Reproducibility and reliability of performance indicators to evaluate the therapeutic effectiveness of biofeedback therapy after elbow surgery: An observational case series.

Electromyographic biofeedback (EMG-BF) therapy provides information on the state of contraction of the targeted muscles and relaxation of their antagonists, which can facilitate early active range of motion (RoM) after elbow surgery. Our aim in this study was to calculate the minimum detectable change (MDC) during EMG-BF therapy, initiated in the early postoperative period after elbow surgery.This study is an observational case series. EMG-BF of muscle contraction and relaxation was provided during active elbow flexion and extension exercises. Patients completed 3 sets of 10 trials each of flexion and extension over 4 weeks. The total range of flexion-extension motion and scores on the Japanese Society for Surgery of the Hand version of the disability of the arm, shoulder, and hand questionnaire and the Japanese version of the Patient-Rated Elbow Evaluation were obtained at baseline and weekly during the 4-week intervention period. A prediction formula was developed from the time-series data obtained during the intervention period, using the least-squares method. The estimated value was calculated by removing the slope from the prediction formula and adding the initial scores to residuals between the measured scores and predicted scores individually. Systematic error, MDC at the 95th percentile cutoff (MDC95), repeatability of the measures, and the change from the baseline to each time-point of intervention were assessed.The MDC95 was obtained for all 3 outcome measures and the range of values was as follows: RoM, 8.3° to 22.5°; Japanese version of the Patient-Rated Elbow Evaluation score, 17.6 to 30.6 points; and disability of the arm, shoulder, and hand questionnaire subscale: disability and symptoms score, 14.2 to 22.9 points.The efficacy of EMG-BF after elbow surgery was reflected in earlier initiation of elbow RoM after surgery and improvement in patient-reported upper limb function scores. The calculated MDC95 cut-offs could be used as reference values to assess the therapeutic effects of EMG-BF in individuals.

Differences between Japan and Taiwan in the treatment of pregnant women with depressive symptoms by omega-3 fatty acids: An open-label pilot study.

OBJECTIVES: Although safe approaches for improving depression in pregnancy are required and the efficacy of omega-3 polyunsaturated fatty acids (PUFAs) has been suggested, the amount of supplemental omega-3 PUFAs has varied among previous studies and adequate amount might be different among countries. The aim of this pilot study is to explore the feasibility of using 1800 mg of omega-3 PUFAs supplementation for our future double-blind, placebo-control trial, and to clarify the clinical difference and the similarity between two sites of Japan and Taiwan. METHODS: Pregnant women between 12 and 24 weeks' gestation with depressive symptoms were recruited. Participants were supplemented daily with omega-3 PUFAs capsules containing 1206 mg eicosapentaenoic acid and 609 mg docosahexaenoic acid for 12 weeks. The primary outcome was change in total score on the 17-item Hamilton Rating Scale for Depression (HAMD) at 12 weeks after supplementation. RESULTS: Eight pregnant women in Japan and five in Taiwan participated in the study. A substantial proportion of pregnant women reported high consumption of omega-3 supplements and dietary fish were excluded in Taiwan rather than in Japan sites. The decrease in HAMD score from baseline to 12 weeks after the start of the intervention was significantly larger in Japanese participants than in Taiwanese participants (Wilcoxon rank sum test; P = 0.045). DISCUSSION: The improvement of depressive symptoms was smaller at the Taiwan site than at the Japan site. Differences in psychopathology of recruited participants identified by self-rating scales might affect the degree of population heterogeneity and the treatment efficacy. A randomized-controlled trial is needed to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01948596.

The synchronized trial on expectant mothers with depressive symptoms by omega-3 PUFAs (SYNCHRO): Study protocol for a randomized controlled trial.

BACKGROUND: Maternal depression can be harmful to both mothers and their children. Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been investigated as an alternative intervention for pregnant women with depressive symptoms because of the supporting evidence from clinical trials in major depression, the safety advantage, and its anti-inflammatory and neuroplasticity effects. This study examines the efficacy of omega-3 PUFA supplementation for pregnant women with depressive symptoms in Taiwan and Japan, to provide evidence available for Asia. The rationale and protocol of this trial are reported here. METHODS: The Synchronized Trial on Expectant Mothers with Depressive Symptoms by Omega-3 PUFAs (SYNCHRO) is a multicenter, double-blind, parallel group, randomized controlled trial. Participants will be randomized to either the omega-3 PUFAs arm (1,200 mg eicosapentaenoic acid and 600 mg docosahexaenoic acid daily) or placebo arm. Primary outcome is total score on the Hamilton Rating Scale for Depression (HAMD) at 12 weeks after the start of the intervention. We will randomize 56 participants to have 90 % power to detect a 4.7-point difference in mean HAMD scores with omega-3 PUFAs compared with placebo. Because seafood consumption varies across countries and this may have a major effect on the efficacy of omega-3 PUFA supplementation, 56 participants will be recruited at each site in Taiwan and Japan, for a total number of 112 participants. Secondary outcomes include depressive symptoms at 1 month after childbirth, diagnosis of major depressive disorder, changes in omega-3 PUFAs concentrations and levels of biomarkers at baseline and at 12 weeks' follow-up, and standard obstetric outcomes. Data analyses will be by intention to treat. The trial was started in June 2014 and is scheduled to end in February 2018. DISCUSSION: The trial is expected to provide evidence that can contribute to promoting mental health among mothers and children in Asian populations. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02166424 . Registered 15 June 2014; University Hospital Medical Information Network (UMIN) Center: UMIN000017979. Registered 20 May 2015.

Relationship between serum isoflavone levels and disability-free survival among community-dwelling elderly individuals: nested case-control study of the Tsurugaya project.

BACKGROUND: The longer healthy life expectancy observed in Japan may be partly attributed to the Japanese diet. The researchers sought to examine whether serum isoflavone levels are associated with disability and death. METHODS: The researchers used a nested case-control study to compare serum isoflavones (daidzein, genistein, glycitein, and equol) levels between 165 participants that died or were certificated as disabled (cases) and 177 controls. Disability was defined by certification of long-term care insurance. Conditional logistic regression models were used to calculate the risk of isoflavones for the composite outcome. RESULTS: The proportion of cases was lower in the group with the highest levels of equol (34/91, 37%) compared with equol nonproducers (84/161, 52%). The risk of disability or death among equol producers remained reduced after adjusting for age and sex (odds ratio: 0.55, 95% confidence interval: 0.33-0.93). In a multivariate model, this risk was also unchanged (odds ratio: 0.51, 95% confidence interval: 0.27-0.96). There were no significant associations between daidzein, genistein, and glycitein with the composite endpoint. CONCLUSIONS: Higher serum equol levels, but not any other isoflavones, were inversely associated with the composite endpoint of disability and death. Although it cannot be concluded that equol per se has preventive effects on disability or death, higher equol levels appear associated with better health.

C-reactive protein (CRP) is a predictor of high medical-care expenditures in a community-based elderly population aged 70 years and over: the Tsurugaya project.

Because CRP is a strong independent predictor of various diseases, it was hypothesized that CRP may be a useful predictor or treatment target for medical-care expenditures. The aim of this study was to investigate the relationship between CRP and medical-care expenditures in a community-dwelling elderly population. This prospective cohort study was conducted including 925 Japanese subjects aged ≥70 years. A high-sensitivity CRP assay was used by applying the nephelometric method. Hospitalizations, outpatient visits, and expenditures were ascertained through computerized linkage with claims lodged between August 2002 and March 2008 with the Miyagi National Health Insurance (NHI) Association. Since medical-care expenditures were not normally distributed, the category of high medical-care expenditures (>75th percentile of medical-care expenditures: inpatient expenditures >$494/month; outpatient expenditure >$522/month; total expenditures >$1103/month) was used to examine the relation of CRP levels with medical-care expenditures. Multiple logistic regression analysis was used to examine the relationship between CRP cutoff points (low concentrations: <1.0mg/L; intermediate concentrations: 1.0-3.0mg/L; or high concentrations: ≥3.0 mg/L) and medical-care expenditures during 6 year-follow up period. After adjustment for potential confounding factors, a positive association of CRP with hospitalization, and total expenditures (p for trend=0.03 and 0.02, respectively) was found. An elevated baseline CRP level is an independent predictor of increases in prospective medical-care expenditures among community-dwelling elderly. Further study is required to clarify whether reducing CRP by intervention is a cost-effective measure.

Green tea consumption and the risk of incident functional disability in elderly Japanese: the Ohsaki Cohort 2006 Study.

BACKGROUND: Previous studies have reported that green tea consumption is associated with a lower risk of diseases that cause functional disability, such as stroke, cognitive impairment, and osteoporosis. Although it is expected that green tea consumption would lower the risk of incident functional disability, this has never been investigated directly. OBJECTIVE: The objective was to determine the association between green tea consumption and incident functional disability in elderly individuals. DESIGN: We conducted a prospective cohort study in 13,988 Japanese individuals aged ≥65 y. Information on daily green tea consumption and other lifestyle factors was collected via questionnaire in 2006. Data on functional disability were retrieved from the public Long-term Care Insurance database, in which subjects were followed up for 3 y. We used Cox proportional hazards regression analysis to investigate the association between green tea consumption and functional disability. RESULTS: The 3-y incidence of functional disability was 9.4% (1316 cases). The multiple-adjusted HR (95% CI) of incident functional disability was 0.90 (0.77, 1.06) among respondents who consumed 1-2 cups green tea/d, 0.75 (0.64, 0.88) for those who consumed 3-4 cups/d, and 0.67 (0.57, 0.79) for those who consumed ≥5 cups/d in comparison with those who consumed <1 cup/d (P-trend < 0.001). CONCLUSION: Green tea consumption is significantly associated with a lower risk of incident functional disability, even after adjustment for possible confounding factors.

Attenuating posttraumatic distress with omega-3 polyunsaturated fatty acids among disaster medical assistance team members after the Great East Japan Earthquake: the APOP randomized controlled trial.

BACKGROUND: On March 11, 2011, a magnitude 9.0 earthquake, the most powerful ever recorded in Japan, and a massive tsunami struck off the coast of the Sanriku region. A Disaster Medical Assistance Team, a mobile medical team with specialized training that is deployed during the acute phase of a disaster, was dispatched to areas with large-scale destruction and multiple injured and sick casualties. Previous studies have reported critical incident stress (i.e. posttraumatic stress disorder symptoms and depressive symptoms) among rescue workers as well as the need for screening and prevention for posttraumatic stress disorder. So far we have shown in an open trial that posttraumatic stress disorder symptoms in critically injured patients can be reduced by taking omega-3 fatty acids intended to stimulate hippocampal neurogenesis. METHOD/DESIGN: This study is designed to determine the effectiveness of attenuating posttraumatic distress with omega-3 polyunsaturated fatty acids among Disaster Medical Assistance Team members after the Great East Japan Earthquake, and is named the APOP randomized controlled trial which is currently ongoing. First, we will provide psycho-education on posttraumatic distress, which is common in responders to the Disaster Medical Assistance Team members deployed to the disaster area. Second, observational research will be conducted to evaluate critical incident stress following the completion of medical activities. Third, team members who provide consent to participate in the intervention research will be randomly divided into a group given an omega-3 fatty acid supplement and a group not given the supplements. Outcome will be evaluated at 12 weeks after the supplements are shipped to the team members. DISCUSSION: Measures that address critical incident stress in disaster responders are important, but there is no substantial evidence that links such measures with prevention of posttraumatic stress disorder. Thus, any confirmation through this study that the intake of omega-3 fatty acid supplements serves as a simple preventative measure for critical incident stress will be of great significance. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000005367.

Coffee consumption and mortality due to all causes, cardiovascular disease, and cancer in Japanese women.

Coffee contains various compounds that have recently been reported to exert beneficial health effects. However, the conclusion of its relation with mortality has not yet been reached. In this study, we aimed to investigate the associations between coffee consumption and all-cause and cause-specific mortality in Japan. We included 37,742 participants (18,287 men and 19,455 women) aged 40-64 y without a history of cancer, myocardial infarction, or stroke at baseline in our analysis, based on the Miyagi Cohort Study initiated in 1990. The outcomes were mortality due to all causes, cardiovascular disease (CVD), and cancer. During the 10.3 y of follow-up, 2454 participants died, including 426 due to CVD and 724 due to cancer. In women, the multivariate hazard ratios (HR) (95% CI) for all-cause mortality in participants who drank coffee never, occasionally, 1-2 cups (150-300 mL)/d, and > or =3 cups/d were 1.00, 0.88 (0.73-1.06), 0.82 (0.66-1.02), and 0.75 (0.53-1.05), respectively (P-trend = 0.04). For CVD mortality in women, the multivariate HR (95% CI) were 1.00, 0.56 (0.36-0.86), 0.48 (0.29-0.80), and 0.45 (0.20-1.03), respectively (P-trend = 0.006). Of the specific CVD diseases, there was a strong inverse association between coffee consumption and mortality due to coronary heart disease (CHD) in women (P-trend = 0.02) but not in men. Death due to cancer was not associated with coffee consumption in either men or women, except for colorectal cancer in women. Our results suggest that coffee may have favorable effects on morality due to all causes and to CVD, especially CHD, in women.

Association between green tea consumption and tooth loss: cross-sectional results from the Ohsaki Cohort 2006 Study.

OBJECTIVE: To examine the association between green tea consumption and tooth loss. METHODS: We analyzed cross-sectional data from the Ohsaki Cohort 2006 Study. Usable self-administered questionnaires about green tea consumption and tooth loss were returned from 25,078 persons (12,019 men and 13,059 women) aged 40 to 64 years in Japan. Multivariate logistic regression analysis was used to calculate odds ratios (ORs) for tooth loss using 3 cut-off points of 10, 20, and 25 teeth relative to each category of green tea consumption. RESULTS: Consumption of > or = 1 cup/day of green tea was significantly associated with decreased odds for tooth loss, and the association appeared to fit a threshold model. In men, the multivariate-adjusted ORs for tooth loss with a cut-off point of <20 teeth associated with different frequencies of green tea consumption were 1.00 (reference) for <1 cup/day, 0.82 (95% CI, 0.74-0.91) for 1-2 cups/day, 0.82 (95% CI, 0.73-0.92) for 3-4 cups/day, and 0.77 (95% CI, 0.66-0.89) for > or = 5 cups/day. The corresponding data for women and the results for cut-off points of 10 and 25 teeth were essentially the same. CONCLUSIONS: The present findings indicate an association of green tea consumption with decreased odds for tooth loss.

Effect of autogenic training on general improvement in patients with irritable bowel syndrome: a randomized controlled trial.

Autogenic training (AT) is a useful and comprehensive relaxation technique. However, no studies have investigated the effects of AT on irritable bowel syndrome (IBS). In this study we tested the hypothesis that AT improves symptoms of IBS. Twenty-one patients with IBS were randomly assigned to AT (n = 11, 5 male, 6 female) or control therapy (n = 10, 5 male, 5 female). AT patients were trained intensively, while the control therapy consisted of discussions about patients' meal habits and life styles. All patients answered a question related to adequate relief (AR) of IBS symptoms and four questionnaires: Self-induced IBS Questionnaire (SIBSQ), Self-reported Depression Scale (SDS), State-Trait Anxiety Inventory (STAI), and Medical Outcome Short Form 36 Health Survey (SF-36). The proportion of AR in the last AT session in the AT group (9/11, 81.8%) was significantly higher than that in the controls (3/10, 30.0%, Chi-square test, p = 0.048). Two subscales of the SF-36, i.e., social functioning and bodily pain, were significantly improved in the AT group (p < 0.05) as compared to the control group. Role emotional (p = 0.051) and general health (p = 0.068) showed a tendency for improvement in the AT group. AT may be useful in the treatment of IBS by enhancing self-control.

Green tea consumption is associated with lower psychological distress in a general population: the Ohsaki Cohort 2006 Study.

BACKGROUND: Although green tea or its constituents might reduce psychological stress, the relation between green tea consumption and psychological distress has not been investigated in a large-scale study. OBJECTIVE: Our aim was to clarify whether green tea consumption is associated with lower psychological distress. DESIGN: We analyzed cross-sectional data for 42,093 Japanese individuals aged > or =40 y from the general population. Information on daily green tea consumption, psychological distress as assessed by the Kessler 6-item psychological distress scale, and other lifestyle factors was collected by using a questionnaire. We used multiple logistic regression analyses adjusted for age, sex, history of disease, body mass index, cigarette smoking, alcohol consumption, time spent walking, dietary factors, social support, and participation in community activities to investigate the relation between green tea consumption and psychological distress. RESULTS: We classified 2774 (6.6%) of the respondents as having psychological distress (Kessler 6-item psychological distress scale > or =13/24). There was an inverse association between green tea consumption and psychological distress in a model adjusted for age and sex. Although the relation was largely attenuated when possible confounding factors were adjusted for, a statistically significant inverse association remained. The odds ratio (with 95% CI) of developing psychological distress among respondents who consumed >/=5 cups of green tea/d was 0.80 (0.70, 0.91) compared with those who consumed <1 cup/d. These relations persisted when respondents were stratified by social support subgroups or by activities in communities. CONCLUSION: Green tea consumption was inversely associated with psychological distress even after adjustment for possible confounding factors.

Green tea consumption is associated with depressive symptoms in the elderly.

BACKGROUND: Green tea is reported to have various beneficial effects (eg, anti-stress response and antiinflammatory effects) on human health. Although these functions might be associated with the development and progression of depressive symptoms, no studies have investigated the relation between green tea consumption and depressive symptoms in a community-dwelling population. OBJECTIVE: The aim of this study was to investigate the relations between green tea consumption and depressive symptoms in elderly Japanese subjects who widely consumed green tea. DESIGN: We conducted a cross-sectional study in 1058 community-dwelling elderly Japanese individuals aged >or=70 y. Green tea consumption was assessed by using a self-administered questionnaire, and depressive symptoms were evaluated by using the 30-item Geriatric Depression Scale with 2 cutoffs: 11 (mild and severe depressive symptoms) and 14 (severe depressive symptoms). If a participant was consuming antidepressants, he or she was considered to have depressive symptoms. RESULTS: The prevalence of mild and severe and severe depressive symptoms was 34.1% and 20.2%, respectively. After adjustment for confounding factors, the odds ratios (95% CI) for mild and severe depressive symptoms when higher green tea consumption was compared with green tea consumption of or=4 cups green tea/d (0.56; 95% CI: 0.39, 0.81) (P for trend: 0.001). Similar relations were also observed in the case of severe depressive symptoms. CONCLUSION: A more frequent consumption of green tea was associated with a lower prevalence of depressive symptoms in the community-dwelling older population.

Green tea consumption and the risk of liver cancer in Japan: the Ohsaki Cohort study.

OBJECTIVES: To investigate the association between green tea consumption and liver cancer incidence. METHODS: We prospectively followed 41,761 Japanese adults aged 40-79 years, without a history of cancer at the baseline or any missing data for green tea consumption frequency. Cox proportional hazards models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, alcohol drinking, smoking, the consumption of coffee, vegetables, dairy products, fruit, fish, and soybean. RESULTS: Over 9 years of follow-up, among 325,947 accrued person-years, the total incidence of liver cancer was 247 cases. We found that green tea consumption was inversely associated with the incidence of liver cancer. In men, the multivariate-adjusted HRs (95% CIs) for liver cancer incidence with different green tea consumption categories were 1.00 (reference) for <1 cup/day, 0.83 (0.53-1.30) for 1-2 cups/day, 1.11 (0.73-1.68) for 3-4 cups/day, and 0.63 (0.41-0.98) for >/=5 cups/day (p for trend = 0.11). The corresponding data among women were 1.00 (reference), 0.68 (0.35-1.31), 0.79 (0.44-1.44), 0.50 (0.27-0.90) (p for trend = 0.04). CONCLUSIONS: Green tea consumption is associated with a reduced risk of liver cancer incidence.

Green tea consumption and hematologic malignancies in Japan: the Ohsaki study.

Several biologic studies have reported that green tea constituents have antitumor effects on hematologic malignancies. However, the effects in humans are uncertain. The authors used data from the Ohsaki National Health Insurance Cohort Study in Japan to evaluate the association between green tea consumption and the risk of hematologic malignancies. Study participants were 41,761 Japanese adults aged 40-79 years without a history of cancer at baseline who answered a food frequency questionnaire survey in 1994. During 9 years of follow-up beginning in 1995, the authors documented 157 hematologic malignancies, including 119 cases of lymphoid neoplasms and 36 cases of myeloid neoplasms. Hazard ratios were calculated by using the Cox proportional hazards regression model. Risk of hematologic malignancies was inversely associated with green tea consumption. The multivariate-adjusted hazard ratio of hematologic malignancies for 5 cups/day or more compared with less than 1 cup/day of green tea was 0.58 (95% confidence interval: 0.37, 0.89). The corresponding risk estimate was 0.52 (95% confidence interval: 0.31, 0.87) for lymphoid neoplasms and 0.76 (95% confidence interval: 0.32, 1.78) for myeloid neoplasms. This inverse association was consistent across sex and body mass index strata. In conclusion, green tea consumption was associated with a lower risk of hematologic malignancies.

Green tea and death from pneumonia in Japan: the Ohsaki cohort study.

BACKGROUND: Experimental and animal studies have shown the activities of catechins, the main constituents of green tea, against infectious agents. No data are available on the association between green tea consumption and the risk of pneumonia in humans. OBJECTIVE: We examined the association between green tea consumption and death from pneumonia in humans. DESIGN: We conducted a population-based cohort study, with follow-up from 1995 to 2006. The participants were National Health Insurance beneficiaries in Japan (19,079 men and 21,493 women aged 40-79 y). We excluded participants for whom data on green tea consumption frequency were missing or who had reported a history of cancer, myocardial infarction, stroke, and extreme daily energy intake at baseline. We used Cox proportional hazards regression analysis to calculate hazard ratios (HRs) and their 95% CIs for death from pneumonia according to green tea consumption. RESULTS: Over 12 y of follow-up, we documented 406 deaths from pneumonia. In women, the multivariate HRs of death from pneumonia that were associated with different frequencies of green tea consumption were 1.00 (reference) for <1 cup/d, 0.59 (95% CI: 0.36, 0.98) for 1-2 cups/d, 0.55 (95% CI: 0.33, 0.91) for 3-4 cups/d, and 0.53 (95% CI: 0.33, 0.83) for > or =5 cups/d, respectively (P for trend: 0.008). In men, no significant association was observed. CONCLUSION: Green tea consumption was associated with a lower risk of death from pneumonia in Japanese women.

Case-control study of green tea consumption and the risk of endometrial endometrioid adenocarcinoma.

OBJECTIVE: To investigate the association between green tea consumption and the risk of endometrial cancer restricted to endometrial endometrioid adenocarcinoma (EEA) using a case-control design in Japan. METHODS: The cases were 152 patients with histopathologically diagnosed EEA, and the controls were 285 healthy women who were matched for age and area of residence with individual cases. The subjects completed a questionnaire regarding health-related lifestyle and reproductive history, and a food frequency questionnaire. Odds ratios (ORs) of EEA for frequency of green tea consumption were calculated by conditional logistic regression analysis. RESULTS: We observed a significant inverse association between green tea consumption and the risk of EEA with a dose-response relationship. The multivariate-adjusted OR of EEA was 0.77 (95% CI: 0.37-1.58) for those in the second quartile of green tea consumption (5-6 cups/week-1 cup/day), 0.61 (0.30-1.23) in the third quartile (2-3 cups/day), and 0.33 (0.15-0.75) in the highest quartile (> or = 4 cups/day), as referenced with those in the lowest quartile (< or = 4 cups/week; p for trend = 0.007). This inverse association was consistently observed regardless of the presence or absence of factors such as obesity and menopause. CONCLUSION: Green tea consumption may be associated with a lower risk of EEA.

Coffee consumption and the risk of oral, pharyngeal, and esophageal cancers in Japan: the Miyagi Cohort Study.

An inverse association between coffee consumption and the risk of oral, pharyngeal, and esophageal cancers has been suggested in case-control studies, but few results from prospective studies are available. Data from the Miyagi Cohort Study in Japan were used to clarify the association between coffee consumption and the risk of these cancers. Information about coffee consumption was obtained from self-administered food frequency questionnaires in 1990. Among 38,679 subjects aged 40-64 years with no previous history of cancer, 157 cases of oral, pharyngeal, and esophageal cancers were identified during 13.6 years of follow-up. Hazard ratios were estimated by the Cox proportional hazards regression model. The risk of oral, pharyngeal, and esophageal cancers was inversely associated with coffee consumption. The multivariate-adjusted hazard ratio of these cancers for > or =1 cups of coffee per day compared with no consumption was 0.51 (95% confidence interval: 0.33, 0.77). This inverse association was consistent regardless of sex and cancer site and was observed both for subjects who did not drink or smoke and for those who currently drank or smoked at baseline. In conclusion, coffee consumption was associated with a lower risk of oral, pharyngeal, and esophageal cancers, even in the group at high risk of these cancers.