Novel insights into cerebral palsy.

Cerebral palsy (CP) is a neurodevelopmental disorder characterized by abnormalities of muscle tone, movement and motor skills, and is attributed to injury to the developing brain. CP affects about 1 in 500 neonates. CP shows clinical features which evolve with age, and these may over time lead to deterioration of motor function although the lesion to the developing brain is non-progressive. The underlying causes for CP remain unclear. Based on recent research we are able to give a physiological explanation on the appearance and development of the condition. The damage to the central nervous system causes a change in collagen structure, with a higher level of deposition of collagen around the muscles, increasing throughout life. Assuming this premise is correct, the question is, will it by any treatment be possible to delay or prevent this collagen accumulation in the CP muscles, thereby giving CP patients a better prognosis in the future.

Multi-frequency bioimpedance: a non-invasive tool for muscle-health assessment of adults with cerebral palsy.

Muscle contracture development is a major complication for individuals with cerebral palsy (CP) and has lifelong implications. In order to recognize contracture development early and to follow up on preventive interventions aimed at muscle health development, non-invasive, and easy to use methods are needed. The aim of the present study was to assess whether multi-frequency Bioimpedance (mfBIA) can be used to detect differences between skeletal muscle of individuals with CP and healthy controls. The mfBIA technique was applied to the medial gastrocnemius muscle of n = 24 adults with CP and n = 20 healthy controls of both genders. The phase angle (PA) and the centre frequency (fc) were significantly lower in individuals with CP when compared to controls; PA: - 25% for women and - 31.8% for men (P < 0.0001); fc: - 5.6% for women and - 5.2% for men (P < 0.009). The reactance (Xc) and the extracellular resistance (Re) of skeletal muscle from individuals with CP were significantly higher when compared to controls; Xc: + 9.9% for women and + 28.9% for men (P < 0.0001); Re: + 39.7% for women and + 91.2% for men (P < 0.0001). The present study shows that several mfBIA parameters differ significantly between individuals with CP and healthy controls. Furthermore, these changes correlated significantly with the severity of CP, as assessed using the GMFCS scale. The present data indicate that mfBIA shows promise in terms of being a useful diagnostic tool, capable of characterizing muscle health and its development in individuals with cerebral palsy.

An acoustic myography functional assessment of cerebral palsy subjects compared to healthy controls during physical exercise.

Individuals with cerebral palsy (CP) participate in reduced levels of physical activity and spend an increased amount of time in a sedentary state compared with healthy control subjects. Whether this in part can be explained by impaired muscle function is still unclear. The aim of the present study was to elucidate differences in muscle fibre recruitment during treadmill exercise between CP subjects and healthy age-, sex- and BMI-matched controls. This is a case-control study. Acoustic myography (AMG), a method recording fibre use and efficiency from contracting muscles, was applied during a period of treadmill exercise. The recorded AMG parameters revealed that the CP subjects had a significantly lower initial S-score (spatial summation) than the controls (P < 0.01). However, the T-score (temporal summation) and the E-score (efficiency) showed no significant differences between individuals with CP and the healthy control subjects. The present findings indicate that CP subjects use a higher degree of spatial summation (more fibres recruited) to keep up the same speed during treadmill exercise when compared to healthy matched control subjects. Our results suggest that individuals with CP have a tendency to recruit far more muscle fibres during bouts of exercise than healthy individuals. This may partly explain why CP subjects experience premature fatigue.

Effect of specific exercise-based football injury prevention programmes on the overall injury rate in football: a systematic review and meta-analysis of the FIFA 11 and 11+ programmes.

OBJECTIVE: To investigate the effect of FIFA injury prevention programmes in football (FIFA 11 and FIFA 11+). DESIGN: Systematic review and meta-analysis. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials comparing the FIFA injury prevention programmes with a control (no or sham intervention) among football players. DATA SOURCES: MEDLINE via PubMed, EMBASE via OVID, CINAHL via Ebsco, Web of Science, SportDiscus and Cochrane Central Register of Controlled Trials, from 2004 to 14 March 2016. RESULTS: 6 cluster-randomised controlled trials had assessed the effect of FIFA injury prevention programmes compared with controls on the overall football injury incidence in recreational/subelite football. These studies included 2 specific exercise-based injury prevention programmes: FIFA 11 (2 studies) and FIFA 11+ (4 studies). The primary analysis showed a reduction in the overall injury risk ratio of 0.75 (95% CI 0.57 to 0.98), p=0.04, in favour of the FIFA injury prevention programmes. Secondary analyses revealed that when pooling the 4 studies applying the FIFA 11+ prevention programme, a reduction in the overall injury risk ratio (incidence rate ratio (IRR) 0.61; 95% CI 0.48 to 0.77, p<0.001) was present in favour of the FIFA 11+ prevention programme. No reduction was present when pooling the 2 studies including the FIFA 11 prevention programme (IRR 0.99; 95% CI 0.80 to 1.23, p=0.940). CONCLUSIONS: An injury-preventing effect of the FIFA injury prevention programmes compared with controls was shown in football. This effect was induced by the FIFA 11+ prevention programme which has a substantial injury-preventing effect by reducing football injuries by 39%, whereas a preventive effect of the FIFA 11 prevention programme could not be documented. TRIAL REGISTRATION NUMBER: PROSPERO CRD42015024120.

Reliability of Pain Measurements Using Computerized Cuff Algometry: A DoloCuff Reliability and Agreement Study.

INTRODUCTION: Computerized pneumatic cuff pressure algometry (CPA) using the DoloCuff is a new method for pain assessment. Intra- and inter-rater reliabilities have not yet been established. Our aim was to examine the inter- and intrarater reliabilities of DoloCuff measures in healthy subjects. METHODS: Twenty healthy subjects (ages 20 to 29 years) were assessed three times at 24-hour intervals by two trained raters. Inter-rater reliability was established based on the first and second assessments, whereas intrarater reliability was based on the second and third assessments. Subjects were randomized 1:1 to first assessment at either rater 1 or rater 2. The variables of interest were pressure pain threshold (PT), pressure pain tolerance (PTol), and temporal summation index (TSI). Reliability was estimated by a two-way mixed intraclass correlation coefficient (ICC) absolute agreement analysis. Reliability was considered excellent if ICC > 0.75, fair to good if 0.4 < ICC < 0.75, and poor if ICC < 0.4. Bias and random errors between raters and assessments were evaluated using 95% confidence interval (CI) and Bland-Altman plots. RESULTS: Inter-rater reliability for PT, PTol, and TSI was 0.88 (95% CI: 0.69 to 0.95), 0.86 (95% CI: 0.65 to 0.95), and 0.81 (95% CI: 0.42 to 0.94), respectively. The intrarater reliability for PT, PTol, and TSI was 0.81 (95% CI: 0.53 to 0.92), 0.89 (95% CI: 0.74 to 0.96), and 0.75 (95% CI: 0.28 to 0.91), respectively. CONCLUSION: Inter-rater reliability was excellent for PT, PTol, and TSI. Similarly, the intrarater reliability for PT and PTol was excellent, while borderline excellent/good for TSI. Therefore, the DoloCuff can be used to obtain reliable measures of pressure pain parameters in healthy subjects.

Aquatic exercise for the treatment of knee and hip osteoarthritis.

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.

Ultrasound colour Doppler is associated with synovial pathology in biopsies from hand joints in rheumatoid arthritis patients: a cross-sectional study.

OBJECTIVES: Little is known regarding the association between ultrasound-determined pathological synovial blood flow and synovial pathology in rheumatoid arthritis (RA). We therefore examined the association between colour Doppler ultrasound imaging and synovitis assessed by histopathology and specific cell markers by immunohistochemistry in patients with RA. METHODS: 81 synovial sites from wrist and finger joints from 29 RA patients were evaluated by ultrasound colour Doppler and subsequently biopsied by needle arthroscopy. The association between ultrasound colour fraction and an overall synovitis score and immunohistochemical staining for CD3, CD68, Ki67 and von Willebrand factor was investigated, including repeated samples from the same patients. The overall synovitis score (total 0-9) assessed synovial lining hyperplasia (0-3), stromal activation (0-3) and inflammatory infiltration (0-3). Data were clustered within patients, thus a linear mixed model was applied for the statistical tests. Parsimony in the statistical models was achieved omitting covariates from the model in the case of what was judged no statistical significance (p>0.1). RESULTS: Doppler colour fraction showed an association with the overall synovitis score (approximated Spearman, approximately r=0.43, p=0.003). The density of all immunohistochemical stainings showed a significant association with Doppler colour fraction: von Willebrand factor (approximately r=0.44, p=0.01), CD68 (approximately r=0.53, p=0.02), Ki67 (approximately r=0.57, p=0.05) and CD3 (approximately r=0.57, p=0.0003). CONCLUSIONS: Colour Doppler activity is associated with the extent of inflammation present in the synovial biopsies from RA patients. However, synovial pathology was also seen in biopsies taken from Doppler negative sites.

Cytokine measurements and possible interference from heterophilic antibodies--problems and solutions experienced with rheumatoid factor.

Cytokines are important in the understanding of the immune process in health and disease and are valuable indicators in diagnostics. Measurements of cytokines are based on immunometric methods, and it is important to understand possible pitfalls in these methods to produce reliable cytokine data. This paper focuses on obtaining optimal measurements when applying enzyme-linked immunosorbent assay (ELISA) or multiplex immunoassays (MIA). Cytokines are measured in serum or plasma, as well as in various other body fluids, all containing a series of antibodies and the possibility of interference from these. Some antibodies, such as heterophilic and human anti-animal antibodies, are able to interfere with all immunoassays, but the immunometric techniques are most prone to serious interference from this source. Another type, rheumatoid factor (RF) is a composite of different autoimmune antibodies which can be present in both blood and synovial fluid. RF is present in some arthritic diseases as well as in some other medical conditions. When present, especially RF IgM is known to interfere with the immunometric measurements. A possible and affordable solution to diminish this interference is PEG precipitation, but other efficient, but more expensive, methods, such as precipitation using Protein L or commercially available blocking agents, are also available. Interference of RF is at present not tested in all cytokine assays, but degree of interference from RF, human anti-animal and heterophilic antibodies, as well as from other possible disease-specific antibodies, must always be considered when developing and applying new assays for cytokine measurements.

Assessment of pressure-pain thresholds and central sensitization of pain in lateral epicondylalgia.

OBJECTIVE.: To assess pain sensitivity and spreading hyperalgesia in lateral epicondylalgia (LE). SUBJECTS.: Twenty-two women with LE, and 38 controls were included. OUTCOME MEASURES.: Computerized cuff pressure algometry was used for assessment of pressure-pain threshold and tolerance. The stimulus was applied using a single (stimulation-area: 241 cm(2) ) or double-chambered (stimulation-area: 482 cm(2) ) tourniquet on the arm and leg. Spatial summation was expressed as the ratio between pressure-pain thresholds to single and double cuff-chamber stimulation. During 10-minute constant pressure stimulation at intensity relative to the individual pain threshold, the pain intensity was continuously recorded using an electronic visual analogue scale (VAS), and from this the degree of temporal summation was estimated. For LE, a Doppler ultrasound examination of the elbow was made to identify inflammation. RESULTS.: In LE compared with controls the pressure-pain threshold and tolerance were on average reduced by respectively 31% (nonsignificant) and 18% (nonsignificant) on the lower arm and by 32% (P < 0.05) and 22% (P < 0.05) on the lower leg (spreading sensitization). Within the LE group, pressure-pain thresholds were on average reduced by 20% (P < 0.05) and pain tolerance by 10% (nonsignificant) on the painful compared with the asymptomatic side. Spatial summation (P < 0.01) and temporal summation (P < 0.05) was facilitated in LE compared with controls. In LE patients without signs of peripheral inflammation assessed by Doppler ultrasound, temporal summation was significantly stronger than in patients with ongoing inflammation (P < 0.01). CONCLUSION.: Patients with LE may be subgrouped based on pain hypersensitivity and Doppler ultrasound into clinically meaningful subgroups with varying duration of symptoms and different degrees of central sensitization. These groups may require different pain management strategies.

Changes in bone marrow lesions in response to weight-loss in obese knee osteoarthritis patients: a prospective cohort study.

BACKGROUND: Patients are susceptible for knee osteoarthritis (KOA) with increasing age and obesity and KOA is expected to become a major disabling disease in the future. An important feature of KOA on magnetic resonance imaging (MRI) is changes in the subchondral bone, bone marrow lesions (BMLs), which are related to the future degeneration of the knee joint as well as prevalent clinical symptoms. The aim of this study was to investigate the changes in BMLs after a 16-week weight-loss period in obese subjects with KOA and relate changes in BMLs to the effects of weight-loss on clinical symptoms. METHODS: This prospective cohort study included patients with a body mass index ≥ 30 kg/m2, an age ≥ 50 years and primary KOA. Patients underwent a 16 weeks supervised diet program which included formula products and dietetic counselling (ClinicalTrials.gov: NCT00655941). BMLs in tibia and femur were assessed on MRI before and after the weight-loss using the Boston-Leeds Osteoarthritis Knee Score. Response to weight-loss in BML scores was dichotomised to patients experiencing a decrease in BML scores (responders) and patients who did not (non-responders). The association of BMLs to weight-loss was assessed by logistic regressions and correlation analyses. RESULTS: 39 patients (23%) were classified as responders in the sum of all BML size scores whereas 130 patients (77%) deteriorated or remained stable and were categorized as non-responders. Logistic regression analyses revealed no association between weight-loss < or ≥ 10% and response in BMLs in the most affected compartment (OR 1.86 [CI 0.66 to 5.26, p=0.24]). There was no association between weight-loss and response in maximum BML score (OR 1.13 [CI 0.39 to 3.28, p=0.81]). The relationship between changes in BMLs and clinical symptoms revealed that an equal proportion of patients classified as BML responders and non-responders experienced an OMERACT-OARSI response (69 vs. 71%, p=0.86). CONCLUSIONS: Weight-loss did not improve the sum of tibiofemoral BML size scores or the maximum tibiofemoral BML score, suggesting that BMLs do not respond to a rapidly decreased body weight. The missing relationship between clinical symptoms and BMLs calls for further investigation.

Probing cellular health at the muscle level-Multi-frequency bioimpedance in Parkinson's disease.

Bioimpedance (mfBIA) non-invasively assesses cellular muscle health. Our aim was to explore whether mfBIA captures abnormal cellular muscle health in patients with Parkinson's Disease (PD) and how such changes are modulated with the use of Parkinson's medication. In patients with PD (n = 20) mfBIA measurements were made of biceps brachii, triceps, and extensor carpi radialis longus muscles of the more affected arm whilst at rest, using a mobile mfBIA device (IMPEDIMED, Australia). mfBIA and assessment of motor symptoms were performed in a pragmatic off-medication state, as well as one and 3 h after oral intake of 200 mg levodopa. Age and sex-matched healthy subjects (HC; n = 20) served as controls. PD and HC mfBIA parameters were compared by applying an unpaired two-tailed adjusted t-test and ANOVA with Tukey's correction for multiple comparisons (p ≤ 0.05). The PD group consisted of 13 men (71 ± 17 years) and 7 women (65 ± 7 years). Independent of medication, internal (Ri ) and external resistance (Re ) were found to be significantly higher, and membrane capacitance (Mc) significantly lower, in m.biceps brachii in PD subjects compared to HC. Center frequency (fc) was significantly higher in m.biceps brachii of PD subjects in the "medication-off" state. There was no difference between PD and HC in mfBIA parameters in the measured extensor muscles. The upper limb flexor muscle shows a difference in mfBIA parameters in PD compared to HC. mfBIA may be useful in the diagnosis and assessment of PD patients and is objective, non-invasive, reliable, and easy to use.

Mortality in a cohort of Danish patients with fibromyalgia: increased frequency of suicide.

OBJECTIVE: A previous study demonstrated an association between self-reported widespread body pain and increased mortality. The aim of this study was to analyze whether fibromyalgia (FM) and FM-like symptoms are related to increased mortality. METHODS: From hospital records, we identified 1,361 patients referred during the period 1984-1999 because of the suspicion of FM. The cases were reviewed by reviewers who were blinded to the outcome. The cohort was followed up for a total of 5,295 person-years at risk and was linked to the Danish Mortality Register. Using the number of years at risk and sex-, age-, and calendar-specific mortality rates from the general population, cause-specific standardized mortality ratios [SMRs] were calculated. RESULTS: We observed no overall increased mortality among patients with FM. Among the 1,269 female patients, the SMRs (95% confidence intervals [95% CIs]) for an increased risk of death from suicide, liver cirrhosis/biliary tract disease, and cerebrovascular disease were 10.5 (95% CI 4.5-20.7), 6.4 (95% CI 2.3-13.9), and 3.1 (95% CI 1.1-6.8), respectively. The suicide risk was increased at the time of diagnosis and remained increased after 5 years. Patients meeting the American College of Rheumatology criteria for FM and patients with possible FM had the same cause-specific mortality pattern. No increased cause-specific mortality was observed in the 84 male patients. CONCLUSION: The causes of a markedly increased rate of suicide among female patients with FM are at present unknown but may be related to increased rates of lifetime depression, anxiety, and psychiatric disorders. Risk factors for suicide should be sought at the time of the diagnosis of FM and at followup. The results also suggest that risk factors for liver disease and cerebrovascular disease should be evaluated in patients with FM.

Liraglutide after diet-induced weight loss for pain and weight control in knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Weight loss is critical for preventing and managing obesity-related diseases. There is a notable lack of valid and reliable means to manage patients with overweight/obesity and knee osteoarthritis (KOA). OBJECTIVE: To determine the efficacy and safety of liraglutide in a 30 mg/d dosing in patients with overweight/obesity and KOA. METHODS: The trial was designed as a randomized controlled trial including patients between the age of 18 and 74 y with KOA and a BMI ≥27 (measured in kg/m2).Patients underwent a pre-random assignment diet intervention (week -8 to 0). At week 0, patients having lost >5% of their body weight were randomly assigned to liraglutide 3 mg/d or placebo for 52 wk. The coprimary outcomes were changes in body weight and the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale from week 0 to 52. RESULTS: In total, 168 patients enrolled and 156 were randomly assigned to receive liraglutide or placebo. Patients experienced a significant reduction in body weight and KOOS pain during the pre-random assignment dietary intervention period (week -8 to 0). From week 0 to 52 there was a significant difference in body weight between the liraglutide and placebo group (mean changes: -2.8 and +1.2 kg, respectively; group difference, 3.9 kg; 95% CI: -6.9, -1.0; P = 0.008). There was, however, no group difference in KOOS pain (mean changes: 0.4 and -0.6 points, respectively; group difference, 0.9 points; 95% CI: -3.9, 5.7; P = 0.71). Treatment-emergent adverse events related to the gastrointestinal system were experienced by 50.2% and 39.2% of patients in the liraglutide and placebo groups, respectively. CONCLUSIONS: In patients with KOA and overweight/obesity liraglutide added after an 8-wk pre-random assignment diet induced a significant weight loss at >52 wk but did not reduce knee pain compared to placebo. This trial was registered at clinicaltrials.gov as NCT02905864.

Muscle function assessed by the non-invasive method acoustic myography (AMG) in a Danish group of healthy adults.

Acoustic myography (AMG) is a non-invasive method to assess muscle function during daily activities. AMG has great scope for assessment of musculoskeletal problems. The aim of this study was to create an AMG data set for general clinical use and relate these findings to age and gender. 10 healthy subjects (5 men/5 women), in each decade from 20 to 69 years of age (n = 50), were assessed. Their clinical health was tested. AMG measurements were carried out on muscles involved in defined movements of the upper and lower extremities. Muscle performance was measured using efficiency (E-score) and fibre recruitment (temporal (T-score) and spatial (S-score) summation). AMG-measurements showed good reproducibility. In each age group, it was found that for all those daily living skills measured, there was no gender difference. A walking and stair climbing test revealed that both legs are used equally and in a balanced way in healthy subjects. Moreover, there was no change in this function with increasing age up to 69 years. However, a cycling test with loading revealed that in elderly subjects the coordination of muscle use is impaired compared to that of the younger adults. Finally, a flexion test of the arm revealed an age-related decrease in the efficiency/coordination of m.Biceps alone, and a keyboard writing test suggests no effect on m.Trapezius. This reference data set now illustrates the reproducibility and ease of use of acoustic myography in the clinic and provides a means of assessing individuals with musculoskeletal problems.

[Mucoid cysts on the fingers].

In this review, we discuss mucoid cysts, which are common benign cysts, most often located dorsally or laterally to the distal interphalangeal joint. The origin of the cyst is suggested to be similar to that of a ganglion, or to be a degeneration of dermis, and it is often linked to osteoarthritis. Two types of mucoid cysts seem to exist, probably needing different treatment. A cyst is usually asymptomatic and needs no treatment, but limited joint movement, pain and nail deformity may occur. In the latter case, conservative or surgical treatment is asked for. If a cyst is atypical, pathology is needed.

Muscle assessment using multi-frequency bioimpedance in a healthy Danish population aged 20-69 years: a powerful non-invasive tool in sports and in the clinic.

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.

Effect of liraglutide on body weight and pain in patients with overweight and knee osteoarthritis: protocol for a randomised, double-blind, placebo-controlled, parallel-group, single-centre trial.

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.

Pain Mechanisms and Ultrasonic Inflammatory Activity as Prognostic Factors in Patients With Psoriatic Arthritis: A Prospective Cohort Study.

OBJECTIVE: To study the prognostic value of widespread pain and of musculoskeletal ultrasound (US) examination for subsequent treatment outcomes in patients with psoriatic arthritis (PsA). METHODS: An exploratory prospective cohort study enrolled patients with PsA initiating biologic or conventional synthetic disease-modifying antirheumatic drugs in routine care. Clinical, US, and patient-reported measures were collected at baseline and after 4 months. Widespread nonarthritic pain (WP) was defined as a Widespread Pain Index score of ≥4 with pain in ≥4 of 5 regions. PsA activity by US was defined as color Doppler (yes/no) in selected entheses, joints, or tendons. The main response criteria included the American College of Rheumatology 20% improvement, the Disease Activity in Psoriatic Arthritis 50% improvement, and minimal disease activity. The primary analyses were age- and sex-adjusted logistic regression. RESULTS: WP was present in 24 of 69 included patients (35%) and was associated with worse patient-reported and composite baseline measures, while US and other objective findings were similar to those in patients without WP. The odds of reaching minimal disease activity after 4 months were significantly greater for patients enrolled without WP (odds ratio 18.43 [95% confidence interval 1.51, 224.41]; P = 0.022), while WP did not impair other response measures. Patients with baseline color Doppler activity (n = 42 [61%]) had a worse objective PsA burden, but their chance of treatment response was comparable to those without color Doppler. CONCLUSION: More than one-third of patients with PsA presented with WP, which was associated with worse patient-reported scores and failure to achieve minimal disease activity following conventional synthetic or biologic disease-modifying antirheumatic drug therapy. PsA activity by color Doppler US had no influence on subsequent treatment response in this PsA cohort.

Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials.

BACKGROUND: Since the prevalence of obesity continues to increase, there is a demand for effective and safe anti-obesity agents that can produce and maintain weight loss and improve comorbidity. We did a meta-analysis of all published randomised controlled trials to assess the efficacy and safety of the newly approved anti-obesity agent rimonabant. METHODS: We searched The Cochrane database and Controlled Trials Register, Medline via Pubmed, Embase via WebSpirs, Web of Science, Scopus, and reference lists up to July, 2007. We collected data from four double-blind, randomised controlled trials (including 4105 participants) that compared 20 mg per day rimonabant with placebo. FINDINGS: Patients given rimonabant had a 4.7 kg (95% CI 4.1-5.3 kg; p<0.0001) greater weight reduction after 1 year than did those given placebo. Rimonabant caused significantly more adverse events than did placebo (OR=1.4; p=0.0007; number needed to harm=25 individuals [95% CI 17-58]), and 1.4 times more serious adverse events (OR=1.4; p=0.03; number needed to harm=59 [27-830]). Patients given rimonabant were 2.5 times more likely to discontinue the treatment because of depressive mood disorders than were those given placebo (OR=2.5; p=0.01; number needed to harm=49 [19-316]). Furthermore, anxiety caused more patients to discontinue treatment in rimonabant groups than in placebo groups (OR=3.0; p=0.03; number needed to harm=166 [47-3716]). INTERPRETATION: Our findings suggest that 20 mg per day rimonabant increases the risk of psychiatric adverse events--ie, depressed mood disorders and anxiety-despite depressed mood being an exclusion criterion in these trials. Taken together with the recent US Food and Drug Administration finding of increased risk of suicide during treatment with rimonabant, we recommend increased alertness by physicians to these potentially severe psychiatric adverse reactions.