Papers by Henning Bliddal
The American Journal of Clinical Nutrition, 2017
Background: A formula low-energy diet (LED) reduces weight effectively in obese patients with kne... more Background: A formula low-energy diet (LED) reduces weight effectively in obese patients with knee osteoarthritis, but the role of LED in long-term weight-loss maintenance is unclear. Objective: We aimed to determine the effect of intermittent LED compared with daily meal replacements on weight-loss maintenance and number of knee replacements over 3 y. Design: The design was a randomized trial with participants aged .50 y who had knee osteoarthritis and a body mass index [BMI (in kg/m 2)] $30. Participants were recruited from the osteoarthritis outpatient clinic at Copenhagen University Hospital in Frederiksberg, Denmark; they had previously completed a 68-wk lifestyle intervention trial and achieved an average weight loss of 10.5 kg (10% of initial body weight). Participants were randomly assigned to either the intermittent treatment (IN) group with LED for 5 wk every 4 mo for 3 y or to daily meal replacements of 1-2 meals for 3 y [regular (RE) group]. Attention by dietitians and the amount of formula products were similar. Primary outcomes were changes in body weight and proportion of participants receiving knee replacements. Outcomes were analyzed on the intention-to-treat-population with the use of baseline-carried-forward imputation for missing data. Results: A total of 153 participants (means 6 SDs: BMI: 33.3 6 4.6; age: 63.8 6 6.3 y; 83% women) were recruited between June and December 2009 and randomly assigned to the IN (n = 76) or RE (n = 77) group. A total of 53 and 56 participants, respectively, completed the trial. Weight increased by 0.68 and 1.75 kg in the IN and RE groups, respectively (mean difference: 21.06 kg; 95% CI: 22.75, 0.63 kg; P = 0.22). Alloplasty rates were low and did not differ (IN group: 8 of 76 participants; RE group: 12 of 77 participants; P = 0.35). Conclusions: After a mean 10% weight-loss and 1-y maintenance, additional use of daily meal replacements or intermittent LED resulted in weight-loss maintenance for 3 y. These results challenge the commonly held assumption that weight regain in the long term is inevitable. This trial was registered at clinicaltrials.gov as NCT00938808.
Archives Of Physiology And Biochemistry, 1985
The clinical course of 12 episodes of native valve endocarditis (NVE) and 15 episodes of prosthet... more The clinical course of 12 episodes of native valve endocarditis (NVE) and 15 episodes of prosthetic valve endocarditis (PVE) was studied. The mortality in NVE was 3/12 episodes and in PVE 5/15. No significant differences in prognosis were observed in relation to the bacterial taxonomy, which was stated in all cases. Though surgical valve replacement was performed on the relative indications heart failure, resistance to treatment, or major embolism, the regimen was primarily conservative, and the results comparable to the reports in the literature of a more surgically active attitude.
Pain Research and Treatment, 2014
Objectives. To assess the effects of intra-articular therapy on pain sensitivity in the knee and ... more Objectives. To assess the effects of intra-articular therapy on pain sensitivity in the knee and surrounding tissues in knee OA patients. Methods. Twenty-five knee OA patients with symptomatic knee OA were included in this interventional cohort study. Pressure pain thresholds (PPT) were recorded before, immediately after, and two weeks after ultrasound guided intra-articular injection of lidocaine combined with glucocorticosteroid. Computer-controlled and manual pressure algometers were used to assess PPT on the knee, vastus lateralis, tibialis anterior, and the extensor carpi radialis longus muscles (control site). Results. Significantly increased PPTs were found following intra-articular injection, at both the knee ( < 0.0001) and the surrounding muscles ( < 0.042). The treatment effects were sustained for two weeks, and at some points the effect was even greater at two weeks ( < 0.026). Albeit not statistically significant, a similar trend was observed at the control site. Conclusions. Intra-articular anesthesia, combined with glucocorticosteroid, reduced pain sensitivity in both the knee and surrounding muscles for at least two weeks.
JAMA internal medicine, Jan 30, 2015
Osteoarthritis (OA) of the knee is the most frequent form of arthritis and a cause of pain and di... more Osteoarthritis (OA) of the knee is the most frequent form of arthritis and a cause of pain and disability. Combined nonpharmacologic and pharmacologic treatments are recommended as the optimal treatment approach, but no evidence supports the recommendation. To assess the clinical benefits of an intra-articular corticosteroid injection given before exercise therapy in patients with OA of the knee. We performed a randomized, blinded, placebo-controlled clinical trial evaluating the benefit of intra-articular corticosteroid injection vs placebo injection given before exercise therapy at an OA outpatient clinic from October 1, 2012, through April 2, 2014. The participants had radiographic confirmation of clinical OA of the knee, clinical signs of localized inflammation in the knee, and knee pain during walking (score >4 on a scale of 0 to 10). Participants were randomly allocated (1:1) to an intra-articular 1-mL injection of the knee with methylprednisolone acetate (Depo-Medrol), 40 ...
BMJ open, 2014
When participants drop out of randomised clinical trials, as frequently happens, the intention-to... more When participants drop out of randomised clinical trials, as frequently happens, the intention-to-treat (ITT) principle does not apply, potentially leading to attrition bias. Data lost from patient dropout/lack of follow-up are statistically addressed by imputing, a procedure prone to bias. Deviations from the original definition of ITT are referred to as modified intention-to-treat (mITT). As yet, the impact of the potential bias associated with mITT has not been assessed. Our objective is to investigate potential bias and disadvantages of performing mITT and evaluate possible concerns when executing different mITT approaches in meta-analyses. Using meta-epidemiology on randomised trials considered less prone to bias (ie, good internal validity) and assessing biological or targeted agents in patients with rheumatoid arthritis, we will meta-analyse data from 10 biological and targeted drugs based on collections of trials that would correspond to 10 individual meta-analyses. This stu...
Pain, 2014
This study examined the functional and psychological outcomes of a 2-week, group-based multicompo... more This study examined the functional and psychological outcomes of a 2-week, group-based multicomponent treatment course that targeted patients with chronic widespread pain. Patients (192 included in the intention-to-treat population), all fulfilling the 1990 American College of Rheumatology classification criteria for fibromyalgia, were consecutively recruited from a tertiary care setting and randomized (1:1) to either the treatment course or a waiting list control group. Co-primary outcomes were the Assessment of Motor and Process Skills (AMPS) and SF-36 Mental Composite Score (MCS) evaluated at 6-month followup. Primary endpoints were partly achieved with a statistically significant improvement in AMPS activities of daily living motor (group mean difference: 0.20 [95% confidence interval (CI): 0.09 to 0.31] logits; P = .0003) and AMPS activities of daily living process (0.20 [95% CI: 0.12 to 0.27] logits, P < .0001) ability measures, whereas no difference in the SF-36 MCS (1.14 [95% CI: À1.52 to 3.81], P = .40) was observed. Individual patient responses varied, and the proportion of patients achieving a clinically meaningful change of at least 0.3 logits on the AMPS seemed influenced by the reporting of a pending social welfare application at the time of enrollment. We conclude that even in fibromyalgia patients presenting with a substantial disability established over many years, the 2-week multicomponent treatment course resulted in observable improvement of functional ability in a subgroup of patients at 6-month followup. This improvement, however, was not reflected in secondary patient reported outcomes, including scores of self-reported functional ability on standardized questionnaires. We suggest including observation-based assessments in future clinical trials focusing on functional outcomes in patients with fibromyalgia.
Seminars in Arthritis and Rheumatism, 2013
To summarize the empirical evidence regarding the effect of treatment intensification on clinical... more To summarize the empirical evidence regarding the effect of treatment intensification on clinical outcomes in patients with rheumatoid arthritis treated with one of the TNF-α-inhibitors, adalimumab, etanercept or infliximab. A systematic search of the bibliographic databases Embase, Medline, Web of Science and Cochrane Central identifying articles concerning treatment with adalimumab, etanercept or infliximab in adult patients with rheumatoid arthritis exposed to dose increase or shortening of dosing intervals was performed. Longitudinal cohorts, both clinical trials and observational studies, were included. ACR and EULAR response criteria and DAS28 were the preferred outcome measures. Out of 1135 records, eleven studies were included in the final evidence synthesis. One article concerned all the three TNF-α-inhibitors, eight used infliximab, one adalimumab and one etanercept. According to GRADE, evidence was weakened in particular by the lack of control groups, and for treatment intensification with adalimumab and etanercept, no conclusions could be drawn. With infliximab, two trials of high quality revealed contradictory results, but six studies described an improved clinical outcome following intensified treatment strategies. Some studies (2/2) also indicated that for infliximab, frequency increase was superior to dose increase. Available studies indicate that intensifying treatment with infliximab in rheumatoid arthritis patients, preferably by increasing the frequency of drug administration, may lead to improved clinical outcome in some patients, but the evidence is weak. There is an urgent need for prospectively designed cohort studies to be able to draw a final conclusion.
Results in Pharma Sciences, 2011
Topical application of NSAIDs is an alternative route to systemic administration when a local ant... more Topical application of NSAIDs is an alternative route to systemic administration when a local antiinflammatory effect of the underlying tissue is a treatment option. The aim of the present microdialysis study was to assess and compare plasma and tissue levels of diclofenac when topically applied with or without iontophoresis in healthy adults. Fourteen healthy adults (26 7 9.4 years) were randomized to diclofenac applied by iontophoresis, or by a gel, in a crossover design. Diclofenac concentrations were measured in plasma and in microdialysis perfusates from the underlying tissues. Iontophoretic application resulted in the highest plasma concentration of 3.4 7 0.5 ng/ml (SEM given) compared to 0.4 ng/ml (at the detection limit) with gel, whereas no differences were observed between tissue concentrations for the two application methods, both being very low, below or around the detection limit. Iontophoresis caused skin reactions in 25% of the participants. Iontophoresis of diclofenac as compared to traditional topical application was not superior in order to increase the NSAID concentration locally and appears to have a higher frequency of skin reactions.
Arthritis, 2015
Objective. To validate the agreement between the 28-joint disease activity score based on erythro... more Objective. To validate the agreement between the 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) and the 28-joint disease activity score based on C-reactive protein (DAS28-CRP) in a group of Danish patients with rheumatoid arthritis (RA). Methods. Data from 109 Danish RA patients initiating biologic treatment were analysed at baseline and following one year of treatment. Participants were retrospectively enrolled from a previous cohort study and were considered eligible for this project if CRP and ESR were measured at baseline and at the follow-up visit. To assess the extent of agreement between the two DAS28 definitions, the "European League Against Rheumatism" (EULAR) response criteria based on each definition were calculated with cross-classification. Weighted Kappa (κ) coefficients were calculated, and Bland-Altman plots were used to illustrate degree of agreement between DAS28 definitions. Results. The 75 eligible patients were clas...
International journal of rheumatology, 2014
The clinical utility of tender point (TP) examination in patients reporting chronic widespread pa... more The clinical utility of tender point (TP) examination in patients reporting chronic widespread pain (CWP) is the subject of contemporary debate. The objective of this study was to assess the relationship between mechanical hyperalgesia assessed by manual TP examination and clinical disease severity. 271 women with CWP were recruited from a clinical setting. Data collection included patient-reported symptoms, health-related quality of life variables, and observation-based measures of functional ability, muscle strength, 6-minute walk, and pressure pain thresholds measured by cuff algometry. TP examination was conducted according to ACR-guidelines. Relationships between disease variables and TP count (TPC) were analyzed with logistic regression in a continuum model, allowing the TPC to depend on the included disease variables and two regression models carried out for a TPC threshold level, varying between 1 and 17. The threshold analyses indicated a TPC threshold at 8, above which a l...
PAIN, 2011
Knowledge about functional ability, including activities of daily living (ADL), in patients with ... more Knowledge about functional ability, including activities of daily living (ADL), in patients with chronic widespread pain (CWP) and fibromyalgia (FMS) is largely based on self-report. The purpose of this study was to assess functional ability by using standardised, observation-based assessment of ADL performance and to examine the relationship between self-reported and observation-based measures of disability. A total of 257 women with CWP, 199 (77%) fulfilling the American College of Rheumatology tender point criteria for FMS, were evaluated with the Assessment of Motor and Process Skills (AMPS), an observation-based assessment providing linear measures of ADL motor and ADL process skill ability (unit: logits). A cutoff for effortless and independent ADL task performance is set at 2.0 for the motor scale and 1.0 for the process scale. A total of 248 (96.5%) had ability measures below the 2.00 ADL motor cutoff and 107 (41.6%) below the 1.00 ADL process cutoff, indicating increased effort and/or inefficiency during task performance as well as a potential need of assistance for community living. Mean ADL motor ability measure was 1.07 and was significantly lower in patients diagnosed with FMS than plain CWP (1.02 vs 1.27 logits, P = .001). Mean ADL process ability measure was 1.09 logits and was without difference between FMS and plain CWP (1.07 vs 1.16 logits, P = .064). Only weak to moderate correlations between self-reported functional ability and observation-based AMPS ability measures were observed. The results of the study support the notion of considerable performance difficulties in women with CWP. The everyday life problems are substantial and place the individual at risk of need of support for community living.
Osteoarthritis and Cartilage, 1994
Regional bone mineral density (BMD, g/cm 2) of the proximal tibia including the subchondral plate... more Regional bone mineral density (BMD, g/cm 2) of the proximal tibia including the subchondral plate was measured in vivo by dual photon absorptiometry (DPA). Twenty-one women and six men with gonarthrosis (GA) were examined.
Osteoarthritis and Cartilage, 2014
To investigate the association between knee pain and signs of inflammation in the infrapatellar f... more To investigate the association between knee pain and signs of inflammation in the infrapatellar fat pad (IPFP) in obese patients with knee osteoarthritis (KOA). In a cross-sectional setting, 3-T conventional contrast-enhanced (CE) magnetic resonance imaging (MRI) and dynamic contrast-enhanced (DCE)-MRI of KOA were analysed to quantify the extent of inflammation in the IPFP, and correlated (Spearman&amp;amp;amp;amp;#39;s rank correlation) to pain and other symptoms assessed via the Knee injury and Osteoarthritis Outcome Score (KOOS) (100 = no pain, 0 = extreme pain). The extent of inflammation in the IPFP was assessed according to the MRI Osteoarthritis Knee Score (MOAKS) using CE-MRI and by DCE-MRI perfusion variables. The perfusion variable, &amp;amp;amp;amp;quot;Inflammation&amp;amp;amp;amp;quot;, was chosen as primary perfusion variable in the analysis. Intraclass correlation coefficients for the perfusion variables ranged from 0.81 to 0.99. MRI and clinical data were obtained in 95 patients. The typical patient was a woman (82%) with an average age of 65 years (SD 6.5) and a body mass index (BMI) of 32 kg/m(2) (SD 3.7). The bivariate association between KOOS pain and the DCE-MRI perfusion variable &amp;amp;amp;amp;quot;Inflammation&amp;amp;amp;amp;quot; showed a statistically significant correlation (r = -0.42, P &amp;amp;amp;amp;lt; 0.0001). A statistically significant correlation was also found between KOOS pain and MOAKS Hoffa-synovitis (r = -0.21, P = 0.046). Perfusion variables on DCE-MRI reflecting the severity of inflammation in the IPFP and MOAKS Hoffa-synovitis were associated with the severity of pain in KOA. These results suggest that severe inflammation in the IPFP is associated with severe pain in KOA and that DCE-MRI is a promising method to study the impact of inflammation in KOA.
Knee Surgery, Sports Traumatology, Arthroscopy, 2007
Sclerosing therapy has in recent studies showed promising results in patients with clinically and... more Sclerosing therapy has in recent studies showed promising results in patients with clinically and ultrasonographically diagnosed tendinosis in Achilles and patellar tendons. The aim of this investigation was to study the presence of intratendinous colour Doppler (CD) flow in horses with clinically diagnosed chronic tendinopathy and to test if experience from human studies could be extrapolated to horses. Special interest was focused on the treatment with sclerosing therapy and whether we could obtain the same successful peroperative findings as in humans. Four horses with clinically diagnosed unilateral chronic tendinosis in the forelimbs were examinated with both grey-scale ultrasonography (US) and CD. The horses were to be euthanised according to standard procedure is such cases. The US findings were used for guidance of sclerosing therapy. All horses showed abnormal findings on US, especially intratendinous neovascularisation in the affected limb but not in the contralateral limb. The CD findings had the same appearance as seen in human Achilles tendons with chronic tendinopathy. In all cases the intratendinous neovascularisation was successfully &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;shut down&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; peroperatively. The horses showed no signs of discomfort or worsening of symptoms during the short follow-up period after the procedure. The results indicate that the promising results from human medicine might be transferred to treatment of horses with chronic tendinopathy. In the future it will hopefully be possible to use the model from overused tendons in the horse to determine the best treatment of overuse injuries in humans as well. The animal model will allow experimental studies including substantial tissue sampling for mechanical and molecular biological analysis.
Journal of Shoulder and Elbow Surgery, 2008
The Journal of Clinical Endocrinology & Metabolism, 1982
The relationship between thyroid-stimulating immunoglobulins, measured by both radioreceptor assa... more The relationship between thyroid-stimulating immunoglobulins, measured by both radioreceptor assay and adenylate cyclase stimulation, and the HLA alleles was studied in 41 patients with Hashimoto&#39;s thyroiditis. TSH binding-inhibiting immunoglobulins (TBII) were detected in 9 (22%) patients, and human thyroid adenylate cyclase-stimulating immunoglobulins (HTACS) were found in 21 (51%) patients. Only 2 patients were positive in both assays, and an inverse relationship was observed between TBII and HTACS. In the 21 HTACS-positive patients, HLA-Dw5 was only found in 1 subject, compared to 8 of the 20 HTACs-negative patients (P less than 0.01), while 4 of the 9 TBII-positive patients had HLA-Dw5 compared to 5 of the 32 TBII-negative subjects (P = -0.09). No significant relations were observed between the presence of HTACS or TBII and HLA-Dw3 or HLA-B8. It is concluded, that TBII and HTACS are produced independently in Hashimoto&#39;s thyroiditis, and that the production of these autoantibodies seems to be related to the HLA-D region in this disease.
European Journal of Endocrinology, 1982
The results of 131I treatment in combination with pre- and post-treatment with carbimazole (n = 1... more The results of 131I treatment in combination with pre- and post-treatment with carbimazole (n = 122) were compared to the results of 131I used as the only antithyroid treatment (n = 203). The two groups of patients were fully comparable in regard to age, size of goitre and time of observation, and the same diagnostic criteria and dosage regimen of 131I were used. The incidence of early myxoedema in patients with diffuse goitre was significantly reduced after combination therapy, 5 per cent, compared to 16 per cent after 131I as the only antithyroid therapy (P less than 0.05). The incidence of late myxoedema was 6 per cent in both groups 3 years after the last treatment, and fully compensated myxoedema was found in 13 and 22 per cent (n.s.). No severe acute side effects were observed after 131I therapy in any of the two groups. It is concluded that--in diffuse toxic goitre--a lower early incidence of myxoedema was obtained on the combined regimen because of either a possibly lower absorbed radiation dose or a more fractionate therapy. A major advantage of the combination therapy is also, that the patients are rendered euthyroid shortly after the diagnosis and remain so during the prolonged period of treatment. 131I treatment in combination with carbimazole is advocated in all patients with diffuse and nodular toxic goitre if the patient is above fertile age and thyroidectomy is not indicated.
Uploads
Papers by Henning Bliddal