formation markers at 1 month and FN BMD increase at 18 months compared to Porosis. [ABSTRACT FROM AUTHOR]

Background: Narcolepsy (NA) is a sleep disorder characterized by excessive daytime sleepiness and an increased propensity of rapid eye movement sleep. If left untreated, NA can lead to academic underachievement or job loss because of dozing off or mistakes caused by inattentiveness due to sleepiness. Purpose: Although untreated narcolepsy patients may suffer from many social disadvantages due to excessive daytime sleepiness, mostly it takes a long time to receive a definitive diagnosis of the disorder. This retrospective study investigated factors related to the period until definitive diagnosis among patients with narcolepsy in Japan. Methods: We enrolled 181 consecutive patients (108 men, 73 women; mean age 37.6 ± 16.6 years old; narcolepsy with cataplexy/narcolepsy without cataplexy = 131:50). Multivariate logistic regression analysis was performed with period until definitive diagnosis as the dependent variable and descriptive clinical variables as the independent variables. Results: The mean period until receiving the diagnosis among the participants was 9.9 ± 10.1 years. More than half of the patients first learned about the disorder from information provided by the media. Multivariate logistic analysis indicated that adult onset ( p < 0.01), onset in 1995 or later ( p < 0.001), and first learning about the disorder from a sleep disorder specialist physician or a general practitioner ( p < 0.001) were associated with a time taken for receiving a definitive diagnosis less than or equal to the median value (7 years). Conclusion: Improving access to information about the concept of the disorder and the medical institutions specialized in sleep disorders, especially via the Internet, would be necessary to promote early diagnosis of the disorder. [ABSTRACT FROM AUTHOR]

Purpose: Although a few prospective studies have addressed the question as to which biomarker of infection in adult patients with febrile neutropenia (FN) is superior, procalcitonin (PCT) or C-reactive protein (CRP), the results have been inconsistent and inconclusive. This was possibly due to the poor sensitivity of previous PCT tests that have a functional sensitivity of 0.5 ng/ml. Methods: Between November 2010 and February 2012, we prospectively compared the diagnostic utility of serum high-sensitivity (hs) PCT (lower limit of detection, 0.02 ng/ml) and CRP levels for detecting bacterial infection in patients with FN. Serum was collected within 72 h after the onset of FN in patients with hematological disorders. Results: Seventy-five febrile episodes were evaluable. The areas under the receiver operating characteristic curves for life-threatening infection defined as septic shock and bacteremia caused by non-coagulase negative staphylococcus were 0.824 (95 % CI 0.711-0.937; P = 0.001) for hsPCT and 0.673 (0.505-0.842; P = 0.068) for CRP, respectively. In contrast, CRP, but not hsPCT, tended to increase significantly with the clinical severity, as indicated by the diagnostic classification ( P = 0.002 for trend). Conclusions: The serum hsPCT test may be more useful than the serum CRP test in the detection of life-threatening infection at an early phase after the onset of FN. In contrast, the serum CRP test may be more useful in diagnosing the severity of infection. However, neither of these tests was able to differentiate the cause of FN with a low probability of fatal outcome. [ABSTRACT FROM AUTHOR]

Summary: This study assessed the effects of physical activity on a 10-year incidence of self-reported vertebral fractures in adult women of a large Japanese cohort. Medium levels of strenuous activity and long-duration sedentary activity were associated with a lower incidence of vertebral fractures; association patterns appear to be different from hip fractures. Introduction: Physical activity helps prevent hip fracture, but little is known about the longitudinal association between physical activity and vertebral fractures. The purpose of this study was to evaluate the effects of physical activity on the 10-year incidence of symptomatic vertebral fractures using data from the Japan Public Health Center-based Prospective Study. Methods: Baseline studies were conducted in 1993-1994, and the follow-up study was conducted 10 years later. We analyzed 23,757 women aged 40-69 years. At baseline, physical activity was assessed as a predictor by using a questionnaire. Subjects were asked to report vertebral fractures that occurred during the 10-year follow-up period. Relative risks (RRs) adjusted for confounders were estimated by multiple logistic regression analysis. Results: The 10-year cumulative incidence of vertebral fractures was 0.67 %. Those who engaged in strenuous physical activity of <1 h/day had a significantly lower incidence of vertebral fractures than those who did not engage in such activity (RR = 0.52, 95 % CI 0.28-0.97), while those engaged in such activity ≥1 h/day did not (RR = 0.82, 95 % CI 0.58-1.14). Long-duration sedentary activity was associated with a low incidence of vertebral fractures ( P for trend = 0.0002), but the frequencies of sports activities and metabolic equivalents were not ( P for trend = 0.0729 and 0.4341, respectively). Conclusions: Strenuous activity and sedentary activity are associated with the incidence of vertebral fractures, although the association may not be linear. The pattern of association between physical activity and vertebral fractures appears to be different from that of hip fractures. [ABSTRACT FROM AUTHOR]

Study design:Cross-sectional study.Objectives:There are ethnic differences in the distribution of abdominal obesity associated with metabolic disorders. In Japan, the appropriate reference values for abdominal obesity have not been established in individuals with spinal cord injury (SCI), although there are a number of studies in Western countries. This study evaluates the associations between visceral fat area (VFA), waist circumference (WC) and body mass index (BMI), to examine cutoffs and estimate the error for WC and BMI equivalent to 100 cm2 VFA in Japanese men with SCI.Setting:National Rehabilitation Center for Persons with Disabilities, Japan.Methods:Seventy-four men (aged 45.6 (s.d. 14.3) years) participated in the study. VFA was quantified using computed tomography at the level of the umbilicus, and associations were determined using nonlinear regression analysis. The error of the estimates from the regression equation was assessed using a Bland-Altman plot.Results:The mean VFA was 101.2 (s.d. 53.0) cm2 and 32 subjects had a VFA ⩾100 cm2. The cutoffs for a VFA of 100 cm2 were WC, 81.3 cm and BMI, 22.5 kg m−2. The relationship between the estimated and actual values showed that the error increased as VFA increased, which resulted in a negative proportional bias.Conclusion:The suggested cutoff for Japanese men with SCI is a VFA of 100 cm2, which is lower than that in the healthy able-bodied population for both WC and BMI. Further investigation is needed to determine the reference value for estimating SCI-specific VF accumulation. [ABSTRACT FROM AUTHOR]

Purpose We aimed to investigate the recommended dose for the combination of TSU-68, a multiple-receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2 and platelet-derived growth factor receptor-β, and S-1, an oral fluoropyrimidine, in patients with advanced hepatocellular carcinoma (HCC) based on its associated dose-limiting toxicity (DLT) frequency. We also determined the safety, tolerability, pharmacokinetics (PK), and efficacy of the combination treatment. Patients and methods Patients without any prior systemic therapy received 400 mg/day TSU-68 orally and 80 mg/day (level 1) or 100 mg/day (level 2) S-1 for 4 or 2 weeks followed by a 2- or 1-week rest period (groups A and B, respectively). According to the treatment, patients progressed from level 1B to level 2A, then level 2B. Safety and response rates were assessed. Results Eighteen patients were enrolled. Two patients at levels 1B and 2A but none at level 2B showed DLTs. The common adverse drug reactions were a decrease in hemoglobin levels, hypoalbuminemia, and anorexia, which were mild in severity (grades 1-2). PK data from levels 1B and 2A indicated that the area under the curve for TSU-68 and 5-fluorouracil was unlikely to be affected by the combination treatment. Response rate, disease control rate, median time to progression, and median overall survival were 27.8 %, 61.1 %, 5.3 months, and 12.8 months, respectively. Conclusion The recommended dose for advanced HCC should be 400 mg/day TSU-68 and 100 mg/day S-1 for 4 weeks followed by 2-week rest. [ABSTRACT FROM AUTHOR]

Purpose: Faster eating is positively associated with body mass index in apparently healthy Japanese populations. In the present study, we examined the associations between self-reported rate of eating and visceral and subcutaneous fat areas in apparently healthy middle-aged Japanese men. Methods: We conducted a cross-sectional study of men who participated in health checkups in Japan. We removed participants who were diagnosed with metabolic diseases by the time of their health checkups. A total of 320 subjects aged 30-64 years (mean ± standard deviation, 47.4 ± 8.6 years) were selected. We compared the associations between rate of eating and various clinical parameters including visceral and subcutaneous fat areas, using analysis of covariance (ANCOVA), which was adjusted by age and lifestyle factors such as alcohol intake, energy intake, smoking, and physical activity. Multivariate logistic regression analyses (MLRA) were performed with visceral fat area (cm) as the dependent variable and independent variables that included self-reported rate of eating. Results: Tukey's multiple test following ANCOVA showed that self-reported rate of eating was positively associated with visceral fat area (cm), but not with subcutaneous fat area (cm). MLRA showed that the odds ratio of rate of eating for visceral fat area in tertile (T) 3 (>100 cm) compared with T1 (≤70 cm) was 1.99 (95 % CI 1.40-2.90, P < 0.01), and the association remained after adjustment for the subcutaneous fat area. Conclusions: The present results show that self-reported faster eating is positively associated with visceral fat accumulation, independently of subcutaneous fat accumulation, in apparently healthy Japanese men. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to examine the possible effects of healthcare resource factors, socioeconomic factors, and sociodemographic factors on variations in hospitalization expenditures of elderly patients in Japan at different levels of urbanization. Subject and methods: A secondary analysis was conducted using data obtained from a regional health care cost report and the Portal Site of Official Statistics of Japan. The regional unit of analysis used was the secondary medical care area. We divided these areas into three groups based on their levels of urbanization (low, middle, and high urbanization), indicated by their respective population densities of inhabitable areas. Multiple linear regression models were used to analyze the candidate factors affecting per capita hospitalization expenditures of elderly residents. Results: The significance and magnitude of associations were observed to vary according to different levels of urbanization. Our findings showed that medical resource factors and sociodemographic factors were more influential in areas of low urbanization, whereas the number of hospital beds and socioeconomic factors appeared more influential in high urbanization areas. Conclusion: Policies designed to contain healthcare expenditures should take regional characteristics and levels of urbanization into account in order to support the development and implementation of region-specific improvements that ensure affordable healthcare for the elderly. [ABSTRACT FROM AUTHOR]

Summary: This study examined the accuracy of thoracic and lumbar kyphotic angles as well as anthropometric indicators for discriminating patients with vertebral fracture among Japanese women >50 years old with back pain. Along with region-specific kyphotic angles and anthropometric indicators, the combination of thoracic and lumbar kyphotic angles offered the highest accuracy. Introduction: Vertebral fractures have been associated with thoracic kyphosis. However, reports on lumbar kyphotic changes in association with vertebral fracture are scarce. This study investigated the accuracy of thoracic kyphotic angle (TKA) and lumbar kyphotic angle (LKA) measurements as well as anthropometric indicators (wall-occiput distance (WOD) and rib-pelvis distance (RPD)) in discriminating patients with vertebral fracture. Methods: Lateral radiographs of the spine were obtained in 70 postmenopausal Japanese women who visited an orthopedic clinic with low back pain (mean age, 76.2 ± 9.0 years). Radiographic vertebral fracture was diagnosed using quantitative measurement according to Japanese criteria. Osteoarthritis (OA) was defined as Kellgren-Lawrence (KL) grade 3 or higher. TKA and LKA were measured using SpinalMouse®. WOD and RPD were also measured. Results: At least one vertebral fracture was present in 49 subjects (70 %). Women with vertebral fractures showed significant increases in LKA, TKA + LKA, and WOD and decreases in RPD. Logistic regression analysis showed significant association between TKA + LKA and vertebral fracture independent of the presence of OA. Receiver operating characteristic analysis revealed that TKA was useful for discriminating thoracic fractures (area under the curve (AUC), 0.730) and LKA was useful for lumbar fractures (AUC, 0.691). The combination of TKA + LKA offered the highest accuracy for detecting thoracic, lumbar, and any vertebral fractures, with AUCs of 0.779, 0.728, and 0.783, respectively. WOD and RPD showed low-to-moderate accuracies for thoracic, lumbar, and any vertebral fractures. Conclusions: Assessment of spinal kyphosis by SpinalMouse® as well as anthropometric indicators proved useful in discriminating subjects with vertebral fractures. These convenient and radiation-free methods could contribute to early diagnosis of vertebral fractures and subsequent appropriate treatment, thus preventing additional osteoporotic fractures. [ABSTRACT FROM AUTHOR]

Summary: A 3-year follow-up study on 334 young Japanese females enrolled in a university at the age of 18 years revealed that discontinuation of leisure time impact-loading exercises performed in junior high and/or high school was associated with increased risk of reduction in calcaneus osteo-sono assessment index (OSI). Introduction: Bone strength rapidly increases during puberty and reaches its peak by the end of adolescence. The aim of this study was to determine the lifestyle factors that influence the maintenance of calcaneus OSI in young adult females around the time when peak bone mass is attained. Methods: Annual health checkups including OSI measurements, anthropometrics, lifestyle analysis, and blood examination were performed 4 times on 334 Japanese females enrolled in a university at the age of 18 years. According to the slope of OSI change during the 3-year follow-up, the subjects were grouped into two categories: OSI loss (the lowest tertile) and OSI gain/stable (the second and third tertiles). Results: At the baseline assessment, the OSI loss group had higher OSI and height and an earlier menarche age than the OSI gain/stable group. Performing leisure time impact-loading exercise in junior high and/or high school but discontinuing it at university was associated with increased risk of OSI loss, independent of OSI, height and weight at the age of 18 years, weight change during follow-up, age of menarche, energy-adjusted nutrient intake, and alcohol drinking; the odds ratios were 4.1-4.9 compared with those performing impact-loading exercise at university. In particular, duration, frequency, and subjective intensity of impact-loading exercise during high school were positively associated with OSI loss. Conclusion: Discontinuation of leisure time impact-loading exercises performed during late adolescence is associated with an increased risk of OSI loss in young adult females during the 3-year follow-up period. [ABSTRACT FROM AUTHOR]

To determine whether the Modified Checklist for Autism in Toddlers (M-CHAT) in conjunction with the routine 18-month health check-up identifies Japanese toddlers with autism spectrum disorder (ASD). Two-stage screening using the M-CHAT was conducted with 1,851 children attending the check-up. Final ASD diagnosis was confirmed at age ≥3 years. Screening identified 20/51 children with ASD: 12/20 true positives were developmentally delayed, whereas 16/22 false negatives were high-functioning. Sensitivity was 0.476, specificity 0.986, positive predictive value 0.455, and likelihood ratio 33.4 for children with ASD. With a few modifications, M-CHAT screening successfully detected toddlers with ASD with and without developmental delay and is a promising screening tool to complement existing community surveillance. [ABSTRACT FROM AUTHOR]

Study design:A cross-sectional analysis.Objective:To examine whether intramedullary stress is related to the appearance of symptoms in cervical spondylotic myelopathy (CSM).Setting:Japan.Methods:Thirty-three consecutive patients with CSM and 30 consecutive patients without CSM were enrolled. A total of 99 disc levels from C3 to C6 in 33 patients with CSM were divided into two groups: 33 disc levels with high signal intensity (HSI) on T2-weighted magnetic resonance image (HSI group) and 66 disc levels without HSI (Non-HSI group). Ninety disc levels from C3 to C6 in patients without CSM were set up in a control group. Intramedullary stress value at each level was analyzed using the finite element method. Stress was compared among the three groups. A cutoff value of stress to present HSI was investigated from receiver operator characteristics (ROC) curve.Results:In all the patients with CSM, the disc level with HSI presented the highest stress among the three disc levels evaluated. The stress was 3.16±0.86 kPa (mean±s.d.) in the HSI group, 1.81±0.72 kPa in the Non-HSI group and 1.01±0.37 kPa in the control group. The stress differed significantly among the three groups (P<0.0001). The qualified cutoff value derived from the ROC curve was 2.30 kPa (sensitivity 78.8%, specificity 91.9%). None of the disc levels in the control group exceeded 2.30 kPa.Conclusion:HSI was strongly associated with intramedullary stress. Threshold of intramedullary stress to present HSI that related closely to the symptoms of myelopathy was revealed. [ABSTRACT FROM AUTHOR]

Purpose: Omeprazole has ( R)- and ( S)-enantiomers, which exhibit different pharmacokinetics (PK) among patients with cytochrome P450 (CYP) 2C19 genotype groups. The aim of this study was to investigate whether the 1-point, 4-h postdose ( R)-omeprazole hydroxylation index (HI) of racemic omeprazole reflects the three CYP2C19 genotype groups in Japanese individuals. Methods: Ninety healthy Japanese individuals were enrolled and classified into the three different CYP2C19 genotype groups: homozygous extensive metabolizers (hmEMs; n = 34), heterozygous EMs (htEMs; n = 44), and poor metabolizers (PMs; n = 12). Blood samples were drawn 4 h after the intake of an oral dose of omeprazole 40 mg, and plasma levels of omeprazole and its metabolites were analyzed by high-performance liquid chromatography (HPLC) using a chiral column. Results: Mean plasma concentrations of ( R)- and ( S)-omeprazole in PMs were significantly higher than those in hmEMs and htEMs, and similar results were obtained in the case of omeprazole sulfone. Additionally, there was a significant difference in plasma concentrations of ( R)-5-hydroxyomeprazole among CYP2C19 genotype groups, whereas no significant differences were observed in that of ( S)-5-hydroxyomeprazole. Similarly, ( R)-omeprazole HI in hmEMs, htEMs, and PMs were 5.6, 3.1, and 0.3, respectively, which were significantly different, but no significant difference was present in the ( S)-omeprazole HI. Conclusion: Our findings demonstrate that ( R)-omeprazole HI correlated better with CYP2C19 genotype groups than racemic-omeprazole HI, and these results may be useful for classification among patients in CYP2C19 genotype groups prior to omeprazole treatment. [ABSTRACT FROM AUTHOR]