Published in 2016

A comparison of Ancient Greek and Roman Sports Diets with Modern Day Practices

Harrison, A. & Bartels, E. M. 2016 I : Sports Nutrition and Therapy. 1, 1, 1000104

Publikation: Forskning - peer reviewTidsskriftartikel

Originalsprog Engelsk
Artikelnummer 1000104
Tidsskrift Sports Nutrition and Therapy
Vol/bind 1
Tidsskriftsnummer 1
ISSN 0000-0000
Status Udgivet - 2016

Study Design Secondary analysis of clinical trial data. Background Knee osteoarthritis (OA) management has changed significantly over recent decades toward nonpharmacological treatments, particularly exercise. However, the optimal exercise program remains to be established. Objective To describe the implementation of standardized rescue exercises for patients with pain exacerbations and to assess whether performing these benefit or further worsen symptoms in patients with exacerbated symptoms of knee OA. Methods The data from 2 randomized controlled studies of exercise in patients with knee OA were used. A supervised, standard exercise program that included standardized "rescue" exercises to be performed in the event of symptomatic exacerbation, defined as knee pain of greater than 5 on a 0-to-10 numeric pain-rating scale, was conducted for 12 weeks at 3 sessions per week. Pain ratings were obtained before and after each exercise session. Results Of 131 participants included, 2 never commenced the exercise program, leaving 129 to be included in the analysis. The analysis was observational and thus had no comparison group. During the program, 36 participants (28%) were referred to the rescue exercises. In 63% of the rescue sessions, the participants experienced decreased pain intensity (average ± SD, -2.6 ± 2.3), 27% reported no change in pain, and 10% reported increased pain intensity (average ± SD, 1.3 ± 0.5). Conclusion Having a predefined and standardized rescue exercise option appears beneficial, and did not result in further worsening of exacerbated knee OA symptoms. The intervention may be particularly relevant for patients with knee OA who have more severe symptoms. Level of Evidence Therapy, level 2b. Registered at www.clinicaltrials.gov (NCT01545258 and NCT01945749). J Orthop Sports Phys Ther 2016;46(11):942-946. Epub 28 Sep 2016. doi:10.2519/jospt.2016.6908.

Originalsprog Engelsk
Tidsskrift The Journal of orthopaedic and sports physical therapy
Vol/bind 46
Tidsskriftsnummer 11
Sider (fra-til) 942-946
Antal sider 5
ISSN 0190-6011
DOI
Status Udgivet - nov. 2016

Agreements and Discrepancies between FDA Reports and Journal Papers on Biologic Agents Approved for Rheumatoid Arthritis: A Meta-Research Project

Amarilyo, G., Furst, D. E., Woo, J. M. P., Li, W., Bliddal, H., Christensen, R. & Tarp, S. 2016 I : P L o S One. 11, 1, s. e0147556

Publikation: Forskning - peer reviewTidsskriftartikel

BACKGROUND: Sponsors that seek to commercialize new drugs apply to the Food and Drug Administration (FDA) which independently analyzes the raw data and reports the results on its website.

OBJECTIVES: This study sought to determine if there are differences between the FDA assessments and journal reports on biologic agents developed for the treatment of rheumatoid arthritis.

METHODS: Available data on FDA-approved drugs were extracted from the website, and a systematic literature search was conducted to identify matching studies in peer-reviewed medical journals. Outcome measures were the American College of Rheumatology response criteria ACR20 (efficacy) and withdrawal due to adverse events (safety). As effect size odds ratios were estimated for each active trial arm vs. control arm (i.e. for both sources: FDA and journal report), followed by calculation of the ratios of the FDA and journal report odds ratios. A ratio of odds ratios not equal to 1 was categorized as a discrepancy.

RESULTS: FDA reports were available for 8 of 9 FDA-approved biologic agents for rheumatoid arthritis; all identified trials (34) except one were published in peer-reviewed journals. Overall, discrepancies were noted for 20 of the 33 evaluated trials. Differences in the apparent benefit reporting were found in 39% (24/61) pairwise comparisons and in 11 cases these were statistically significant; the FDA report showed greater benefit than the journal publication in 15 comparisons and lesser benefit in 9. Differences in the reported harms were found in 51% (28/55) pairwise comparisons and were statistically significant in 5. The "signal" in FDA reports showed a less harmful effect than the journal publication in 17 comparisons whereas a more harmful effect in 11. The differences were attributed to differences in analytic approach, patient inclusion, rounding effect, and counting discrepancies. However, no differences were categorized as critical.

CONCLUSION: There was no empirical evidence to suggest biased estimates between the two sources. Increased and detailed transparency in publications would improve the understanding and credibility of published results. Further, the FDA report was found to be a useful source when data are missing in the published report (i.e. reporting bias).

Originalsprog Engelsk
Tidsskrift P L o S One
Vol/bind 11
Tidsskriftsnummer 1
Sider (fra-til) e0147556
ISSN 1932-6203
DOI
Status Udgivet - 2016

OBJECTIVES: With the present study we wanted to explore the impact of treatment with a tumor necrosis factor-α -inhibitor (TNFi) on levels of soluble biomarkers in rheumatoid arthritis (RA) patients and to identify predictors of impaired drug levels and development of anti-TNFi antibodies (anti-TNFi Abs).

METHODS: Blood samples from 26 patients with established RA were taken at baseline and following 6 months of treatment with adalimumab or infliximab. Samples were analyzed for levels of TNFi, interleukin (IL)-6, and soluble TNF-receptors 1 and -2 (sTNF-R1 and -2) and for presence of anti-TNFi Abs. Clinical and demographic data were recorded as well.

RESULTS: During the initial 6 months treatment, DAS28(CRP) (Disease activity score in 28 joints using C-reactive protein) and levels of IL-6 and sTNF-R2 decreased significantly in patients without anti-TNFi Abs and in patients retaining detectable drug levels. The levels of other tested cytokines (TNF-α, TNF-β, IL-1ra, IL-1b, IL-8, IL-10, IL-12(p70), IL-13, IL-17A, IL-17F, and IL-33) were generally below detection limits. Higher baseline levels of IL-6 associated with undetectable levels of TNFi at follow-up. Anti-TNFi Abs were associated with decreased drug levels, but no predictors for anti-TNFi Ab development could be found.

CONCLUSION: The effect of treatment with TNFi on RA disease activity depends on levels of active drug, and by presence of anti-TNFi Abs. In patients who retain detectable drug levels, and in the absence of anti-TNFi Abs, clinical outcome is improved during treatment, and circulating levels of IL-6 and sTNF-R2 decrease. Baseline levels of IL-6 may predict depletion of TNFi and may identify patients at risk of treatment failure.

Originalsprog Engelsk
Tidsskrift P L o S One
Vol/bind 11
Tidsskriftsnummer 9
Sider (fra-til) e0162316
ISSN 1932-6203
DOI
Status Udgivet - 2016

Aquatic exercise for the treatment of knee and hip osteoarthritis

Bartels, E. M., Juhl, C. B., Christensen, R., Hagen, K. B., Danneskiold-Samsøe, B., Dagfinrud, H. & Lund, H. 2016 I : Cochrane Database of Systematic Reviews. 3, s. CD005523

Publikation: Forskning - peer reviewTidsskriftartikel

BACKGROUND: Osteoarthritis is a chronic disease characterized by joint pain, tenderness, and limitation of movement. At present, no cure is available. Thus only treatment of the person's symptoms and treatment to prevent further development of the disease are possible. Clinical trials indicate that aquatic exercise may have advantages for people with osteoarthritis. This is an update of a published Cochrane review.

OBJECTIVES: To evaluate the effects of aquatic exercise for people with knee or hip osteoarthritis, or both, compared to no intervention.

SEARCH METHODS: We searched the following databases up to 28 April 2015: the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library Issue 1, 2014), MEDLINE (from 1949), EMBASE (from 1980), CINAHL (from 1982), PEDro (Physiotherapy Evidence Database), and Web of Science (from 1945). There was no language restriction.

SELECTION CRITERIA: Randomized controlled clinical trials of aquatic exercise compared to a control group (e.g. usual care, education, social attention, telephone call, waiting list for surgery) of participants with knee or hip osteoarthritis.

DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, extracted data and assessed risk of bias of the included trials. We analysed the pooled results using standardized mean difference (SMD) values.

MAIN RESULTS: Nine new trials met the inclusion criteria and we excluded two earlier included trials. Thus the number of participants increased from 800 to 1190 and the number of included trials increased from six to 13. Most participants were female (75%), with an average age of 68 years and a body mass index (BMI) of 29.4. Osteoarthritis duration was 6.7 years, with a great variation of the included participants. The mean aquatic exercise duration was 12 weeks. We found 12 trials at low to unclear risk of bias for all domains except blinding of participants and personnel. They showed that aquatic exercise caused a small short term improvement compared to control in pain (SMD -0.31, 95% CI -0.47 to -0.15; 12 trials, 1076 participants) and disability (SMD -0.32, 95% CI -0.47 to -0.17; 12 trials, 1059 participants). Ten trials showed a small effect on quality of life (QoL) (SMD -0.25, 95% CI -0.49 to -0.01; 10 trials, 971 participants). These effects on pain and disability correspond to a five point lower (95% CI three to eight points lower) score on mean pain and mean disability compared to the control group (scale 0 to 100), and a seven point higher (95% CI 0 to 13 points higher) score on mean QoL compared with control group (scale 0 to 100). No included trials performed a radiographic evaluation. No serious adverse events were reported in the included trials with relation to aquatic exercise.

AUTHORS' CONCLUSIONS: There is moderate quality evidence that aquatic exercise may have small, short-term, and clinically relevant effects on patient-reported pain, disability, and QoL in people with knee and hip OA. The conclusions of this review update does not change those of the previous published version of this Cochrane review.

Originalsprog Engelsk
Tidsskrift Cochrane Database of Systematic Reviews
Vol/bind 3
Sider (fra-til) CD005523
ISSN 1469-493X
DOI
Status Udgivet - 2016
Originalsprog Engelsk
Tidsskrift Disability and Rehabilitation
ISSN 0963-8288
Status Udgivet - jun. 2016
Originalsprog Dansk
Udgivelses sted København
Vol/bind 1
Udgave 1
Status Udgivet - 18 aug. 2016

BACKGROUND: Previous studies have suggested a direct association between hair cortisol concentration (HCC) and Body Mass Index (BMI), as well as other adiposity measures. However, these studies have mostly been conducted among adult populations.

OBJECTIVE: To examine the association between HCC and different measures of adiposity among a selected group of children predisposed to obesity and their parents.

METHODS: We conducted a cross-sectional study based on 363 children and their parents (301 mothers and 231 fathers) participating in the "Healthy Start" study. Linear regression analysis was used to investigate associations between HCC and adiposity measures while taking into account possible confounding factors. Analyses were performed examining the association between HCC and BMI, fat mass and fat free mass index Z-scores, as well as waist circumference and waist-hip ratio among the children. Likewise, the association between HCC and BMI among the parents was explored. Finally, we examined the association between parental HCC and children's adiposity measures.

RESULTS: HCC was directly associated with a higher BMI among the fathers (0.49 kg/m2 [95% CI: 0.09, 0.90, P = 0.02] per 100 pg/mg) and the mothers (0.93 kg/m2 [95% CI: 0.24, 1.61, P = 0.01] per 100 pg/mg). We found no clear evidence of an association between HCC and adiposity measures among children. However, a high maternal HCC was associated with a high fat mass index and low fat free mass index z-score in the offspring (0.14 SD [95% CI: 0.02, 0.26, P = 0.02] and -0.17 SD [95% CI: -0.30, -0.05, P = 0.01] per 100 pg/mg, respectively).

CONCLUSIONS: Our study found no evidence of an association between HCC and measures of adiposity among children predisposed to obesity. However, HCC may be directly associated with BMI among men and women, and maternal HCC may be related to a higher fat mass and a lower fat free mass among their children.

Originalsprog Engelsk
Tidsskrift P L o S One
Vol/bind 11
Tidsskriftsnummer 9
Sider (fra-til) e0163639
ISSN 1932-6203
DOI
Status Udgivet - 24 sep. 2016

Association between Maternal Fish Consumption and Gestational Weight Gain: Influence of Molecular Genetic Predisposition to Obesity

Larsen, S. C., Ängquist, L., Laurin, C., Schmidt Morgen, C., Jakobsen, M. U., Paternoster, L., Smith, G. D., Olsen, S. F., Sørensen, T. I. A. & Nohr, E. A. 2016 I : P L o S One. 11, 3, s. e0150105

Publikation: Forskning - peer reviewTidsskriftartikel

BACKGROUND: Studies suggest that fish consumption can restrict weight gain. However, little is known about how fish consumption affects gestational weight gain (GWG), and whether this relationship depends on genetic makeup.

OBJECTIVE: To examine the association between fish consumption and GWG, and whether this relationship is dependent on molecular genetic predisposition to obesity.

DESIGN: A nested case-cohort study based on the Danish National Birth Cohort (DNBC) sampling the most obese women (n = 990) and a random sample of the remaining participants (n = 1,128). Replication of statistically significant findings was attempted in the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 4,841). We included 32 body mass index (BMI) associated single nucleotide polymorphisms (SNPs) and 5 SNPs found associated with GWG. BMI associated SNPs were combined in a genetic risk score (GRS). Associations between consumption of fish, GRS or individual variants and GWG were analysed, and interactions between fish and the GRS or individual variants were examined.

RESULTS: In the DNBC, each portion/week (150 g) of fatty fish was associated with a higher GWG of 0.58 kg (95% CI: 0.16, 0.99, P<0.01). For total fish and lean fish, similar patterns were observed, but these associations were not statistically significant. We found no association between GRS and GWG, and no interactions between GRS and dietary fish on GWG. However, we found an interaction between the PPARG Pro12Ala variant and dietary fish. Each additional Pro12Ala G-allele was associated with a GWG of -0.83 kg (95% CI: -1.29, -0.37, P<0.01) per portion/week of dietary fish, with the same pattern for both lean and fatty fish. In ALSPAC, we were unable to replicate these findings.

CONCLUSION: We found no consistent evidence of association between fish consumption and GWG, and our results indicate that the association between dietary fish and GWG has little or no dependency on GRS or individual SNPs.

Originalsprog Engelsk
Tidsskrift P L o S One
Vol/bind 11
Tidsskriftsnummer 3
Sider (fra-til) e0150105
ISSN 1932-6203
DOI
Status Udgivet - 2016

Association of Physical Fitness with Depression in Women with Fibromyalgia

Soriano-Maldonado, A., Estévez-López, F., Segura-Jiménez, V., Aparicio, V. A., Álvarez-Gallardo, I. C., Herrador-Colmenero, M., Ruiz, J. R., Henriksen, M., Amris, K., Delgado-Fernández, M. & al-Ándalus Project 2016 I : Pain medicine (Malden, Mass.). 17, 8

Publikation: Forskning - peer reviewTidsskriftartikel

OBJECTIVE: . The aim of this study was to examine the association between physical fitness and depressive symptoms in women with fibromyalgia (FM). We also assessed whether different fitness components present independent relationships with depressive symptoms.

DESIGN: . Cross-sectional study.

SETTING: . University facilities and FM associations.

SUBJECTS: . Four hundred and forty-four patients with FM according to the 1990 American College of Rheumatology criteria.

METHODS: . Depressive symptoms were assessed using the Beck Depression Inventory (BDI-II). Physical fitness (aerobic fitness, muscle strength, flexibility, and motor agility) was assessed using the standardized Senior Fitness Test battery and the handgrip strength test. A standardized composite score for fitness was computed and divided into quintiles.

RESULTS: . Overall, the fitness tests presented inverse associations with the total BDI-II score (P < 0.05). The patients in the highest fitness quintile had 8.4% lower depressive symptoms than the patients in the lowest fitness quintile (P = 0.014). The odds of severe symptoms of depression were between 3.7% and 16.9% lower for each performance unit in the back-scratch, handgrip, arm-curl, and eight-feet up-and-go tests. When all the fitness tests were simultaneously considered, the back-scratch test was the only one independently associated with the total BDI-II score (P = 0.001; R(2) = 0.023).

CONCLUSIONS: . Although higher physical fitness was generally associated with lower symptoms of depression in women with FM, the observed associations were somewhat weak and inconsistent, differing from those previously observed in healthy adults. Further research to determine the clinical relevance of the association between physical fitness and depression in FM is warranted.

Originalsprog Engelsk
Tidsskrift Pain medicine (Malden, Mass.)
Vol/bind 17
Tidsskriftsnummer 8
ISSN 1526-2375
DOI
Status Udgivet - 2016

Biologic interventions for fatigue in rheumatoid arthritis

Almeida, C., Choy, E. H. S., Hewlett, S., Kirwan, J. R., Cramp, F., Chalder, T., Pollock, J. & Christensen, R. 2016 I : Cochrane Database of Systematic Reviews. 6, s. CD008334

Publikation: Forskning - peer reviewTidsskriftartikel

BACKGROUND: Fatigue is a common and potentially distressing symptom for patients with rheumatoid arthritis (RA), with no accepted evidence-based management guidelines. Evidence suggests that biologic interventions improve symptoms and signs in RA as well as reducing joint damage.

OBJECTIVES: To evaluate the effect of biologic interventions on fatigue in rheumatoid arthritis.

SEARCH METHODS: We searched the following electronic databases up to 1 April 2014: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Current Controlled Trials Register, the National Research Register Archive, The UKCRN Portfolio Database, AMED, CINAHL, PsycINFO, Social Science Citation Index, Web of Science, and Dissertation Abstracts International. In addition, we checked the reference lists of articles identified for inclusion for additional studies and contacted key authors.

SELECTION CRITERIA: We included randomised controlled trials if they evaluated a biologic intervention in people with rheumatoid arthritis and had self reported fatigue as an outcome measure.

DATA COLLECTION AND ANALYSIS: Two reviewers selected relevant trials, assessed methodological quality and extracted data. Where appropriate, we pooled data in meta-analyses using a random-effects model.

MAIN RESULTS: We identified 32 studies for inclusion in this current review. Twenty studies evaluated five anti-tumour necrosis factor (anti-TNF) biologic agents (adalimumab, certolizumab, etanercept, golimumab and infliximab), and 12 studies focused on five non-anti-TNF biologic agents (abatacept, canakinumab, rituximab, tocilizumab and an anti-interferon gamma monoclonal antibody). All but two of the studies were double-blind randomised placebo-controlled trials. In some trials, patients could receive concomitant disease-modifying anti-rheumatic drugs (DMARDs). These studies added either biologics or placebo to DMARDs. Investigators did not change the dose of the latter from baseline. In total, these studies included 9946 participants in the intervention groups and 4682 participants in the control groups. Overall, quality of randomised controlled trials was moderate with a low to unclear risk of bias in the reporting of the outcome of fatigue. We downgraded the quality of the studies from high to moderate because of potential reporting bias (studies included post hoc analyses favouring reporting of positive result and did not always include all randomised individuals). Some studies recruited only participants with early disease. The studies used five different instruments to assess fatigue in these studies: the Functional Assessment of Chronic Illness Therapy Fatigue Domain (FACIT-F), Short Form-36 Vitality Domain (SF-36 VT), Visual Analogue Scale (VAS) (0 to 100 or 0 to 10) and the Numerical Rating Scale (NRS). We calculated standard mean differences for pooled data in meta-analyses. Overall treatment by biologic agents led to statistically significant reduction in fatigue with a standardised mean difference of -0.43 (95% confidence interval (CI) -0.38 to -0.49). This equates to a difference of 6.45 units (95% CI 5.7 to 7.35) of FACIT-F score (range 0 to 52). Both types of biologic agents achieved a similar level of improvement: for anti-TNF agents, this stood at -0.42 (95% CI -0.35 to -0.49), equivalent to 6.3 units (95% CI 5.3 to 7.4) on the FACIT-F score; and for non-anti-TNF agents, it was -0.46 (95% CI -0.39 to -0.53), equivalent to 6.9 units (95% CI 5.85 to 7.95) on the FACIT-F score. In most studies, the double-blind period was 24 weeks or less. No study assessed long-term changes in fatigue.

AUTHORS' CONCLUSIONS: Treatment with biologic interventions in patients with active RA can lead to a small to moderate improvement in fatigue. The magnitude of improvement is similar for anti-TNF and non-anti-TNF biologics. However, it is unclear whether the improvement results from a direct action of the biologics on fatigue or indirectly through reduction in inflammation, disease activity or some other mechanism.

Originalsprog Engelsk
Tidsskrift Cochrane Database of Systematic Reviews
Tidsskriftsnummer 6
Sider (fra-til) CD008334
ISSN 1469-493X
DOI
Status Udgivet - 2016

Biologics or tofacitinib for rheumatoid arthritis in incomplete responders to methotrexate or other traditional disease-modifying anti-rheumatic drugs: a systematic review and network meta-analysis

Singh, J. A., Hossain, A., Tanjong Ghogomu, E., Kotb, A., Christensen, R., Mudano, A. S., Maxwell, L. J., Shah, N. P., Tugwell, P. & Wells, G. A. 2016 I : Cochrane Database of Systematic Reviews. 5, s. CD012183

Publikation: Forskning - peer reviewTidsskriftartikel

BACKGROUND: This is an update of the 2009 Cochrane overview and network meta-analysis (NMA) of biologics for rheumatoid arthritis (RA).

OBJECTIVES: To assess the benefits and harms of nine biologics (abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab) and small molecule tofacitinib, versus comparator (MTX, DMARD, placebo (PL), or a combination) in adults with rheumatoid arthritis who have failed to respond to methotrexate (MTX) or other disease-modifying anti-rheumatic drugs (DMARDs), i.e., MTX/DMARD incomplete responders (MTX/DMARD-IR).

METHODS: We searched for randomized controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (via The Cochrane Library Issue 6, June 2015), MEDLINE (via OVID 1946 to June 2015), and EMBASE (via OVID 1947 to June 2015). Data extraction, risk of bias and GRADE assessments were done in duplicate. We calculated both direct estimates using standard meta-analysis and used Bayesian mixed treatment comparisons approach for NMA estimates to calculate odds ratios (OR) and 95% credible intervals (CrI). We converted OR to risk ratios (RR) which are reported in the abstract for the ease of interpretation.

MAIN RESULTS: This update included 73 new RCTs for a total of 90 RCTs; 79 RCTs with 32,874 participants provided usable data. Few trials were at high risk of bias for blinding of assessors/participants (13% to 21%), selective reporting (4%) or major baseline imbalance (8%); a large number had unclear risk of bias for random sequence generation (68%) or allocation concealment (74%).Based on direct evidence of moderate quality (downgraded for inconsistency), biologic+MTX/DMARD was associated with a statistically significant and clinically meaningful improvement in ACR50 versus comparator (RR 2.71 (95% confidence interval (CI) 2.36 to 3.10); absolute benefit 24% more patients (95% CI 19% to 29%), number needed to treat for an additional beneficial outcome (NNTB) = 5 (4 to 6). NMA estimates for ACR50 in tumor necrosis factor (TNF) biologic+MTX/DMARD (RR 3.23 (95% credible interval (Crl) 2.75 to 3.79), non-TNF biologic+MTX/DMARD (RR 2.99; 95% Crl 2.36 to 3.74), and anakinra + MTX/DMARD (RR 2.37 (95% Crl 1.00 to 4.70) were similar to the direct estimates.Based on direct evidence of moderate quality (downgraded for inconsistency), biologic+MTX/DMARD was associated with a clinically and statistically important improvement in function measured by the Health Assessment Questionnaire (0 to 3 scale, higher = worse function) with a mean difference (MD) based on direct evidence of -0.25 (95% CI -0.28 to -0.22); absolute benefit of -8.3% (95% CI -9.3% to -7.3%), NNTB = 3 (95% CI 2 to 4). NMA estimates for TNF biologic+MTX/DMARD (absolute benefit, -10.3% (95% Crl -14% to -6.7%) and non-TNF biologic+MTX/DMARD (absolute benefit, -7.3% (95% Crl -13.6% to -0.67%) were similar to respective direct estimates.Based on direct evidence of moderate quality (downgraded for inconsistency), biologic+MTX/DMARD was associated with clinically and statistically significantly greater proportion of participants achieving remission in RA (defined by disease activity score DAS < 1.6 or DAS28 < 2.6) versus comparator (RR 2.81 (95% CI, 2.23 to 3.53); absolute benefit 18% more patients (95% CI 12% to 25%), NNTB = 6 (4 to 9)). NMA estimates for TNF biologic+MTX/DMARD (absolute improvement 17% (95% Crl 11% to 23%)) and non-TNF biologic+MTX/DMARD (absolute improvement 19% (95% Crl 12% to 28%) were similar to respective direct estimates.Based on direct evidence of moderate quality (downgraded for inconsistency), radiographic progression (scale 0 to 448) was statistically significantly reduced in those on biologics + MTX/DMARDs versus comparator, MD -2.61 (95% CI -4.08 to -1.14). The absolute reduction was small, -0.58% (95% CI -0.91% to -0.25%) and we are unsure of the clinical relevance of this reduction. NMA estimates of TNF biologic+MTX/DMARD (absolute reduction -0.67% (95% Crl -1.4% to -0.12%) and non-TNF biologic+MTX/DMARD (absolute reduction, -0.68% (95% Crl -2.36% to 0.92%)) were similar to respective direct estimates.Based on direct evidence of moderate quality (downgraded for imprecision), results for withdrawals due to adverse events were inconclusive, with wide confidence intervals encompassing the null effect and evidence of an important increase in withdrawals, RR 1.11 (95% CI 0.96 to 1.30). The NMA estimates of TNF biologic+MTX/DMARD (RR 1.24 (95% Crl 0.99 to 1.57)) and non-TNF biologic+MTX/DMARD (RR 1.20 (95% Crl 0.87 to 1.67)) were similarly inconclusive and downgraded to low for both imprecision and indirectness.Based on direct evidence of high quality, biologic+MTX/DMARD was associated with clinically significantly increased risk (statistically borderline significant) of serious adverse events on biologic+MTX/DMARD (Peto OR [can be interpreted as RR due to low event rate] 1.12 (95% CI 0.99 to 1.27); absolute risk 1% (0% to 2%), As well, the NMA estimate for TNF biologic+MTX/DMARD (Peto OR 1.20 (95% Crl 1.01 to 1.43)) showed moderate quality evidence of an increase in the risk of serious adverse events. The other two NMA estimates were downgraded to low quality due to imprecision and indirectness and had wide confidence intervals resulting in uncertainty around the estimates: non-TNF biologics + MTX/DMARD: 1.07 (95% Crl 0.89 to 1.29) and anakinra: RR 1.06 (95% Crl 0.65 to 1.75).Based on direct evidence of low quality (downgraded for serious imprecision), results were inconclusive for cancer (Peto OR 1.07 (95% CI 0.68 to 1.68) for all biologic+MTX/DMARD combinations. The NMA estimates of TNF biologic+MTX/DMARD (Peto OR 1.21 (95% Crl 0.63 to 2.38) and non-TNF biologic+MTX/DMARD (Peto OR 0.99 (95% Crl 0.58 to 1.78)) were similarly inconclusive and downgraded to low quality for both imprecision and indirectness.Main results text shows the results for tofacitinib and differences between medications.

AUTHORS' CONCLUSIONS: Based primarily on RCTs of 6 months' to 12 months' duration, there is moderate quality evidence that the use of biologic+MTX/DMARD in people with rheumatoid arthritis who have failed to respond to MTX or other DMARDs results in clinically important improvement in function and higher ACR50 and remission rates, and increased risk of serious adverse events than the comparator (MTX/DMARD/PL; high quality evidence). Radiographic progression is slowed but its clinical relevance is uncertain. Results were inconclusive for whether biologics + MTX/DMARDs are associated with an increased risk of cancer or withdrawals due to adverse events.

Originalsprog Engelsk
Tidsskrift Cochrane Database of Systematic Reviews
Tidsskriftsnummer 5
Sider (fra-til) CD012183
ISSN 1469-493X
DOI
Status Udgivet - 2016

Calcium, vitamin D, casein and whey protein intakes and periodontitis among Danish adults

Adegboye, A. R., Boucher, B. J., Kongstad, J., Fiehn, N-E., Christensen, L. B. & Heitmann, B. L. feb. 2016 I : Public Health Nutrition. 19, 3, s. 503-10 8 s.

Publikation: Forskning - peer reviewTidsskriftartikel

OBJECTIVE: To investigate whether intakes of Ca, vitamin D, casein and whey are associated with periodontitis and to investigate the possibility of interactions between them.

DESIGN: Cross-sectional study. An Internet-based, 267-item FFQ was used to assess dietary intake. Intakes of casein (32·0 g/d), whey proteins (9·6 g/d) and vitamin D (5·8 μg/d) were classified as within v. above the 50th percentile. Ca intake was classified as within v. below age-specific recommendations. Severe periodontitis was defined as having ≥2 inter-proximal sites with clinical attachment loss ≥6 mm (not on the same tooth) and ≥1 inter-proximal site with pocket depth ≥5 mm. Since vitamin D influences Ca absorption, models were stratified by lower and higher (<5·8 v. ≥5·8 µg/d) vitamin D intake.

SETTING: Danish Health Examination Survey (DANHES) 2007-2008.

SUBJECTS: Adult participants (n 3287) in the oral health study of DANHES 2007-2008.

RESULTS: Intakes of Ca within recommendations (OR=0·76; 95 % CI 0·58, 0·99), whey ≥9·6 g/d (OR=0·75; 95 % CI 0·58, 0·97) and casein ≥32 g/d (OR=0·75 95 % CI 0·58, 0·97) were associated with lower likelihood of severe periodontitis after adjustment for age, gender, education, smoking, sucrose intake, alcohol consumption, number of teeth, daily brushing, regular visits to the dentist and chronic illness, irrespective of vitamin D intake levels. Intake of vitamin D alone was not associated severe with periodontitis.

CONCLUSIONS: Intakes of Ca, casein and whey protein were inversely associated with periodontitis. Consumption of foods rich in Ca, casein and whey (e.g. dairy foods) should be promoted, as they may contribute to the prevention of periodontitis. Further longitudinal studies are required to confirm these associations.

Originalsprog Engelsk
Tidsskrift Public Health Nutrition
Vol/bind 19
Tidsskriftsnummer 3
Sider (fra-til) 503-10
Antal sider 8
ISSN 1368-9800
DOI
Status Udgivet - feb. 2016

BACKGROUND: Positional MRI (pMRI) allows for three-dimensional visual assessment of navicular position. In this exploratory pilot study pMRI was validated against a stretch sensor device, which measures movement of the medial plantar arch. We hypothesized that a combined pMRI measure incorporating both vertical and medial displacement of the navicular bone induced by loading would be correlated with corresponding stretch sensor measurements.

METHODS: 10 voluntary participants were included in the study. Both pMRI and subsequent stretch sensor measurements were performed in a) supine, b) standing and c) standing position with addition of 10 % body weight during static loading of the foot. Stretch sensor measurements were also performed during barefoot walking.

RESULTS: The total change in navicular position measured by pMRI was 10.3 mm (CI: 7.0 to 13.5 mm). No further displacement occurred when adding 10 % bodyweight (mean difference: 0.7 mm (CI: -0.7 to 2.0 mm), P = 0.29). The total navicular displacement correlated with stretch sensor measurement under static loading conditions (Spearman's rho = 0.66, P = 0.04) but not with measurements during walking (Spearman's rho = 0.58, P = 0.08).

CONCLUSIONS: Total navicular bone displacements determined by pMRI showed concurrent validity with stretch sensor measurements but only so under static loading conditions. Although assessment of total navicular displacement by combining concomitant vertical and medial navicular bone movements would appear advantageous compared to monoplanar measurement the combined measure did not seem to predict dynamic changes of the medial foot arch during walking, which are among several possible factors depending on different walking patterns.

Originalsprog Engelsk
Tidsskrift Journal of Foot & Ankle Surgery
Vol/bind 9
Sider (fra-til) 35
ISSN 1067-2516
DOI
Status Udgivet - 2016

OBJECTIVE: Knee osteoarthritis (KOA) is a multifactorial joint disease affecting many people worldwide. Recommended treatments for KOA include exercise and steroid injections, or a combination of these. The objective of this exploratory outcome analysis of a randomized trial was to assess changes in inflammation markers assessed by ultrasound imaging (US) in KOA secondary to intra-articular corticosteroid injection given prior to exercise therapy.

DESIGN: This study is a sub-study to a larger clinical trial which compared the clinical effects of steroid injection in KOA to placebo injection, both given prior to exercise therapy. The US outcomes were changes from baseline in US-assessed synovial size, Doppler activity presence in the synovial membrane, and numbers of US-detected Baker's cysts. US was performed at baseline, week 14 (exercise stop), and week 26 (follow-up).

RESULTS: Fifty participants received steroid injection, and 50 received placebo injection. All participants received 12 weeks of exercise. Forty-five and 44, respectively, completed the study. At week 14, the group difference in the change in synovium thickness was 2.2 mm (95%, confidence interval (CI) -0.5 to 4.8), P = 0.11. There were no group differences in the changes in distribution of patients with presence of synovial Doppler activity (P = 0.98) or Baker's cysts (P = 0.35). There were no statistically significant differences between groups at week 26 in any outcome.

CONCLUSION: Intra-articular steroid injection of KOA-patients prior to a 3 months exercise programme did not reduce synovial hypertrophy, synovial Doppler activity, or Baker's cyst presence more than a placebo saline injection according to US-assessments.

TRIAL REGISTRATION: EudraCT: 2012-002607-18.

Originalsprog Engelsk
Tidsskrift Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society
Vol/bind 24
Tidsskriftsnummer 5
Sider (fra-til) 814-21
Antal sider 8
ISSN 1063-4584
DOI
Status Udgivet - maj 2016

Clinical benefit of intra-articular saline as a comparator in clinical trials of knee osteoarthritis treatments: A systematic review and meta-analysis of randomized trials

Altman, R. D., Devji, T., Bhandari, M., Fierlinger, A., Niazi, F. & Christensen, R. okt. 2016 I : Seminars in Arthritis and Rheumatism. 46, 2, s. 151-9 9 s.

Publikation: Forskning - peer reviewTidsskriftartikel

OBJECTIVES: Hyaluronic acid and corticosteroids are common intra-articular (IA) therapies widely used for the management of mild to moderate knee osteoarthritis (OA). Many trials evaluating the efficacy of IA administered therapies commonly use IA saline injections as a placebo comparator arm. Using a systematic review and meta-analysis, our objective was to assess the clinical benefit associated with use of IA saline in trials of IA therapies in the treatment of patients with painful knee OA.

METHODS: MEDLINE and Embase databases were searched for articles published up to and including August 14th, 2014. Two reviewers assessed the eligibility of potential reports and the risk of bias of included trials. We analyzed short (≤3 months) and long-term (6-12 months) pain reduction of the saline arm of included trials using standardized mean differences (SMDs; estimated assuming a null effect in a comparator group) that were combined and weighted using a random effects model. Treatment-related adverse events (AEs) were tabulated and presented using descriptive statistics.

RESULTS: From 40 randomized controlled trials (RCTs) eligible for inclusion only 38 provided sufficient data to be included in the meta-analysis. Based on data with moderate inconsistency IA saline was found to significantly improve short-term knee pain in 32 studies involving 1705 patients (SMD = -0.68; 95% CI: -0.78 to -0.57; P < 0.001; I(2) = 50%). Long-term knee pain was significantly decreased following IA injection with saline in 19 studies involving 1445 patients (SMD = -0.61; 95% CI: -0.76 to -0.45; P < 0.001) with a substantial degree of inconsistency (I(2) = 74%). Overall, 29 of the included trials reported on adverse events, none of which found any serious treatment-related AEs following IA injection with saline.

CONCLUSIONS: Pain relief observed with IA saline should prompt health care providers to consider the additional effectiveness of current IA treatments that use saline comparators in clinical studies, and challenges of identifying IA saline injection as a "placebo."

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 46
Tidsskriftsnummer 2
Sider (fra-til) 151-9
Antal sider 9
ISSN 0049-0172
DOI
Status Udgivet - okt. 2016

AIM: Evidence of comparative effectiveness of different treatment approaches is important for clinical decision-making, yet absent for most recommended treatments of knee osteoarthritis pain. The objective of this study was to estimate the comparative effectiveness of exercise versus orally administered analgesics for pain in patients with knee osteoarthritis.

METHODS: The Cochrane Database of systematic reviews was searched for meta-analyses of randomized controlled studies comparing exercise or analgesics with a control group (placebo or usual care) and with pain as an outcome. Individual study estimates were identified and effect sizes were calculated from group differences. We combined study-level effects on pain with a random effects meta-analysis and compared effect sizes between exercise trials and trials with analgesic interventions.

RESULTS: We included six Cochrane reviews (four pharmacology, two exercise). From these, 54 trials were eligible (20 pharmacology, 34 exercise), with 9806 participants (5627 pharmacology, 4179 exercise). The pooled effect size of pharmacological pain interventions was 0.41 (95% CI: 0.23-0.59) and for exercise 0.46 standardized mean difference (95% CI: 0.34-0.59). There was no statistically significant difference between the two types of intervention (difference: 0.06 standardized mean difference [95% CI: -0.28-0.16; p = 0.61]).

CONCLUSION: This meta-epidemiological study provides indirect evidence that for knee osteoarthritis pain, the effects from exercise and from oral analgesics are comparable. These results may support shared decision-making where a patient for some reason is unable to exercise or who consider exercise as unviable and analgesics as a more feasible choice. PROSPERO registration: CRD42013006924.

Originalsprog Engelsk
Tidsskrift Journal of Comparative Neurology
Vol/bind 5
Tidsskriftsnummer 4
Sider (fra-til) 417-31
Antal sider 15
ISSN 0021-9967
DOI
Status Udgivet - jul. 2016

OBJECTIVES: Rheumatoid arthritis (RA) patients suffer from disabling fatigue but the causes of this condition are unknown. Our aim was to assess which of the variables disease activity, disease duration, and pain is associated with fatigue.

METHOD: We conducted a systematic literature search in MEDLINE and EMBASE, followed by selection of studies according to set criteria, data extraction, and statistical analyses of the relationships in RA between fatigue and the following covariates: disease duration, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the 28-joint Disease Activity Score (DAS28), swollen to tender joint count ratio (STR), and pain. Linear regression analyses of fatigue regressed on each of the six covariates, and a multiple regression analysis where fatigue was regressed on the six covariates through a forward selection procedure was carried out with construction of correlation measures between fatigue and the covariates.

RESULTS: A total of 121 studies were included in the analyses, including > 100 000 RA patients. A high level of fatigue was seen even in well-treated patients, demonstrating fatigue as a major problem in RA. Fatigue was found to be positively correlated with pain, CRP, DAS28, and ESR but not with the STR or disease duration, with pain as the overall domineering factor.

CONCLUSIONS: Fatigue has a substantial influence on the lives of RA patients, independent of disease duration. Pain is the domineering factor in the experience and degree of fatigue. Disease activity is positively correlated to fatigue but does not contribute substantially when pain is considered. Optimal pain relief is therefore an important part of the treatment to improve fatigue in RA.

Originalsprog Engelsk
Tidsskrift Scandinavian Journal of Rheumatology
Vol/bind 45
Tidsskriftsnummer 4
Sider (fra-til) 255-61
Antal sider 7
ISSN 0300-9742
DOI
Status Udgivet - jul. 2016

Costs in Relation to Disability, Disease Activity, and Health-related Quality of Life in Rheumatoid Arthritis: Observational Data from Southern Sweden

Wallman, J. K., Eriksson, J. K., Nilsson, J-Å., Olofsson, T., Kristensen, L-E., Neovius, M. & Geborek, P. jul. 2016 I : Journal of Rheumatology. 43, 7, s. 1292-9 8 s.

Publikation: Forskning - peer reviewTidsskriftartikel

OBJECTIVE: To compare how costs relate to disability, disease activity, and health-related quality of life (HRQOL) in rheumatoid arthritis (RA).

METHODS: Antitumor necrosis factor (anti-TNF)-treated patients with RA in southern Sweden (n = 2341) were monitored 2005-2010. Health Assessment Questionnaire (HAQ), 28-joint Disease Activity Score (DAS28), and EQ-5D scores were linked to register-derived costs of antirheumatic drugs (excluding anti-TNF agents), patient care, and work loss from 30 days before to 30 days after each visit (n = 13,289). Associations of HAQ/DAS28/EQ-5D to healthcare (patient care and drugs) and work loss costs (patients < 65 yrs) were studied in separate regression models, comparing standardized β coefficients by nonparametric bootstrapping to assess which measure best reflects costs. Analyses were conducted based on both individual means (linear regression, comparing between-patient associations) and by generalized estimating equations (GEE), using all observations to also account for within-patient associations of HAQ/DAS28/EQ-5D to costs.

RESULTS: Regardless of the methodology (linear or GEE regression), HAQ was most closely related to both cost types, while work loss costs were also more closely associated with EQ-5D than DAS28. The results of the linear models for healthcare costs were standardized β = 0.21 (95% CI 0.15-0.27), 0.16 (0.11-0.21), and -0.15 (-0.21 to -0.10) for HAQ/DAS28/EQ-5D, respectively (p < 0.05 for HAQ vs DAS28/EQ-5D). For work loss costs, the results were standardized β = 0.43 (95% CI 0.39-0.48), 0.27 (0.23-0.32), and -0.34 (-0.38 to -0.29) for HAQ/DAS28/EQ-5D, respectively (p < 0.05 for HAQ vs DAS28/EQ-5D and for EQ-5D vs DAS28).

CONCLUSION: Overall, HAQ disability is a better marker of RA costs than DAS28 or EQ-5D HRQOL.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 43
Tidsskriftsnummer 7
Sider (fra-til) 1292-9
Antal sider 8
ISSN 0315-162X
DOI
Status Udgivet - jul. 2016

Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR task force

Strehl, C., Bijlsma, J. W. J., de Wit, M., Boers, M., Caeyers, N., Cutolo, M., Dasgupta, B., Dixon, W. G., Geenen, R., Huizinga, T. W. J., Kent, A., de Thurah, A. L., Listing, J., Ray, D. W., Scherer, H. U., Seror, R., Spies, C. M., Tarp, S., Wiek, D. & Buttgereit, F. jun. 2016 I : Annals of the Rheumatic Diseases. 75, 6, s. 952-7 6 s.

Publikation: Forskning - peer reviewTidsskriftartikel

There is convincing evidence for the known and unambiguously accepted beneficial effects of glucocorticoids at low dosages. However, the implementation of existing recommendations and guidelines on the management of glucocorticoid therapy in rheumatic diseases is lagging behind. As a first step to improve implementation, we aimed at defining conditions under which long-term glucocorticoid therapy may have an acceptably low level of harm. A multidisciplinary European League Against Rheumatism task force group of experts including patients with rheumatic diseases was assembled. After a systematic literature search, breakout groups critically reviewed the evidence on the four most worrisome adverse effects of glucocorticoid therapy (osteoporosis, hyperglycaemia/diabetes mellitus, cardiovascular diseases and infections) and presented their results to the other group members following a structured questionnaire for final discussion and consensus finding. Robust evidence on the risk of harm of long-term glucocorticoid therapy was often lacking since relevant study results were often either missing, contradictory or carried a high risk of bias. The group agreed that the risk of harm is low for the majority of patients at long-term dosages of ≤5 mg prednisone equivalent per day, whereas at dosages of >10 mg/day the risk of harm is elevated. At dosages between >5 and ≤10 mg/day, patient-specific characteristics (protective and risk factors) determine the risk of harm. The level of harm of glucocorticoids depends on both dose and patient-specific parameters. General and glucocorticoid-associated risk factors and protective factors such as a healthy lifestyle should be taken into account when evaluating the actual and future risk.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 75
Tidsskriftsnummer 6
Sider (fra-til) 952-7
Antal sider 6
ISSN 0003-4967
DOI
Status Udgivet - jun. 2016

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