Published in 2019

A portfolio of biologic self-injection devices in rheumatology: how patient involvement in device design can improve treatment experience

van den Bemt, B. J. F., Gettings, L., Domańska, B., Bruggraber, R., Mountian, I. & Kristensen, L. E., dec. 2019, I : Drug Delivery . 26, 1, s. 384-392 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Biologic drugs (e.g. anti-tumor necrosis factors) are effective treatments for multiple chronic inflammatory diseases including rheumatoid arthritis, axial spondyloarthritis, and psoriatic arthritis. Administration of biologic drugs is usually via subcutaneous self-injection, which provides many patient benefits compared to infusions including increased flexibility, reduced costs, and reduced caregiver burden. However, it is also associated with challenges such as needle phobia, patient treatment misconceptions and incorrect drug administration, and can be impacted by dexterity problems. Evidence suggests these problems, along with other drug administration challenges (e.g. patient forgetfulness, busy lifestyles, and polypharmacy), can reduce patient adherence to treatment. To combat these challenges, patient feedback has been used to develop a range of self-injection devices, including pre-filled syringes, pre-filled pens, and electronic injection devices. Providing different devices for drug administration gives patients the opportunity to choose a device that addresses the challenges they face as an individual. Research suggests involving patients in medical device development, providing patients with a choice of devices and enrolling individuals in patient support programs can empower patients to take control of their treatment journey. By providing a portfolio of self-injection devices, designed based on patient needs, patient experience will improve, potentially improving adherence and hence, long-term treatment outcomes.

Originalsprog Engelsk
Tidsskrift Drug Delivery
Vol/bind 26
Udgave nummer 1
Sider (fra-til) 384-392
Antal sider 9
ISSN 1071-7544
DOI
Status Udgivet - dec. 2019

BACKGROUND: The association between chronically elevated cortisol, as measured by hair cortisol concentration (HCC), and dietary intake among children has generally not been explored. Moreover, it is unknown whether there is an association between parental HCC and dietary intake among their children.

OBJECTIVE: To examine associations between HCC and dietary intake among children, and to explore the association between parental HCC and dietary intake among their children.

METHODS: We conducted a cross-sectional study based on 296 children predisposed to overweight and obesity who participated in the Healthy Start study. Multiple Linear regression analyses were conducted to assess the association between HCC and total energy intake, macronutrients, fruit and vegetables, added sugar, sugar-sweetened beverages (SSB), and a diet quality index (DQI).

RESULTS: Among the children, we found that higher HCC was associated with a lower consumption of dietary fat (β: -0.7 g/day [95% CI: -1.3, -0.0] per 100 pg/mg HCC). We found no statistically significant association between HCC and intake of total energy, protein, carbohydrate, fruit and vegetables, added sugar, SSB or DQI. We found no association between parental HCC and intake of total energy, added sugar, selected food groups or DQI among their children. However, stratified analyses showed that paternal HCC was associated with a borderline significant lower total energy intake and significantly lower protein intake, but only among daughters (adjusted β: -42 kcal/day [95% CI: -85, 0] and -2.6 g/day [95% CI: -4.4, -0.8] per 100 pg/mg HCC, respectively).

CONCLUSION: Among children, chronic stress as measured by HCC may be associated with a lower fat consumption, and paternal HCC may be associated with a lower intake of energy and protein among their daughters. However, the associations observed were weak, and any clinical relevance of these findings remains questionable.

Originalsprog Engelsk
Tidsskrift PLoS One
Vol/bind 14
Udgave nummer 3
Sider (fra-til) e0213573
ISSN 1932-6203
DOI
Status Udgivet - 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.

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

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., 10 jan. 2019, I : Brain structure & function.

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
ISSN 0177-5154
DOI
Status E-pub ahead of print - 10 jan. 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

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

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
Tidsskriftsnummer 1
Sider (fra-til) 110-119
ISSN 1462-0324
DOI
Status Udgivet - 2019

Bibliografisk note

COPECARE

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
Sider (fra-til) e024065
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.

Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial

Wedell-Neergaard, A-S., Lang Lehrskov, L., Christensen, R. H., Legaard, G. E., Dorph, E., Larsen, M. K., Launbo, N., Fagerlind, S. R., Seide, S. K., Nymand, S., Ball, M., Vinum, N., Dahl, C. N., Henneberg, M., Ried-Larsen, M., Nybing, J. D., Christensen, R., Rosenmeier, J. B., Karstoft, K., Pedersen, B. K., Ellingsgaard, H. & Krogh-Madsen, R., 2 apr. 2019, I : Cell Metabolism. 29, 4, s. 844-855.e3

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Visceral adipose tissue is harmful to metabolic health. Exercise training reduces visceral adipose tissue mass, but the underlying mechanisms are not known. Interleukin-6 (IL-6) stimulates lipolysis and is released from skeletal muscle during exercise. We hypothesized that exercise-induced reductions in visceral adipose tissue mass are mediated by IL-6. In this randomized placebo-controlled trial, we assigned abdominally obese adults to tocilizumab (IL-6 receptor antibody) or placebo during a 12-week intervention with either bicycle exercise or no exercise. While exercise reduced visceral adipose tissue mass, this effect of exercise was abolished in the presence of IL-6 blockade. Changes in body weight and total adipose tissue mass showed similar tendencies, whereas lean body mass did not differ between groups. Also, IL-6 blockade increased cholesterol levels, an effect not reversed by exercise. Thus, IL-6 is required for exercise to reduce visceral adipose tissue mass and emphasizes a potentially important metabolic consequence of IL-6 blockade.

Originalsprog Engelsk
Tidsskrift Cell Metabolism
Vol/bind 29
Udgave nummer 4
Sider (fra-til) 844-855.e3
ISSN 1550-4131
DOI
Status Udgivet - 2 apr. 2019

Exposure to Vitamin D Fortification Policy in Prenatal Life and the Risk of Childhood Asthma: Results From the D-Tect Study

Thorsteinsdottir, F., Maslova, E., Jacobsen, R., Frederiksen, P., Keller, A., Backer, V. & Heitmann, B. L., 24 apr. 2019, I : Nutrients. 11, 4

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Prenatal vitamin D insufficiency may be associated with an increased risk of developing childhood asthma. Results from epidemiological studies are conflicting and limited by short follow-up and small sample sizes. The objective of this study was to examine if children born to women exposed to the margarine fortification policy with a small dose of extra vitamin D during pregnancy had a reduced risk of developing asthma until age 9 years, compared to children born to unexposed women. The termination of a Danish mandatory vitamin D fortification policy constituted the basis for the study design. We compared the risk of inpatient asthma diagnoses in all Danish children born two years before (n = 106,347, exposed) and two years after (n = 115,900, unexposed) the termination of the policy. The children were followed in the register from 0-9 years of age. Data were analyzed using Cox proportional hazards regression. The Hazard Ratio for the first inpatient asthma admission among exposed versus unexposed children was 0.96 (95%CI: 0.90-1.04). When stratifying by sex and age, 0-3 years old boys exposed to vitamin D fortification showed a lower asthma risk compared to unexposed boys (HR 0.78, 95%CI: 0.67-0.92). Prenatal exposure to margarine fortification policy with extra vitamin D did not affect the overall risk of developing asthma among children aged 0-9 years but seemed to reduce the risk among 0-3 years old boys. Taking aside study design limitations, this could be explained by different sensitivity to vitamin D from different sex-related asthma phenotypes in children with early onset, and sex differences in lung development or immune responses.

Originalsprog Engelsk
Tidsskrift Nutrients
Vol/bind 11
Udgave nummer 4
ISSN 2072-6643
DOI
Status Udgivet - 24 apr. 2019

Hand exercise for women with rheumatoid arthritis and decreased hand function: an exploratory randomized controlled trial

Ellegaard, K., von Bülow, C., Røpke, A., Bartholdy, C., Hansen, I. S., Rifbjerg-Madsen, S., Henriksen, M. & Wæhrens, E. E., 26 jun. 2019, I : Arthritis Research & Therapy. 21, 1, s. 158

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: People with hand-related rheumatoid arthritis (RA) experience problems performing activities of daily living (ADL). Compensatory strategies to improve ADL ability have shown effective. Similarly, hand exercise has shown effect on pain, grip strength, and self-reported ability. A combination has shown positive effects based on self-report, but self-report and observation provide distinct information about ADL. The purpose of this study was to examine whether hand exercise as add on to compensatory intervention (CIP) will improve observed ADL ability in RA.

METHODS: Women (n = 55) with hand-related RA were randomized to CIPEXERCISE (intervention) or CIP only (control). CIP is focused on joint protection, assistive devices, and alternative ways of performing AD. The hand-exercise program addressed range of motion and muscle strength. Primary outcome was change in observed ADL motor ability measured by the Assessment of Motor and Process Skills (AMPS). Baseline measures were repeated after 8 weeks.

RESULTS: Improvements in ADL motor ability in CIPEXERCISE (mean change = 0.24 logits; 95% CI = 0.09 to 0.39) and CIPCONTROL (mean change =0.20 logits; 95% CI = 0.05 to 0.35) were statistically significant, with no differences between groups (mean difference = 0.04 logits; 95% CI = - 0.16 to 0.25). Thirteen (46.4%) participants in the CIPEXERCISE and 12 (44.4%) in the CIPCONTROL obtained clinically relevant improvements (≥ 0.30 logits) in ADL motor ability; this group difference was not significant (z = 0.15; p = 0.88).

CONCLUSION: Adding hand exercise to a compensatory intervention did not yield additional benefits in women with hand-related RA. The study was approved by the ethics committee 14th of April 2014 (H-3-2014-025) and registered at ClinicalTrials.gov 16th of May 2014 (NCT02140866).

Originalsprog Engelsk
Tidsskrift Arthritis Research & Therapy
Vol/bind 21
Udgave nummer 1
Sider (fra-til) 158
ISSN 1478-6354
DOI
Status Udgivet - 26 jun. 2019

Management of skin, mucosa and joint involvement of Behçet's syndrome: A systematic review for update of the EULAR recommendations for the management of Behçet's syndrome

Leccese, P., Ozguler, Y., Christensen, R., Esatoglu, S. N., Bang, D., Bodaghi, B., Celik, A. F., Fortune, F., Gaudric, J., Gül, A., Kötter, I., Mahr, A., Moots, R. J., Richter, J., Saadoun, D., Salvarani, C., Scuderi, F., Sfikakis, P. P., Siva, A., Stanford, M., Tugal-Tutkun, I., West, R., Yurdakul, S., Olivieri, I., Yazici, H. & Hatemi, G., feb. 2019, I : Seminars in Arthritis and Rheumatism. 48, 4, s. 752-762 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: The aim of this systematic review was to inform the update of European League Against Rheumatism (EULAR) Recommendations for the management of Behçet's syndrome (BS), on the evidence for the treatment of skin, mucosa and joint involvement of BS.

METHODS: A systematic literature search, data extraction, statistical analyses and assessment of the quality of evidence were performed according to a pre-specified protocol using the PRISMA guidelines. Studies that assessed the efficacy of an intervention in comparison to an active comparator or placebo for oral ulcers, genital ulcers, papulopustular lesions, nodular lesions or arthritis were included. Where possible, risk ratios were calculated for binary outcomes and mean difference for continuous outcomes.

RESULTS: Among the 3927 references that were screened, 37 were included in the analyses. Twenty-seven of these assessed mucocutaneous and 17 assessed joint involvement. Twenty-one of these studies were randomised controlled trials (RCTs). RCTs with colchicine, azathioprine, interferon-alpha, thalidomide, etanercept and apremilast showed beneficial results with some differences according to lesion type and gender. These agents were generally well tolerated with few adverse events causing withdrawal from the study.

CONCLUSIONS: RCTs comprised more than a half (21/37, 57%) of the sources included in the evidence synthesis related to skin, mucosa and joint involvement applicable for the EULAR Recommendations for the management of BS. Differences in the outcome measures that were used across the included studies often made it difficult to combine and compare the results.

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 48
Udgave nummer 4
Sider (fra-til) 752-762
Antal sider 11
ISSN 0049-0172
DOI
Status Udgivet - feb. 2019

Bibliografisk note

Copyright © 2018 Elsevier Inc. All rights reserved.

The condition of active muscles determines an individual's ability to carry out daily activities and has implications for an athlete's performance. Multi-frequency bioimpedance (mfBIA) is a non-invasive, well-known, validated, and much used method to assess muscle condition. However, it is rarely used to its full potential. Our aim was to apply mfBIA fully in the assessment of an adult healthy population, to compare muscle condition in different functional rested muscle groups, with age, and between men and women, and establish a control data set. Fifty healthy subjects (25 men/25 women) aged 20-69 years, participated. mfBIA measurements at a frequency range of 4-1000 kHz were taken from muscles of the lower and the upper extremities, the upper back, and the hand. Data were analyzed using ImpediMed software, giving Impedance, Resistance, Reactance, Phase Angle, Center Frequency, external and internal Resistance, and Membrane Capacitance. Differences between means were tested for statistical significance. A P value >0.05 was considered nonsignificant. While no difference in the mfBIA parameters was seen with age, a highly significant gender difference was seen. At rest, women's muscles cf men's showed a significantly higher center frequency and intra- and extra-cellular resistance, while the membrane capacitance was lower. A set of values for mfBIA parameters for healthy adult individuals are given for some of the main muscles which are frequently part of muscle assessment. The documented gender difference in muscle condition at rest has important implications in work situations, during physical rehabilitation and when training for competitive sports.

Originalsprog Engelsk
Tidsskrift Physiological Reports
Vol/bind 7
Udgave nummer 11
Sider (fra-til) e14109
ISSN 2051-817X
DOI
Status Udgivet - jun. 2019

Bibliografisk note

© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Night work and miscarriage: a Danish nationwide register-based cohort study

Begtrup, L. M., Specht, I. O., Hammer, P. E. C., Flachs, E. M., Garde, A. H., Hansen, J., Hansen, Å. M., Kolstad, H. A., Larsen, A. D. & Bonde, J. P., maj 2019, I : Occupational and Environmental Medicine. s. 302-308 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: Observational studies indicate an association between working nights and miscarriage, but inaccurate exposure assessment precludes causal inference. Using payroll data with exact and prospective measurement of night work, the objective was to investigate whether working night shifts during pregnancy increases the risk of miscarriage.

METHODS: A cohort of 22 744 pregnant women was identified by linking the Danish Working Hour Database (DWHD), which holds payroll data on all Danish public hospital employees, with Danish national registers on births and admissions to hospitals (miscarriage). The risk of miscarriage during pregnancy weeks 4-22 according to measures of night work was analysed using Cox regression with time-varying exposure adjusted for a fixed set of potential confounders.

RESULTS: In total 377 896 pregnancy weeks (average 19.7) were available for follow-up. Women who had two or more night shifts the previous week had an increased risk of miscarriage after pregnancy week 8 (HR 1.32 (95% CI 1.07 to 1.62) compared with women, who did not work night shifts. The cumulated number of night shifts during pregnancy weeks 3-21 increased the risk of miscarriages in a dose-dependent pattern.

CONCLUSIONS: The study corroborates earlier findings that night work during pregnancy may confer an increased risk of miscarriage and indicates a lowest observed threshold level of two night shifts per week.

Originalsprog Engelsk
Tidsskrift Occupational and Environmental Medicine
Sider (fra-til) 302-308
Antal sider 7
ISSN 1351-0711
DOI
Status Udgivet - maj 2019

Bibliografisk note

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Night work and sick leave during pregnancy: a national register-based within-worker cohort study

Hammer, P. E. C., Garde, A. H., Begtrup, L. M., Flachs, E. M., Hansen, J., Hansen, Å. M., Hougaard, K. S., Kolstad, H. A., Larsen, A. D., Pinborg, A. B., Specht, I. O. & Bonde, J. P., mar. 2019, I : Occupational and Environmental Medicine. 76, 3, s. 163-168 6 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: The aim of our study was to investigate the acute effect of night work during pregnancy on the risk of calling in sick the following day using register-based information and the workers as their own controls.

METHODS: Using the payroll-based national Danish Working Hour Database, including all public hospital employees in Denmark, we identified 9799 pregnant women with ≥1 day shift and ≥1 night shift and ≥1 day of sick leave during the first 32 pregnancy weeks from January 2007 to December 2013. We performed fixed effects logistic regression, that is, within-worker comparisons, of the risk of sick leave of any duration starting within 24 hours after night shifts of different length versus day shifts.

RESULTS: Most of the participants were nurses (64%) or physicians (16%). We found an increased relative risk of sick leave following night shifts compared with day shifts during all pregnancy trimesters. The risk was highest for night shifts lasting >12 hours (OR 1.37, 95% CI 1.15 to 1.63 for nurses; OR 1.87, 95% CI 1.69 to 2.08 for physicians) and among women aged >35 years (OR 1.42, 95% CI 1.24 to 1.63).

CONCLUSION: Among Danish public hospital employees night shifts during pregnancy, especially shifts longer than 12 hours, increased the risk of calling in sick the following day independent of personal factors and time-invariant confounders in all pregnancy trimesters.

Originalsprog Engelsk
Tidsskrift Occupational and Environmental Medicine
Vol/bind 76
Udgave nummer 3
Sider (fra-til) 163-168
Antal sider 6
ISSN 1351-0711
DOI
Status Udgivet - mar. 2019

Night work during pregnancy and preterm birth-A large register-based cohort study

Specht, I. O., Hammer, P. E. C., Flachs, E. M., Begtrup, L. M., Larsen, A. D., Hougaard, K. S., Hansen, J., Hansen, Å. M., Kolstad, H. A., Rugulies, R., Garde, A. H. & Bonde, J. P., 2019, I : PLoS One. 14, 4, s. e0215748

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Melatonin stimulates the production of progesterone, which is essential for the maintenance of pregnancy. Since melatonin in blood is reduced due to work under illuminated conditions during night work, it has been hypothesized that night work may increase the risk of preterm birth. Previous meta-analyses have not revealed increased risk of preterm birth in women working night shifts during pregnancy. Still, these studies might have been limited by inaccurate self-reports of timing, intensity and duration of night work most likely causing bias towards the null. The aim of this is study was to investigate if the frequency and duration of night work during the first (week 1-12) and second (week 13-22) trimester of pregnancy were associated with risk of preterm birth when objective and prospective data on night work are used.

METHOD: In a register-based prospective cohort study, we obtained individual day-to-day information on working hours from The Danish Working Hour Database (DWHD, a payroll database including all public service employees in administrative Danish Regions from 2007-2013) and information on preterm birth from the Danish Medical Birth Registry. Night-shift was defined as at least three working hours between 23:00 and 06:00. Preterm birth was defined as giving birth during gestational weeks 23-37. Odds of preterm birth according to working night shifts were analysed by logistic regression.

RESULTS: We identified 16,501 pregnant women eligible for the study, of which 10,202 women (61.8%) had at least one night-shift during the first 22 gestational weeks. The risk of preterm birth was not elevated among women working night shifts compared to women working only day shifts during either the first or second trimester. Within night-shift workers, the risk was not related to the number of night shifts, the duration of night shifts, consecutive night shifts or quick returns defined as short intervals between shifts. Odds of preterm birth was not related to change of working schedule from the first to second trimester, although women changing from night shifts in the first trimester to day work only in the second trimester displayed a weak increased odds of preterm birth (OR 1.21, 95%CI 0.98-1.49) compared to women working night shifts in both trimesters.

CONCLUSION: Our results, which are without bias from self-report of either exposure or outcome, are in line with the results of previous meta-analyses. Due to the detailed information on hours worked during pregnancy, we were able to investigate several dimensions of night work not previously investigated, of which none were associated with elevated risk of preterm birth.

Originalsprog Engelsk
Tidsskrift PLoS One
Vol/bind 14
Udgave nummer 4
Sider (fra-til) e0215748
ISSN 1932-6203
DOI
Status Udgivet - 2019

Opioid-Induced Reductions in Gait Variability in Healthy Volunteers and Individuals with Knee Osteoarthritis

Henriksen, M., Alkjær, T., Raffalt, P. C., Jørgensen, L., Bartholdy, C., Hansen, S. H. & Bliddal, H., 12 jan. 2019, I : Pain medicine (Malden, Mass.).

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Objective: To investigate differences in gait variability induced by two different single-dose opioid formulations and an inert placebo in healthy volunteers and knee osteoarthritis patients.

Design: Experimental, randomized, double-blinded, crossover study of inert placebo (calcium tablets), 50 mg of tapentadol, and 100 mg of tramadol.

Setting: Laboratory setting.

Subjects: Healthy volunteers and knee osteoarthritis patients.

Methods: At three visits, separated by seven days, one tablet was administered per visit according to the randomization code. At each visit, a baseline measurement was done before tablet administration, after which hourly measurements were performed for six hours, yielding a total of seven measurements per visit. Gait variability was measured by three-dimensional gait analysis, recorded during six minutes of continuous treadmill walking at self-selected speed. One hundred seventy gait cycles were identified from detection of clear events of the knee joint angle trajectories. Gait variability was assessed as average standard deviations over a gait cycle of the sacrum displacements and accelerations; sagittal plane ankle, knee, and hip joint angles; step widths; and stride times.

Results: Twenty-four opioid-naïve and neurologically intact participants (12 healthy volunteers and 12 knee osteoarthritis patients) were included and completed the experiment. Tapentadol reduced the variability of sacrum displacements and accelerations compared with placebo and tramadol. There were no differences between experimental conditions regarding the variability in lower-extremity joint angle variability, step widths, or stride times.

Conclusions: In opioid-naïve and neurologically intact individuals, tapentadol seems to reduce movement variability during treadmill walking, compared with placebo and tramadol. This can be interpreted as a loss of adaptability that might increase the risk of falling if the system is perturbed.

Originalsprog Engelsk
Tidsskrift Pain medicine (Malden, Mass.)
ISSN 1526-2375
DOI
Status E-pub ahead of print - 12 jan. 2019

Physical demand at work and sick leave due to low back pain: a cross-sectional study

Petersen, J., Kirkeskov, L., Hansen, B. B., Begtrup, L. M., Flachs, E. M., Boesen, M., Hansen, P., Bliddal, H. & Kryger, A. I., 22 maj 2019, I : BMJ Open. 9, 5, s. e026917

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: To investigate if self-reported high physical demand at work, objective physical workload using a job exposure matrix (JEM) and fear-avoidance beliefs are associated with reported sick leave in the previous year in persons with low back pain (LBP). Second, to investigate if the effects of fear-avoidance and self-reported high physical demand at work on sick leave are modified by the objective physical workloads.

SETTINGS: Participants were recruited from general practice and by advertisement in a local newspaper.

PARTICIPANTS: 305participants with a current period of 2-4 weeks LBP and self-reported difficulty in maintaining physically demanding jobs due to LBP were interviewed, clinically examined and had an MRI at baseline.

MAIN OUTCOME MEASURES: Independent variables were high fear-avoidance, self-reported high physical demand at work and objective measures of physical workloads (JEM). Outcome was self-reported sick leave due to LBP in the previous year. Logistic regression and tests for interaction were used to identify risk factors and modifiers for the association with self-reported sick leave.

RESULTS: Self-reported physically demanding work and high fear-avoidance were significantly associated with prior sick leave due to LBP in the previous year with OR 1.75 95% CI (1.10 to 2.75) and 2.75 95% CI (1.61to 4.84), respectively. No objective physical workloads had significant associations. There was no modifying effect of objective physical workloads on the association between self-reported physical demand at work/high fear-avoidance and sick leave.

CONCLUSIONS: Occupational interventions to reduce sick leave due to LBP may have to focus more on those with high self-reported physical demands and high fear-avoidance, and less on individuals with the objectively highest physical workload.

TRIAL REGISTRATION NUMBER: NCT02015572; Post-results.

Originalsprog Engelsk
Tidsskrift BMJ Open
Vol/bind 9
Udgave nummer 5
Sider (fra-til) e026917
ISSN 2044-6055
DOI
Status Udgivet - 22 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.

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