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.

Effectiveness and Tolerability of 12-Month Brivaracetam in the Real World: EXPERIENCE, an International Pooled Analysis of Individual Patient Records.

BACKGROUND AND OBJECTIVE: Real-world evidence studies of brivaracetam (BRV) have been restricted in scope, location, and patient numbers. The objective of this pooled analysis was to assess effectiveness and tolerability of brivaracetam (BRV) in routine practice in a large international population. METHODS: EXPERIENCE/EPD332 was a pooled analysis of individual patient records from multiple independent non-interventional studies of patients with epilepsy initiating BRV in Australia, Europe, and the United States. Eligible study cohorts were identified via a literature review and engagement with country lead investigators, clinical experts, and local UCB Pharma scientific/medical teams. Included patients initiated BRV no earlier than January 2016 and no later than December 2019, and had ≥ 6 months of follow-up data. The databases for each cohort were reformatted and standardised to ensure information collected was consistent. Outcomes included ≥ 50% reduction from baseline in seizure frequency, seizure freedom (no seizures within 3 months before timepoint), continuous seizure freedom (no seizures from baseline), BRV discontinuation, and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months. Patients with missing data after BRV discontinuation were considered non-responders/not seizure free. Analyses were performed for all adult patients (≥ 16 years), and for subgroups by seizure type recorded at baseline; by number of prior antiseizure medications (ASMs) at index; by use of BRV as monotherapy versus polytherapy at index; for patients who switched from levetiracetam to BRV versus patients who switched from other ASMs to BRV; and for patients with focal-onset seizures and a BRV dose of ≤ 200 mg/day used as add-on at index. Analysis populations included the full analysis set (FAS; all patients who received at least one BRV dose and had seizure type and age documented at baseline) and the modified FAS (all FAS patients who had at least one seizure recorded during baseline). The FAS was used for all outcomes other than ≥ 50% seizure reduction. All outcomes were summarised using descriptive statistics. RESULTS: Analyses included 1644 adults. At baseline, 72.0% were 16-49 years of age and 92.2% had focal-onset seizures. Patients had a median (Q1, Q3) of 5.0 (2.0, 8.0) prior antiseizure medications at index. At 3, 6, and 12 months, respectively, ≥ 50% seizure reduction was achieved by 32.1% (n = 619), 36.7% (n = 867), and 36.9% (n = 822) of patients; seizure freedom rates were 22.4% (n = 923), 17.9% (n = 1165), and 14.9% (n = 1111); and continuous seizure freedom rates were 22.4% (n = 923), 15.7% (n = 1165), and 11.7% (n = 1111). During the whole study follow-up, 551/1639 (33.6%) patients discontinued BRV. TEAEs since prior visit were reported in 25.6% (n = 1542), 14.2% (n = 1376), and 9.3% (n = 1232) of patients at 3, 6, and 12 months, respectively. CONCLUSIONS: This pooled analysis using data from a variety of real-world settings suggests BRV is effective and well tolerated in routine clinical practice in a highly drug-resistant patient population.

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.

The Association Between Sleep Duration, Insulin Sensitivity, and ß-Cell Function: The EGIR-RISC Study.

CONTEXT: In the past decade, over 3 dozen studies reported a relationship between self-reported short sleep and disturbed glucose metabolism. A study with insulin sensitivity assessed according to the gold standard hyperinsulinemic-euglycemic clamp is, however, still missing. OBJECTIVE: To evaluate the cross-sectional association of sleep duration with insulin sensitivity and ß-cell function in the European group for the study of insulin resistance (EGIR-RISC) study cohort. DESIGN, SETTING, PARTICIPANTS, AND MEASURES: We used data from the baseline measurements of the European, multicentre EGIR-RISC study that included 1319 clinically healthy participants. Sleep and physical activity were measured using a single-axis accelerometer. Insulin sensitivity and ß-cell function were estimated by hyperinsulinemic-euglycemic clamp and from the oral glucose insulin sensitivity index model, using an oral glucose tolerance test. Associations of sleep duration with insulin sensitivity and ß-cell function were analyzed by multiple linear regression, stratified by sex. RESULTS: In our current analysis, we included 788 participants (57% women, age 44 ± 8 y), who had an average sleep duration of 7.3 ± 1.5 hours. In men, we observed an inverted U-shaped association between sleep duration categorized per hour and M/I (in µmol/min per kgFFM/nM per hour) (ß-estimate [95% confidence intervals] 41 [2, 80]; P = .04 and ß(2)-estimate -3 [-6, -0.2], P = .04) as well as a trend for the oral glucose insulin sensitivity index (in mL/min per kgFFM) (ß-estimate [95% confidence intervals] 0.8 [-0.4, 2]; P = .17). In women, we observed a U-shaped association between sleep duration and ß-cell function (in pmol/min per m(2)/mM per hour) (ß-estimate -45 [-86, -3]; P = .04 and ß(2)-estimate 3 [0.2, 6]; P = .04). CONCLUSIONS: Sleep duration is associated with insulin sensitivity and ß-cell function in a sex-specific manner in clinically healthy people.

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.

Correlates of objectively measured physical activity and sedentary behaviour in English children.

BACKGROUND: Evidence on the correlates of objectively measured physical activity and sedentary behaviour in childhood is limited. This study aimed to identify correlates of physical activity and sedentary behaviour among 7-year-old children in England. METHODS: Physical activity was measured using Actigraph accelerometry in 480 participants as part of the Gateshead Millennium Study during 2006-07. Twenty-two potential correlates across five domains (demographic and biological; psychological, cognitive and emotional; behavioural; social and cultural; physical environmental) were tested for associations with total volume of habitual physical activity, moderate-vigorous intensity physical activity (MVPA) and sedentary behaviour. Multiple linear regression analysis was used. RESULTS: Seven correlates, including four that are potentially modifiable, were significantly associated with total physical activity, MVPA and sedentary behaviour in final models: gender, child weight status, maternal age, child interest in active play, active commuting to school, parenting practice and season. Four of these variables were significantly associated with all three constructs in final models. The final models explained 18, 18 and 24% of variance in total volume of physical activity, MVPA and sedentary behaviour, respectively. CONCLUSION: A number of potentially modifiable factors are associated with increased physical activity and/or reduced sedentary behaviour in English children. These could be valuable targets of future interventions.

Objectively measured physical activity during pregnancy: a study in obese and overweight women.

BACKGROUND: Obese and overweight women may benefit from increased physical activity (PA) during pregnancy. There is limited published data describing objectively measured PA in such women. METHODS: A longitudinal observational study of PA intensity, type and duration using objective and subjective measurement methods. Fifty five pregnant women with booking body mass index (BMI) ≥ 25 kg/m2 were recruited from a hospital ultrasound clinic in North East England. 26 (47%) were nulliparous and 22 (40%) were obese (BMI ≥ 30 kg/m2). PA was measured by accelerometry and self report questionnaire at 13 weeks, 26 weeks and/or 36 weeks gestation. Outcome measures were daily duration of light, moderate or vigorous activity assessed by accelerometry; calculated overall PA energy expenditure, (PAEE), and PAEE within four domains of activity based on self report. RESULTS: At median 13 weeks gestation, women recorded a median 125 mins/day light activity and 35 mins/day moderate or vigorous activity (MVPA). 65% achieved the minimum recommended 30 mins/day MVPA. This proportion was maintained at 26 weeks (62%) and 36 weeks (71%). Women achieving more than 30 mins/day MVPA in the first trimester showed a significant reduction in duration of MVPA by the third trimester (11 mins/day, p = 0.003). Walking, swimming and floor exercises were the most commonly reported recreational activities but their contribution to estimated energy expenditure was small. CONCLUSION: Overweight and obese pregnant women can achieve and maintain recommended levels of PA throughout pregnancy. Interventions to promote PA should target changes in habitual activities at work and at home, and in particular walking.

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.

Assessment of physical activity - a review of methodologies with reference to epidemiological research: a report of the exercise physiology section of the European Association of Cardiovascular Prevention and Rehabilitation.

Physical activity has a fundamental role in the prevention and treatment of chronic disease. The precise measurement of physical activity is key to many surveillance and epidemiological studies investigating trends and associations with disease. Public health initiatives aimed at increasing physical activity rely on the measurement of physical activity to monitor their effectiveness. Physical activity is multidimensional, and a complex behaviour to measure; its various domains are often misunderstood. Inappropriate or crude measures of physical activity have serious implications, and are likely to lead to misleading results and underestimate effect size. In this review, key definitions and theoretical aspects, which underpin the measurement of physical activity, are briefly discussed. Methodologies particularly suited for use in epidemiological research are reviewed, with particular reference to their validity, primary outcome measure and considerations when using each in the field. It is acknowledged that the choice of method may be a compromise between accuracy level and feasibility, but the ultimate choice of tool must suit the stated aim of the research. A framework is presented to guide researchers on the selection of the most suitable tool for use in a specific study.

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.

Adherence to the Mediterranean diet is associated with lower abdominal adiposity in European men and women.

Given the lack of consistent evidence of the relationship between Mediterranean dietary patterns and body fat, we assessed the cross-sectional association between adherence to a modified Mediterranean diet, BMI, and waist circumference (WC). A total of 497,308 individuals (70.7% women) aged 25-70 y from 10 European countries participated in this study. Diet was assessed at baseline using detailed validated country-specific questionnaires, and anthropometrical measurements were collected using standardized procedures. The association between the degree of adherence to the modified-Mediterranean Diet Score (mMDS) (including high consumption of vegetables, legumes, fruits and nuts, cereals, fish and seafood, and unsaturated:saturated fatty acids ratio; moderate alcohol intake; and low consumption of meat and meat products and dairy products) and BMI (kg.m(-2)) or WC (cm) was modeled through mixed-effects linear regression, controlling for potential confounders. Overall, the mMDS was not significantly associated with BMI. Higher adherence to the Mediterranean diet was significantly associated with lower WC, for a given BMI, in both men (-0.09; 95% CI -0.14 to -0.04) and women (-0.06; 95% CI -0.10 to -0.01). The association was stronger in men (-0.20; 95% CI -0.23 to -0.17) and women (-0.17; 95% CI -0.21 to -0.13) from Northern European countries. Despite the observed heterogeneity among regions, results of this study suggest that adherence to a modified Mediterranean diet, high in foods of vegetable origin and unsaturated fatty acids, is associated with lower abdominal adiposity measured by WC in European men and women.