Effectiveness and tolerability of brivaracetam in patients with epilepsy stratified by comorbidities and etiology in the real world: 12-month subgroup data from the international EXPERIENCE pooled analysis.

OBJECTIVE: To assess the effectiveness and tolerability of brivaracetam (BRV) in adults with epilepsy by specific comorbidities and epilepsy etiologies. METHODS: EXPERIENCE/EPD332 was a pooled analysis of individual patient records from several non-interventional studies of patients with epilepsy initiating BRV in clinical practice. Outcomes included ≥ 50% reduction from baseline in seizure frequency, seizure freedom (no seizures within prior 3 months), continuous seizure freedom (no seizures since baseline), BRV discontinuation, and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months. Analyses were performed for all adult patients (≥ 16 years of age) and stratified by comorbidity and by etiology at baseline (patients with cognitive/learning disability [CLD], psychiatric comorbidity, post-stroke epilepsy, brain tumor-related epilepsy [BTRE], and traumatic brain injury-related epilepsy [TBIE]). RESULTS: At 12 months, ≥ 50% seizure reduction was achieved in 35.6% (n = 264), 38.7% (n = 310), 41.7% (n = 24), 34.1% (n = 41), and 50.0% (n = 28) of patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE, respectively; and continuous seizure freedom was achieved in 5.7% (n = 318), 13.7% (n = 424), 29.4% (n = 34), 11.4% (n = 44), and 13.8% (n = 29), respectively. During the study follow-up, in patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE, 37.1% (n = 403), 30.7% (n = 605), 33.3% (n = 51), 39.7% (n = 68), and 27.1% (n = 49) of patients discontinued BRV, respectively; and TEAEs since prior visit at 12 months were reported in 11.3% (n = 283), 10.0% (n = 410), 16.7% (n = 36), 12.5% (n = 48), and 3.0% (n = 33), respectively. CONCLUSIONS: BRV as prescribed in the real world is effective and well tolerated among patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE.

Single-agent ibrutinib in RESONATE-2™ and RESONATE™ versus treatments in the real-world PHEDRA databases for patients with chronic lymphocytic leukemia.

After analyzing treatment patterns in chronic lymphocytic leukemia (CLL) (objective 1), we investigated the relative effectiveness of ibrutinib versus other commonly used treatments (objective 2) in patients with treatment-naïve and relapsed/refractory CLL, comparing patient-level data from two randomized registration trials with two real-world databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using a multivariate Cox proportional hazards model, adjusted for differences in baseline characteristics. Rituximab-containing regimens were often prescribed in clinical practice. The most frequently prescribed regimens were fludarabine + cyclophosphamide + rituximab (FCR, 29.3%), bendamustine + rituximab (BR, 17.7%), and other rituximab-containing regimens (22.0%) in the treatment-naïve setting (n = 604), other non-FCR/BR rituximab-containing regimens (38.7%) and non-rituximab-containing regimens (28.5%) in the relapsed/refractory setting (n = 945). Adjusted HRs (95% CI) for progression-free survival (PFS) and overall survival (OS), respectively, with ibrutinib versus real-world regimens were 0.23 (0.14-0.37; p < 0.0001) and 0.40 (0.22-0.76; p = 0.0048) in the treatment-naïve setting, and 0.21 (0.16-0.27; p < 0.0001) and 0.29 (0.21-0.41; p < 0.0001) in the relapsed/refractory setting. When comparing real-world use of ibrutinib (n = 53) versus other real-world regimens in relapsed/refractory CLL (objective 3), adjusted HRs (95% CI) were 0.37 (0.22-0.63; p = 0.0003) for PFS and 0.53 (0.27-1.03; p < 0.0624) for OS. This adjusted analysis, based on nonrandomized patient data, suggests ibrutinib to be more effective than other commonly used regimens for CLL.

Adjusted comparison of daratumumab monotherapy versus real-world historical control data from the Czech Republic in heavily pretreated and highly refractory multiple myeloma patients.

OBJECTIVES: We conducted an adjusted comparison of progression-free survival (PFS) and overall survival (OS) for daratumumab monotherapy versus standard of care, as observed in a real-world historical cohort of heavily pretreated multiple myeloma patients from Czech Republic. METHODS: Using longitudinal chart data from the Registry of Monoclonal Gammopathies (RMG) of the Czech Myeloma Group, patient-level data from the RMG was pooled with pivotal daratumumab monotherapy studies (GEN501 and SIRIUS; 16 mg/kg). RESULTS: From the RMG database, we identified 972 treatment lines in 463 patients previously treated with both a proteasome inhibitor and an immunomodulatory drug. Treatment initiation dates for RMG patients were between March 2006 and March 2015. The most frequently used treatment regimens were lenalidomide-based regimens (33.4%), chemotherapy (18.1%), bortezomib-based regimens (13.6%), thalidomide-based regimens (8.0%), and bortezomib plus thalidomide (5.3%). Few patients were treated with carfilzomib-based regimens (2.5%) and pomalidomide-based regimens (2.4%). Median observed PFS for daratumumab and the RMG cohort was 4.0 and 5.8 months (unadjusted hazard ratio [HR], 1.14; 95% confidence interval [CI], 0.94-1.39), respectively, and unadjusted median OS was 20.1 and 11.9 months (unadjusted HR, 0.61; 95% CI, 0.48-0.78), respectively. Statistical adjustments for differences in baseline characteristics were made using patient-level data. The adjusted HRs (95% CI) for PFS and OS for daratumumab versus the RMG cohort were 0.79 (0.56-1.12; p = .192) and 0.33 (0.21-0.52; p < .001), respectively. CONCLUSIONS: Adjusted comparisons between trial data and historical cohorts can provide useful insights to clinicians and reimbursement decision makers on relative treatment efficacies in the absence of head-to-head comparison studies for daratumumab monotherapy.

PHEDRA: using real-world data to analyze treatment patterns and ibrutinib effectiveness in hematological malignancies.

AIM: PHEDRA (Platform for Haematology in EMEA: Data for Real World Analysis) is a unique, noninterventional project based on secondary data collection from real-world (RW) patient-level (health record) databases to understand treatment patterns in hematological malignancies. It compares ibrutinib's effectiveness with alternative treatments using RW data (RWD) and randomized clinical trials data. MATERIALS & METHODS: RWD are cleaned, validated, harmonized into a Common Data Model, and analyzed statistically alongside randomized clinical trial data. Treatment outcomes include overall and progression-free survival. RESULTS: To date, RWD (four databases) are available for 2840 patients in three indications, collected between 1990 and 2017. CONCLUSION: PHEDRA is an innovative approach to generate evidence to inform optimal treatment decisions in RW settings.

Incidence of intraoperative hypersensitivity reactions: a registry analysis: a registry analysis.

BACKGROUND: Previously reported incidences for intraoperative hypersensitivity reactions vary more than 15-fold. The goal was to determine the incidence of intraoperative hypersensitivity events at a U.S. surgical center. METHODS: With institutional review board (Cleveland, Ohio) approval and waiver of written/informed consent, the anesthesia records of adult patients undergoing noncardiac surgery from 2005 to 2011 at the Cleveland Clinic were queried using a novel electronic search protocol developed to identify potential hypersensitivity reactions: cardiovascular collapse defined as systolic arterial blood pressure less than 50 mmHg; administration of epinephrine; administration of diphenhydramine; physician comments in the anesthesia record suggestive of hypersensitivity reactions; laboratory tests for histamine, tryptase, or immunoglobulin-E within 24 h of surgery; and International Classification of Diseases, Ninth Revision, codes suggestive of hypersensitivity reactions. Each electronically identified candidate chart was evaluated by an adjudication committee. Hypersensitivity reactions were graded on a 5-point severity scale. From these data, the authors determined the proportion of operations having adjudicated hypersensitivity reactions, and calculated the 95% exact binomial CI. RESULTS: Among 178,746 records, 4,008 charts were identified by the search strategies. After adjudication, 264 hypersensitivity cases were identified. The overall incidence of hypersensitivity reactions was 1:677 surgeries, corresponding to 15 (95% CI, 13 to 17) cases per 10,000 operations. The incidence of severe hypersensitivity reactions (grades 3 to 5) was 1:4,583, corresponding to 2 (95% CI, 2 to 3) cases per 10,000 operations. CONCLUSIONS: The incidence of severe hypersensitivity reactions was similar to previous reports. However, the overall incidence of hypersensitivity reactions was much greater than reported elsewhere, possibly because of a comprehensive search strategy.

A systematic review of reliability and objective criterion-related validity of physical activity questionnaires.

Physical inactivity is one of the four leading risk factors for global mortality. Accurate measurement of physical activity (PA) and in particular by physical activity questionnaires (PAQs) remains a challenge. The aim of this paper is to provide an updated systematic review of the reliability and validity characteristics of existing and more recently developed PAQs and to quantitatively compare the performance between existing and newly developed PAQs.A literature search of electronic databases was performed for studies assessing reliability and validity data of PAQs using an objective criterion measurement of PA between January 1997 and December 2011. Articles meeting the inclusion criteria were screened and data were extracted to provide a systematic overview of measurement properties. Due to differences in reported outcomes and criterion methods a quantitative meta-analysis was not possible.In total, 31 studies testing 34 newly developed PAQs, and 65 studies examining 96 existing PAQs were included. Very few PAQs showed good results on both reliability and validity. Median reliability correlation coefficients were 0.62-0.71 for existing, and 0.74-0.76 for new PAQs. Median validity coefficients ranged from 0.30-0.39 for existing, and from 0.25-0.41 for new PAQs.Although the majority of PAQs appear to have acceptable reliability, the validity is moderate at best. Newly developed PAQs do not appear to perform substantially better than existing PAQs in terms of reliability and validity. Future PAQ studies should include measures of absolute validity and the error structure of the instrument.

Television viewing and incident cardiovascular disease: prospective associations and mediation analysis in the EPIC Norfolk Study.

BACKGROUND: Although television viewing time is detrimentally associated with intermediate cardiovascular risk factors, the relationship with incident total (i.e. combined fatal and non-fatal) cardiovascular disease (CVD), non-fatal CVD and coronary heart disease is largely unknown. This study examined whether television viewing time is associated with these three outcomes, independently of physical activity energy expenditure and other confounding variables. METHODOLOGY/PRINCIPAL FINDINGS: A population-based cohort of 12,608 men and women (aged 61.4±9.0), free from stroke, myocardial infarction and cancer at baseline in 1998-2000 were followed up until 2007 (6.9±1.9 years). Participants self-reported education, smoking, alcohol use, antihypertensive, lipid lowering and antidepressant medication, disease history, total energy intake, sleep duration, physical activity and television viewing. BMI, waist circumference, blood pressure, triglycerides, HDL cholesterol and glycated haemoglobin (HbA(1c)) were measured by standardized procedures; a clustered metabolic risk score was constructed. Every one hour/day increase in television viewing was associated with an increased hazard for total (HR = 1.06, 95%CI = 1.03-1.08; 2,620 cases), non-fatal CVD (HR = 1.06, 95%CI = 1.03-1.09; 2,134 cases), and coronary heart disease (HR = 1.08, 95%CI = 1.03-1.13; 940 cases), independent of gender, age, education, smoking, alcohol, medication, diabetes status, CVD family history, sleep duration and physical activity energy expenditure. Energy intake, BMI, waist circumference, blood pressure, triglycerides, HDL cholesterol, HbA(1c) and the clustered metabolic risk score only partially mediated these associations. CONCLUSIONS: These results indicate that the most prevalent leisure time (sedentary) behaviour, television viewing, independently contributes to increased CVD risk. Recommendations on reducing television viewing time should be considered.

The association of education with body mass index and waist circumference in the EPIC-PANACEA study.

BACKGROUND: To examine the association of education with body mass index (BMI) and waist circumference (WC) in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHOD: This study included 141,230 male and 336,637 female EPIC-participants, who were recruited between 1992 and 2000. Education, which was assessed by questionnaire, was classified into four categories; BMI and WC, measured by trained personnel in most participating centers, were modeled as continuous dependent variables. Associations were estimated using multilevel mixed effects linear regression models. RESULTS: Compared with the lowest education level, BMI and WC were significantly lower for all three higher education categories, which was consistent for all countries. Women with university degree had a 2.1 kg/m2 lower BMI compared with women with lowest education level. For men, a statistically significant, but less pronounced difference was observed (1.3 kg/m2). The association between WC and education level was also of greater magnitude for women: compared with the lowest education level, average WC of women was lower by 5.2 cm for women in the highest category. For men the difference was 2.9 cm. CONCLUSION: In this European cohort, there is an inverse association between higher BMI as well as higher WC and lower education level. Public Health Programs that aim to reduce overweight and obesity should primarily focus on the lower educated population.

Physical activity and gain in abdominal adiposity and body weight: prospective cohort study in 288,498 men and women.

BACKGROUND: The protective effect of physical activity (PA) on abdominal adiposity is unclear. OBJECTIVE: We examined whether PA independently predicted gains in body weight and abdominal adiposity. DESIGN: In a prospective cohort study [the EPIC (European Prospective Investigation into Cancer and Nutrition)], we followed 84,511 men and 203,987 women for 5.1 y. PA was assessed by a validated questionnaire, and individuals were categorized into 4 groups (inactive, moderately inactive, moderately active, and active). Body weight and waist circumference were measured at baseline and self-reported at follow-up. We used multilevel mixed-effects linear regression models and stratified our analyses by sex with adjustments for age, smoking status, alcohol consumption, educational level, total energy intake, duration of follow-up, baseline body weight, change in body weight, and waist circumference (when applicable). RESULTS: PA significantly predicted a lower waist circumference (in cm) in men (ß = -0.045; 95% CI: -0.057, -0.034) and in women (ß = -0.035; 95% CI: -0.056, -0.015) independent of baseline body weight, baseline waist circumference, and other confounding factors. The magnitude of associations was materially unchanged after adjustment for change in body weight. PA was not significantly associated with annual weight gain (in kg) in men (ß = -0.008; 95% CI: -0.02, 0.003) and women (ß = -0.01; 95% CI: -0.02, 0.0006). The odds of becoming obese were reduced by 7% (P < 0.001) and 10% (P < 0.001) for a one-category difference in baseline PA in men and women, respectively. CONCLUSION: Our results suggest that a higher level of PA reduces abdominal adiposity independent of baseline and changes in body weight and is thus a useful strategy for preventing chronic diseases and premature deaths.

Television viewing time independently predicts all-cause and cardiovascular mortality: the EPIC Norfolk study.

BACKGROUND: Television viewing (TV), a highly prevalent behaviour, is associated with higher cardiovascular risk independently of physical activity. The relationship with mortality, however, is relatively unknown. METHODS: We examined the prospective relationship between TV time and all-cause, cardiovascular and cancer mortality in a population-based cohort [The European Prospective Investigation into Cancer and Nutrition (EPIC), Norfolk] of 13 197 men and women {age [SD (standard deviation)]: 61.5 ± 9.0 years}. Participants were free from stroke, myocardial infarction and cancer at baseline in 1998-2000 and were followed up for death ascertainment until 2009 (9.5 ± 1.6 years). TV time, total physical activity energy expenditure (PAEE), education level, smoking status, alcohol consumption, anti-hypertensive and lipid-lowering medication use, participant and family history of disease and total energy intake were self-reported; height and weight were measured by standardized procedures. Hazard ratios (HRs) [95% confidence interval (CI)] for mortality were estimated per 1-h/day increase in TV. RESULTS: Each 1-h/day increase in TV time was associated with increased hazard of all-cause (HR = 1.04, 95% CI = 1.01-1.09; 1270 deaths) and cardiovascular (HR = 1.07, 95% CI = 1.01-1.15; 373 deaths), but not cancer mortality (HR = 1.04, 95% CI = 0.98-1.10; 570 deaths). This was independent of gender, age, education, smoking, alcohol, medication, diabetes history, family history of cardiovascular disease and cancer, body mass index (BMI) and PAEE. They were similar when stratified by gender, age, education, BMI and PAEE. The population-attributable fraction for all-cause mortality comparing the highest TV tertile (>3.6 h/day) with the lowest (<2.5 h/day) was 5.4%. CONCLUSIONS: These findings suggest that public health recommendations should consider advising a reduction in TV time, a predominant leisure activity in modern society, in addition to advocating physical activity.

The association between physical activity in different domains of life and risk of osteoporotic fractures.

A large body of epidemiological evidence suggests an inverse relationship between physical activity and risk of fractures. However, it is unclear how this association varies according to the domain of life in which the activity is undertaken. In this analysis of the European Prospective Investigation of Cancer-Norfolk study, we assessed total and domain-specific physical activity using a validated questionnaire (EPAQ2) in 14,903 participants (6514 men, mean age 62 year) who also underwent quantitative ultrasound of the heel. After a median follow-up of 7.5 years, there were 504 fractures of which 164 were hip fractures. In multivariable linear regression analysis, broadband ultrasound attenuation (BUA) was positively associated with total and leisure-time activities while showing no association with transportation and work activities. Home activities were associated with a lower BUA among younger participants. In multivariable Cox proportional-hazards models, moderate activities at home and in leisure time were associated with lower hip fracture risk among women (hazard ratios [HR] 0.51 and 0.55, p value 0.02 and 0.03, respectively). Among men, leisure-time activities were associated with lower risk of hip fracture (HR=0.58; p for trend<0.001) whereas activities at home were associated with higher risk of any fracture (HR=1.25; p for trend=0.008). Walking for leisure or transport was associated with lower risk of fracture in both men and women. Multivariable fractional polynomial modelling showed a U-shaped association between home activities and fracture risk especially among women. This study suggests that different domains of physical activity may relate differently to fracture risk and these relationships may vary by sex.

Validation of the historical adulthood physical activity questionnaire (HAPAQ) against objective measurements of physical activity.

BACKGROUND: Lifetime physical activity energy expenditure (PAEE) is an important determinant of risk for many chronic diseases but remains challenging to measure. Previously reported historical physical activity (PA) questionnaires appear to be reliable, but their validity is less well established. METHODS: We sought to design and validate an historical adulthood PA questionnaire (HAPAQ) against objective PA measurements from the same individuals. We recruited from a population-based cohort in Cambridgeshire, UK, (Medical Research Council Ely Study) in whom PA measurements, using individually calibrated heart rate monitoring, had been obtained in the past, once between 1994 and 1996 and once between 2000 and 2002. 100 individuals from this cohort attended for interview. Historical PA within the domains of home, work, transport, sport and exercise was recalled using the questionnaire by asking closed questions repeated for several discrete time periods from the age of 20 years old to their current age. The average PAEE from the 2 periods of objective measurements was compared to the self-reported data from the corresponding time periods in the questionnaire. RESULTS: Significant correlations were observed between HAPAQ-derived and objectively measured total PAEE for both time periods (Spearman r = 0.44; P < 0.001). Similarly, self-reported time spent in vigorous PA was significantly correlated with objective measurements of vigorous PA (Spearman r = 0.40; P < 0.001). CONCLUSIONS: HAPAQ demonstrates convergent validity for total PAEE and vigorous PA. This instrument will be useful for ranking individuals according to their past PA in studies of chronic disease aetiology, where activity may be an important underlying factor contributing to disease pathogenesis.

Estimating physical activity energy expenditure, sedentary time, and physical activity intensity by self-report in adults.

BACKGROUND: Few questionnaires that assess usual physical activity have been reported to be valid for all different subdimensions of physical activity. OBJECTIVE: The objective was to assess the validity and reliability of the Recent Physical Activity Questionnaire (RPAQ), which assesses usual physical activity (PA) in 4 domains (work, travel, recreation, and domestic life). DESIGN: Total energy expenditure (TEE) was measured for 14 d by using the doubly labeled water technique combined with a measure of resting metabolic rate to yield PA energy expenditure (PAEE) in 25 men and 25 women. Simultaneously, intensity of activity was measured by using combined heart rate and movement sensing for 11 d. Repeatability of the RPAQ was assessed in an independent sample of 71 women and 60 men aged 31-57 y. RESULTS: Estimated TEE and PAEE were significantly associated with criterion measures (TEE: r = 0.67; PAEE: r = 0.39) with mean (+/-SD) biases of -3452 +/- 2025 kJ/d and -13 +/- 24 kJ d(-1) kg(-1). The correlation between self-reported and measured time spent was significant for vigorous PA (r = 0.70) and marginally insignificant for sedentary time (r = 0.27, P = 0.06). The mean biases were relatively small for sedentary time and vigorous PA: 0.7 +/- 2.8 h/d and -12 +/- 24 min/d, respectively. The intraclass correlation coefficient for repeatability of total PAEE (kJ/d) was 0.76 (P < 0.0001). CONCLUSION: The RPAQ is the first questionnaire with demonstrated validity for ranking individuals according to their time spent at vigorous-intensity activity and overall energy expenditure.

Smoking and body fatness measurements: a cross-sectional analysis in the EPIC-PANACEA study.

OBJECTIVE: The present study investigates the cross-sectional relationship between tobacco smoking and body fatness. METHODS: This cross-sectional study consisted of 469,543 men and women who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study between 1992 and 2000 providing anthropometric measurements and information on smoking. Adjusted multilevel mixed-effects linear regression models were used to assess the association between smoking and body fat mass. RESULTS: The analyses showed that BMI and WC were positively associated with smoking intensity in current smokers but negatively associated with time since quitting in former smokers. When compared to never smokers, average current smokers (17 and 13 cig/day for men and women, respectively) showed a lower BMI. When average former smokers (men and women who had stopped smoking for 16 and 15 years, respectively) were compared to never smokers, higher BMI and WC were observed in men, whereas no significant associations were observed in women. CONCLUSIONS: This cross-sectional study suggests that smoking may be associated with body fatness and fat distribution. Although our findings cannot establish cause and effect, they suggest that providing information and support to those who want to stop may help in preventing weight gain and therefore weaken a barrier against stopping smoking.

Randomized controlled trial of the efficacy of aerobic exercise in reducing metabolic risk in healthy older people: The Hertfordshire Physical Activity Trial.

BACKGROUND: While there are compelling observational data confirming that individuals who exercise are healthier, the efficacy of aerobic exercise interventions to reduce metabolic risk and improve insulin sensitivity in older people has not been fully elucidated. Furthermore, while low birth weight has been shown to predict adverse health outcomes later in life, its influence on the response to aerobic exercise is unknown. Our primary objective is to assess the efficacy of a fully supervised twelve week aerobic exercise intervention in reducing clustered metabolic risk in healthy older adults. A secondary objective is to determine the influence of low birth weight on the response to exercise in this group. METHODS/DESIGN: We aim to recruit 100 participants born between 1931-1939, from the Hertfordshire Cohort Study and randomly assign them to no intervention or to 36 fully supervised one hour sessions on a cycle ergometer, over twelve weeks. Each participant will undergo detailed anthropometric and metabolic assessment pre- and post-intervention, including muscle biopsy, magnetic resonance imaging and spectroscopy, objective measurement of physical activity and sub-maximal fitness testing. DISCUSSION: Given the extensive phenotypic characterization, this study will provide valuable insights into the mechanisms underlying the beneficial effects of aerobic exercise as well as the efficacy, feasibility and safety of such interventions in this age group. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN60986572.

Relationship between subdomains of total physical activity and mortality.

PURPOSE: The purpose of this study was to describe the association of the overall and domain-specific physical activity on all-cause and cardiovascular mortality. A large body of epidemiological evidence suggests a strong and consistent inverse association between physical activity and mortality risk. However, it is unclear how this association varies according to the domain of life in which the activity takes place. METHODS: In an English population-based cohort of 14,903 participants (mean age = 63 yr), total and domain-specific physical activity was assessed using a validated questionnaire (EPAQ2). After a median follow-up of 7 yr, there were 1128 deaths, with 370 from cardiovascular disease. RESULTS: The relative risks (95% confidence interval) for all-cause mortality due to physical activity undertaken at home, during exercise, at work, for transport, and in total were 0.81 (0.66-0.99), 0.66 (0.54-0.80), 0.84 (0.55-1.30), 0.82 (0.67-1.00), and 0.77 (0.61-0.98), respectively, after adjustment for baseline age, sex, social class, alcohol consumption, smoking status, history of diabetes, history of cancer, and history of cardiovascular disease and stroke. Cardiovascular mortality was inversely associated with physical activity undertaken at home (P for trend = 0.03), during exercise (P for trend = 0.001), and in total (P for trend = 0.007). The results were unchanged after excluding individuals with a history of heart disease, stroke, and cancer at baseline and those who died within the first 2 yr of follow-up. CONCLUSIONS: In this study, physical activities at home and during exercise are associated with lower risk of mortality, whereas occupational and transportation-related activities are not. Promoting the potential benefits of physical activity undertaken at home and during exercise may be an important public health message for aging populations.

Anthropometric characteristics and non-Hodgkin's lymphoma and multiple myeloma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND: The incidences of non-Hodgkin's lymphoma and multiple myeloma are increasing steadily. It has been hypothesized that this may be due, in part, to the parallel rising prevalence of obesity. It is biologically plausible that anthropometric characteristics can infuence the risk of non-Hodgkin's lymphoma and multiple myeloma. DESIGN AND METHODS: In the context of the European Prospective Investigation into Cancer and Nutrition (EPIC), anthropometric characteristics were assessed in 371,983 cancer-free individuals at baseline. During the 8.5 years of follow-up, 1,219 histologically confirmed incident cases of non-Hodgkin's lymphoma and multiple myeloma occurred in 609 men and 610 women. Gender-specific proportional hazards models were used to estimate relative risks and 95% confidence intervals (95% CI) of development of non-Hodgkin's lymphoma and multiple myeloma in relation to the anthropometric characteristics. RESULTS: Height was associated with overall non-Hodgkin's lymphoma and multiple myeloma in women (RR 1.50, 95% CI 1.14-1.98) for highest versus lowest quartile; p-trend < 0.01) but not in men. Neither obesity (weight and body mass index) nor abdominal fat (waist-to-hip ratio, waist or hip circumference) measures were positively associated with overall non-Hodgkin's lymphoma and multiple myeloma. Relative risks for highest versus lowest body mass index quartile were 1.09 (95% CI 0.85-1.38) and 0.92 (95% CI 0.71-1.19) for men and women, respectively. Women in the upper body mass index quartile were at greater risk of diffuse large B-cell lymphoma (RR 2.18, 95% CI 1.05-4.53) and taller women had an elevated risk of follicular lymphoma (RR 1.25, 95% CI 0.59-2.62). Among men, height and body mass index were non-significantly, positively related to follicular lymphoma. Multiple myeloma risk alone was elevated for taller women (RR 2.34, 95% CI 1.29-4.21) and heavier men (RR 1.77, 95% CI 1.02-3.05). CONCLUSIONS: The EPIC analyses support an association between height and overall non-Hodgkin's lymphoma and multiple myeloma among women and suggest heterogeneous subtype associations. This is one of the first prospective studies focusing on central adiposity and non-Hodgkin's lymphoma subtypes.

Time spent being sedentary and weight gain in healthy adults: reverse or bidirectional causality?

BACKGROUND: Whether obesity is a cause or a consequence of a sedentary lifestyle has not yet been fully elucidated, which leaves uncertainty about the direction of causality. OBJECTIVE: We aimed to assess the longitudinal associations between objectively measured time spent being sedentary (sedentary time) and obesity indicators. DESIGN: The study was a prospective, population-based cohort study in 393 middle-aged healthy whites (n = 176 M, 217 F). Sedentary time (% of daytime hours) was measured by individually calibrated monitoring of the heart rate. Body weight (BW), body mass index (BMI), and waist circumference (WC) were assessed by standard clinical procedures. Fat mass (FM) was assessed with bioimpedance. All measurements were collected at baseline and at 5.6-y follow-up. RESULTS: At baseline, sedentary time was significantly correlated with FM (partial r = 0.10, P = 0.043) and WC (partial r = 0.11, P = 0.027) after adjustment for sex and age. At follow-up, sedentary time was significantly correlated with BW (partial r = 0.19, P < 0.0001), BMI (partial r = 0.20, P < 0.0001), WC (partial r = 0.15, P = 0.003), and FM (partial r = 0.19, P < 0.0001). Sedentary time did not predict any of the obesity indicators at follow-up. In contrast, BW (beta = 0.33; 95% CI: 0.15, 0.50), BMI (1.10; 0.58, 1.63), FM (0.59; 0.11, 0.40), and WC (0.44; 0.23, 0.66) predicted sedentary time at follow-up after adjustment for sex, baseline age, baseline sedentary time, baseline physical activity energy expenditure, and follow-up time. CONCLUSION: BMI, FM, and WC may predict sedentary time, but our results do not suggest that sedentary time predicts future obesity.

Tobacco smoking, alcohol drinking and non-Hodgkin's lymphoma: A European multicenter case-control study (Epilymph).

To study the role of tobacco smoking and alcohol drinking in the etiology of non-Hodgkin's lymphoma (NHL), we conducted a multicenter case-control study in Spain, France, Germany, Italy, Ireland and Czech Republic between 1998 and 2004, which included 1,742 cases of NHL and 2,465 controls matched on age, sex and recruitment area. Tobacco smoking was not associated with the risk of NHL overall or with risk of specific histological subtypes. Similarly, there was no association between alcohol drinking and the risk of NHL overall or across histological subtypes. However, a protective effect of alcohol drinking was observed among men (OR = 0.76, 95% CI = 0.62-0.93) and in non-Mediterranean countries (OR = 0.73, 95% CI = 0.61-0.86). There was no evidence of interaction between alcohol drinking and tobacco smoking in NHL etiology. The results of this large-scale European study did not support an association between tobacco and NHL and suggested a protective effect of alcohol on development of NHL for men and in non-Mediterranean countries.

Cancer mortality among butchers: a 24-state death certificate study.

OBJECTIVE: The objective of this study was to document cancer mortality among American butchers. METHODS: Death certificates collected in 24 American states were used to calculate mortality odds ratios (ORs) and their confidence intervals (CIs) for 18,639 butchers. RESULTS: Butchers experienced an increased mortality of cancer of the oral cavity (OR, 1.40; 95% CI = 1.09-1.81), esophagus (OR, 1.19; 95% CI = 1.01-1.40), pharynx (OR, 1.22; 95% CI = 0.91-1.64), and larynx (OR, 1.19; 95% CI = 0.92-1.54), as well as a reduced mortality from melanoma (OR, 0.70; 95% CI = 0.52-0.94), non-Hodgkin lymphoma (OR, 0.82; 95% CI = 0.69-0.97), and breast cancer (OR, 0.76; 95% CI = 0.58-0.99). CONCLUSIONS: It is likely that occupational exposures experienced by butchers have contributed to the increased risk of cancers of the oral cavity and esophagus.