Probing motor dynamics at the muscle level-Acoustic myography in Parkinson's disease.

Acoustic myography (AMG) noninvasively probes muscle activity. We explored whether AMG captures abnormal motor activity in patients with Parkinson's disease (PD) and how this activity is modulated by antiparkinsonian medication. Twenty patients with PD underwent AMG of the biceps, triceps, extensor carpi radialis longus, and adductor policis muscles of the more affected arm during active and passive movements, using a mobile AMG device (CURO, Denmark). AMG 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. Three AMG parameters were calculated using the CURO analysis system. Motor efficiency was expressed by the E-score, muscle fiber recruitment by the temporal T-score, spatial summation by the S-score, and S/T ratio. Twenty age- and sex-matched healthy subjects served as controls. Group mean values were statistically compared using unpaired two-tailed adjusted t-test and ANOVA with Tukey´s correction for multiple comparison (p ≤ 0.05). For the biceps and extensor carpi radialis longus muscles, the active movement S:T ratio was lower in PD relative to healthy controls. The E-score was also lower during active and passive flexion/extension movements in the off-medication state. No significant between-group differences in the AMG scores were noted for the triceps muscle during active or passive movements. The active S:T ratio and the E-score during active elbow flexion and extension may offer a useful means to quickly assess abnormal motor activity and the effect of drug treatment in PD.

The effects of weight loss on imaging outcomes in osteoarthritis of the hip or knee in people who are overweight or obese: a systematic review.

OBJECTIVE: To evaluate the structural effects of weight loss on hip or knee osteoarthritis (OA) and to summarize which structural joint pathologies have been examined and the evidence for the outcome measurement instruments applied. DESIGN: Based on a pre-specified protocol (available: PROSPERO CRD42017065263), we conducted a systematic search of the bibliographic databases, Medline, Embase and Web of Science identifying longitudinal articles reporting the effects of weight loss on structural imaging outcomes in OA of the hip or knee in people who are overweight or obese. RESULTS: From 1625 potentially eligible records, 14 articles (from 6 cohorts) were included. 2 cohorts were derived from RCTs. Evaluated pathologies were: articular cartilage (n = 7), joint space width (n = 3), bone marrow lesions (n = 5), synovitis (n = 2), effusion (n = 1), meniscus (n = 3), bone marrow density (n = 1) and infrapatellar fat pad (IPFP; n = 2). Cartilage showed conflicting results when evaluating cartilage thickness by direct thickness measurements. Compositional dGEMRIC and T2 mapping measures in early knee OA showed trends towards reduced cartilage degeneration. Joint space width on conventional radiographs showed no change. Weight loss reduced the size of the IPFP. Synovitis and effusion were not affected. Following weight loss DXA showed bone loss at the hip. CONCLUSION: We did not find consistent evidence of the effects of weight loss on OA structural pathology in people who are overweight or obese. There is a need to achieve consensus on which structural pathologies and measurements to apply in weight loss and OA research.

Relationship between weight loss in obese knee osteoarthritis patients and serum biomarkers of cartilage breakdown: secondary analyses of a randomised trial.

OBJECTIVE: To explore effects of weight loss and maintenance on serum cartilage biomarkers denaturation neoepitope for Collagen2 (Coll2-1) and Fibulin3 fragment (Fib3-2), as well as correlations between Coll2-1 and Fib3-2 and symptomatic improvement, in a knee osteoarthritis (KOA) population. DESIGN: 192 obese KOA patients followed a 16 week weight loss intervention and 52 weeks weight maintenance (ClinicalTrials.gov identifier: NCT00655941). Assessments were at 0, 8, 16 and 68 weeks. Serum Coll2-1 and Fib3-2 were determined with ELISA, and symptoms by the Knee Osteoarthritis Outcome Score (KOOS) questionnaire. Changes from week 0 and association between changes from baseline in body weight and Coll2-1, Fib3-2, and the 5 KOOS domains were assessed at all time points. RESULTS: Coll2-1 changes from baseline showed a decrease at week 8 (P = 0.0002), no change at week 16 (P = 0.49), and an increase at week 68 (P = 0.036). Fib3-2 showed an increase from baseline at week 8 (P = 0.0015) and 16 (P < 0.0001), but none at week 68 (P = 0.23). No statistically significant correlations were found between changes in body weight and Coll2-1 and Fib3-2 at any time point (r < 0.05; P > 0.49). At all time-points there were significant positive correlations between changes from baseline in Coll2-1 and in KOOSSports/Recreation (week 8, 16, 68: r = 0.17; P = 0.03; r = 0.16; P = 0.04; and r = 0.17; P = 0.04, respectively). CONCLUSION: The clinical improvement after a substantial weight loss and weight maintenance in KOA patients was not associated with decrease in markers of cartilage breakdown Coll2-1 or Fib3-2, even with indications of a slightly negative effect.

Osteoarthritis year in review 2016: imaging.

PURPOSE: The current narrative review covers original research related to imaging in osteoarthritis (OA) in humans published in English between April 1st 2015 and March 31st 2016, in peer reviewed journals available in Medline via PubMed (http://www.ncbi.nlm.nih.gov/pubmed/). METHODS: Relevant studies in humans, subjectively decided by the authors, contributing significantly to the OA imaging field, were selected from an extensive Medline search using the terms "Osteoarthritis" in combination with "MRI", "Imaging", "Radiography", "X-rays", "Ultrasound", "Computed tomography", "Nuclear medicine", "PET-CT", "PET-MRI", "Scintigraphy", "SPECT". Publications were sorted according to relevance for the OA imaging research community with an emphasis on high impact special interest journals using the software for systematic reviews www.covidence.org. RESULTS: An overview of newly published studies compared to studies reported previous years is presented, followed by a review of selected imaging studies of primarily knee, hip and hand OA focussing on (1) results for detection of OA and OA-related pathology (2) studies dealing with treatments and (3) studies focussing on prognosis of disease progression or joint replacement. A record high number of 1420 articles were published, among others, of new technologies and tools for improved morphological and pathophysiological understanding of OA-related changes in joints. Also, imaging data were presented of monitoring treatment effect and prognosis of OA progression, primarily using established radiographic, magnetic resonance imaging (MRI), and ultrasound (US) methods. CONCLUSION: Imaging continues to play an important role in OA research, where several exciting new technologies and computer aided analysis methods are emerging to complement the conventional imaging approaches.

New perspectives on the development of muscle contractures following central motor lesions.

Muscle contractures are common in patients with central motor lesions, but the mechanisms responsible for the development of contractures are still unclear. Increased or decreased neural activation, protracted placement of a joint with the muscle in a short position and muscle atrophy have been suggested to be involved, but none of these mechanisms are sufficient to explain the development of muscle contractures alone. Here we propose that changes in tissue homeostasis in the neuromuscular-tendon-connective tissue complex is at the heart of the development of contractures, and that an integrated physiological understanding of the interaction between neural, mechanical and metabolic factors, as well as genetic and epigenetic factors, is necessary in order to unravel the mechanisms that result in muscle contractures. We hope thereby to contribute to a reconsideration of how and why muscle contractures develop in a way which will open a window towards new insight in this area in the future.

Knee Injury and Osteoarthritis Outcome Score (KOOS): systematic review and meta-analysis of measurement properties.

OBJECTIVE: To conduct a systematic review and meta-analysis to synthesize evidence regarding measurement properties of the Knee injury and Osteoarthritis Outcome Score (KOOS). DESIGN: A comprehensive literature search identified 37 eligible papers evaluating KOOS measurement properties in participants with knee injuries and/or osteoarthritis (OA). Methodological quality was evaluated using the COSMIN checklist. Where possible, meta-analysis of extracted data was conducted for all studies and stratified by age and knee condition; otherwise narrative synthesis was performed. RESULTS: KOOS has adequate internal consistency, test-retest reliability and construct validity in young and old adults with knee injuries and/or OA. The ADL subscale has better content validity for older patients and Sport/Rec for younger patients with knee injuries, while the Pain subscale is more relevant for painful knee conditions. The five-factor structure of the original KOOS is unclear. There is some evidence that the KOOS subscales demonstrate sufficient unidimensionality, but this requires confirmation. Although measurement error requires further evaluation, the minimal detectable change for KOOS subscales ranges from 14.3 to 19.6 for younger individuals, and ≥20 for older individuals. Evidence of responsiveness comes from larger effect sizes following surgical (especially total knee replacement) than non-surgical interventions. CONCLUSIONS: KOOS demonstrates adequate content validity, internal consistency, test-retest reliability, construct validity and responsiveness for age- and condition-relevant subscales. Structural validity, cross-cultural validity and measurement error require further evaluation, as well as construct validity of KOOS Physical function Short form. Suggested order of subscales for different knee conditions can be applied in hierarchical testing of endpoints in clinical trials. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42011001603).

Changes in ultrasound assessed markers of inflammation following intra-articular steroid injection combined with exercise in knee osteoarthritis: exploratory outcome from a randomized trial.

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.

Danish VISA-A questionnaire with validation and reliability testing for Danish-speaking Achilles tendinopathy patients.

The VISA-A questionnaire has proven to be a valid and reliable tool for assessing severity of Achilles tendinopathy (AT). The aim was to translate and cross-culturally adapt the VISA-A questionnaire for a Danish-speaking AT population, and subsequently perform validity and reliability tests. Translation and following cross-cultural adaptation was performed as translation, synthesis, reverse translation, expert review, and pretesting. The final Danish version (VISA-A-DK) was tested for reliability on healthy controls (n = 75) and patients (n = 36). Tests for internal consistency, validity, and structure were performed on 71 patients. VISA-A-DK showed good reliability for patients (r = 0.80 ICC = 0.79) and healthy individuals (r = 0.98 ICC = 0.97). Internal consistency was 0.73 (Cronbach's alpha). The mean VISA-A-DK score in AT patients was 51 [47-55]. This was significantly lower than healthy controls with a score of 93 (90-95). Criterion validity was considered good when comparing the scores of the Danish version with the original version in both healthy individuals and patients. VISA-A-DK is a valid and reliable instrument and has shown compatible to the original version in assessment of AT patients. VISA-A-DK is a useful tool in the assessment of AT, both in research and in a clinical setting.

Correlations between fatigue and disease duration, disease activity, and pain in patients with rheumatoid arthritis: a systematic review.

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.

Agreement between touch-screen and paper-based patient-reported outcomes for patients with fibromyalgia: a randomized cross-over reproducibility study.

OBJECTIVES: To compare data based on computerized and paper versions of health status questionnaires (HSQs) for sampling patient-reported outcomes (PROs) in patients with fibromyalgia (FM). In addition, to examine associations between patient characteristics (age, education, computer experience) and differences between versions. Finally, to evaluate the acceptability of computer-based questionnaires among patients with FM. METHOD: The study population comprised female patients diagnosed with FM. All patients completed six HSQs: the Fibromyalgia Impact Questionnaire (FIQ), the Major Depression Inventory (MDI), the 36-item Short Form Health Survey (SF-36), the painDETECT questionnaire (PDQ), the Coping Strategies Questionnaire (CSQ), and the Generalized Anxiety Disorder Self-Assessment Questionnaire (GAD-10), both on paper and using a touch screen. One HSQ was tested at a time in a repeated randomized cross-over design. The two versions were completed with a 5-min interval and between each HSQ the participants had a 5-min break. Means, mean differences with 95% confidence intervals (CIs), medians, median differences, and intraclass correlation coefficients (ICCs) were calculated for all HSQs, including relevant subscales. Associations between patient characteristics and differences between versions were explored using Spearman's correlation coefficients. RESULTS: Twenty women, mean age 48.4 years, participated in the study. Except for one item, ICCs between touch-screen and paper versions of the HSQs examined indicated acceptable agreement (ICC = 0.71-0.99). Overall, mean and median differences revealed no differences between versions. No significant associations were observed for patient characteristics. None of the participants preferred paper questionnaires over computerized versions. CONCLUSIONS: The computerized HSQs using a touch screen gave comparable results to answers given on paper and were generally preferred by the participants.

Patient-Reported Outcome (PRO) questionnaires for young to middle-aged adults with hip and groin disability: a systematic review of the clinimetric evidence.

BACKGROUND/AIM: To recommend Patient-Reported Outcome (PRO) questionnaires to measure hip and groin disability in young-aged to middle-aged adults. METHODS: A systematic review was performed in June 2014. The methodological quality of the studies included was determined using the COnsensus-based Standards for the selection of health Measurement INstruments list (COSMIN) together with standardised evaluations of measurement properties of each PRO. RESULTS: Twenty studies were included. Nine different questionnaires for patients with hip disability, and one for hip and groin disability, were identified. Hip And Groin Outcome Score (HAGOS), Hip Outcome Score (HOS), International Hip Outcome Tool-12 (IHOT-12) and IHOT-33 were the most thoroughly investigated PROs and studies including these PROs reported key aspects of the COSMIN checklist. HAGOS and IHOT-12 were based on studies with the least ratings of poor study methodology (23% and 31%, respectively), whereas IHOT-33 and HOS had a somewhat larger distribution (46%). These PROs all contain adequate measurement qualities for content validity (except HOS), test-retest reliability, construct validity, responsiveness and interpretability. No information or poor quality rating on methodological aspects made it impossible to fully evaluate the remaining PROs at present. CONCLUSIONS: HAGOS, HOS, IHOT-12 and IHOT-33 can be recommended for assessment of young-aged to middle-aged adults with pain related to the hip joint, undergoing non-surgical treatment or hip arthroscopy. At present, HAGOS is the only PRO also aimed for young-aged to middle-aged adults presenting with groin pain and is recommended for use in this population. TRIAL REGISTRATION NUMBER: CRD42014009995.

Efficacy and safety of ginger in osteoarthritis patients: a meta-analysis of randomized placebo-controlled trials.

The aim of this study was to assess the clinical efficacy and safety of oral ginger for symptomatic treatment of osteoarthritis (OA) by carrying out a systematic literature search followed by meta-analyses on selected studies. Inclusion criteria were randomized controlled trials (RCTs) comparing oral ginger treatment with placebo in OA patients aged >18 years. Outcomes were reduction in pain and reduction in disability. Harm was assessed as withdrawals due to adverse events. The efficacy effect size was estimated using Hedges' standardized mean difference (SMD), and safety by risk ratio (RR). Standard random-effects meta-analysis was used, and inconsistency was evaluated by the I-squared index (I(2)). Out of 122 retrieved references, 117 were discarded, leaving five trials (593 patients) for meta-analyses. The majority reported relevant randomization procedures and blinding, but an inadequate intention-to-treat (ITT) analysis. Following ginger intake, a statistically significant pain reduction SMD = -0.30 ([95% CI: [(-0.50, -0.09)], P = 0.005]) with a low degree of inconsistency among trials (I(2) = 27%), and a statistically significant reduction in disability SMD = -0.22 ([95% CI: ([-0.39, -0.04)]; P = 0.01; I(2) = 0%]) were seen, both in favor of ginger. Patients given ginger were more than twice as likely to discontinue treatment compared to placebo ([RR = 2.33; 95% CI: (1.04, 5.22)]; P = 0.04; I(2) = 0%]). Ginger was modestly efficacious and reasonably safe for treatment of OA. We judged the evidence to be of moderate quality, based on the small number of participants and inadequate ITT populations. Prospero: CRD42011001777.

Effect of a 16 weeks weight loss program on osteoarthritis biomarkers in obese patients with knee osteoarthritis: a prospective cohort study.

OBJECTIVE: Changes in biomarkers for bone and cartilage in knee osteoarthritis (KOA) may reflect changes in tissue turnover induced by interventions. The aim of this study was to assess the effect on osteoarthritis biomarkers of an intensive weight loss intervention in obese KOA patients. METHODS: 192 obese KOA patients followed a 16 weeks weight loss intervention (ClinicalTrials.gov: NCT00655941). Serum Cartilage Oligomeric Matrix Protein (sCOMP), Urine C-terminal telopeptide of collagen type II (uCTX-II) and type I (uCTX-I) were determined by enzyme-linked immunoassay (ELISA) at baseline and after 16 weeks. Patient-reported symptoms were assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS) Questionnaire without the sports and recreation score (KOOS-4). Change from baseline was analyzed using Analysis of CoVariance (ANCOVA) adjusting for sex, age, and body mass index (BMI). Bivariate associations were analyzed using Spearman's test of rank correlation. RESULTS: 175 patients completed the treatment and lost mean 13.4 (95% CI: 12.5-14.4) kg. sCOMP concentration decreased on average 1.1 (95% CI: -1.5 to -0.8) U/L with a correlation to weight loss (r = -0.17, P = 0.028), but not to change in KOOS-4 (r = -0.13, P = 0.091). uCTX-II increased significantly, mean 69 (95% CI: 31-106) ng/mmol creatinine, with no relation to weight loss (P = 0.14). Change in uCTX-II was reversely related to change in KOOS-4 (r = -0.28, P = 0.0003). uCTX-I increased, mean 67 (95% CI: 47-87) µg/mmol creatinine, and correlated to weight loss (r = 0.22, P = 0.0007), while not to KOOS-4 (P = 0.93). CONCLUSION: A rapid substantial weight loss in obese KOA patients was weakly, while significantly associated with a reduction in sCOMP, and increases in both uCTX-II and uCTX-I.

Knee pain and inflammation in the infrapatellar fat pad estimated by conventional and dynamic contrast-enhanced magnetic resonance imaging in obese patients with osteoarthritis: a cross-sectional study.

OBJECTIVE: To investigate the association between knee pain and signs of inflammation in the infrapatellar fat pad (IPFP) in obese patients with knee osteoarthritis (KOA). DESIGN: 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'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, "Inflammation", was chosen as primary perfusion variable in the analysis. Intraclass correlation coefficients for the perfusion variables ranged from 0.81 to 0.99. RESULTS: 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 "Inflammation" showed a statistically significant correlation (r = -0.42, P < 0.0001). A statistically significant correlation was also found between KOOS pain and MOAKS Hoffa-synovitis (r = -0.21, P = 0.046). CONCLUSIONS: 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.

Correlations between radiographic assessments and MRI features of knee osteoarthritis--a cross-sectional study.

OBJECTIVES: To assess correlations between Kellgren & Lawrence (KL) gradings, minimum joint space width (mJSW) measurements and the Boston Leeds Osteoarthritis Knee Score (BLOKS) within a cohort of obese patients with knee osteoarthritis (KOA). METHODS: 192 Participants were recruited from an outpatient clinic (ClinicalTrials.gov: NCT00655941). Inclusion criteria were age ≥50 years, body mass index (BMI) ≥30 kg/m(2) plus symptomatic and verified KOA. 1.5 T magnetic resonance imaging (MRI) scans were assessed using BLOKS and bi-plane radiography by mJSW and KL. Statistics used were Spearman rank correlation coefficients. RESULTS: The average patient was 63 years of age, female and had a BMI of 37. KL gradings correlated to cartilage damage, bone marrow lesions and meniscus pathology (r = 0.15-0.76) and similar results were found for the relationship between BLOKS and mJSW. BLOKS assessed knee joint pathology co-segregated with compartment and grade specific KL (P < 0.0001). BLOKS variables were statistically significant correlated, particularly in the medial tibiofemoral compartment (r = 0.42-0.80). Adjusting for age, gender and BMI did not alter these associations. CONCLUSION: Extensive pathological damage is present even in mild radiographic KOA and BLOKS gradings and KL scores increase together. Analyses of compartment specific KL scores revealed differences in their relationship to the assessed MRI variables. Our study displays the segregation of MRI gradings with respect to location and level of radiographic scores, reveals a high inter-dependency of MRI-assessed structures, and describes some redundancy of specific BLOKS variables.

Weight loss is effective for symptomatic relief in obese subjects with knee osteoarthritis independently of joint damage severity assessed by high-field MRI and radiography.

OBJECTIVE: With an increasing prevalence of older and obese citizens, the problems of knee osteoarthritis (KOA) will escalate. Weight loss is recommended for obese KOA patients and in a majority of cases this leads to symptomatic relief. We hypothesized that pre-treatment structural status of the knee joint, assessed by radiographs, 1.5 T magnetic resonance imaging (MRI) and knee-joint alignment, may influence the symptomatic changes following a significant weight reduction. DESIGN: Patients were recruited from a Department of Rheumatology. Eligibility criteria were age above 50 years, body mass index ≥ 30 kg/m(2), primary KOA diagnosed according to the American College of Rheumatology (ACR) criteria and having verified structural damage. Patients underwent a 16 weeks dietary programme with formula products and counselling. MRI and radiographs of the most symptomatic knee were obtained at baseline and assessed for structural damage using the Boston-Leeds Osteoarthritis of the Knee Score, minimum joint space width and Kellgren-Lawrence score. Imaging variables, muscle strength and degree of alignment, were examined as predictors of changes in Knee Osteoarthritis Outcome Score (KOOS) and Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) - Osteoarthritis Research Society International (OARSI) Responder Criterion. RESULTS: Structural damage at baseline assessed by imaging, muscle strength or knee-joint alignment showed no statistically significant association to changes in KOOS pain and function in daily living (r ≤ 0.13; P>0.05) or the OMERACT-OARSI Responder Criterion (OR 0.48-1.68; P-values ≥ 0.13). CONCLUSIONS: Presence of joint damage did not preclude symptomatic relief following a clinically relevant weight loss in older obese patients with KOA. Neither muscle strength nor knee-joint alignment was associated with the degree of symptomatic relief.

Improved nutritional status and bone health after diet-induced weight loss in sedentary osteoarthritis patients: a prospective cohort study.

BACKGROUND/OBJECTIVES: Obese subjects are commonly deficient in several micronutrients. Weight loss, although beneficial, may also lead to adverse changes in micronutrient status and body composition. The objective of the study is to assess changes in micronutrient status and body composition in obese individuals after a dietary weight loss program. SUBJECTS/METHODS: As part of a dietary weight loss trial, enrolling 192 obese patients (body mass index >30 kg/m2) with knee osteoarthritis (>50 years of age), vitamin D, ferritin, vitamin B12 and body composition were measured at baseline and after 16 weeks. All followed an 8-week formula weight-loss diet 415-810 kcal per day, followed by 8 weeks on a hypo-energetic 1200 kcal per day diet with a combination of normal food and formula products. Statistical analyses were based on paired samples in the completer population. RESULTS: A total of 175 patients (142 women), 91%, completed the 16-week program and had a body weight loss of 14.0 kg (95% confidence interval: 13.3-14.7; P<0.0001), consisting of 1.8 kg (1.3-2.3; P<0.0001) lean body mass (LBM) and 11.0 kg (10.4-11.6; P<0.0001) fat mass. Bone mineral content (BMC) did not change (-13.5 g; P=0.18), whereas bone mineral density (BMD) increased by 0.004 g/cm2 (0.001-0.008 g/cm2; P=0.025). Plasma vitamin D and B(12) increased by 15.3 nmol/l (13.2-17.3; P<0.0001) and 43.7 pmol/l (32.1-55.4; P<0.0001), respectively. There was no change in plasma ferritin. CONCLUSIONS: This intensive program with formula diet resulted in increased BMD and improved vitamin D and B12 levels. Ferritin and BMC were unchanged and loss of LBM was only 13% of the total weight loss. This observational evidence supports use of formula diet-induced weight loss therapy in obese osteoarthritis patients.

Calcium-dependence of Donnan potentials in glycerinated rabbit psoas muscle in rigor, at and beyond filament overlap; a role for titin in the contractile process.

In glycerinated rabbit psoas muscle, Donnan potential measurements demonstrated that the net electric charge on the actin-myosin matrix undergoes a sharp switch-like transition at pCa(50) = 6.8. The potentials are 2 mV less negative at the lower pCa(2+) (P < 0.001). If ATP is present, the muscle contracts and breaks the microelectrode. Therefore the rigor state was studied. There is no reason to suppose a priori that a similar voltage switch does not occur during contraction, however. Calcium dependence is still apparent in muscles stretched beyond overlap (sarcomere length>3.8 µm) and is also seen in the gap filaments between the A- and I-band ends; further stretching abolishes the dependence. These experiments strongly suggest that calcium dependence is controlled initially by the titin component, and that this control is lost when titin filaments break. We suppose that that effect is mediated by the titin kinase in the M-line region and may involve the extensible PEVK region of titin. There is great interest in the electric charge on proteins in muscle within the structural system. We suggest how changes in these charges may control the calcium activation process. We also suggest some simple experimental approaches that could clarify these effects.

Consumption of industrial and ruminant trans fatty acids and risk of coronary heart disease: a systematic review and meta-analysis of cohort studies.

The aim of this systematic review and meta-analysis was to summarize the evidence from observational studies assessing the association between intake of trans fatty acids (TFA) and the risk of coronary heart disease (CHD), with a specific emphasis on distinguishing between TFA of industrial and ruminant origin. By searching five bibliographic databases, analyses from six published and two unpublished prospective cohort studies, assessing the association of intake of TFA with fatal and/or non-fatal CHD, were identified. Four and three studies reported separate associations for intake of ruminant or industrial-TFA, respectively. The pooled relative risk estimates for comparison of extreme quintiles of total-TFA intake (corresponding to intake increments ranging from 2.8 to ∼10 g/day) were 1.22 (95% confidence interval: 1.08-1.38; P=0.002) for CHD events and 1.24 (1.07-1.43; P=0.003) for fatal CHD. Ruminant-TFA intake (increments ranging from 0.5 to 1.9 g/day) was not significantly associated with risk of CHD (risk ratio (RR)=0.92 (0.76-1.11); P=0.36), and neither was industrial-TFA intake, although there was a trend towards a positive association (RR=1.21 (0.97-1.50); P=0.09). In conclusion, our analysis suggests that industrial-TFA may be positively related to CHD, whereas ruminant-TFA is not, but the limited number of available studies prohibits any firm conclusions concerning whether the source of TFA is important. The null association of ruminant-TFA with CHD risk may be due to lower intake levels.

The number needed to treat for second-generation biologics when treating established rheumatoid arthritis: a systematic quantitative review of randomized controlled trials.

OBJECTIVE: To evaluate the number needed to treat (NNT) and the number needed to harm (NNH) of the second-generation biologics abatacept, certolizumab, golimumab, rituximab, and tocilizumab in patients with established rheumatoid arthritis (RA) taking concomitant methotrexate (MTX). METHODS: A systematic literature search of MEDLINE, EMBASE, Web of Science, and the Cochrane Register of Controlled Trials was conducted up to 1 November 2009. We selected any published randomized, double-blind, MTX-controlled study including RA patients with a mean disease duration of at least 5 years before entering a pivotal trial on second-generation biological therapy. Studies eligible for inclusion involved patients, who had previously shown inadequate response to conventional disease-modifying anti-rheumatic drug (DMARD) therapy. Pre-specified binary outcomes were extracted with a preference for 1-year data (6-month data were used if no data were available for 1 year). Two reviewers independently extracted the data necessary to estimate the absolute measures in a non-responder intention-to-treat (ITT) analysis. RESULTS: Five randomized controlled trials, one for each of the drugs, were selected and data extracted according to published data at endpoint for American College of Rheumatology 50% (ACR50)-responding patients, and withdrawals due to adverse events. NNT ranged from four to six treated patients to achieve one ACR50 response, while withdrawals due to adverse events were few and non-significant compared to the placebo group, except for rituximab administered as 1000 mg. CONCLUSION: Comparable efficacy was shown by the five biological agents studied, with few adverse events. However, for rituximab, tocilizumab, and golimumab, only 6-month data were available, hampering the external validity with regard to long-term efficacy and tolerability. A low dose (500 mg) of rituximab may be as effective as the recommended dose of 1000 mg.