Dose-Response Relationships between Diet Quality and Mortality among Frail and Non-Frail Older Adults: A Population-Based Kyoto-Kameoka Prospective Cohort Study.

OBJECTIVES: Although better diet quality is inversely associated with mortality risk, the association between diet quality and mortality remains unclear in frail and non-frail older adults. Thus, we aimed to examine this association in older Japanese adults. DESIGN: A prospective cohort study. SETTING AND PARTICIPANTS: We used the data of 8,051 Japanese older adults aged ≥65 years in the Kyoto-Kameoka study. MESUREMENTS: Dietary intake was estimated using a validated food frequency questionnaire. Diet quality was evaluated by calculating the adherence scores to the Japanese Food Guide Spinning Top (range, 0 [worst] to 80 [best]), which were stratified into quartiles. Frailty status was assessed using the validated self-administered Kihon Checklist (KCL) and the Fried phenotype (FP) model. Survival data were collected between February 15, 2012 and November 30, 2016. Statistical analysis was performed using the multivariate Cox proportional hazard analysis and the spline model. RESULTS: During the median 4.75-year follow-up (36,552 person-years), we recorded 661 deaths. After adjusting for confounders, compared with the bottom adherence score quartile, the top quartile was associated with lower hazard ratio (HR) of mortality in frailty (HR, 0.73; 95% confidence interval [CI], 0.54-1.00) and non-frailty, as defined by the KCL (HR, 0.72; 95% CI, 0.52-1.01). In the spline model, regardless of frailty status defined by the KCL and FP model, adherence score showed a strongly dose-dependent inverse association with mortality up to approximately 55 points; however, no significant differences were observed thereafter. This association was similar to the results obtained in individuals with physical, cognitive, and depression as domains of KCL in the spline model. CONCLUSIONS: Our findings demonstrate an L-shaped association between diet quality and mortality in both frail and non-frail individuals. This study may provide important knowledge for improving poor diet quality in older individuals with frailty or domains of frailty.

Effects of polypharmacy on the prevalence of adverse drug events resulting in outpatient visits and hospitalization.

A high proportion of hospitalizations is attributable to the prevalence of adverse drug events. This retrospective study included outpatients and inpatients to determine the prevalence of adverse drug events and if polypharmacy increases it. The prevalence, classification, and causality of adverse drug events were assessed based on medical records, laboratory values, and other data. Multivariate analysis (multiple logistic regression analysis) was performed with the presence or absence of adverse drug events at the time of the visit as the dependent variable and items for which the P-value was <0.25 in the univariate analysis as independent variables. The prevalence of adverse drug events was 13.0%, 10.9%, and 16.0% among all patients, the outpatient group, and the inpatient group, respectively. Multivariate analysis showed that polypharmacy (≥5 drugs) significantly increased the risk of adverse drug events in all patients. The prevalence of adverse drug events significantly increased with each additional drug used. We expect that minimizing the number of medications through moderation of the number of prescription drugs and elimination of polypharmacy will reduce the number of outpatient visits and hospitalizations due to adverse drug events.

Cost utility analysis of pharmacist counseling care for breast cancer chemotherapy outpatients.

Chemotherapy for cancer is increasingly implemented in the outpatient setting. Pharmacists contribute to cancer treatment by conducting counseling during outpatient chemotherapy visits. They provide guidance on drug treatment, side effects, and side effect countermeasures on every visit. However, there have been few economic evaluations of pharmacist involvement in outpatient chemotherapy. Therefore, we performed a cost utility analysis. We assigned usual care (control) and pharmacist counseling to two groups of 19 patients receiving outpatient chemotherapy for breast cancer at Gifu Municipal hospital. Quality of life was measured at three timepoints before and during chemotherapy treatment using the EuroQol 5 dimension instrument (EQ-5D). EQ-5D values across the timepoints were 0.831, 0.757, and 0.791 for the control group, and 0.882, 0.883, and 0.921 for the pharmacist counseling group. The additional cost in the pharmacist counseling group was 2,227 yen per counseling session. The change in quality-adjusted life years (QALY) was a maximum of -0.021±0.186 in the control group and 0.007±0.199 in the pharmacist counseling group. The maximum cost for one QALY was 1,360,558 yen (≈12,460 US dollars). Pharmacists' counseling in outpatient cancer chemotherapy for breast cancer patients had an acceptable incremental cost-effect ratio, contributing to improved patient quality of life without significant additional expenditure to healthcare.

Relationship Between Initial Renal Function and the Inhibitory Effect of Dipeptidyl Peptidase-4 Inhibitor Treatment on Renal Function Decline.

We retrospectively investigated the renal function index of patients with type 2 diabetes mellitus (T2DM) to examine the influence of dipeptidyl peptidase-4 (DPP-4) inhibitors on renal function between patients up to early nephropathy and after overt nephropathy. Patients with T2DM (>18 years old) who had been prescribed hypoglycemic agents for ≥3 months at Gifu Municipal Hospital between March 2010 and April 2014 were included in the study. Renal function was evaluated as the estimated glomerular filtration rate (eGFR) decline from baseline at 12 months. Patients in the DPP-4 inhibitor-treated and untreated groups with an eGFR ≥60 (358 [58.2 %] and 257 [41.8 %], respectively) and eGFR <60 (115 [60.2 %] and 76 [39.8 %], respectively) were subjected to multiple logistic regression analysis. Among patients with an eGFR ≥60, no significant differences were observed in eGFR decline rates over time. However, among patients with an eGFR <60, significant decreases were observed in eGFR decline rates >10 % (6 months; odds ratio, 0.476; P = 0.043, 12 months; odds ratio, 0.413; P = 0.010). Similar results were obtained for an eGFR decline rate >20 % (12 months; odds ratio, 0.369; P = 0.049). DPP-4 inhibitors are renoprotective in patients with T2DM and an eGFR <60.

Natural occurrence of mycotoxins in maize and sorghum in Togo.

Mycotoxins are fungal secondary metabolites frequently affecting agronomical crops and consequently imposing a major challenge for food safety and public health. In this study, a total of 67 raw cereals (55 maize and 12 sorghum) were collected from the market of Togo. The samples were investigated on the occurrence of 21 mycotoxins using state-of-the-art high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). The most frequent occurring mycotoxins were fumonisins (88 and 67% for maize and sorghum respectively) with concentrations ranging from 101 to 1838 µg/kg for maize and 81.5 to 361 µg/kg for sorghum, respectively. Aflatoxin B1 was detected in 38% of the maize samples with maximum contamination levels of 256 µg/kg, and 25% of the sorghum samples (range 6-16 µg/kg). The concentrations of aflatoxins were high in maize, with some cases exceeding the maximum legislative limits (EU) for unprocessed maize placed on the market. In addition to these high contamination levels, the co-occurrence of three classes of mycotoxins (i.e., aflatoxins, fumonisins, and trichothecenes) was observed in this study. For the first time, the multi-mycotoxins occurrence in agronomical crops in Togo was reported.

Relationship between ethanol consumption and TBL2 rs17145738 on LDL-C concentration in Japanese adults: a four season 3-day weighed diet record study.

BACKGROUND: LDL cholesterol (LDL-C) concentration is modified by dietary and genetic factors; however, little is known about the details of this relationship. Our aim was to investigate the associations taking into account dietary assessment methods, seasonal effects and missing values. METHODS: Study subjects completed food frequency questionnaires (FFQ) and supplied 3-day weighed dietary records (WDRs) and blood samples in four seasons. Approximately 660,000 single nucleotide polymorphisms (SNPs) were measured. Candidate SNPs related to LDL-C concentration were systematically selected. Multiple imputation was applied for missing values. A total of 312 repeated measures data were used for analyses. After adjusting for season and subjects as fixed and random effects, effects of nutrient intake and SNPs on LDL-C concentration were assessed according to three dietary assessment methods: the FFQ and first and four season 3-day WDRs (4 s-3d WDRs). RESULTS: For LDL-C concentration, ethanol consumption derived from all three dietary assessment methods was consistently associated (P < 0.09 for all). Positive and negative relationships were consistently shown with rs651007 and rs1160985 in the first and four seasons; but the latter remained after adjusting for total dietary fiber intake derived from the FFQ and 4 s-3d WDRs (P < 0.05, excepting the first 3-day WDRs). rs599839 was negatively associated after cholesterol intakes derived from the first and 4 s-3d WDRs were considered (P < 0.05 and 0.07, respectively). Each rs17145738 and ethanol consumption based on the 4 s-3d WDRs was related to LDL-C concentration (P < 0.05). Seasonal variations of LDL-C concentration were observed only in summer. CONCLUSIONS: In contrast to nutrient intake, ethanol consumption was shown to be comprehensively related to LDL-C concentration, regardless of dietary assessment methods. Taking into account seasonal effects, critical relationships with LDL-C concentration for some SNPs, after adjustment for specific nutrients, were revealed. Our findings can be used to help to interpret the relationships between dietary and genetic factors on LDL-C concentration in large-scale epidemiological studies.(10/10 keywords).

Nutritional factors affecting length of hospital stay in patients undergoing cardiovascular surgery.

Cardiovascular surgery is a highly invasive intervention that is often performed in elderly patients at risks of complications because of malnutrition and reduced immunity. This study investigated nutritional factors that affected length of hospital stay in patients undergoing cardiovascular surgery. Among 68 patients who underwent surgery at the Department of Cardiovascular Surgery of Gifu Municipal Hospital between April 2013 and March 2015, 55 with complete data were included in the analysis. Data on serum albumin (ALB), transferrin (Tf), pre-albumin (PA) and retinol binding protein (RBP) levels were collected. The median length of hospital stay was 29 days (stays of ≥30 days were considered long-term hospitalization). Multivariate analysis (multiple logistic regression) included age (≥ 65 years), sex (female), and ALB (≤ 3.0 g/dL), Tf (≤ 150.0 mg/dL), PA (≤ 10.0 mg/dL) and RBP (≤ 1.5 mg/dL) levels. ALB [odds ratio (OR) 10.37, 95% CI (confidence interval): 1.185-90.80, P = 0.035] and Tf [OR 4.743, 95% CI: 1.375-16.36, P = 0.014] were significantly associated with length of hospital stay. Nutritional management of patients and careful monitoring of ALB and Tf levels can shorten length of hospital stay in patients undergoing cardiovascular surgery.

Factors influencing the use of over-the-counter drugs and health foods/supplements.

Over-the-counter (OTC) drugs and health foods/supplements are used as means of self-medication with the aim of preventing diseases and maintaining health. No reports have yet addressed the relationship between healthcare systems and self-medication. Here, we carried out a retrospective survey to identify healthcare system factors affecting OTC drug and health food/supplement usage. Patients hospitalized at Gifu Municipal Hospital between October 1, 2014 and March 31, 2015 were given a survey. The items surveyed were age, gender, disease, alcohol intake/smoking status, insurance classification, and medical pharmaceuticals, OTC drugs, and health foods/supplements used immediately before hospitalization. We performed multiple logistic regression analysis using OTC drugs and health foods/supplements as dependent variables with patient attributes, medical insurance, etc. as independent variables. A total of 5,965 patients were analyzed. OTC users comprised 2.6 % (156 people) of the total. The use of OTC drugs was significantly higher for females and alcohol consumers than in other categories. In contrast, the use of OTC drugs was significantly lower for participants in public expense/medical subsidy programs. Health foods/supplements were used by 4.0 % of all subjects (240 people); their use was significantly higher among females and users of medical pharmaceuticals. On the other hand, the use of health foods/supplements was significantly lower for smokers, users of the latter-stage elderly healthcare system, and users of public expense/medical subsidy programs.

Risk factors for developing infusion reaction after rituximab administration in patients with B-cell non-Hodgkin's lymphoma.

Rituximab (RTX), a monoclonal antibody against CD20, is known to cause fewer side effects than conventional anti-cancer drugs; however, infusion reaction (IR), which is specific to monoclonal antibody therapy, is frequently triggered by RTX. Therefore, we designed this study to identify risk factors based on clinical test values for developing IR after RTX administration. Eighty-nine patients with B-cell non-Hodgkin's lymphoma who had received RTX for the first time between February 2010 and March 2013, at the Gifu Municipal Hospital were enrolled as subjects. Analysis of data was conducted for 87 patients, after excluding patients whose data were missing. Univariate analysis showed significant differences in the number of patients exhibiting a soluble interleukin-2 receptor (sLL-2R) level > 2,000 U/L and hemoglobin (Hb) < lower standard limit (LSL) between the IR and non-IR groups. Multivariate analysis showed significant differences with respect to slL-2R > 2,000 U/L [odds ratio (OR), 4.463; 95% confidence interval (Cl), 1.262-15.779; P = 0.020], Hb < LSL [OR, 3.568; 95% CI, 1.071-11.890; P = 0.038], and steroid administration [OR, 0.284; 95% Cl, 0.094-0.852; P = 0.025]. Our findings show that sIL-2R > 2,000 U/L, Hb < LSL, and a lack of steroid premedication are risk factors for developing IR following RTX treatment.

Hyponatremia and hypokalemia as risk factors for falls.

BACKGROUND/OBJECTIVES: Fall accidents may reduce an individual's quality of life and ability to perform the activities of daily life, and may delay recovery from illness. Consequently, medical institutions need to take measures to prevent falls. There are various risk factors for falls, including advanced age, illness and medication effects. Although hyponatremia and hypokalemia have been reported to increase the rate of falls, how they affect falls is not fully understood. SUBJECTS/METHODS: We retrospectively examined 2948 patients, ⩾18 years old who had been hospitalized for ⩾3 days at Gifu (Japan) Municipal Hospital between May 2012 and April 2013 to determine the effects of hyponatremia and hypokalemia on the risk of falls. After the patients had been divided into fall and non-fall groups, their data were subjected to univariate and multiple regression analysis to identify significant differences. RESULTS: The univariate analysis results revealed significant differences between the groups in terms of age (⩾65 years); the presence of hyponatremia, hypokalemia, central nervous system disease, cardiovascular disease and/or peripheral nerve/muscular disease; intake of medications that increase the risk of falls; and increased sedative dosage. The multivariate analysis results revealed significant differences between the groups in terms of the presence of hyponatremia (odds ratio (OR), 1.751; 95% confidence interval (CI), 1.020-3.005), hypokalemia (OR, 2.209; 95% CI, 1.280-3.813), central nervous system disease (OR, 2.492; 95% CI, 1.629-3.814) and/or age ⩾65 years (OR, 2.180; 95% CI, 1.242-3.826). CONCLUSIONS: The results indicated that the presence of hyponatremia or hypokalemia increases the risk of falls.

Risk factors for Clostridium difficile-associated diarrhea and the effectiveness of prophylactic probiotic therapy.

Measures for prevention of Clostridium difficile-associated diarrhea, a common nosocomial infection, in hospital settings are urgently needed. This study was conducted to identify the risk factors contributing to C. difficile-associated diarrhea and to evaluate the clinical benefit of probiotics in its prevention. The study included 2716 patients at least 20 years old who received an injected antibiotic at any time between February 2010 and February 2011; a total of 2687 patients (98.9%) were assigned to the non-C. difficile-associated diarrhea group, and 29 patients (1.1%) were assigned to the C. difficile-associated diarrhea group. Univariate analysis revealed a significant difference between the two groups for the following factors: antibiotic therapy for > or = 8 days; enteral nutrition; intravenous hyperalimentation; fasting; proton pump inhibitor use; H2 blocker use; and serum albumin < or = 2.9g/dL (p<0.05). Multivariate logistic regression analysis revealed a significant difference between the two groups for several factors. Antibiotic therapy for > or = 8 days, intravenous hyperalimentation, proton pump inhibitor use, and H2 blocker use were therefore shown to be risk factors for C. difficile-associated diarrhea. Prophylactic probiotic therapy was not shown to suppress the occurrence of C. difficile-associated diarrhea.

Risk factors contributing to urinary protein expression resulting from bevacizumab combination chemotherapy.

Proteinuria following administration of bevacizumab is reported to be a specific adverse effect, but the risk factors for proteinuria have not been elucidated. In this study, the risk factors for urinary protein expression resulting from bevacizumab combination chemotherapy were investigated. The subjects were 47 patients aged > or = 20 years who had received bevacizumab combination chemotherapy at Gifu Municipal Hospital between February 2010 and February 2011. A total of 13 patients were excluded based on exclusion criteria; of the remaining 34 patients, 24 (70.6%) were assigned to the urinary protein non-expression group, and 10 (29.4%) were assigned to the urinary protein expression group. The results of multivariate logistic regression analysis revealed a significant difference in systolic blood pressure (> or =130 mmHg) between the two groups (OR: 14.499, 95%CI: 1.326-158.577, p=0.028). This finding shows that systolic blood pressure (> or =130 mmHg) is a risk factor for urinary protein expression resulting from bevacizumab combination chemotherapy.

Pharmacoeconomic analysis of DPP-4 inhibitors.

Dipeptidyl peptidase-4 (DPP-4) inhibitors and other incretin-related drugs have attracted attention as antidiabetic agents, but they are expensive. The Japanese government has adopted a policy of reducing healthcare costs, and medical institutions must provide medical care while considering economic efficiency. This study was a comparative survey of the usage, treatment effectiveness, and cost of DPP-4 inhibitors. The subjects were patients prescribed DPP-4 inhibitors (sitagliptin, vildagliptin, and alogliptin) at Gifu Municipal Hospital between February 2010 and August 2011. HbA1c: Japan Diabetes Society values (%) and concomitant antidiabetic agents were surveyed for 12 weeks after the start of DPP-4 inhibitors. A cost-effectiveness analysis showed that the cost required for a 0.1% decrease in HbA1c for 12 weeks was the lowest with vildagliptin (2,478 yen; decrease in HbA1c: 0.75% +/- 0.85%). In a cost analysis with a virtual cohort of 1000 patients, the number of patients who achieved the treatment target (HbA1c 6.5%) was estimated with respect to a virtual cohort created based on the HbA1c level (7.59 +/- 1.13%) at baseline of 307 patients, in cases assuming the use of each DPP-4 inhibitor. In addition, the incremental cost-effectiveness ratio (ICER) was obtained with sitagliptin 50 mg as the reference. The number of patients achieving the treatment target was the highest with vildagliptin 100 mg (413 of 1000 patients), and the estimated ICER of 28,359 yen was the lowest. Robustness was also confirmed with a sensitivity analysis. These results suggest that vildagliptin provides a superior cost-benefit.

Impact of levofloxacin dose adjustments by dispensing pharmacists on adverse reactions and costs in the treatment of elderly patients.

Ensuring an appropriate dosage of renally eliminated drugs for patients with renal insufficiency is important for preventing adverse drug reactions. We investigated the effectiveness of interventions by pharmacists in a hospital pharmaceutical department. The comparative study was performed at Gifu Municipal Hospital in Japan from March to August 2011, and included an intervention (142 patients) and a control group (98 patients). Upon receiving a prescription of levofloxacin for patients aged > or = 75 years, pharmacists evaluated the patients' kidney function and adjusted the appropriate dosage at the time of dispensation. In the intervention and control groups, levofloxacin-induced adverse reactions developed in 6 of 142 (4.2%) and 13 of 98 (13.3%) patients, respectively (p < 0.05). The cost of reducing levofloxacin per patient was yen 191.1 and yen 0 in the intervention and control groups, respectively. The cost per patient for adverse reaction treatments and examinations was yen 15.5 and yen 290.0 in the intervention and control groups, respectively. The intergroup difference in the total cost per patient was yen 465.6. Dose adjustment of levofloxacin at the time of dispensation by the pharmacist for patients aged > or = 75 years resulted in a decrease in the incidence of adverse reactions and cost. These findings can be applied not only to hospitals, but also to community pharmacies, because the intervention, which is a manual system, is simply performed when pharmacists are dispensing drugs.

Effects of transglucosidase on diabetes, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes: a 12-week, randomized, double-blind, placebo-controlled trial.

In this 12-week, randomized, double-blind, placebo-controlled trial, the efficacy and safety of transglucosidase (TGD) were compared with placebo in patients with type 2 diabetes mellitus (T2DM). At 12 weeks, TGD 300 mg/day and TGD 900 mg/day significantly reduced HbA1c (0.18 and 0.21%) and insulin concentration (19.4 and 25.0 pmol/l), respectively, vs. placebo. TGD 300 mg/day and TGD 900 mg/day also significantly reduced low-density lipoprotein cholesterol (0.22 and 0.17 mmol/l, respectively). TGD 900 mg/day significantly reduced triglyceride by 0.24 mmol/l and diastolic blood pressure by 8 mmHg. Placebo was associated with a significant increase from baseline in body mass index, alanine aminotransferase and aspartate aminotransferase (0.17 kg/m(2) , 3 and 2 U/l, respectively), whereas TGD was not. TGD 300 mg/day significantly increased high-molecular-weight adiponectin by 0.6 µg/ml. Adverse events did not differ significantly between the groups. TGD resulted in lowering of HbA1c and blood insulin level and improvements in metabolic and cardiovascular risk factors in T2DM.

Changes of ROS during a two-day ultra-marathon race.

To assess oxidative stress (OS) induced by endurance exercise, concentrations of serum reactive oxygen species (ROS) were determined in 70 Japanese male amateur runners completing a two-day ultra-marathon race. Serum ROS levels were analyzed at three time points: before the race (baseline), after the 1st day race (mid-race), and after the 2nd day race (goal) (post-race). The means (SE) of ROS were 151.4(3.7) (U. CARR.), 168.7(4.4), and 156.8(4.4), respectively. Significant positive trends were noted between age and serum ROS concentrations at the three race points (p<0.05 for all). After adjusting for age, BMI and average monthly running distance, the baseline serum ROS concentrations were positively associated with completion times of the first-day race, in particular (p<0.05), suggesting that the concentrations may predict physical performance. The ROS production increased at mid-race (p<0.05), but the levels returned to baseline levels at post-race, indicating that an antioxidant defense system may develop post-race to reduce OS.

Changes of mental stress biomarkers in ultramarathon.

We investigated the possible influence of an exhaustive physical exercise on mental stress biomarkers (serotonin, tryptophan, and beta-endorphin) along with dopamine, noradrenaline and free fatty acids in an ultramarathon race in which 45 km was run on the first day and 90 km on the second. We obtained serum samples at 6 different time points during and after the race from 18 Japanese male runners who completed the marathon. Overall changes of serum serotonin and tryptophan concentrations were statistically significant according to ANOVA for repeated measurements (p < 0.05). Serum serotonin levels elevated rapidly on the first day with the post hoc Tukey's test. Tryptophan concentrations inversely decreased during the race, possibly because of utilization for synthesis of serotonin. Levels of beta-endorphin appeared to increase on the first and second days, but were not statistically significant. In conclusion, serum serotonin, tryptophan and beta-endorphin appeared to be used for mental stress markers in physical exercise.

Changes of urinary 8-hydroxydeoxyguanosine levels during a two-day ultramarathon race period in Japanese non-professional runners.

Using the urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration, effects of participation in a two-day ultramarathon race period on oxidative DNA damage were investigated in Japanese nonprofessional runners. Before the first day (baseline), after the first day (mid-race) of 40-km running, and after the second day (post-race) of 90 km running, biomaterials were successfully sampled from 95 participants (males, 79; females, 16) who completed the full race. We analyzed urine for 8-OHdG and blood for aspartate aminotransferase (AST), creatine phosphokinase (CPK) and myoglobin, and evaluated fluctuation in the values at three sampling time points. Adjusted baseline urinary 8-OHdG levels (microg/g creatinine) (mean +/- standard deviation) showed no significant differences between males and females, at 2.85 +/- 1.17 and 3.04 +/- 1.56, respectively. In males, mid-race urinary 8-OHdG levels rose to 3.29 +/- 1.15 (p < 0.01), but then returned to 2.73 +/- 1.16 at the post-race time point (p < 0.01). In females, a similar increase to 3.32 +/- 1.47 and subsequent decline to 2.80 +/- 1.47 were noted. In contrast, AST, CPK and myoglobin were increased at both mid- and post-time points and particularly the latter, independent of the sex. Extreme prolonged exercise in a two-day ultramarathon race period causes oxidative DNA damage but antioxidant repair systems are apparently induced to protect against oxidative DNA stress with physical exercise.

Soybean products and reduction of breast cancer risk: a case-control study in Japan.

Components of the Japanese diet, which might contribute to the relatively low breast cancer incidence rates in Japan, have not been clarified in detail. Since soybean products are widely consumed in Japan, a case-control study taking account of the menopausal status was conducted using data from the hospital-based epidemiologic research program at Aichi Cancer Center (HERPACC). In total, 167 breast cancer cases were included and 854 women confirmed as free of cancer were recruited as the control group. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by multiple logistic regression analysis. There were reductions in risk of breast cancer associated with high intake of soybean products among premenopausal women. Compared with women in the lowest tertile, the adjusted ORs for top tertile intake of tofu (soybean curd) was 0.49 (95% CI, 0.25-0.95). A significant decrease in premenopausal breast cancer risk was also observed for increasing consumption of isoflavones (OR=0.44; 95% CI, 0.22-0.89 for highest vs lowest tertile; P for trend=0.02). The present study found a statistically inverse association between tofu or isoflavone intake and risk of breast cancer in Japanese premenopausal women, while no statistically significant association was evident with the risk among postmenopausal women.