Published in 2019

Association Between Long-Term Exposure to Wind Turbine Noise and the Risk of Stroke: Data From the Danish Nurse Cohort

Bräuner, E. V., Jørgensen, J. T., Duun-Henriksen, A. K., Backalarz, C., Laursen, J. E., Pedersen, T. H., Simonsen, M. K. & Andersen, Z. J., 16 jul. 2019, I : Journal of the American Heart Association. 8, 14, s. e013157

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Background Epidemiological studies suggest that road traffic noise increases the risk of stroke. Similar effects may be expected from wind turbine noise (WTN) exposure, but epidemiological evidence is lacking. The present study investigated the association between long-term exposure to WTN and the risk for stroke. Methods and Results First-ever stroke in 28 731 female nurses in the Danish Nurse Cohort was identified in the Danish National Patient register until the end of 2013. WTN, traffic noise, and air pollution exposures were estimated for all historic and present residential addresses between 1982 and 2013. Time-varying Cox proportional hazard regression was used to examine the associations between the 11-, 5-, and 1-year rolling means of WTN levels and stroke incidence. Of 23 912 nurses free of stroke at the cohort baseline, 1097 nurses developed stroke by the end of follow-up. At the cohort baseline, 10.3% of nurses were exposed to WTN (≥1 turbine within a 6000-meter radius of the residence) and 13.3% in 2013. Mean baseline residential noise levels among exposed nurses were 26.3 dB(A). No association between long-term WTN exposure and stroke incidence was found. The adjusted hazard ratios and 95% CIs for the 11-, 5-, and 1-year running mean residential WTN exposures preceding stroke diagnosis, comparing nurses with residential WTN levels above and below 20 dB(A) were 1.09 (0.90-1.31), 1.08 (0.89-1.31) and 1.08 (0.89-1.32), respectively. Conclusions This comprehensive cohort study lends no support to an association between long-term WTN exposure and stroke risk.

Originalsprog Engelsk
Tidsskrift Journal of the American Heart Association
Vol/bind 8
Udgave nummer 14
Sider (fra-til) e013157
ISSN 2047-9980
DOI
Status Udgivet - 16 jul. 2019

OBJECTIVE: To describe spontaneous changes in time spent physically inactive measured continuously by accelerometry during an 8-week weight loss intervention in overweight/obese individuals with knee osteoarthritis.

METHOD: This study was designed as an observational cohort study including individuals with concomitant overweight/obesity and symptomatic knee osteoarthritis from an osteoarthritis outpatient clinic. Participants completed an 8-week dietary intervention previously shown to induce substantial weight loss. The main outcome was accelerometer-based measurement of physical inactivity for 24 hours daily during the 8-week intervention period presented as change in the average daily time spent inactive (sitting, reclined or sleeping) from one week prior to intervention to the last week of the intervention.

RESULTS: A total of 124 participants completed the dietary intervention and had valid accelerometer recordings. The mean weight loss was 12.7 kg [95% CI -13.2 to -12.1; P<.0001] after 8 weeks corresponding to a decrease in BMI of 4.3 kg/m2 [95%CI -4.5 to -4.2; P<.0001]. Significant improvements in osteoarthritis symptoms (assessed by the Knee Injury and Osteoarthritis Outcome Score) was found across all subscales; for KOOS pain an improvement of 12.8 points [95% CI, 10.6 to 15.0; P<.0001] was observed. No statistically significant change occurred in the average daily time spent inactive from baseline to follow-up (mean change: 8.8 minutes/day [95% CI, -12.1 to 29.7]; P=0.41).

CONCLUSION: Physical inactivity remains stable despite a clinically significant weight loss and improvements in knee osteoarthritis symptoms. Change in inactivity does not seem to occur spontaneously, suggesting that focused efforts to reduce inactive behaviors are needed. This article is protected by copyright. All rights reserved.

Originalsprog Engelsk
Tidsskrift Arthritis Care & Research
ISSN 2151-464X
DOI
Status E-pub ahead of print - 1 mar. 2019

Bibliografisk note

This article is protected by copyright. All rights reserved.

Associations between vitamin D status in pregnancy and offspring neurodevelopment: a systematic literature review

Janbek, J., Specht, I. O. & Heitmann, B. L., 1 maj 2019, I : Nutrition Reviews. 77, 5, s. 330-349 20 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

CONTEXT: Vitamin D plays an important role in the development of the brain, which is one of the earliest fetal organs to develop. Results from epidemiological studies investigating associations between maternal levels of vitamin D during pregnancy and offspring neurodevelopment are mixed and inconclusive.

OBJECTIVE: This systematic review of studies that examined vitamin D levels in pregnancy and offspring neurodevelopment used 3 specific domains-timing of exposure during pregnancy trimesters, neurodevelopmental outcomes, and offspring age at assessment of outcomes-to determine whether vitamin D status in pregnancy is associated with offspring neurodevelopment.

DATA SOURCES: A search of the Embase, PsychInfo, Scopus, and The Cochrane Library databases in September 2017 and February 2018 identified 844 articles, of which 46 were retrieved for full-text assessment.

STUDY SELECTION: Eligibility criteria were used to select studies. All authors examined the studies, and consensus was reached through discussion. Results were divided according to the 3 domains.

DATA EXTRACTION: Authors examined the studies independently, and data from eligible studies were extracted using a modified version of the Cochrane data collection form. Using the modified Downs and Black checklist, 2 authors assessed the quality of the studies independently and were blinded to each other's assessment. Consensus was reached upon discussion and with the involvement of the third author.

RESULTS: Fifteen observational studies were included. Vitamin D in pregnancy was associated with offspring language and motor skills in young children. Associations persisted into adolescence, and results were not dependent on the timing of vitamin D exposure during pregnancy. No supplementation studies were identified.

CONCLUSIONS: There is some evidence that low vitamin D status in pregnancy is associated with offspring language and motor development, particularly in young children.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42017078312.

Originalsprog Engelsk
Tidsskrift Nutrition Reviews
Vol/bind 77
Udgave nummer 5
Sider (fra-til) 330-349
Antal sider 20
ISSN 0029-6643
DOI
Status Udgivet - 1 maj 2019

Bibliografisk note

© The Author(s) 2019. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Attribution of weight regain to emotional reasons amongst European adults with overweight and obesity who regained weight following a weight loss attempt

Sainsbury, K., Evans, E. H., Pedersen, S., Marques, M. M., Teixeira, P. J., Lähteenmäki, L., Stubbs, R. J., Heitmann, B. L. & Sniehotta, F. F., apr. 2019, I : Eating and Weight Disorders. 24, 2, s. 351-361 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

PURPOSE: Despite the wide availability of effective weight loss programmes, maintenance of weight loss remains challenging. Difficulties in emotion regulation are associated with binge eating and may represent one barrier to long-term intervention effectiveness in obesity. The purpose of this study was to determine the relationship between emotion regulation difficulties and the extent of weight regain in a sample of adults who had lost, and then regained, weight, and to examine the characteristics associated with emotional difficulties.

METHODS: 2000 adults from three European countries (UK, Portugal, and Denmark) completed an online survey assessing self-reported weight loss and regain following their most recent weight loss attempt. They also completed a binge eating disorder screening questionnaire and, if they had regained weight, were asked if they attributed it to any emotional factors (a proxy for emotion regulation difficulties). Spearman's correlations and logistic regression were used to assess the associations between emotion regulation, weight regain, and strategy use.

RESULTS: Emotion regulation difficulties were associated with greater weight regain (N = 1594 who lost and regained weight). Attribution to emotional reasons was associated with younger age, female gender, loss of control and binge eating, lower perceptions of success at maintenance, using more dietary and self-regulatory strategies in weight loss, and fewer dietary strategies in maintenance.

CONCLUSIONS: Weight-related emotion regulation difficulties are common amongst regainers and are associated with regaining more weight. Affected individuals are already making frequent use of behavioural strategies during weight loss, but do not apply these consistently beyond active attempts. Simply encouraging the use of more numerous strategies, without concurrently teaching emotion regulation skills, may not be an effective means to improving weight outcomes in this group.

LEVEL OF EVIDENCE: Level V, descriptive (cross-sectional) study.

Originalsprog Engelsk
Tidsskrift Eating and Weight Disorders
Vol/bind 24
Udgave nummer 2
Sider (fra-til) 351-361
Antal sider 11
ISSN 1124-4909
DOI
Status Udgivet - apr. 2019

Biomarkers of Whole-Grain and Cereal-Fiber Intake in Human Studies: A Systematic Review of the Available Evidence and Perspectives

Jawhara, M., Sørensen, S. B., Heitmann, B. L. & Andersen, V., 6 dec. 2019, I : Nutrients. 11, 12

Publikation: Bidrag til tidsskriftReviewForskningpeer review

High whole-grain consumption is related to better health outcomes. The specific physiological effect of these compounds is still unrevealed, partly because the accurate estimation of the intake of whole grains from dietary assessments is difficult and prone to bias, due to the complexity of the estimation of the intake by the consumer. A biomarker of whole-grain intake and type of whole-grain intake would be useful for quantifying the exposure to whole-grain intake. In this review, we aim to review the evidence on the potential biomarkers for whole-grain intake in the literature. We conducted a systematic search in Medline, Embase, Web of Science, and the Cochrane database. In total, 39 papers met the inclusion criteria following the PRISMA guidelines and were included. The relative validity, responsiveness, and reproducibility of these markers were assessed for short-, medium-, and long-term exposure as important criteria for the potential use of these biomarkers from a clinical and research perspective. We found three major groups of biomarkers: (1) alkylresorcinol, as well as its homologs and metabolites, assessed in plasma, adipose tissue biopsies, erythrocyte membranes, and urine; (2) avenacosides, assessed in urine samples; and (3) benzoxazinoid-derived phenylacetamide sulfates, assessed in blood and urine samples. The reviewed biomarkers may be used for improved assessment of associations between whole-grain intake and health outcomes.

Originalsprog Engelsk
Tidsskrift Nutrients
Vol/bind 11
Udgave nummer 12
ISSN 2072-6643
DOI
Status Udgivet - 6 dec. 2019

Brain resting-state connectivity in the development of secondary hyperalgesia in healthy men

Hansen, M. S., Becerra, L., Dahl, J. B., Borsook, D., Mårtensson, J., Christensen, A., Nybing, J. D., Havsteen, I., Boesen, M. & Asghar, M. S., 1 apr. 2019, I : Brain structure & function. 224, 3, s. 1119-1139 21 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Central sensitization is a condition in which there is an abnormal responsiveness to nociceptive stimuli. As such, the process may contribute to the development and maintenance of pain. Factors influencing the propensity for development of central sensitization have been a subject of intense debate and remain elusive. Injury-induced secondary hyperalgesia can be elicited by experimental pain models in humans, and is believed to be a result of central sensitization. Secondary hyperalgesia may thus reflect the individual level of central sensitization. The objective of this study was to investigate possible associations between increasing size of secondary hyperalgesia area and brain connectivity in known resting-state networks. We recruited 121 healthy participants (male, age 22, SD 3.35) who underwent resting-state functional magnetic resonance imaging. Prior to the scan session, areas of secondary hyperalgesia following brief thermal sensitization (3 min. 45 °C heat stimulation) were evaluated in all participants. 115 participants were included in the final analysis. We found a positive correlation (increasing connectivity) with increasing area of secondary hyperalgesia in the sensorimotor- and default mode networks. We also observed a negative correlation (decreasing connectivity) with increasing secondary hyperalgesia area in the sensorimotor-, fronto-parietal-, and default mode networks. Our findings indicate that increasing area of secondary hyperalgesia is associated with increasing and decreasing connectivity in multiple networks, suggesting that differences in the propensity for central sensitization, assessed as secondary hyperalgesia areas, may be expressed as differences in the resting-state central neuronal activity.

Originalsprog Engelsk
Tidsskrift Brain structure & function
Vol/bind 224
Udgave nummer 3
Sider (fra-til) 1119-1139
Antal sider 21
ISSN 0177-5154
DOI
Status Udgivet - 1 apr. 2019

Calcium and vitamin D supplementation and/or periodontal therapy in the treatment of periodontitis among Brazilian pregnant women: protocol of a feasibility randomised controlled trial (the IMPROVE trial)

Cocate, P. G., Kac, G., Heitmann, B. L., Nadanovsky, P., da Veiga Soares Carvalho, M. C., Benaim, C., Schlüssel, M. M., de Castro, M. B. T., Alves-Santos, N. H., Baptista, A. F., Holick, M. F., Mokhtar, R. R., Bomfim, A. R. & Adegboye, A. R. A., 2019, I : Pilot and Feasibility Studies. 5, s. 38

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Background: Periodontitis is a common oral inflammation, which is a risk factor for adverse pregnancy outcomes. Intakes of vitamin D and calcium are inversely associated with occurrence and progression of periodontitis. This study aims to assess the feasibility of a multi-component intervention, including provision of milk powder supplemented with calcium and vitamin D and periodontal therapy (PT), for improving maternal periodontal health and metabolic and inflammatory profiles of low-income Brazilian pregnant women with periodontitis.

Methods: The IMPROVE trial is a feasibility randomised controlled trial (RCT) with a 2 × 2 factorial design with a parallel process evaluation. Pregnant women with periodontitis, aged 18-40 years and with < 20 gestational weeks (n = 120) were recruited and randomly allocated into four groups: (1) fortified sachet (vitamin D and calcium) and powdered milk plus PT during pregnancy, (2) placebo sachet and powdered milk plus PT during pregnancy, (3) fortified sachet (vitamin D and calcium) and powdered milk plus PT after delivery and (4) placebo sachet and powdered milk plus PT after delivery. Dentists and participants are blinded to fortification. Acceptability of study design, recruitment strategy, random allocation, data collection procedures, recruitment rate, adherence and attrition rate will be evaluated. Data on serum levels of vitamin D, calcium and inflammatory biomarkers; clinical periodontal measurements; anthropometric measurements; and socio-demographic questionnaires are collected at baseline, third trimester and 6-8 weeks postpartum. Qualitative data are collected using focus group, for analysis of favourable factors and barriers related to study adherence.

Discussion: Oral health and mineral/vitamin supplementation are much overlooked in the public prenatal assistance in Brazil and of scarcity of clinical trials addressing these issues in low and middle-income countries,. To fill this gap the present study was designed to assess the feasibility of a RCT on acceptability of a multi-component intervention combining conventional periodontal treatment and consumption of milk fortified with calcium-vitamin D for improving periodontal conditions and maternal metabolic and inflammation status, among Brazilian low-income pregnant women with periodontitis. Thus, we hope that this relatively low-cost and safe multicomponent intervention can help reduce inflammation, improve maternal periodontal health and metabolic profile and consequently prevent negative gestational outcomes.

Trial registration: NCT, NCT03148483. Registered on May 11, 2017.

Originalsprog Engelsk
Tidsskrift Pilot and Feasibility Studies
Vol/bind 5
Sider (fra-til) 38
ISSN 2055-5784
DOI
Status Udgivet - 2019

Can legal restrictions of prenatal exposure to industrial trans-fatty acids reduce risk of childhood hematopoietic neoplasms? A population-based study

Specht, I. O., Huybrechts, I., Frederiksen, P., Steliarova-Foucher, E., Chajes, V. & Heitmann, B. L., feb. 2019, I : European Journal of Clinical Nutrition. 73, 2, s. 311-318 8 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Causes of most childhood hematopoietic neoplasms are unknown. Early age of occurrence suggests prenatal etiology. Positive associations have been reported between industrially produced trans-fatty acids (iTFAs) and risks of some cancers in adults. iTFAs are pro-inflammatory and adversely affect the beneficial effects of essential fatty acids, the latter is diminishing tumor growth. In 2004 Denmark legislated against the use of iTFA in foodstuffs. Using the entire population, we investigated if the changes in the legislation as a proxy to the reduced exposure to iTFA had affected the incidence of childhood hematopoietic neoplasms.

METHODS: We used a Cox proportional hazard model to compare the hazard of childhood hematopoietic neoplasms among children born before and after the iTFA ban, as a proxy for fetal iTFA exposure. To take the potential secular trend in hematopoietic neoplasms into account, we modeled the variation in cancer risk across birth cohorts by a piecewise linear spline with a knot in 2004, which allowed a comparison of the hazard of childhood hematopoietic neoplasms between the time before and after the iTFA ban.

RESULTS: Among children born in 1988-2008 in Denmark, 720 were diagnosed with hematopoietic neoplasms before the age of 7 years, corresponding to an overall incidence rate of 7.6 per 100 000 person years. The incidence rates increased by 2% per cohort in 1988-2004 (hazard ratio: 1.02 [1.01; 1.04]) and in 2004-2008 (hazard ratio: 1.02 [0.95; 1.11]).

CONCLUSIONS: No apparent benefit of the iTFA legislation in reducing childhood hematopoietic neoplasms was observed on population basis. Individual-level data are needed to investigate any possible associations between biomarkers of iTFA intake and risk of childhood hematopoietic neoplasms.

Originalsprog Engelsk
Tidsskrift European Journal of Clinical Nutrition
Vol/bind 73
Udgave nummer 2
Sider (fra-til) 311-318
Antal sider 8
ISSN 0954-3007
DOI
Status Udgivet - feb. 2019

Cause-specific mortality in patients with psoriasis and psoriatic arthritis

Skov, L., Thomsen, S. F., Kristensen, L. E., Dodge, R., Hedegaard, M. S. & Kjellberg, J., jan. 2019, I : British Journal of Dermatology. 180, 1, s. 100-107 8 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: There are limited data regarding causes of mortality in patients with psoriasis or psoriatic arthritis (PsA).

OBJECTIVES: This retrospective cohort study evaluated the risk and leading causes of mortality in patients with psoriasis or PsA.

METHODS: Individuals with a hospital-based diagnosis of PsA or psoriasis were identified using the Danish National Patient Registry. Matched control individuals were identified from the general population. The main outcome measures were risk of death and cause-specific mortality in patients with psoriasis or PsA.

RESULTS: Death rates per 1000 patient-years (with 95% confidence intervals) vs. controls were 22·3 (19·7-24·9) vs. 13·9 (11·8-16·0) for patients with psoriasis and 10·8 (8·9-12·8) vs. 11·6 (9·6-13·6) for patients with PsA. Survival, according to stratified hazard ratios (HRs), was significantly lower in patients with psoriasis than in controls (HR 1·74, P < 0·001), but not in patients with PsA (HR 1·06, P = 0·19). Significantly increased risk of death was observed in patients with psoriasis vs. controls due to a number of causes; the highest risks were observed for diseases of the digestive system; endocrine, nutritional and metabolic diseases; and certain infectious and parasitic diseases (HRs 3·61, 3·02 and 2·71, respectively). In patients with PsA, increased mortality was observed only for certain infectious and parasitic diseases (HR 2·80) and diseases of the respiratory system (HR 1·46). Patients with psoriasis died at a younger age than controls (mean age 71·0 vs. 74·5 years, P < 0·001).

CONCLUSIONS: Patients with severe psoriasis have increased mortality risk compared with matched controls, due to a number of causes. Evidence to support an increased risk for patients with PsA was less convincing.

Originalsprog Engelsk
Tidsskrift British Journal of Dermatology
Vol/bind 180
Udgave nummer 1
Sider (fra-til) 100-107
Antal sider 8
ISSN 0007-0963
DOI
Status Udgivet - jan. 2019

Bibliografisk note

© 2018 British Association of Dermatologists.

Child behaviour and subsequent changes in body weight, composition and shape

Christensen, K. G., Nielsen, S. G., Olsen, N. J., Dalgård, C., Heitmann, B. L. & Larsen, S. C., 2019, I : PLoS One. 14, 12, s. e0226003

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: Studies have found an association between child behavioural problems and overweight, but the existing evidence for this relationship is inconsistent, and results from longitudinal studies are sparse. Thus, we examined the association between behavioural problems and subsequent changes in body mass index (BMI) and anthropometry over a follow-up period of 1.3 years among children aged 2-6 years.

DESIGN: The study was based on a total of 345 children from The Healthy Start Study; all children were healthy weight but predisposed to develop overweight. The Danish version of the Strengths and Difficulties Questionnaire (SDQ), classified as SDQ Total Difficulties (SDQ-TD) and SDQ Prosocial Behaviour (SDQ-PSB), was used to assess child behaviour. Linear regression analyses were used to examine associations between SDQ scores and subsequent change in BMI z-score, body fat percentage, waist circumference and waist-hip ratio, while taking possible confounding factors into account.

RESULTS: We found an association between SDQ-PSB and subsequent change in BMI z-score (β: 0.040 [95% CI: 0.010; 0.071, p = 0.009]). However, there was no evidence of an association between SDQ-PSB and measures of body composition or body shape.

CONCLUSIONS: Among 2 to 6 years old children predisposed to overweight, the association between SDQ-scores and weight gain is either absent or marginal. The SDQ-PSB score may be associated with subsequent increases in BMI z-score, but this association does not seem driven by an increased relative fat accumulation.

Originalsprog Engelsk
Tidsskrift PLoS One
Vol/bind 14
Udgave nummer 12
Sider (fra-til) e0226003
ISSN 1932-6203
DOI
Status Udgivet - 2019

Compliance with the Very Integrated Program (VIP) for Smoking Cessation, Nutrition, Physical Activity and Comorbidity Education Among Patients in Treatment for Alcohol and Drug Addiction

Hovhannisyan, K., Günther, M., Raffing, R., Wikström, M., Adami, J. & Tønnesen, H., 28 jun. 2019, I : International Journal of Environmental Research and Public Health. 16, 13, s. E2285

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Meeting adherence is an important element of compliance in treatment programmes. It is influenced by several factors one being self-efficacy. We aimed to investigate the association between self-efficacy and meeting adherence and other factors of importance for adherence among patients with alcohol and drug addiction who were undergoing an intensive lifestyle intervention. The intervention consisted of a 6-week Very Integrated Programme. High meeting adherence was defined as >75% participation. The association between self-efficacy and meeting adherence were analysed. The qualitative analyses identified themes important for the patients and were performed as text condensation. High self-efficacy was associated with high meeting adherence (ρ = 0.24, p = 0.03). In the multivariate analyses two variables were significant: avoid complications (OR: 0.51, 95% CI: 0.29-0.90) and self-efficacy (OR: 1.28, 95% CI: 1.00-1.63). Reflections on lifestyle change resulted in the themes of Health and Wellbeing, Personal Economy, Acceptance of Change, and Emotions Related to Lifestyle Change. A higher level of self-efficacy was positively associated with meeting adherence. Patients score high on avoiding complications but then adherence to the intervention drops. There was no difference in the reflections on lifestyle change between the group with high adherence and the group with low adherence.

Originalsprog Engelsk
Tidsskrift International Journal of Environmental Research and Public Health
Vol/bind 16
Udgave nummer 13
Sider (fra-til) E2285
ISSN 1661-7827
DOI
Status Udgivet - 28 jun. 2019

Continuous glucose monitoring in pregnant women with type 1 diabetes: an observational cohort study of 186 pregnancies

Kristensen, K., Ögge, L. E., Sengpiel, V., Kjölhede, K., Dotevall, A., Elfvin, A., Knop, F. K., Wiberg, N., Katsarou, A., Shaat, N., Kristensen, L. & Berntorp, K., jul. 2019, I : Diabetologia. 62, 7, s. 1143-1153 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

AIMS/HYPOTHESIS: The aim of this study was to analyse patterns of continuous glucose monitoring (CGM) data for associations with large for gestational age (LGA) infants and an adverse neonatal composite outcome (NCO) in pregnancies in women with type 1 diabetes.

METHODS: This was an observational cohort study of 186 pregnant women with type 1 diabetes in Sweden. The interstitial glucose readings from 92 real-time (rt) CGM and 94 intermittently viewed (i) CGM devices were used to calculate mean glucose, SD, CV%, time spent in target range (3.5-7.8 mmol/l), mean amplitude of glucose excursions and also high and low blood glucose indices (HBGI and LBGI, respectively). Electronic records provided information on maternal demographics and neonatal outcomes. Associations between CGM indices and neonatal outcomes were analysed by stepwise logistic regression analysis adjusted for confounders.

RESULTS: The number of infants born LGA was similar in rtCGM and iCGM users (52% vs 53%). In the combined group, elevated mean glucose levels in the second and the third trimester were significantly associated with LGA (OR 1.53, 95% CI 1.12, 2.08, and OR 1.57, 95% CI 1.12, 2.19, respectively). Furthermore, a high percentage of time in target in the second and the third trimester was associated with lower risk of LGA (OR 0.96, 95% CI 0.94, 0.99 and OR 0.97, 95% CI 0.95, 1.00, respectively). The same associations were found for mean glucose and for time in target and the risk of NCO in all trimesters. SD was significantly associated with LGA in the second trimester and with NCO in the third trimester. Glucose patterns did not differ between rtCGM and iCGM users except that rtCGM users had lower LBGI and spent less time below target.

CONCLUSIONS/INTERPRETATION: Higher mean glucose levels, higher SD and less time in target range were associated with increased risk of LGA and NCO. Despite the use of CGM throughout pregnancy, the day-to-day glucose control was not optimal and the incidence of LGA remained high.

Originalsprog Engelsk
Tidsskrift Diabetologia
Vol/bind 62
Udgave nummer 7
Sider (fra-til) 1143-1153
Antal sider 11
ISSN 0012-186X
DOI
Status Udgivet - jul. 2019

Core Outcome Sets Specifically for Longterm Observational Studies: OMERACT Special Interest Group Update in Rheumatoid Arthritis

Lopez-Olivo, M. A., Negrón, J. B., Zogala, R. J., Carmona, L., Criner, K., Goel, N., Gonzalez-Lopez, L., Ingegnoli, F., Leong, A., March, L., Shea, B., Strand, V., Tugwell, P., Westrich-Robertson, T., Zamora, N. V., Christensen, R. & Suarez-Almazor, M. E., sep. 2019, I : Journal of Rheumatology. 46, 9, s. 1164-1167 4 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: This is an update from the Outcome Measures in Rheumatology (OMERACT) Core Outcomes in Longterm Observational Studies Special Interest Group with a focus on rheumatoid arthritis.

METHODS: Preliminary data and proposed next steps were outlined and discussed by participants.

RESULTS: Domains identified after initial steps (systematic review and qualitative research) were pain, physical functioning, participation (i.e., work, social), longterm symptoms, fertility/family planning, emotional well-being, coping, financial status, and adverse events including death.

CONCLUSION: The group agreed conceptually that short-term core outcomes could be different from longer term ones. Participants emphasized the importance of analyzing the need for core domains specifically for longterm longitudinal observational studies.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 46
Udgave nummer 9
Sider (fra-til) 1164-1167
Antal sider 4
ISSN 0315-162X
DOI
Status Udgivet - sep. 2019

Current state of evidence for endolymphatic sac surgery in Menière's disease: a systematic review

Devantier, L., Schmidt, J. H., Djurhuus, B. D., Hougaard, D. D., Händel, M. N., Liviu-Adelin Guldfred, F. & Edemann-Callesen, H., nov. 2019, I : Acta Oto-Laryngologica. 139, 11, s. 953-958 6 s.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Background: Endolymphatic sac surgery is an invasive procedure recommended to patients with Menière's disease. Aims/Objectives: To provide an overview and quality assessment of the existing evidence and to provide an updated assessment of the utility of endolymphatic sac surgery in Menière's disease. Material and Methods: We performed a systematic literature search for systematic reviews and randomized controlled trials (RCTs). The AMSTAR tool was used to assess the quality of systematic reviews and the Cochrane risk of bias tool for RCTs. The overall certainty of effects for the individual outcomes was evaluated using the GRADE approach. Results: One systematic review of high quality matched the inclusion criteria, and included three RCTs. An updated literature search from the last search date of the included review provided no further relevant RCTs. The identified RCTs individually reported a positive effect of both the placebo and active treatment groups following surgery, strongly indicative of a placebo effect. The overall certainty of the effect was very low. Conclusions and significance: There is still a lack of high-quality research suggesting that endolymphatic sac surgery provides a significant amount of symptomatic relief for Menière's patients.

Originalsprog Engelsk
Tidsskrift Acta Oto-Laryngologica
Vol/bind 139
Udgave nummer 11
Sider (fra-til) 953-958
Antal sider 6
ISSN 0001-6489
DOI
Status Udgivet - nov. 2019

Development of HiSQOL: A Hidradenitis Suppurativa-Specific Quality of Life Instrument

Thorlacius, L., Esmann, S., Miller, I., Vinding, G. & Jemec, G. B. E., 1 jun. 2019, I : Skin appendage disorders. 5, 4, s. 221-229 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Background: Hidradenitis suppurativa (HS) is a chronic and painful skin disease. In addition, HS lesions may be associated with pus and odour, potentially leading to significant stigma and, consequently, greatly affected quality of life (QOL). QOL is a multidimensional construct, which can be measured in various ways. However, generic or dermatologic QOL measures may not capture changes in QOL particularly affected in HS. Accordingly, patients and experts included in the HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC) agreed that future clinical HS trials should measure HS-specific QOL.

Objectives: To develop an HS-specific QOL instrument (HiSQOL, Hidradenitis Suppurativa Quality of life).

Method: The initial phases of the questionnaire development, described in this study, included item generation by patient interviews, development of a pilot questionnaire, questionnaire refinement, and pilot testing.

Results: For item generation, 21 patients were interviewed individually or in focus groups. Analysis of the interviews identified 105 candidate items and, next, a pilot questionnaire was developed. Finally, item reduction and two rounds of pilot testing resulted in a 23-item questionnaire representing physical, psychological, and social QOL dimensions.

Conclusions: We have comprehensively explored on HS's possible effect on the QOL of the affected individuals and identified a 23-item HS-specific QOL questionnaire. The questionnaire proved to be feasible, acceptable, and comprehensible in the second round of pilot testing. With HiSQOL, researchers can measure HS-specific QOL in future clinical trials, potentially enabling them to discover more effective treatment options. It is envisaged, that after thorough validation in a trial setting, a streamlined version of HISQOL may also become available for clinical use in daily practice.

Originalsprog Engelsk
Tidsskrift Skin appendage disorders
Vol/bind 5
Udgave nummer 4
Sider (fra-til) 221-229
Antal sider 9
ISSN 2296-9195
DOI
Status Udgivet - 1 jun. 2019

Objectives: A cohort of routine care RA patients in sustained remission had biological DMARD (bDMARDs) tapered according to a treatment guideline. We studied: the proportion of patients whose bDMARD could be successfully tapered or discontinued; unwanted consequences of tapering/discontinuation; and potential baseline predictors of successful tapering and discontinuation.

Methods: One-hundred-and-forty-three patients (91% receiving TNF inhibitor and 9% a non-TNF inhibitor) with sustained disease activity score (DAS28-CRP)⩽2.6 and no radiographic progression the previous year were included. bDMARD was reduced to two-thirds of standard dose at baseline, half after 16 weeks, and discontinued after 32 weeks. Patients who flared (defined as either DAS28-CRP ⩾ 2.6 and ΔDAS28-CRP ⩾ 1.2 from baseline, or erosive progression on X-ray and/or MRI) stopped tapering and were escalated to the previous dose level.

Results: One-hundred-and-forty-one patients completed 2-year follow-up. At 2 years, 87 patients (62%) had successfully tapered bDMARDs, with 26 (18%) receiving two-thirds of standard dose, 39 (28%) half dose and 22 (16%) having discontinued; and 54 patients (38%) were receiving full dose. ΔDAS28-CRP0-2yrs was 0.1((-0.2)-0.4) (median (interquartile range)) and mean ΔTotal-Sharp-Score0-2yrs was 0.01(1.15)(mean(s.d.)). Radiographic progression was observed in nine patients (7%). Successful tapering was independently predicted by: ⩽1 previous bDMARD, male gender, low baseline MRI combined inflammation score or combined damage score. Negative IgM-RF predicted successful discontinuation.

Conclusion: By implementing a clinical guideline, 62% of RA patients in sustained remission in routine care were successfully tapered, including 16% successfully discontinued at 2 years. Radiographic progression was rare. Maximum one bDMARDs, male gender, and low baseline MRI combined inflammation and combined damage scores were independent predictors for successful tapering.

Originalsprog Engelsk
Tidsskrift Rheumatology (Oxford, England)
Vol/bind 58
Udgave nummer 1
Sider (fra-til) 110-119
Antal sider 10
ISSN 1462-0332
DOI
Status Udgivet - 1 jan. 2019

BACKGROUND: Occupational medicine seeks to reduce sick leave; however, evidence for an add-on effect to usual care is sparse. The objective of the GOBACK trial was to test whether people with low back pain (LBP) in physically demanding jobs and at risk of sick leave gain additional benefit from a 3-month complex intervention that involves occupational medicine consultations, a work-related evaluation and workplace intervention plan, an optional workplace visit, and a physical activity program, over a single hospital consultation and an MRI.

METHODS AND FINDINGS: We enrolled people from the capital region of Denmark to an open-label, parallel-group randomized controlled trial with a superiority design from March 2014 through December 2015. In a hospital setting 305 participants (99 women) with LBP and in physically demanding jobs were randomized to occupational intervention (n = 153) or no additional intervention (control group; n = 152) added to a single hospital consultation giving a thorough explanation of the pain (i.e., clinical examination and MRI) and instructions to stay active and continue working. Primary outcome was accumulated sick leave days due to LBP during 6 months. Secondary outcomes were changes in neuropathic pain (painDETECT questionnaire [PDQ]), pain 0-10 numerical rating scale (NRS), Fear-Avoidance Beliefs Questionnaire (FABQ), Roland-Morris Disability Questionnaire (RMDQ), Short Form Health Survey (SF-36) for physical and mental health-related quality of life (HRQoL), and self-assessed ability to continue working (range 0-10). An intention-to-treat analysis of sick leave at 6 months showed no significant difference between groups (mean difference in days suggestively in favor of no additional intervention: 3.50 [95% CI -5.08 to 12.07], P = 0.42). Both groups showed significant improvements in average pain score (NRS), disability (RMDQ), fear-avoidance beliefs about physical activities and work (FABQ), and physical HRQoL (SF-36 physical component summary); there were no significant differences between the groups in any secondary outcome. There was no statistically significant improvement in neuropathic pain (PDQ score), mental HRQoL (SF-36 mental component summary), and self-assessed ability to stay in job. Four participants could not complete the MRI or the intervention due to a claustrophobic attack or accentuated back pain. Workplace visits may be an important element in the occupational intervention, although not always needed. A per-protocol analysis that included the 40 participants in the intervention arm who received a workplace visit as part of the additional occupational intervention did not show an add-on benefit in terms of sick leave (available cases after 6 months, mean difference: -0.43 days [95% CI -12.8 to 11.94], P = 0.945). The main limitations were the small number of sick leave days taken and that the comprehensive use of MRI may limit generalization of the findings to other settings, for example, general practice.

CONCLUSIONS: When given a single hospital consultation and MRI, people in physically demanding jobs at risk of sick leave due to LBP did not benefit from a complex additional occupational intervention. Occupational interventions aimed at limiting biopsychological obstacles (e.g., fear-avoidance beliefs and behaviors), barriers in the workplace, and system barriers seem essential to reduce sick leave in patients with LBP. This study indicates that these obstacles and barriers may be addressed by thorough usual care.

TRIAL REGISTRATION: Clinical Trials.gov: NCT02015572.

Originalsprog Engelsk
Tidsskrift PLOS Medicine
Vol/bind 16
Udgave nummer 8
Sider (fra-til) e1002898
ISSN 1549-1277
DOI
Status Udgivet - 16 aug. 2019

Effect of Aerobic and Resistance Exercise on Cardiac Adipose Tissues: Secondary Analyses From a Randomized Clinical Trial

Christensen, R. H., Wedell-Neergaard, A-S., Lehrskov, L. L., Legaard, G. E., Dorph, E., Larsen, M. K., Launbo, N., Fagerlind, S. R., Seide, S. K., Nymand, S., Ball, M., Vinum, N. B., Dahl, C. N., Henneberg, M., Ried-Larsen, M., Boesen, M. P., Christensen, R., Karstoft, K., Krogh-Madsen, R., Rosenmeier, J. B., Pedersen, B. K. & Ellingsgaard, H., 2019, I : JAMA Cardiology. 4, 8, s. 778-787 10 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Importance: Epicardial and pericardial adipose tissues are emerging as important risk factors for cardiovascular disease, and there is a growing interest in discovering strategies to reduce the accumulation of fat in these depots. Objective: To investigate whether a 12-week endurance or resistance training intervention regulates epicardial and pericardial adipose tissue mass. Design, Setting, and Participants: Secondary analysis of a randomized, assessor-blinded clinical trial initiated on August 2016 and completed April 2018. This single-center, community-based study included 50 physically inactive participants with abdominal obesity. Interventions: Participants were randomized to a supervised high-intensity interval endurance training (3 times a week for 45 minutes), resistance training (3 times a week for 45 minutes), or no exercise (control group). Main Outcomes and Measures: Change in epicardial and pericardial adipose tissue mass assessed by magnetic resonance imaging, based on a prespecified secondary analysis plan including 3 of 5 parallel groups. Results: Of 50 participants (mean [SD] age, 41 [14] years, 10 men [26%]; mean [SD] body mass index [calculated as weight in kilograms divided by height in meters squared], 32 [5]), 39 [78%] completed the study. Endurance training and resistance training reduced epicardial adipose tissue mass by 32% (95% CI, 10%-53%) and 24% (95% CI, 1%-46%), respectively, compared with the no exercise control group (56% [95% CI, 24%-88%]; P =.001 and 48% [95% CI, 15%-81%]; P <.001, respectively). While there was a nonsignificant reduction in pericardial adipose tissue mass after endurance training (11% [95% CI, -5% to 27%]; P =.17), resistance training significantly reduced pericardial adipose tissue mass by 31% (95% CI, 16%-47%; P <.001) when compared with the no exercise control group. Compared with the no exercise control group, there was an increase in left ventricular mass by endurance (20 g [95% CI, 11%-30%]; P <.001) and resistance training (18 g [95% CI, 8%-28%]; P <.001). Other cardiometabolic outcomes remained unchanged after the 12-week trial period. Conclusions and Relevance: In individuals with abdominal obesity, both endurance and resistance training reduced epicardial adipose tissue mass, while only resistance training reduced pericardial adipose tissue mass. These data highlight the potential preventive importance of different exercise modalities as means to reduce cardiac fat in individuals with abdominal obesity. Trial Registration: ClinicalTrials.gov identifier: NCT02901496.

Originalsprog Engelsk
Tidsskrift JAMA Cardiology
Vol/bind 4
Udgave nummer 8
Sider (fra-til) 778-787
Antal sider 10
ISSN 2380-6583
DOI
Status Udgivet - 2019

INTRODUCTION: With an increasing prevalence of citizens of older age and with overweight, the health issues related to knee osteoarthritis (OA) will intensify. Weight loss is considered a primary management strategy in patients with concomitant overweight and knee OA. However, there are no widely available and feasible methods to sustain weight loss in patients with overweight and knee OA. The present protocol describes a randomised controlled trial evaluating the efficacy and safety of the glucagon-like peptide-1 receptor agonist liraglutide in a 3 mg/day dosing in patients with overweight and knee OA.

METHODS AND ANALYSIS: 150 volunteer adult patients with overweight or obesity and knee OA will participate in a randomised, double-blind, placebo-controlled, parallel-group and single-centre trial. The participants will partake in a run-in diet intervention phase (week -8 to 0) including a low calorie diet and dietetic counselling. At week 0, patients will be randomised to either liraglutide 3 mg/day or liraglutide placebo 3 mg/day for 52 weeks as an add-on to dietetic guidance on re-introducing regular foods and a focus on continued motivation to engage in a healthy lifestyle. The co-primary outcomes are changes in body weight and the Knee Injury and Osteoarthritis Outcome Score pain subscale from week 0 to week 52.

ETHICS AND DISSEMINATION: The trial has been approved by the regional ethics committee in the Capital Region of Denmark, the Danish Medicines Agency and the Danish Data Protection Agency. An external monitoring committee (The Good Clinical Practice Unit at Copenhagen University Hospitals) will oversee the trial. The results will be presented at international scientific meetings and through publications in peer-reviewed journals.

TRIAL REGISTRATION NUMBERS: 2015-005163-16, NCT02905864, U1111-1171-4970 BASED ON PROTOCOL VERSION: V.6; 30 January 2017, 15:30 hours.

Originalsprog Engelsk
Artikelnummer e024065
Tidsskrift BMJ Open
Vol/bind 9
Udgave nummer 5
Antal sider 12
ISSN 2044-6055
DOI
Status Udgivet - 5 maj 2019

Bibliografisk note

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Effect of Magnetic Resonance Imaging vs Conventional Treat-to-Target Strategies on Disease Activity Remission and Radiographic Progression in Rheumatoid Arthritis: The IMAGINE-RA Randomized Clinical Trial

Møller-Bisgaard, S., Hørslev-Petersen, K., Ejbjerg, B., Hetland, M. L., Ørnbjerg, L. M., Glinatsi, D., Møller, J., Boesen, M., Christensen, R., Stengaard-Pedersen, K., Madsen, O. R., Jensen, B., Villadsen, J. A., Hauge, E-M., Bennett, P., Hendricks, O., Asmussen, K., Kowalski, M., Lindegaard, H., Nielsen, S. M., Bliddal, H., Krogh, N. S., Ellingsen, T., Nielsen, A. H., Balding, L., Jurik, A. G., Thomsen, H. S. & Østergaard, M., 5 feb. 2019, I : JAMA - Journal of the American Medical Association. 321, 5, s. 461-472 12 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Importance: Whether using magnetic resonance imaging (MRI) to guide treatment in patients with rheumatoid arthritis (RA) improves disease activity and slows joint damage progression is unknown.

Objective: To determine whether an MRI-guided treat-to-target strategy vs a conventional clinical treat-to-target strategy improves outcomes in patients with RA in clinical remission.

Design, Setting, and Participants: Two-year, randomized, multicenter trial conducted at 9 hospitals in Denmark. Two hundred patients with RA in clinical remission (disease activity score in 28 joints-C-reactive protein [DAS28-CRP] <3.2 and no swollen joints) were enrolled between April 2012 and June 2015. The final follow-up visit was April 2017.

Interventions: Patients were randomly allocated (1:1) to an MRI-guided vs a conventional treat-to-target strategy. In the MRI-guided group, the treatment goal was absence of MRI bone marrow edema combined with clinical remission, defined as DAS28-CRP of 3.2 or less and no swollen joints. In the conventional group, the treatment goal was clinical remission.

Main Outcomes and Measures: Co-primary outcomes were proportions of patients achieving DAS28-CRP remission (DAS28-CRP <2.6) and with no radiographic progression (no increase in total van der Heijde-modified Sharp score) at 24 months. Significance testing for the primary outcome was based on 1-sided testing. Secondary outcomes were clinical and MRI measures of disease activity, physical function, and quality of life.

Results: Of 200 patients randomized (133 women [67%]; mean [SD] age, 61.6 [10.5] years; median baseline DAS28-CRP, 1.9 [interquartile range, 1.7-2.2]; van der Heijde-modified Sharp score, 18.0 [interquartile range, 7.0-42.5]), 76 patients (76%) in the MRI-guided group and 95 (95%) in the conventional group completed the study. Of these, 64 (85%) vs 83 (88%), respectively, reached the primary clinical end point (risk difference, -4.8% [1-sided 95% CI, -13.6% to + ∞; 1-sided P = .19]) and 49 (66%) vs 58 (62%), respectively, reached the primary radiographic end point (risk difference, 4.7% [1-sided 95% CI, -7.0% to + ∞; 1-sided P = .25). Of 10 key secondary end points, 8 were null and 2 showed statistically significant benefit for the MRI treat-to-target group. Seventeen patients (17%) in the MRI-guided treat-to-target group and 6 patients (6%) in the conventional treat-to-target group experienced serious adverse events.

Conclusions and Relevance: Among patients with RA in clinical remission, an MRI-guided treat-to-target strategy compared with a conventional treat-to-target strategy did not result in improved disease activity remission rates or reduce radiographic progression. These findings do not support the use of an MRI-guided strategy for treating patients with RA.

Trial Registration: ClinicalTrials.gov Identifier: NCT01656278.

Originalsprog Engelsk
Tidsskrift JAMA - Journal of the American Medical Association
Vol/bind 321
Udgave nummer 5
Sider (fra-til) 461-472
Antal sider 12
ISSN 0002-9955
DOI
Status Udgivet - 5 feb. 2019

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