Publications by authors named "Mette Aadahl"

89 Publications

Non-linear interaction between physical activity and polygenic risk score of body mass index in Danish and Russian populations.

PLoS One 2021 18;16(10):e0258748. Epub 2021 Oct 18.

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Body mass index (BMI) is a highly heritable polygenic trait. It is also affected by various environmental and behavioral risk factors. We used a BMI polygenic risk score (PRS) to study the interplay between the genetic and environmental factors defining BMI. First, we generated a BMI PRS that explained more variance than a BMI genetic risk score (GRS), which was using only genome-wide significant BMI-associated variants (R2 = 13.1% compared to 6.1%). Second, we analyzed interactions between BMI PRS and seven environmental factors. We found a significant interaction between physical activity and BMI PRS, even when the well-known effect of the FTO region was excluded from the PRS, using a small dataset of 6,179 samples. Third, we stratified the study population into two risk groups using BMI PRS. The top 22% of the studied populations were included in a high PRS risk group. Engagement in self-reported physical activity was associated with a 1.66 kg/m2 decrease in BMI in this group, compared to a 0.84 kg/m2 decrease in BMI in the rest of the population. Our results (i) confirm that genetic background strongly affects adult BMI in the general population, (ii) show a non-linear interaction between BMI genetics and physical activity, and (iii) provide a standardized framework for future gene-environment interaction analyses.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258748PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523041PMC
October 2021

Participant evaluation of a behavioral intervention targeting reduction of sedentary behavior in patients with rheumatoid arthritis: a mixed methods study.

Disabil Rehabil 2021 Aug 20:1-12. Epub 2021 Aug 20.

Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet, Denmark.

The "Joint Resources - Sedentary Behavior Study" (JR-SB) revealed significant behavioral and cardio-metabolic effects of reducing daily sedentary behavior replaced by light-intensity physical activity in patients with rheumatoid arthritis. This study explores the participant perception and experiences of the intervention and impact on the participants' health, family and physical activity behavior. A mixed-methods study design, including quantitative and qualitative data, was applied. Quantitative data were collected post-intervention using a questionnaire ( = 69) evaluating experiences of participation in the intervention. By maximum variation sampling, 18 participants were recruited to three focus group interviews with discussions of intervention elements. Data from the two sub-studies were collected and analyzed separately, although integrated at the interpretation and reporting level. Based on four overarching themes, results indicated participant satisfaction with the individually tailored, behavioral approach and the focus on light-intensity physical activity rather than higher intensities. Study participation had an additional positive impact on the behaviors of family and social relations. Conversely, the family motivated the participants to achieve their physical activity goals. The study results support the use of individually tailored and behavioral approaches to reduce sedentary behavior, increase light-intensity physical activity and improve physical abilities in patients with rheumatoid arthritis. IMPLICATIONS FOR REHABILITATIONThis paper presents positive participant perception and motivation for an individually tailored, behavioural intervention that aimed to reduce sedentary behaviour replaced by light-intensity physical activity in patients with rheumatoid arthritis.The results indicate that especially the focus on light-intensity physical activity, a consistent focus on the individual's everyday life and continuous support from health professionals motivated the participants to reduce their daily sedentary behaviour - also in the long term.Involvement of participants' family members seems to have influence on their own physical activity behavior as well as on the participants' motivation for changing physical activity behavior.Together with earlier evidence, the results underpin the use of behavioural strategies to support patients with rheumatoid arthritis in achieving their physical activity goals and in improving the abilities needed to manage their everyday lives.
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http://dx.doi.org/10.1080/09638288.2021.1966676DOI Listing
August 2021

Fatigue, physical activity and associated factors in 779 patients with myasthenia gravis.

Neuromuscul Disord 2021 08 27;31(8):716-725. Epub 2021 May 27.

Copenhagen Neuromuscular Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Inge Lehmanns Vej 8, 2100 Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

The objective of the study was to examine the association between fatigue (measured by the Multidimensional Fatigue Inventory; MFI-20) and physical activity (measured by the Saltin-Grimby Physical Activity Level Scale; SGPALS) in a large cohort of patients (≥18 years) with myasthenia gravis (MG) including relevant disease - and lifestyle-related factors. A total of 1463 persons, registered at the Danish National Registry of Patients with a MG diagnosis, according to the International Classification of Diseases, received a web-based survey. A total of 779 patients (53% women, mean [SD] age 60.8 [15.5]) responded. The remaining persons were either non-responders (n = 390) or could not confirm the MG diagnosis (n = 294). The most prominent MFI-20 fatigue domains were general fatigue (median [inter-quartile ranges, IQR], 13 [10-16]) and physical fatigue (median [IQR], 13 [9-15]), and 386 (53%) patients reported low levels of physical activity. All fatigue domains were associated with physical activity (p<.01). Higher level of physical activity was associated with lower levels of fatigue. Important factors for the association were myasthenia gravis disease severity (measured by the Myasthenia Gravis Activities of Daily Living profile), body mass index, insomnia (measured by the Insomnia Severity Index) job-status, comorbidity, and cohabitation.
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http://dx.doi.org/10.1016/j.nmd.2021.05.007DOI Listing
August 2021

Sex Difference in the Association between Physical Activity and All-Cause Mortality in Ambulatory Patients with Chronic Kidney Disease.

Int J Environ Res Public Health 2021 04 1;18(7). Epub 2021 Apr 1.

Center for Clinical Research and Prevention, Frederiksberg and Bispebjerg Hospital, 2000 Fredeiksberg, Denmark.

(1) Background: The purpose of this article was to investigate the association between self-reported physical activity (PA) and all-cause mortality in ambulatory patients with chronic kidney disease (CKD), stage 4-5 including maintenance dialysis. (2) Methods: Ambulatory patients with CKD (eGFR < 30 mL/min/1.73 m) with conservative treatment or chronic dialysis were included. PA was assessed using the Saltin-Grimby Physical Activity Level Scale. A Cox proportional hazards regression model--adjusted for age, sex, plasma-albumin, body mass index, socioeconomic status, and treatment--was applied. (3) Results: Participants ( = 374) were followed 39 ± 15 months from entry to death or censoring. Throughout the study period of 39 months, 156 deaths (42%) were registered. Regarding physical activity, 128 (34%) of the participants were inactive, 212 (57%) were moderately active, and 34 (9%) were highly or vigorously active. Moderate PA was associated with a decreased mortality risk in women ( = 150) compared to inactivity (HR 0.27 (0.15; 0.51), < 0.001), whereas a high/vigorous level of PA was not significantly associated with mortality risk compared to inactivity. In men ( = 224), the associations between PA levels and mortality risk were not significant. (4) Conclusions: Moderate PA was associated with reduced all-cause mortality in ambulatory women with stage 4-5 CKD with or without maintenance dialysis treatment. Physical activity was not significantly associated with mortality in men.
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http://dx.doi.org/10.3390/ijerph18073698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036673PMC
April 2021

Physical activity, self-rated fitness and stress among 55,185 men and women in the Danish Capital Region Health survey 2017.

Prev Med Rep 2021 Jun 3;22:101373. Epub 2021 Apr 3.

Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Hovedvejen, Entrance 5, Nordre Fasanvej 57, 2000 Frederiksberg, Denmark.

Previous studies have indicated that both low physical activity and low physical fitness are associated with a higher level of stress but the influence of age and health status on the associations is unknown. This was examined in a cross-sectional study based on data from the Danish Capital Region Health Survey 2017. Among all adults ≥ 16 years residing in the largest of five regions in Denmark 1. January 2017 a random sample of 104,950 was invited to participate. Hereof, 55.185 responded (52,6%). Physical activity during leisure time, fitness, self-rated health and stress (Cohens Perceived Stress Scale) was self-reported by questionnaire. Logistic regression weighted for size of municipality and non-response was used. Age modified the associations. In all age-groups odds ratio (OR) for a high level of stress was increasingly higher the lower the level of physical activity. The association was strongest among the 16-24-year-olds and persisted after adjustment for self-rated health, that otherwise attenuated the associations to an increasing extent the older the age-group. Similar models investigating the modifying effect of age on the association between self-rated fitness and stress showed the same patterns and tendencies. This study showed that physical activity and self-rated fitness were both associated with stress. The OR for a high level of stress was increasingly higher the lower the level of physical activity or self-rated fitness. This was found in all age-groups, but most pronounced among the 16-24-year-olds. Furthermore, findings suggest that health condition explains the associations to an increasing extent with increasing age.
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http://dx.doi.org/10.1016/j.pmedr.2021.101373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044425PMC
June 2021

Validity of the Danish Physical Activity Scale, adapted to Spanish speaking population.

Aten Primaria 2021 05 18;53(5):101949. Epub 2021 Mar 18.

University of Copenhagen, Faculty of Health and Medical Sciences, Institute of Public Health, Copenhagen, Denmark; Center for Clinical Research and Prevention, Frederiksberg and Bispebjerg Hospital, Frederiksberg, Denmark.

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http://dx.doi.org/10.1016/j.aprim.2020.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985467PMC
May 2021

Should leisure-time sedentary behavior be replaced with sleep or physical activity for prevention of diabetes?

Scand J Med Sci Sports 2021 May 23;31(5):1105-1114. Epub 2021 Feb 23.

Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark.

The aim was to examine the effects of replacing self-reported leisure-time sedentary behavior with sleep, light-to-moderate physical activity, or vigorous physical activity on incident diabetes among Danish adults using isotemporal substitution modeling. Participants ≥25 years from the Danish Capital Region Health Survey 2007 (N = 69 800, response rate 52.3%), 2010 (N = 95 150, response rate 52.3%), and 2013 (N = 95 150, response rate 43.5%) were included. Information on daily sleep duration, leisure-time sedentary behavior, and movement behaviors was collected by questionnaire. Information on incident diabetes was obtained from National registers. Analyses included Cox proportional hazards regression models and isotemporal substitution analyses, with time (in years) from baseline to incident diabetes or censoring December 31, 2017. Potential confounders, sex, age, BMI, ethnicity, education, smoking, inflammatory joint disease, perceived stress, physical and mental component scale and work status, were included. Out of N = 87 339 in the final study sample, n = 3007 had incident diabetes during a mean follow-up time of 7.4 years. Adults with incident diabetes included more men, higher mean age, and higher BMI, compared to respondents without incident diabetes. Theoretically substituting 30 minutes of leisure-time sedentary behavior with light-to-moderate PA (HR: 0.96; 95% CI: 0.94; 0.98) or with vigorous PA (HR: 0.82; 95% CI: 0.72; 0.94) decreased the risk of incident diabetes. We found no change in incident diabetes risk of substituting sedentary time with sleep (HR: 1.00; 95% CI: 0.97; 1.02). Substituting 30 minutes per day of leisure-time sedentary behavior with light-to-moderate or vigorous PA may significantly reduce the risk of incident diabetes among adults.
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http://dx.doi.org/10.1111/sms.13924DOI Listing
May 2021

Self-rated physical fitness and measured cardiorespiratory fitness, muscular strength, and body composition.

Scand J Med Sci Sports 2021 May 27;31(5):1086-1095. Epub 2021 Feb 27.

National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.

The purpose was to examine the correlation and association between a single-item question of self-rated physical fitness and objective measures of fitness and cardiometabolic risk factors in a large population-based study. Participants were 3441 men and women aged 18-85 years who filled in a questionnaire and participated in a clinical health examination in the Danish Health Examination Survey 2007-2008. Cardiorespiratory fitness was estimated by an indirect maximal exercise test. Muscle strength was measured by (a) sit-to-stand test, (b) handgrip strength, and (c) bent arm strength. Body mass index and fat percentage were used as measures for body composition. Associations were derived from regression analyses, correlations were calculated using Spearman's correlation test, and agreement was tested by kappa statistics. Within categories of self-rated physical fitness moving from lowest to highest, objectively measured cardiorespiratory fitness increased. Self-rated physical fitness was strongly correlated to cardiorespiratory fitness (r  = 0.69 and r  = 0.65) and moderately correlated to the sit-to-stand test (r  = 0.49 and r  = 0.48), bent arm strength (r = 0.45) and fat percentage (r = 0.46) among men, and handgrip strength among women (r =0.41). Mutually adjusted analysis showed a significant association between self-reported physical fitness and cardiorespiratory fitness for men and women and bent arm strength for women. The single-item question of physical fitness was correlated to cardiorespiratory fitness, muscle strength, and body composition. However, this study suggests that it mainly captures cardiorespiratory fitness. At the population level, the single-item question could be a useful tool to identify and monitor variation in fitness levels.
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http://dx.doi.org/10.1111/sms.13918DOI Listing
May 2021

Thigh-worn accelerometry for measuring movement and posture across the 24-hour cycle: a scoping review and expert statement.

BMJ Open Sport Exerc Med 2020 24;6(1):e000874. Epub 2020 Dec 24.

School of Public Health, The University of Sydney Faculty of Medicine and Health, Sydney, New South Wales, Australia.

Introduction: The Prospective Physical Activity Sitting and Sleep consortium (ProPASS) is an international collaboration platform committed to harmonise thigh-worn accelerometry data. The aim of this paper is to (1) outline observational thigh-worn accelerometry studies and (2) summarise key strategic directions arising from the inaugural ProPASS meeting.

Methods: (1) We performed a systematic scoping review for observational studies of thigh-worn triaxial accelerometers in free-living adults (n≥100, 24 hours monitoring protocols). (2)Attendees of the inaugural ProPASS meeting were sent a survey focused on areas related to developing ProPASS: important terminology (Q1); accelerometry constructs (Q2); advantages and distinct contribution of the consortium (Q3); data pooling and harmonisation (Q4); data access and sharing (Q5 and Q6).

Results: (1) Eighty eligible articles were identified (22 primary studies; n~17 685). The accelerometers used most often were the ActivPAL3 and ActiGraph GT3X. The most commonly collected health outcomes were cardiometabolic and musculoskeletal. (2) None of the survey questions elicited the predefined 60% agreement. Survey responses recommended that ProPASS: use the term physical behaviour or movement behaviour rather than 'physical activity' for the data we are collecting (Q1); make only minor changes to ProPASS's accelerometry construct (Q2); prioritise developing standardised protocols/tools (Q4); facilitate flexible methods of data sharing and access (Q5 and Q6).

Conclusions: Thigh-worn accelerometry is an emerging method of capturing movement and posture across the 24 hours cycle. In 2020, the literature is limited to 22 primary studies from high-income western countries. This work identified ProPASS's strategic directions-indicating areas where ProPASS can most benefit the field of research: use of clear terminology, refinement of the measured construct, standardised protocols/tools and flexible data sharing.
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http://dx.doi.org/10.1136/bmjsem-2020-000874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768971PMC
December 2020

Abdominal visceral and subcutaneous adipose tissue and associations with cardiometabolic risk in Inuit, Africans and Europeans: a cross-sectional study.

BMJ Open 2020 09 14;10(9):e038071. Epub 2020 Sep 14.

Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark.

Objectives: Abdominal fat has been identified as a risk marker of cardiometabolic disease independent of overall adiposity. However, it is not clear whether there are ethnic disparities in this risk. We investigated the associations of visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) with cardiometabolic risk factors in three ethnic diverse populations of Inuit, Africans and Europeans.

Design: Cross-sectional pooled study.

Setting: Greenland, Kenya and Denmark.

Methods: A total of 5113 participants (2933 Inuit, 1397 Africans and 783 Europeans) from three studies in Greenland, Kenya and Denmark were included. Measurements included abdominal fat distribution assessed by ultrasound, oral glucose tolerance test, hepatic insulin resistance, blood pressure and lipids. The associations were analysed using multiple linear regressions.

Results: Across ethnic group and gender, an increase in VAT of 1 SD was associated with higher levels of hepatic insulin resistance (ranging from 14% to 28%), triglycerides (8% to 16%) and lower high-density lipoprotein cholesterol (HDL-C, -1.0 to -0.05 mmol/L) independent of body mass index. VAT showed positive associations with most of the other cardiometabolic risk factors in Inuit and Europeans, but not in Africans. In contrast, SAT was mainly associated with the outcomes in Inuit and Africans. Of notice was that higher SAT was associated with higher HDL-C in African men (0.11 mmol/L, 95% CI: 0.03 to 0.18) and with lower HDL-C in Inuit (-0.07 mmol/L, 95% CI: -0.12 to -0.02), but not in European men (-0.02 mmol/L, 95% CI: -0.09 to 0.05). Generally weaker associations were observed for women. Furthermore, the absolute levels of several of the cardiometabolic outcomes differed between the ethnic groups.

Conclusions: VAT and SAT were associated with several of the cardiometabolic risk factors beyond overall adiposity. Some of these associations were specific to ethnicity, suggesting that ethnicity plays a role in the pathway from abdominal fat to selected cardiometabolic risk factors.
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http://dx.doi.org/10.1136/bmjopen-2020-038071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490939PMC
September 2020

Dropout at Danish vocational schools: does the school's health promotion capacity play a role? A survey- and register-based prospective study.

BMC Public Health 2020 May 26;20(1):786. Epub 2020 May 26.

Health Promotion, Steno Diabetes Center Copenhagen, Niels Steensens vej 6, 2820, Gentofte, Denmark.

Background: School dropout rates and risky health behavior is common among students in vocational education and training (VET) schools. Students with poor physical and mental health are more likely to drop out, and as such VET schools may be an important setting for health promotion initiatives, not only to support a healthy lifestyle, but also to assure completion of education. A common feature of successful health promotion at VET schools is a high health promotion capacity at the school level. This study aimed to investigate the association between VET school's health promotion capacity and later student dropout rates. Secondary, we explored other school characteristics associated with student dropout rates.

Methods: This prospective study comprised 58 Danish VET schools offering basic programs. Health promotion capacity was assessed using questionnaire data from 2017 from school managers and teachers, and this was combined with register-based data on student dropouts the following year. Health promotion capacity was assessed using six scales, representing six underlying domains, and managers and teachers' ratings of these were compared using t-test. Associations between health promotion capacity and student dropout rates as well as associations between school characteristics and student dropout rates were analyzed using multiple linear regression.

Results: No associations between VET schools' health promotion capacity and student dropout rates were observed, neither for the schools' overall health promotion capacity or for any of the six underlying domains (p = 0.17-0.84). School managers assessed health promotion capacity significantly higher than teachers overall and within all domains (p < 0.05). Moreover, student dropout rates were significantly lower at schools with a higher proportion of ethnic Danish students, VET-students at higher educational level and schools located in the Western part of Denmark (p < 0.05).

Conclusion: No associations between VET schools' health promotion capacity and student dropout rates were observed. This may be due to a relatively short follow-up time in our study and future research may reveal if VET school health promotion capacity may affect dropout rates over a longer time period. Moreover, more work is needed to further develop instruments for measuring health promotion capacity in a VET school context as well as other contexts.
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http://dx.doi.org/10.1186/s12889-020-08955-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249319PMC
May 2020

Sustained Long-Term Efficacy of Motivational Counseling and Text Message Reminders on Daily Sitting Time in Patients With Rheumatoid Arthritis: Long-Term Follow-up of a Randomized, Parallel-Group Trial.

Arthritis Care Res (Hoboken) 2020 11;72(11):1560-1570

Rigshospitalet, Glostrup, and University of Copenhagen, Copenhagen, Denmark.

Objective: To evaluate the 18-month postintervention efficacy following a 4-month individually tailored behavioral intervention on daily sitting time in patients with rheumatoid arthritis (RA).

Methods: In an observer-blinded randomized trial, 150 RA patients were included. During 4 months, the intervention group (n = 75) received 3 motivational counseling sessions and tailored text messages aimed at increasing light-intensity physical activity through reduction of sedentary behavior. The control group (n = 75) maintained their usual lifestyle. The primary outcome was change from baseline to 18 months postintervention in objectively measured daily sitting time (using ActivPAL). Secondary outcomes included changes in clinical patient-reported outcomes and cardiometabolic biomarkers. A mixed-effect repeated measures analysis of covariance model in the intent-to-treat population was applied.

Results: At 22 months follow-up from baseline, 12 participants were lost to follow-up. Compared to baseline, sitting time in the intervention group decreased 1.10 hours/day, whereas it increased by 1.32 hours/day in the control group, a between-group difference of -2.43 hours/day (95% confidence interval [95% CI] -2.99, -1.86; P < 0.0001) favoring the intervention group. For most secondary outcomes, between-group differences favored the intervention: visual analog scale (VAS) pain -15.51 mm (95% CI -23.42, -7.60), VAS fatigue -12.30 mm (95% CI -20.71, -3.88), physical function -0.39 Health Assessment Questionnaire units (95% CI -0.53, -0.26), total cholesterol -0.86 mmoles/liter (95% CI -1.03, -0.68), triglycerides -0.26 mmoles/liter (95% CI -0.43, -0.09), and average glucose -1.15 mmoles/liter (95% CI -1.39, -0.91).

Conclusion: The 4-month postintervention results showed that patients in the intervention reduced their daily sitting time and improved patient-reported outcomes and total cholesterol levels compared to the control group. Eighteen months after intervention, patients in the intervention group were still significantly less sedentary than controls. Findings suggest that a behavioral approach is beneficial for promoting long-term physical activity and health in patients with RA.
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http://dx.doi.org/10.1002/acr.24060DOI Listing
November 2020

Comparison of physical behavior estimates from three different thigh-worn accelerometers brands: a proof-of-concept for the Prospective Physical Activity, Sitting, and Sleep consortium (ProPASS).

Int J Behav Nutr Phys Act 2019 08 16;16(1):65. Epub 2019 Aug 16.

The National Research Centre for the Work Environment, Copenhagen, Denmark.

Background: Pooling data from thigh-worn accelerometers across multiple studies has great potential to advance evidence on the health benefits of physical activity. This requires harmonization of information on body postures, physical activity types, volumes and time patterns across different brands of devices. The aim of this study is to compare the physical behavior estimates provided by three different brands of thigh-worn accelerometers.

Methods: Twenty participants volunteered for a 7-day free-living measurement. Three accelerometers - ActiGraph GT3X+, Axivity AX3 and ActivPAL Micro4 - were randomly placed in a vertical line on the midsection of the right thigh. Raw data from each accelerometer was processed and classified into 8 physical activities and postures using the Acti4 software. Absolute differences between estimates and the respective coefficient of variation (CV) were calculated.

Results: We observed very minor differences between physical behavior estimates from three different accelerometer brands. When averaged over 24 h (1,440 min), the absolute difference (CV) between accelerometers were: 1.2 mins (0.001) for lying/sitting, 3.4 mins (0.02) for standing, 3.5 mins (0.06) for moving, 1.9 mins (0.03) for walking, 0.1 mins (0.19) for running, 1.2 mins (0.19) for stair climbing, 1.9 mins (0.07) for cycling. Moreover, there was an average absolute difference of 282 steps (0.03) per 24 h.

Conclusions: Physical behaviors were classified with negligible difference between the accelerometer brands. These results support harmonization of data from different thigh-worn accelerometers across multiple cohorts when analyzed in an identical manner.
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http://dx.doi.org/10.1186/s12966-019-0835-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697962PMC
August 2019

Exercise training is associated with reduced pains from the musculoskeletal system in patients with type 2 diabetes.

Diabetes Res Clin Pract 2019 Aug 9;154:124-129. Epub 2019 Jul 9.

Department of Clinical Research, Nordsjællands Hospital, Denmark. Electronic address:

Aims: To investigate the effect of exercise training on musculoskeletal pain in patients with type 2 diabetes.

Methods: The intervention was exercise twice weekly for 12 weeks. The primary outcome was musculoskeletal pain assessed using a 0-10 Numeric Rating Scale (NRS) in 11 body sites. Secondary outcomes were use of analgesics, glycaemic control and body weight.

Results: The participants (n = 69) were 66 ± 10 years old, 38 were men and 50 completed the intervention. Pain in the limbs was more frequently reported by the participants compared to a matched general population (80.9% vs 65.3%, p = 0.007). The participants who had any pain at baseline (NRS > 0) and severe pain (NRS > 3) reported significantly decreased pain in the feet, calf muscles, knees, thighs, hips, lower back and arms after the training period. Use of analgesics was unchanged, HbA1c (mmol/mol) decreased from 60 ± 15 to 54 ± 11, p < 0.001 and body weight (kg) decreased from 100.5 ± 19.1 to 98.6 ± 17.7, p = 0.005.

Conclusions: The participants with type 2 diabetes reported more frequent pain than a matched general population. The training intervention was associated with reduced musculoskeletal pain. Reduced pain may together with a positive impact on glycaemic control be an important motivational factor in patients with type 2 diabetes to perform exercise training.
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http://dx.doi.org/10.1016/j.diabres.2019.07.003DOI Listing
August 2019

Sedentary Behavior, Physical Activity, and All-Cause Mortality: Dose-Response and Intensity Weighted Time-Use Meta-analysis.

J Am Med Dir Assoc 2019 10 2;20(10):1206-1212.e3. Epub 2019 Jul 2.

Department of Population Medicine, College of Medicine, Qatar University, Doha, Qatar. Electronic address:

Objectives: Previous studies have placed those with excessive sedentary behavior at increased risk of all-cause mortality. There is evidence of interdependency of sedentary behavior with physical activity, and its elucidation will have implications for guidelines and practice. This study investigated if sedentary behavior-related mortality risk can be offset by moderate- to vigorous-intensity physical activity (MVPA) considered in a time-use fashion.

Design: PubMed was searched (from its inception till May 2018) for studies or meta-analyses that used data harmonized for MVPA. Of the 17 data-custodians located, 7 provided data on sitting time or TV viewing time, or both. A dose-response meta-analysis modeling log relative risks of all-cause mortality against uncompensated sedentary behavior metabolic equivalent hours (USMh) was run using the robust error meta-regression method. (Registration: CRD42017062439) SETTING: Individual subject data held by data custodians on this topic.

Participants: General adults.

Measurements: Sedentary time, MVPA.

Results: Five harmonized cohorts of sitting time (258,688 participants) and 4 of TV viewing time (156,593 participants) demonstrated that sedentary behavior was significantly associated with mortality, but this risk was attenuated with increasing energy expenditure through MVPA modeled in a time-use fashion. The average increment in mortality per USMh spent on sitting was 1% [relative risk (RR) 1.01, 95% confidence interval (CI) 1.00, 1.02; P = .01] and that per USMh spent on TV viewing was 7% (RR 1.07, 95% CI 1.04, 1.10; P < .001). The thresholds for risk started at 7 USMh for sitting and 3 USMh for TV viewing.

Conclusions/implications: Our findings suggest that overall daily sitting time energy expenditure of 7 MET-hours (or TV viewing of 3 MET-hours) in excess of that expended on MVPA is independently related to all-cause mortality. These findings support the view that sitting is strongly influenced by consideration of concurrent MVPA in its impact on adverse health consequences and that the USMh is a more practical metric of sedentary behavior.
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http://dx.doi.org/10.1016/j.jamda.2019.05.001DOI Listing
October 2019

Motivational Counseling and Text Message Reminders: For Reduction of Daily Sitting Time and Promotion of Everyday Physical Activity in People with Rheumatoid Arthritis.

Rheum Dis Clin North Am 2019 05;45(2):231-244

Centre for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Nordre Fasanvej 57, Hovedvejen 5, Frederiksberg 2000, Denmark; Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.

Most patients with rheumatoid arthritis tend to be physically inactive and spend more time in sedentary behaviors compared with the general population. This inactive lifestyle can lead to serious health consequences, for example, increased risk of cardiovascular disease. For this reason, there is an interest in increasing participation in physical activity in patients with rheumatoid arthritis. The relatively new approach of reducing sedentary behavior and replacing it with light-intensity physical activity has been shown to be feasible and effective in promoting physical activity in patients with rheumatoid arthritis. However, methods to facilitate this behavior have not yet been fully explored.
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http://dx.doi.org/10.1016/j.rdc.2019.01.005DOI Listing
May 2019

Estimated impact of replacing sitting with standing at work on indicators of body composition: Cross-sectional and longitudinal findings using isotemporal substitution analysis on data from the Take a Stand! study.

PLoS One 2018 13;13(6):e0198000. Epub 2018 Jun 13.

National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.

The purpose was to examine and compare the effects of replacing time spent sitting with standing at work on fat-free mass, fat mass and waist circumference using isotemporal substitution. Analyses were conducted on work hours on both cross-sectional and longitudinal data. The study included 223 persons from an intervention study aimed at reducing sitting time at work among office employees. Sitting, standing and anthropometry were measured objectively. Cross-sectional isotemporal substitution analyses were modelled on baseline data, while longitudinal analyses were modelled based on differences in sitting and standing time at work between baseline and 1-month follow-up in relation to differences in anthropometric measures between baseline and 3-months follow-up. Replacing one hour of sitting time with one hour of standing was associated with a 0.21 kg higher fat-free mass in the longitudinal analysis and 0.95 kg in the cross-sectional analysis. Fat mass was 0.32 kg lower in the longitudinal analysis and 0.61 kg lower in the cross-sectional analysis. Waist circumference decreased by 0.38 cm in the longitudinal analysis and 0.81 cm in the cross-sectional analysis. Both cross-sectional and longitudinal analyses showed an effect on body composition measures by replacing one hour of sitting with standing however, this effect was largest in the cross-sectional analyses. Trial registration ClinicalTrials.gov NCT01996176.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198000PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999077PMC
December 2018

The Association Between Self-Rated Fitness and Cardiorespiratory Fitness in Adults.

Int J Sports Med 2018 Jun 17;39(6):419-425. Epub 2018 Apr 17.

Centre for Clinical Research and Prevention, Frederiksberg-Bispebjerg Hospital, Copenhagen, Denmark.

To assess criterion validity of a single item question on self-rated physical fitness against objectively measured cardiorespiratory fitness. From the Health2008 study 749 men and women between 30 and 60 years of age rated their fitness as excellent, very good, good, fair or poor. Cardiorespiratory fitness was estimated with the watt-max test. Agreement between self-rated and objectively measured physical fitness was assessed by Cohen's weighted kappa coefficient. Correlation was determined by Goodman & Kruskal's gamma correlation coefficient. All analyses were stratified according to gender. Data from 323 men and 426 women were analysed. There was a slight agreement between self-rated and objectively measured fitness in men (weighted kappa: 0.18, [95%CI: 0.13;0.23]) and a fair agreement in women (weighted kappa: 0.27, [95%CI: 0.22;0.32]). In both genders, self-rated fitness was positively correlated with objectively measured fitness (moderate correlation; gamma correlation coefficient for men: 0.63 [95%CI: 0.54;0.72] and women: 0.67 [95%CI: 0.59;0.75]). There was a slight to fair agreement and moderate, positive correlations between self-rated physical fitness and watt-max estimated cardiorespiratory fitness. Hence, a single-item question on physical fitness may be a cost-effective method of assessing fitness in large population studies, but is not valid for individual assessments.
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http://dx.doi.org/10.1055/s-0044-102128DOI Listing
June 2018

Total sitting time, leisure time physical activity and risk of hospitalization due to low back pain: The Danish Health Examination Survey cohort 2007-2008.

Scand J Public Health 2019 Feb 1;47(1):45-52. Epub 2018 Mar 1.

2 National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.

Aims: This study aimed to test the hypotheses that a high total sitting time and vigorous physical activity in leisure time increase the risk of low back pain and herniated lumbar disc disease.

Methods: A total of 76,438 adults answered questions regarding their total sitting time and physical activity during leisure time in the Danish Health Examination Survey 2007-2008. Information on low back pain diagnoses up to 10 September 2015 was obtained from The National Patient Register. The mean follow-up time was 7.4 years. Data were analysed using Cox regression analysis with adjustment for potential confounders. Multiple imputations were performed for missing values.

Results: During the follow-up period, 1796 individuals were diagnosed with low back pain, of whom 479 were diagnosed with herniated lumbar disc disease. Total sitting time was not associated with low back pain or herniated lumbar disc disease. However, moderate or vigorous physical activity, as compared to light physical activity, was associated with increased risk of low back pain (HR = 1.16, 95% CI: 1.03-1.30 and HR = 1.45, 95% CI: 1.15-1.83). Moderate, but not vigorous physical activity was associated with increased risk of herniated lumbar disc disease.

Conclusions: The results suggest that total sitting time is not associated with low back pain, but moderate and vigorous physical activity is associated with increased risk of low back pain compared with light physical activity.
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http://dx.doi.org/10.1177/1403494818758843DOI Listing
February 2019

Associations and predictions of readmission or death in acutely admitted older medical patients using self-reported frailty and functional measures. A Danish cohort study.

Arch Gerontol Geriatr 2018 May - Jun;76:65-72. Epub 2018 Feb 13.

Department of Cardiology, Aalborg University Hospital, Hobrovej 18-22, 9000, Aalborg, Denmark; Section for Epidemiology, Department of Public Health, Aarhus University, Bartholins Alle 2, 8000, Aarhus C, Denmark. Electronic address:

Objective: To assess whether frailty in acutely admitted older medical patients, assessed by a self-report questionnaire and evaluation of functional level at discharge, was associated with readmission or death within 6 months after discharge. A second objective was to assess the predictive performance of models including frailty, functional level, and known risk factors.

Methods: A cohort study including acutely admitted older patients 65+ from seven medical and two acute medical units. The Tilburg Frailty Indicator (TFI), Timed-Up-and-Go (TUG), and grip strength (GS) exposure variables were measured. Associations were assessed using Cox regression with first unplanned readmission or death (all-causes) as the outcome. Prediction models including the three exposure variables and known risk factors were modelled using logistic regression and C-statistics.

Results: Of 1328 included patients, 50% were readmitted or died within 6 months. When adjusted for gender and age, there was an 88% higher risk of readmission or death if the TFI scores were 8-13 points compared to 0-1 points (HR 1.88, CI 1.38;2.58). Likewise, higher TUG and lower GS scores were associated with higher risk of readmission or death. The area under the curve for the prediction models ranged from 0.64 (0.60;0.68) to 0.72 (0.68;0.76).

Conclusion: In acutely admitted older medical patients, higher frailty assessed by TFI, TUG, and GS was associated with a higher risk of readmission or death within 6 months after discharge. The performance of the prediction models was mediocre, and the models cannot stand alone as risk stratification tools in clinical practice.
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http://dx.doi.org/10.1016/j.archger.2018.01.013DOI Listing
March 2019

Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness.

Nat Commun 2017 07 12;8:16015. Epub 2017 Jul 12.

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK.

Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.
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http://dx.doi.org/10.1038/ncomms16015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510175PMC
July 2017

Is objectively measured sitting at work associated with low-back pain? A cross sectional study in the DPhacto cohort.

Scand J Work Environ Health 2018 01 27;44(1):96-105. Epub 2017 Oct 27.

National Research Centre for the Working Environment (NRCWE), Lersø Parkallé 105, 2100 Copenhagen, Denmark.

Objectives Low-back pain (LBP) is a substantial health challenge due to the risk for long-term sickness absence and early retirement. Several biomechanical exposures at work, including sitting, have been suggested to increase the risk for LBP. The objectives of this study were to determine (i) the extent to which temporal patterns and total amount of objectively measured sitting is associated with LBP intensity and (ii) whether selected modifiers influence these associations. Methods This cross sectional study uses baseline data from the Danish PHysical ACTivity cohort with Objective measurements (DPhacto) of physical activities in the cleaning, transport and manufacturing sectors. Peak intensity of LBP was collected by questionnaire on a 0-10 scale and sitting was expressed in terms of total duration and temporal pattern, ie, time spent in brief bursts (≤5 minutes), moderate periods (>5-≤20 minutes), and prolonged periods of sitting (>20 minutes); both during work and whole day (waking hours only). Associations were determined using linear regression in models accounting for moderation and confounding. Factors evaluated as moderators or confounders were assessed by questionnaire. Results The population consisted of 704 participants. No significant associations were found between total duration or temporal patterns of sitting and LBP intensity, neither during work nor for the whole day. Body mass index (BMI) significantly moderated the association between sitting and LBP; participants with a high and low BMI showing a negative and positive association, respectively. Conclusion Sitting was not independently associated with peak LBP intensity, suggesting other exposures are more powerful risk factors for LBP.
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http://dx.doi.org/10.5271/sjweh.3680DOI Listing
January 2018

Patterns of sedentary time and ambulatory physical activity in a Danish population of girls and women with Rett syndrome.

Disabil Rehabil 2019 01 2;41(2):133-141. Epub 2017 Oct 2.

a Department of Health Sciences, Faculty of Medicine , Lund University , Lund , Sweden.

Background: Rett syndrome (RTT) is a rare neurodevelopmental disorder leading to multiple disabilities and high dependency on caregivers. This study aimed to: (1) describe the patterns of sedentary time and daily steps and (2) identify the association of individual and environmental characteristics with sedentary time.

Methods: All Danish females with RTT older than 5 years of age and with a MECP2 mutation were invited to participate. The activPAL and StepWatch Activity Monitor (SAM) were worn by participants for at least four days. Sedentary time and step counts were plotted by time to examine daily activity patterns. Associations between sedentary time and individual and environmental covariates were assessed with linear regression models.

Results: The median (interquartile range) age of participants was 22.0 (14.3-36.5) years. On average 83.3% (standard deviation 13.9%) of waking hours were spent in sedentary behaviours (n = 48) and the median (interquartile range) daily step count was 5128 (2829-7704) (n = 28). Females older than 33.5 years, and those unable to walk independently were more sedentary.

Conclusions: This study demonstrated high levels of sedentary time and low daily step counts in a Danish population of females with RTT. Advancing age and lower walking skills were associated with higher levels of sedentary time. Implications for Rehabilitation Sedentary lifestyles in individuals with disabilities have a negative impact on health and quality of life. High levels of sedentary time and low daily step counts were demonstrated in a Danish population of females with Rett syndrome. Advancing age and inability to walk independently were strongly associated with higher levels of sedentary time in females with Rett syndrome. Understanding patterns of sedentary behaviour and physical activity can aid health care professionals in developing health-promoting physical activity interventions.
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http://dx.doi.org/10.1080/09638288.2017.1381181DOI Listing
January 2019

Self-rated health and all-cause and cause-specific mortality of older adults: Individual data meta-analysis of prospective cohort studies in the CHANCES Consortium.

Maturitas 2017 Sep 17;103:37-44. Epub 2017 Jun 17.

Hellenic Health Foundation, 115 27, Athens, Greece; Department of Epidmiology, Harvard School of Public Health, Boston, MA 02115, USA; Bureau of Epidemiologic Research, Academy of Athens, 115 27Athens, Greece.

Objectives: To evaluate, among the elderly, the association of self-rated health (SRH) with mortality, and to identify determinants of self-rating health as "at-least-good".

Study Design: Individual data on SRH and important covariates were obtained for 424,791 European and United States residents, ≥60 years at recruitment (1982-2008), in eight prospective studies in the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES). In each study, adjusted mortality ratios (hazard ratios, HRs) in relation to SRH were calculated and subsequently combined with random-effect meta-analyses.

Main Outcome Measures: All-cause, cardiovascular and cancer mortality.

Results: Within the median 12.5 years of follow-up, 93,014 (22%) deaths occurred. SRH "fair" or "poor" vs. "at-least-good" was associated with increased mortality: HRs 1.46 (95% CI 1·23-1.74) and 2.31 (1.79-2.99), respectively. These associations were evident: for cardiovascular and, to a lesser extent, cancer mortality, and within-study, within-subgroup analyses. Accounting for lifestyle, sociodemographic, somatometric factors and, subsequently, for medical history explained only a modest amount of the unadjusted associations. Factors favourably associated with SRH were: sex (males), age (younger-old), education (high), marital status (married/cohabiting), physical activity (active), body mass index (non-obese), alcohol consumption (low to moderate) and previous morbidity (absence).

Conclusion: SRH provides a quick and simple tool for assessing health and identifying groups of elders at risk of early mortality that may be useful also in clinical settings. Modifying determinants of favourably rating health, e.g. by increasing physical activity and/or by eliminating obesity, may be important for older adults to "feel healthy" and "be healthy".
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http://dx.doi.org/10.1016/j.maturitas.2017.06.023DOI Listing
September 2017

The efficacy of motivational counselling and SMS reminders on daily sitting time in patients with rheumatoid arthritis: a randomised controlled trial.

Ann Rheum Dis 2017 Sep 5;76(9):1603-1606. Epub 2017 Jun 5.

Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet, University of Copenhagen, Glostrup, Denmark.

Objectives: The aim of this report is to investigate the efficacy of an individually tailored, theory-based behavioural intervention for reducing daily sitting time, pain and fatigue, as well as improving health-related quality of life, general self-efficacy, physical function and cardiometabolic biomarkers in patients with rheumatoid arthritis (RA).

Methods: In this randomised controlled trial 150 patients with RA were randomised to an intervention or a no-intervention control group. The intervention group received three individual motivational counselling sessions and short message service or text messages aimed at reduction of sedentary behaviour during the 16-week intervention period. Primary outcome was change in daily sitting time measured objectively by ActivPAL. Secondary outcomes included change in pain, fatigue, physical function, general self-efficacy, quality of life, blood pressure, blood lipids, haemoglobin A1c, body weight, body mass index, waist circumference and waist-hip ratio.

Results: 75 patients were allocated to each group. Mean reduction in daily sitting time was -1.61 hours/day in the intervention versus 0.59 hours/day increase in the control group between-group difference -2.20 (95% CI -2.72 to -1.69; p<0.0001) hours/day in favour of the intervention group. Most of the secondary outcomes were also in favour of the intervention.

Conclusion: An individually tailored, behavioural intervention reduced daily sitting time in patients with RA and improved patient-reported outcomes and cholesterol levels.

Trial Registration Number: NCT01969604; Results.
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http://dx.doi.org/10.1136/annrheumdis-2016-210953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561370PMC
September 2017

Self-Reported Versus Accelerometer-Assessed Daily Physical Activity in Childhood Obesity Treatment.

Percept Mot Skills 2017 Aug 31;124(4):795-811. Epub 2017 May 31.

1 Section of Metabolic Genetics, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark.

We investigated the relationship between interview-based subjective ratings of physical activity (PA) engagement and accelerometer-assessed objectively measured PA in children and adolescents with overweight or obesity. A total of 92 children and adolescents (40 males, 52 females) with BMI ≥ 90th percentile for sex and age, aged 5-17 years had valid GT3X + accelerometer-assessed PA and interview-assessed self-reported information on PA engagement at the time of enrollment in a multidisciplinary outpatient tertiary treatment for childhood obesity. Accelerometer-derived mean overall PA and time spent in moderate to vigorous physical intensity were generated, applying cut-offs based on Vector Magnitude settings as defined by Romanzini et al. (2014), and a physical activity score (PAS) based on self-reported data. Overall, a higher self-reported PAS was correlated with higher accelerometer-assessed daily total PA levels ( r = 0.34, p < .01) and children who reported a high PAS were more physically active compared with children who reported a low PAS. There was a fair level of agreement between self-reported PAS and accelerometer-assessed PA (Kappa agreement = 0.23; 95% CI = [0.03, 0.43]; p = .01). PAS, derived from self-report, may be a useful instrument for evaluating PA at a group level among children and adolescents enrolled in multidisciplinary obesity treatment.
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http://dx.doi.org/10.1177/0031512517710880DOI Listing
August 2017

Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.

PLoS Genet 2017 Apr 27;13(4):e1006528. Epub 2017 Apr 27.

Estonian Genome Center, University of Tartu, Tartu, Estonia.

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
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http://dx.doi.org/10.1371/journal.pgen.1006528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5407576PMC
April 2017

Effects on musculoskeletal pain from "Take a Stand!" - a cluster-randomized controlled trial reducing sitting time among office workers.

Scand J Work Environ Health 2017 07 3;43(4):350-357. Epub 2017 Apr 3.

National Institute of Public Health, Øster Farimagsgade 5a, 2nd, 1353 Copenhagen C, Denmark.

Objectives Prolonged sitting at work has been found to increase risk for musculoskeletal pain. The office-based intervention "Take a Stand!" was effective in reducing sitting time at work. We aimed to study the effect of the intervention on a secondary outcome: musculoskeletal pain. Methods Take a Stand! included 19 offices (317 workers) at four workplaces cluster randomized to intervention or control. The multicomponent intervention lasted three months and included management support, environmental changes, and local adaptation. Control participants behaved as usual. Musculoskeletal pain was measured by self-report questionnaire assessing pain in neck-shoulders, back and extremities in three categories at baseline, and one and three months follow-up. Results At one month, there was no difference in odds ratio (OR) for pain in neck-shoulders between the two groups. However, after three months, the OR was 0.52 [95% confidence interval (95% CI) 0.30-0.92] for pain in neck-shoulders in the intervention compared to the control group. No differences were found between the intervention and control group for pain in back and extremities over the three months. For total pain score a slight reduction was found in the intervention compared to the control group at one and three months [-0.13 (95% CI -0.23- -0.03) and -0.17 (95% CI -0.32- -0.01)]. Conclusions The secondary analyses showed that the office-based intervention Take a Stand! reduced neck-shoulder pain after three months and total pain score after one and three months among office workers, but not neck-shoulder pain after one month or pain in the back and extremities.
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http://dx.doi.org/10.5271/sjweh.3639DOI Listing
July 2017
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