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3,100 | 24,721 | To evaluate whether the classification of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) according to ANCA type (anti-proteinase 3 (PR3) or anti-myeloperoxidase (MPO) antibodies) predicts treatment response.
Treatment responses were assessed among patients enrolled in the Rituximab in ANCA-associated Vasculitis trial according to both AAV diagnosis (granulomatosis with polyangiitis (GPA)/microscopic polyangiitis (MPA)) and ANCA type (PR3-AAV/MPO-AAV). Complete remission (CR) was defined as disease activity score of 0 and successful completion of the prednisone taper.
PR3-AAV patients treated with rituximab (RTX) achieved CR at 6 months more frequently than did those randomised to cyclophosphamide (CYC)/azathioprine (AZA) (65% vs 48%; p=0.04). The OR for CR at 6 months among PR3-AAV patients treated with RTX as opposed to CYC/AZA was 2.11 (95% CI 1.04 to 4.30) in analyses adjusted for age, sex and new-onset versus relapsing disease at baseline. PR3-AAV patients with relapsing disease achieved CR more often following RTX treatment at 6 months (OR 3.57; 95% CI 1.43 to 8.93), 12 months (OR 4.32; 95% CI 1.53 to 12.15) and 18 months (OR 3.06; 95% CI 1.05 to 8.97). No association between treatment and CR was observed in the MPO-AAV patient subset or in groups divided according to AAV diagnosis.
NCT00104299; post-results. | Patients with PR3-AAV respond better to RTX than to CYC/AZA. An ANCA type-based classification may guide immunosuppression in AAV. |
3,101 | 8,718 | Knee osteoarthritis (KOA) is a prevalent form of chronic joint disease associated with functional restrictions and pain. Activity limitations negatively impact social connectedness and psychological well-being, reducing the quality of life (QoL) of patients. The purpose of this review is to summarize the existing information on QoL in KOA patients and share the reported individual factors, which may influence it.
We conducted a systematic review examining the literature up to JAN/2017 available at MEDLINE, EMBASE, Cochrane, and PsycINFO using KOA and QOL related keywords. Inclusion criteria were QOL compared to at least one demographic factor (e.g., age, gender), lifestyle factor (e.g., functional independence), or comorbidity factor (e.g., diabetes, obesity) and a control group. Analytical methods were not considered as part of the original design.
A total of 610 articles were reviewed, of which 62 met inclusion criteria. Instruments used to measure QoL included: SF-36, EQ-5D, KOOS, WHOQOL, HAS, AIMS, NHP and JKOM. All studies reported worse QoL in KOA patients when compared to a control group. When females were compared to males, females reported worse QOL. Obesity as well as lower level of physical activity were reported with lower QoL scores. Knee self-management programs delivered by healthcare professionals improved QoL in patients with KOA. Educational level and higher total mindfulness were reported to improve QoL whereas poverty, psychological distress, depression and lacking familial relationships reduce it. Surgical KOA interventions resulted in good to excellent outcomes generally; although, results varied by age, weight, and depression. | KOA has a substantial impact on QoL. In KOA patients, QoL is also influenced by specific individual factors including gender, body weight, physical activity, mental health, and education. Importantly, education and management programs designed to support KOA patients report improved QoL. QoL data is a valuable tool providing health care professionals with a better comprehension of KOA disease to aid implementation of the most effective management plan. |
3,102 | 18,413 | To investigate the efficacy and safety of lesinurad in combination with febuxostat in a 12-month phase III trial in patients with tophaceous gout.
Patients with serum urate (UA) ≥8.0 mg/dl (≥6.0 mg/dl with urate-lowering therapy) and ≥1 measurable target tophus were given febuxostat 80 mg/day for 3 weeks before randomization to receive lesinurad (200 or 400 mg daily) or placebo in addition to the febuxostat. The primary end point was the proportion of patients achieving a serum UA level of <5.0 mg/dl (month 6). The key secondary end point was the proportion of patients with complete resolution of ≥1 target tophus (month 12). Other end points included the percentage change in total target tophi area. Safety assessments included adverse events and laboratory data.
Patients (n = 324) were predominantly male, with a mean age of 54.1 years. Significantly more patients achieved the serum UA target by month 6 with the addition of lesinurad 400 mg (76.1%; P < 0.0001), but not 200 mg (56.6%; P = 0.13), to the febuxostat therapy as compared with febuxostat alone (46.8%). At all other time points, significantly more patients in the lesinurad 200 mg group achieved the serum UA target. The number of patients with complete tophus resolution was not different between groups. Treatment with lesinurad (200 mg and 400 mg) plus febuxostat reduced the total target tophi area as compared with febuxostat alone (50.1% and 52.9% versus 28.3%, respectively; P < 0.05). Safety was generally comparable with that of febuxostat alone, except for higher rates of predominantly reversible elevations in the serum creatinine level, particularly with lesinurad 400 mg. | Treatment with lesinurad in combination with febuxostat demonstrated superior lowering of serum UA levels as compared with febuxostat alone, with clinically relevant added effects on tophi and an acceptable safety profile with lesinurad 200 mg in patients with tophaceous gout warranting additional therapy. |
3,103 | 4,006 | To evaluate the therapeutic responsiveness of office-based salivary gland ductal irrigation in patients with chronic sialoadenitis.
Between August 2017 and April 2019, 55 patients comprising the following three disease groups were enrolled: Sjogren's syndrome: 39 patients; postradiotherapy sialoadenitis: ten patients; and post-RAI sialoadenitis: six patients. Quantitative salivary scintigraphy was recorded, and a formulated questionnaire including the Summated Xerostomia Inventory was utilized to assess acute/chronic symptoms. All patients received at least three serial salivary gland ductal irrigations with a one-month interval in our outpatient department.
The general response rates for each disease groups are as follows: Sjogren's syndrome: 61.5% (24/39); postradiotherapy: 60% (6/10); and post-RAI: 83.3% (5/6). Among the patients with Sjogren's syndrome, the parotid scintigraphic T | Simple salivary ductal irrigation without complex equipment can be performed as an outpatient procedure to alleviate glandular swelling or xerostomia in patients with Sjogren's syndrome, postradiotherapy sialoadenitis or post-RAI sialoadenitis, and it can be considered an alternative management approach for patients refractory to conventional strategies. |
3,104 | 61,679 | Angiopoietin- I (Ang-1) and Ang-2 are ligands for the receptor tyrosine kinase, Tie-2. Ang-1, a Tie-2 agonist, may have a vascular stabilizing role in angiogenesis, while Ang-2, an endogenous antagonist of Tie-2, may have an early role in angiogenesis, destabilizing existing vasculature. We show that these ligands are expressed by rheumatoid synovial fibroblasts (RSF) and investigate whether their expression was modulated by proinflammatory cytokines present in the joint in rheumatoid arthritis (RA).
Using quantitative PCR we determined the level of expression of these 2 ligands in RSF and chronic inflamed synovial tissue. The level of expression of these ligands after treatment with proinflammatory cytokines and hypoxia was also determined.
We observed constitutive expression of Ang-1 and Ang-2 in RSF and chronic inflamed synovial tissue. Ang-1 was the most highly expressed ligand in late stage RA synovial fibroblasts; however, in chronic inflamed synovial tissue, Ang-2 was predominant and was expressed at strikingly high levels (70 to 120-fold increase). We observed that tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), but not interleukin 1beta or hypoxia, stimulated Ang-1 gene expression in RSE This was confirmed at the protein level as media from TNF-alpha treated RSF resulted in increased autophosphorylation of Tie-2. In contrast, TNF-alpha and TGF-beta had no effect on Ang-2 expression in RSF, but augmented expression of Ang-2 in normal synovial fibroblasts. | The angiopoietins are important angiogenic factors constitutively present in RA, and their expression is modulated by certain cytokines. Ang-2 may have an important role in rheumatoid tissue where vigorous angiogenesis is occurring. |
3,105 | 56,453 | To examine the effects of pulsed short-wave diathermy (PSWD), delivered at an intensity sufficient to induce a thermal sensation and at an athermal intensity, in comparison with a placebo short-wave diathermy treatment, on reported pain, stiffness and functional ability and on mobility performance of patients with osteoarthritis of the knee.
A placebo-controlled double-blind trial with sequential allocation of patients to different treatment groups.
Outpatient physiotherapy department.
One hundred and three consecutive patients, mean age 73.7 (+/-6.6) years with osteoarthritis of one or both knees for at least three months.
All participants received three 20-min-long treatments per week for three weeks. One group received PSWD with mean power of 18 W (thermal effect), one group received PSWD with mean power of 1.8 W (athermal effect), and one group received sham short-wave diathermy treatment. Patients were assessed before the initial treatment, immediately following the last treatment, and at a three-month follow-up.
Outcome measures included the WOMAC Osteoarthritis Index, which assessed reported pain, stiffness, and functional ability, and four measures of mobility performance: Timed Get Up and Go test (TGUG), stair-climbing, stair, descending and a 3-min walk.
A difference across time was observed for the pain and stiffness categories of the WOMAC Osteoarthritis Index (p = 0.033 and p = 0.008, respectively), with no differences between groups. No other significant differences across time or between groups were observed in any of the other measures. | The findings do not demonstrate pulsed short-wave diathermy, as it is utilized in clinical settings, to be effective in the treatment of osteoarthritis of the knee. |
3,106 | 37,571 | We investigated early systemic sclerosis (SSc) (that is, Raynaud's phenomenon with SSc marker autoantibodies and/or typical capillaroscopic findings and no manifestations other than puffy fingers or arthritis) versus undifferentiated connective tissue disease (UCTD) to identify predictors of short-term disease evolution.
Thirty-nine early SSc and 37 UCTD patients were investigated. At baseline, all patients underwent clinical evaluation, B-mode echocardiography, lung function tests and esophageal manometry to detect preclinical alterations of internal organs, and were re-assessed every year. Twenty-one early SSc and 24 UCTD patients, and 25 controls were also investigated for serum endothelial, T-cell and fibroblast activation markers.
At baseline, 48.7% of early SSc and 37.8% of UCTD patients had at least one preclinical functional alteration (P > 0.05). Ninety-two percent of early SSc patients developed manifestations consistent with definite SSc (that is, skin sclerosis, digital ulcers/scars, two or more teleangectasias, clinically visible nailfold capillaries, cutaneous calcinosis, X-ray bibasilar lung fibrosis, X-ray esophageal dysmotility, ECG signs of myocardial fibrosis and laboratory signs of renal crisis) within five years versus 17.1% of UCTD patients (X² = 12.26; P = 0.0005). Avascular areas (HR = 4.39 95% CI 1.18 to 16.3; P = 0.02), increased levels of soluble IL-2 receptor alpha (HR = 4.39; 95% CI 1.03 to 18.6; P = 0.03), and of procollagen III aminopropeptide predicted disease evolution (HR = 4.55; 95% CI 1.18 to 17; P = 0.04). | Most early SSc but only a few UCTD patients progress to definite SSc within a short-term follow-up. Measurement of circulating markers of T-cell and fibroblast activation might serve to identify early SSc patients who are more likely to develop features of definite SSc. |
3,107 | 8,813 | Pain catastrophizing has been associated with pain severity and disability in patients with knee osteoarthritis (OA). However, the literature is not consistent and other studies have failed to find this association. We examined the preoperative association between pain catastrophizing and physical function and pain, as well as the correlation between radiographic OA and physical symptoms and knee arthroplasty (KA).
This study was a cross-sectional study of all patients referred to the orthopaedic outpatient Knee Clinic from March to October 2013 with clinical symptoms of knee OA. Prior to clinical examination, the patients completed EuroQol-5D (EQ-5D), The Short Form-36 (SF-36 (PF)), The Oxford Knee Score (OKS) and The Pain Catastrophizing Scale (PCS). The severity of radiographic OA was graded with the Kellgren-Lawrence Scale (KLS).
Of the 325 patients, 158 (48.6%) patients received a knee arthroplasty, 130 (40%) were treated conservatively, and 37 (11.4%) were scheduled for a knee arthroscopy. Mean age was 64.3 (SD 11.1) years and 53.9% were females. We found a strong correlation between PCS and OKS (r = -0.60, P = 0.000). Furthermore, the regression analysis showed statistically significant associations between PCS and both physical function and pain. We found no correlation between radiographic OA and physical function or pain. | Our results reveal that PCS is an important psychological factor when dealing with patients with OA. Furthermore, our results confirm the importance of a combined evaluation of symptoms, clinical examination, and radiographs when deciding on the right treatment for individual knee patients. |
3,108 | 63,380 | To describe the extent of radiographic damage of large joints in long-term rheumatoid arthritis (RA) and its relationship to small joint involvement and physical function.
After 12 yr of follow-up, radiographs of all large joints (Larsen large joint score 0-60) of 105 recent RA patients were assessed. Correlations were evaluated between the Larsen large joint score and radiographic damage of the hands and feet as measured by the van der Heijde modification of the Sharp score (SHS) and the health assessment questionnaire (HAQ). We determined the relative contributions of radiographic damage of small and large joints, disease activity and psychological function to the HAQ.
The median Larsen large joint score was 3. In 54% of the patients at least one large joint was erosive. The correlation of the Larsen score with the SHS and HAQ scores was 0.76 and 0.60, respectively. Disease activity and radiographic damage of the large joints were the major determinants of the HAQ score. | Large joint involvement after 12 yr of follow-up is extensive and is associated with functional disability. Large joint involvement is closely associated with small joint involvement. |
3,109 | 55,308 | Although surgical treatment of meniscus injuries has made great progress, meniscectomy remains the most frequently indicated intervention. The aim of this retrospective study was to evaluate the long-term radiological results of isolated subtotal and total meniscectomies and compare them with the clinical results.
The assessed group included 22 men and 8 women at an average age of 35 years; nine and 21 knees, respectively, were treated by isolated subtotal and total meniscectomy in the period from 1987 to 1989. The lateral meniscus was operated on in six knees and the medial meniscus in 24 knees. Patients with other injuries to the knee joint or with a systemic disease were not evaluated. The average follow-up was 16 years. The results were compared with the other, non-treated knee.
The results were assessed by means of the Lysholm scoring system which takes into account limping, support requirement, walking distances, instability, edema, stair ascent and descent, ability to squat and pain. Radiographic osteoarthritis of the knee was classified by the Kellgren and Lawrence system. A grade greater or equal to 2 was taken for a clear sign of arthritis. In addition, the anatomical axis of the lower extremity was evaluated. Anteroposterior projection of both knees under load was made in a standing position on long films and lateral projection was obtained separately on short films.
The average Lysholm scores were 87 points (range, 41-100) and 91 points (range, 67-100) in the treated and non-treated knees, respectively. The outcome of meniscectomy was excellent in 14 (47 %), good in eight (27 %), satisfactory in five (16 %) and poor in three (10 %) knees. In 12 patients (40 %) the state of the treated knee was evaluated as being equal to that of the non-treated knee and in eight patients (27 %) it was even better. Osteoarthritis of the affected compartment was found in eight treated knees and that of the corresponding compartment on the opposite side in four knees. Grade 2 Kellgren- Lawrence radiographic changes were present in four, grade 3 in two and grade 4 in two knees treated by meniscectomy. The anatomic femoro-tibial angle differed between the treated and non-treated side, by 4 degrees on average (range, 2 degrees to 10 degrees ), in 13 (43 %) patients.
Johnson et al. found at follow-up for about 17 years that osteoarthritis developed more often in the treated than in healthy contralateral knees (40 % as against 6 %). Tapper and Hoover reported that 45 % of men and 10 % of women were without subjective complaints at 10 to 30 years of follow up. In the relevant Czech literature, only Pasa et al. have recently paid attention to the development of lesions in knees treated by meniscectomy, but they have largely evaluated changes occurring after partial arthroscopic meniscectomies. | The present study showed that osteoarthritis after subtotal or total meniscectomy developed in 27 % of the patients at an average follow-up of 16 years. In less than half of the patients, a deviation of the anatomical axis occurred in the treated lower extremity, as compared with the other healthy side. Lysholm scores worse in the treated than the non-treated knee were found in one third of the patients.However, a deviated knee joint axis and/or osteoarthritic lesions did not always correlate with deteriorated clinical findings. |
3,110 | 62,940 | To assess the efficacy and safety of chondroitin sulfate (CS) 1 g/day per os compared to placebo, in a double blind, randomized, parallel group study, with 3 months treatment followed by a 3 month posttreatment period, in patients with femorotibial osteoarthritis (OA).
The main criterion was the functional handicap assessed by Lequesne's algofunctional index (AFI). Secondary efficacy criteria were: self-assessed pain with activity and at rest, self-assessed impact of OA on daily living, patient and physician assessed overall change in patient state since the previous visit, and daily NSAID and analgesic consumption, all evaluated monthly. The main analysis was performed on the intent-to-treat (ITT) population at treatment endpoint compared to baseline (Day 0).
The ITT efficacy data set comprised 130 patients (63 in CS group and 67 in placebo group). At treatment endpoint, the AFI showed greater but nonsignificant improvement in the CS than in the placebo group. Improvement became significant (p = 0.02) in the completer population (n = 114). In the ITT population, all variables tended towards greater improvement in the CS than the placebo group. In the completer population, pain at rest also significantly decreased in the CS group compared to the placebo group (p = 0.03), and, one month after treatment, CS had a significantly higher persistent effect than placebo on the AFI (p = 0.01), pain with activity (p = 0.001), physician assessed patient state (p = 0.05), and most other efficacy criteria. Adverse event rates did not differ significantly. | We observed a trend towards efficacy of CS 1 g/day compared to placebo with good tolerability after 3 month treatment, and persistent efficacy one month posttreatment. Further investigations are required to confirm this trend. |
3,111 | 32,693 | To update the evidence for the safety of synthetic disease-modifying antirheumatic drugs (sDMARDs), glucocorticoids (GC) and biological DMARDs (bDMARDs) in patients with rheumatoid arthritis (RA) to inform the European League Against Rheumatism (EULAR) recommendations for the management of RA.
Systematic literature review (SLR) of observational studies (including registries). Interventions were any bDMARD (anakinra, infliximab, etanercept, adalimumab, rituximab, abatacept, tocilizumab, golimumab or certolizumab pegol) or sDMARD (methotrexate, leflunomide, hydroxychloroquine, sulfasalazine, gold/auranofin, azathioprine, chlorambucil, chloroquine, cyclosporin, cyclophosphamide, mycophenolate, minocycline, penicillamine, tacrolimus or tofacitinib) and a comparator was required. Information on GCs was collected from the included studies. All safety outcomes were included.
Forty-nine observational studies addressing diverse safety outcomes of therapy with bDMARDs met eligibility criteria. Substantial heterogeneity precluded meta-analysis of any of the outcomes. Patients on tumour necrosis factor inhibitors (TNFi) compared to patients on conventional sDMARDs had a higher risk of serious infections (adjusted HR (aHR) 1.1-1.8), a higher risk of tuberculosis, and an increased risk of infection by herpes zoster cannot be excluded. Patients on TNFi did not have an increased risk for malignancies in general, lymphoma or non-melanoma skin cancer, but the risk of melanoma may be slightly increased (aHR 1.5). From the studies identified on conventional sDMARDs, no new safety signals were found. | The findings from this SLR confirm the known safety pattern of sDMARDs and bDMARDs for the treatment of RA. |
3,112 | 52,306 | Fibromyalgia (FMS) is a chronic syndrome characterized by widespread pain, troubled sleep, disturbed mood, and fatigue. Several analgesic strategies have been evaluated but the results are moderate and inconsistent. Antidepressant agents are now considered the treatment of choice in most patients. It has been recently suggested that FMS may be associated with metabolic alterations including a deficit of carnitine. In this multicenter randomized clinical trial we evaluated the efficacy of acetyl L-carnitine (LAC) in patients with overt FMS.
One hundred and two patients meeting the American College of Rheumatology criteria for FMS were randomized into the study. The treatment consisted of 2 capsules/day of 500 mg LAC or placebo plus one intramuscular (i.m.) injection of either 500 mg LAC or placebo for 2 weeks. During the following 8 weeks the patients took 3 capsules daily containing either 500 mg LAC or placebo. The patients were seen during treatment after 2 (visit 3), 6 (visit 4) and 10 weeks (visit 5). The patients were also visited 4 weeks after treatment discontinuation (follow-up visit). Outcome measures included the number of positive tender points, the sum of pain threshold (kg/cm2 or "total myalgic score"), the Short Form 36 (SF36), a 100 mm visual analog scale (VAS) for self-perceived stiffness, fatigue, tiredness on awakening, sleep, work status, depression, and muscular-skeletal pain, and the Hamilton depression scale.
The "total myalgic score" and the number of positive tender points declined significantly and equally in both groups until the 6th week of treatment. At the 10th week both parameters remained unchanged in the placebo group but they continued to improve in the LAC group with a statistically significant between-group difference. Most VAS scores significantly improved in both groups. A statistically significant between-group difference was observed for depression and musculo-skeletal pain. Significantly larger improvements in SF36 questionnaire were observed in LAC than in placebo group for most parameters. Treatment was well-tolerated. | Although this experience deserves further studies, these results indicate that LAC may be of benefit in patients with FMS, providing improvement in pain as well as the general and mental health of these patients. |
3,113 | 5,210 | Differences in the expression of variants across ethnic groups in the systemic lupus erythematosus (SLE) patients have been well documented. However, the genetic architecture in the Thai population has not been thoroughly examined. In this study, we carried out genome-wide association study (GWAS) in the Thai population.
Two GWAS cohorts were independently collected and genotyped: discovery dataset (487 SLE cases and 1606 healthy controls) and replication dataset (405 SLE cases and 1590 unrelated disease controls). Data were imputed to the density of the 1000 Genomes Project Phase 3. Association studies were performed based on different genetic models, and pathway enrichment analysis was further examined. In addition, the performance of disease risk estimation for individuals in Thai GWAS was assessed based on the polygenic risk score (PRS) model trained by other Asian populations.
Previous findings on SLE susceptible alleles were well replicated in the two GWAS. The SNPs on HLA class II (rs9270970, A>G, OR = 1.82, p value = 3.61E-26), STAT4 (rs7582694, C>G, OR = 1.57, p value = 8.21E-16), GTF2I (rs73366469, A>G, OR = 1.73, p value = 2.42E-11), and FAM167A-BLK allele (rs13277113, A>G, OR = 0.68, p value = 1.58E-09) were significantly associated with SLE in Thai population. Meta-analysis of the two GWAS identified a novel locus at the FBN2 that was specifically associated with SLE in the Thai population (rs74989671, A>G, OR = 1.54, p value = 1.61E-08). Functional analysis showed that rs74989671 resided in a peak of H3K36me3 derived from CD14+ monocytes and H3K4me1 from T lymphocytes. In addition, we showed that the PRS model trained from the Chinese population could be applied in individuals of Thai ancestry, with the area under the receiver-operator curve (AUC) achieving 0.76 for this predictor. | We demonstrated the genetic architecture of SLE in the Thai population and identified a novel locus associated with SLE. Also, our study suggested a potential use of the PRS model from the Chinese population to estimate the disease risk for individuals of Thai ancestry. |
3,114 | 26,754 | To determine benefits and harms of arthroscopic knee surgery involving partial meniscectomy, debridement, or both for middle aged or older patients with knee pain and degenerative knee disease.
Systematic review and meta-analysis.
Pain and physical function.
Systematic searches for benefits and harms were carried out in Medline, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to August 2014. Only studies published in 2000 or later were included for harms.
Randomised controlled trials assessing benefit of arthroscopic surgery involving partial meniscectomy, debridement, or both for patients with or without radiographic signs of osteoarthritis were included. For harms, cohort studies, register based studies, and case series were also allowed.
The search identified nine trials assessing the benefits of knee arthroscopic surgery in middle aged and older patients with knee pain and degenerative knee disease. The main analysis, combining the primary endpoints of the individual trials from three to 24 months postoperatively, showed a small difference in favour of interventions including arthroscopic surgery compared with control treatments for pain (effect size 0.14, 95% confidence interval 0.03 to 0.26). This difference corresponds to a benefit of 2.4 (95% confidence interval 0.4 to 4.3) mm on a 0-100 mm visual analogue scale. When analysed over time of follow-up, interventions including arthroscopy showed a small benefit of 3-5 mm for pain at three and six months but not later up to 24 months. No significant benefit on physical function was found (effect size 0.09, -0.05 to 0.24). Nine studies reporting on harms were identified. Harms included symptomatic deep venous thrombosis (4.13 (95% confidence interval 1.78 to 9.60) events per 1000 procedures), pulmonary embolism, infection, and death.
PROSPERO CRD42014009145. | The small inconsequential benefit seen from interventions that include arthroscopy for the degenerative knee is limited in time and absent at one to two years after surgery. Knee arthroscopy is associated with harms. Taken together, these findings do not support the practise of arthroscopic surgery for middle aged or older patients with knee pain with or without signs of osteoarthritis. |
3,115 | 42,031 | To analyze the association of diverse cerebral anomalies in a series of pediatric patients with cerebellar tonsillar ectopia.
We reviewed the medical records of 60 children diagnosed with Chiari type 1 malformation (CM1), of these, 20 patients (11 boys and 9 girls; mean age 7.2 years, range 2-16 years) had an associated cerebral anomaly. Symptoms of tonsillar ectopia evolved over a mean of 12 months (range 3 months to 4 years). Syringomyelia was present in 5 cases. All patients underwent a posterior fossa decompression.
Disclosed anomalies included: congenital hydrocephalus (n = 11), cervicomedullary kinking (n = 5), focal cerebral heterotopia with epilepsy (n = 4), partial agenesis of the corpus callosum (n = 4), hypoplastic brain stem (n = 2), holoprosencephaly (n = 1), and subcortical dysplasia in the context of neurofibromatosis type 1 (n = 1). Other malformations included: subcortical hamartoma associated with neurofibromatosis type 1, craniofacial dysmorphism secondary to Noonan syndrome, congenital occipital plagiocephaly, os odontoideum, craniofacial cleft, juvenile rheumathoid arthritis with platybasia, and osteogenesis imperfecta with bathrocephaly and scoliosis. | Craniocerebral anomalies in children treated for CM1 may be found consistently. The association of hydrocephalus, which was the most common anomaly in this cohort, with cerebellar tonsillar ectopia may contribute to a poor outcome in regard to tonsillar herniation symptoms. |
3,116 | 37,675 | To select sub-clinical patients with symptoms of knee osteoarthritis (KOA) without X-ray changes by measuring the serum level of cartilage oligomeric matrix protein (COMP) with ELISA, so as to diagnose and treat patients with knee osteoarthritis at early stage.
The 115 patients with KOA or with symptomatic primary KOA were enrolled from August 2007 to September 2009, which was OA group; and 35 healthy people in the control group. In OA group, there were 55 males and 60 females,ranging in age from 39 to 76 years, with an average of (55 +/- 13.32) years; the body mass index (BMI) ranged from 15.1 to 29.8; the disease course ranged from 6 to 60 months. In the control group, there were 16 males and 19 females, ranging in age from 36 to 77 years, with an average of (53 +/- 12.53) years; the BMI ranged from 14.8 to 29.2. Patients with symptomatic primary knee OA of Kellgren-Lawrence (K-L) grade I-IV were evaluated. Serum level of COMP and its correlation with OA grade were analyzed by ELISA method. The patients were treated with Celecoxib capsules. The patients in OA group were followed up, and the duration ranged from 24 to 38 months (averaged, 33.4 months), and the serum level of COMP were analyzed before and after treatment.
The serum level of COMP in the control group varied with age (t= 2.50, P=0.02). The serum level of COMP did not correlate with gender (control group: t=0.98, P=0.34; OA group: t=0.18, P= 0.86), BMI (control group: t=0.56, P=0.92; OA group: t=0.17, P=0.85) and smoking (control group: t=1.89, P=0.08; OA group: t=0.70, P=0.49). The serum level of COMP was higher in the patients with higher K-L grades than in the patients with lower K-L grades (F=15.56, P=0.001) . The sub-clinical KOA patients without X-ray changes can be detected significant higher COMP levels than sub-clinical patients with other diseases (t=2.55, P=0.03). Therefore, according to this method, subclinical OA patients can be detected from people with other sub-clinical diseases successfully. | The serum level of COMP can be used as a potential prognostic marker to diagnose KOA. |
3,117 | 34,193 | Previous studies of long-term treatment response in fibromyalgia and other chronic pain states have generally been limited to approximately one year, leaving questions about the longer-term durability of response. The purpose of this study was to demonstrate continuing efficacy of milnacipran by characterizing changes in pain and other fibromyalgia symptoms after discontinuing long-term treatment. The mean length of milnacipran treatment at the time of randomized withdrawal was 36.1 months from initial exposure to milnacipran (range, 17.9 to 54.4 months).
After completing a long-term, open-label, lead-in study of milnacipran (which followed varying periods of exposure in previous studies), adult patients with fibromyalgia entered the four-week open-label period of the current study for evaluation of ongoing treatment response. After the four-week period to confirm new baseline status, 151 patients taking milnacipran ≥100 mg/day and reporting ≥50% improvement from pre-milnacipran exposure in Visual Analogue Scale (VAS) pain scores were classified as responders. These responders entered the 12-week, double-blind withdrawal period in which they were randomized 2:1 to continue milnacipran or switched to placebo. The prespecified primary parameter was loss of therapeutic response (LTR), defined as increase in VAS pain score to <30% reduction from pre-milnacipran exposure or worsening of fibromyalgia requiring alternative treatment. Adverse events and vital signs were also monitored.
Time to LTR was shorter in patients randomized to placebo than in patients continuing milnacipran (P < 0.001). Median time to LTR was 56 days with placebo and was not calculable for milnacipran, because less than half of the latter group of patients lost therapeutic response by study end. Additionally, 81% of patients continuing on milnacipran maintained clinically meaningful pain response (≥30% improvement from pre-milnacipran exposure), compared with 58% of patients switched to placebo (sensitivity analysis II; P < 0.001). The incidences of treatment-emergent adverse events were 58% and 47% for placebo and milnacipran, respectively. Mean decreases in blood pressure and heart rate were found in both groups, with greater decreases for patients switched to placebo.
ClinicalTrials.gov: NCT01014585. | Continuing efficacy of milnacipran was demonstrated by the loss of effect following withdrawal of treatment in patients who received an average of three years of milnacipran treatment. |
3,118 | 22,056 | The concept of containment as an effective approach to reduce the risk of femoral head deformity has been questioned because modest results have been achieved after nonoperative and operative treatments for severely involved Legg-Calvé-Perthes disease. Several reports have shown the limited effectiveness of some conventional single procedures. However, there is limited data on the effectiveness of combined procedures.
The surgical group comprised 77 patients (mean age 8.3 y) and involved 79 hips. The average follow-up term was 9.5 years. Sixty-five patients were unilaterally involved and 12 patients were bilaterally involved (although 10 of the latter patients only received surgery on 1 hip). Among patients, 28 hips were classified as Herring class B/C border (>8 y old) and 51 hips were Herring class C. The 79 hips were divided into 2 treatment groups for further analysis: group 1, single procedures (femoral varus osteotomy) (n=47); group 2, combined procedures [femoral varus osteotomy+Dega (Pemberton) osteotomy] (n=32).
Using Stulberg classification I and II (acceptable outcome), the final outcome was statistically significant for group 2 (21 hips, 65.6%) compared with group 1 (18 hips, 38.3%) (P=0.031). The average remodeling efficacy, defined as the change in caput index between preoperation and postoperation, was better in group 2 (12.7%) than in group 1 (3.9%) (P=0.005). The acetabulum-head index and α-angle were also statistically significant in group 2 than in group 1 at the last follow-up. Clinical evaluations were statistically significant in group 2 compared with group 1.
Level III-therapeutic study. | Both clinically and radiologically, the combined procedure group demonstrated significantly better outcomes with accelerated remodeling in both the severely affected femoral heads and the acetabula compared with the single procedure group. With this procedure, we anticipate the increased likelihood of preventing or delaying coxarthroses in adulthood. |
3,119 | 33,623 | To examine changes in patient reported outcome measures (PROs) over 15 years in a representative population of patients with rheumatoid arthritis (RA), with a particular focus on gender differences.
Patients in the Oslo RA register filled in questionnaires including the Modified Health Assessment Questionnaire (MHAQ), the Short-Form 36 (SF-36) with physical (PCS) and mental component summaries and derived utility (SF-6D), visual analogue scales (VAS) for pain, patient global assessment of disease (PtGA) and fatigue, and checklists of medication commonly used in the treatment of RA. Data were collected at five time points during a 15-year period from 1994. Mixed model analyses were used to analyse longitudinal changes in PROs from 1994 to 1996, 2001, 2004 and 2009.
Data were available from 829-1025 RA patients at each time point. PROs were statistically significantly improved from 1994 to 2009 (MHAQ, SF-36 PCS, SF-6D, pain VAS, PtGA VAS and fatigue VAS; all p<0.001), and also with clinically important improvement. Men reported significantly better health status than women in 1994, but women improved significantly more than men over 15 years with a reduction of the gender gap in 2009. Antirheumatic medication was increasingly used over 15 years with no gender differences. | RA patients reported statistically significantly improved health status for most PROs from 1994 to 2009. Women improved most, and although they still reported higher disease impact than men, the gender differences were small at the final data collection in 2009. |
3,120 | 44,211 | To describe the anatomical distribution of synovitis and its association with joint effusion on non-enhanced and contrast-enhanced (CE) MRI in patients with knee osteoarthritis (OA).
Baseline MRI was performed at 1.5T using axial proton density (PD)-weighted (w) fat suppressed (fs) and axial and sagittal T1-w fs CE sequences. Synovial enhancement was scored in nine articular subregions. Maximum synovial enhancement was grouped as absent (0), equivocal (1) and definite (2 and 3). Effusion was scored from 0 to 3 on the axial sequences. We described the anatomical distribution of synovitis, its association with effusion and compared assessment of effusion on T1-w fs CE and PD fs sequences.
111 subjects were included and examined by MRI. 89.2% of knees exhibited at least one subregion with a minimum grade 2 and 39.6% at the maximum of a grade 3. The commonest sites for definite synovitis were posterior to the posterior cruciate ligament (PCL) in 71.2% and in the suprapatellar region in 59.5% of all knees. On T1-w fs CE, 73.0% of knees showed any effusion. Definite synovitis in at least one location was present in 96.3% knees with an effusion and in 70.0% without an effusion. Higher grades of effusion were scored on the PD fs sequence. | Definite synovitis was present in the majority of knees with or without effusion with the commonest sites being posterior to the PCL and in the suprapatellar recess. Joint effusion as measured on PD fs images does not only represent effusion but also synovial thickening. |
3,121 | 3,528 | To analyze the incidence of Covid-19 in patients who are chronic users of hydroxychloroquine.
Cross-sectional retrospective observational multicenter study in health areas and districts from Castilla La-Mancha and Andalucia. Of the 4451 participants included in the first recruitment, 3817 with valid data were selected. The main variable of the study is the presence or absence of Covid-19 infection by clinical, serological or polymerase chain reaction diagnosis. Sociodemographic and clinical variables and treatment and concomitant comorbidities were recorded.
169 (4,45%) patients had Covid-19 infection, of which 12 (7.1%) died and 32 (18.9%) required hospital admission. Previous respiratory pathology was related to Covid-19 infection (P<.05). Maculopathy appears in 5.3% of patients and is significantly related to the dose of hydroxychloroquine consumed (P<.05). | There is no relationship between chronic use of hydroxychloroquine and the incidence of Covid-19. |
3,122 | 32,597 | Advising patients about when they can drive after surgery is common practice after arthroplasty of the knee or hip. In the literature, the preoperative braking performance values of the patients are frequently taken as the "safe" landmark. We hypothesised that osteoarthritis (OA), the most frequent reason for arthroplasty, already compromises the ability to perform an emergency stop. We expected that both Reaction Time (RT) and Movement Time (MT) as components of the Total Brake Response Time (TBRT), would be prolonged in patients with OA of the knee or hip in comparison with healthy subjects. We also expected maximum pressure levels on the brake pedal to be reduced in such cases.
A real car cabin was equipped with pressure sensors on the accelerator and brake pedals to measure RT, MT, TBRT and maximum Brake Force (BF) under realistic spatial constraints. Patients with OA of the knee (right n = 18, left n = 15) or hip (right n = 20, left n = 19) were compared with a healthy control group (n = 21).
All measured values for TBRT in the control group remained below 600 ms. OA of the right hip or knee significantly prolonged the braking performance (right hip: TBRT p = 0.025, right knee: TBRT p < 0.001), whereas OA of the left hip did not impair driving ability (TBRT p = 0.228). Intriguingly, OA of the left knee prolonged RT and MT to the same degree as OA on the contralateral side (RT p = 0.001, MT p < 0.001).
Project number of the ethics committee of the University of Tübingen: 268/2009BO2; 267/2009BO2. | This study demonstrates that depending on the localisation of OA, driving capability can be impaired; OA can significantly increase the total braking distance. To ensure safe traffic participation the safety margin for TBRT should be strictly set, under our experimental conditions, at around 600 ms. Moreover, therapeutic approaches to OA, such as physiotherapy, and patients receiving surgery of the left knee should take into account that left knee OA can also impair driving ability. |
3,123 | 63,465 | Little is known about risk factors for patellofemoral (PF) osteoarthritis (OA). The lateral vector at the PF joint increases the likelihood of lateral PF versus medial PF pathology. Both valgus and varus malalignments affect forces at the PF joint and may predispose to PF OA. We examined whether lateral PF OA is more common than medial PF OA, whether valgus malalignment is more frequent in lateral PF OA than in medial PF OA, and whether knees with PF OA are more often valgus than knees with isolated tibiofemoral (TF) OA.
In 292 knee OA patients, we obtained semiflexed, fluoroscopy-confirmed radiographs of the TF joint and weight-bearing, 30 degrees flexion, axial views of the PF joint. Varus-valgus alignment (the angle formed by the intersection of the mechanical axes of the femur and tibia) was measured on a full-limb radiograph.
Lateral PF OA was more common than medial PF OA (P<0.0001). Forty-three of 75 knees with lateral PF OA had valgus malalignment compared with only 5 of 21 patients with medial PF OA (P = 0.0066). Conversely, varus malalignment was more likely in the medial PF OA group. Knees with isolated PF OA were more likely to have valgus malalignment than those with isolated TF OA (P = 0.0002), as were knees with mixed PF-TF OA (P = 0.0006). | Varus-valgus alignment may influence the risk of PF OA and, in particular, which compartment is affected. |
3,124 | 59,383 | To study the effectiveness of elastic sleeves in patients with knee osteoarthritis (knee OA).
Patients with knee OA attending the outpatient clinic of Siriraj Hospital, who met the eligibility criteria, were randomly allocated to receive an 8-week treatment protocol. The control group received acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs) and education. The study group received the same treatment, in combination with a daytime elastic knee sleeve. Primary outcome variable included change in aggregated functional performance time (AFPT).
In the immediate period after treatment, the study group had a mean improvement in AFPT of 1.63 seconds more than the control group (95% CI: 0.21-3.05, p = 0.025). At the end of the 8th week, the changes of AFPT were not statistically different between the two groups. | This study shows small short-term beneficial effects of an elastic sleeve in patients with knee OA in cases with acute exacerbation. |
3,125 | 59,371 | To describe characteristics of non-steroidal anti-inflammatory drugs (NSAIDs; Anatomical Therapeutic Chemical code M01A) users in Finland, with emphasis on intensity of use.
Nationwide prescription database study over years 1997-2000 using a random sample of 500,000 persons. Low use was defined as 30 or fewer defined daily doses (DDDs) per year, moderate between 31 and 181 DDDs, and heavy 182 or more DDDs. Persons with rheumatoid arthritis (RA) were identified and analysed separately from non-RA patients.
The total NSAID consumption was 61.2 and reimbursed prescription NSAID use 31.2 DDD/1000 inhabitants per day in 2000. The annual prevalence of use varied between 17.1% and 18.8% throughout 1997-2000, and that of low, moderate and heavy use was 7.6%, 8.0% and 1.5%, respectively, in 2000. Females used more NSAIDs than men in all adult non-RA age groups, and of non-RA patients 58.4% were females. The share of females among the non-RA users increased with the intensity of use, as did the share of female patients 65 years or older. Among RA patients, the intensity of use was independent of age and gender, and 70% of RA patients were females. Of the heavy users in 2000, 27.7% ( n=2117) had continuously used 182 or more DDDs per year throughout the years 1997-2000. Non-RA users accounted for 78.4% of the annual heavy and 64.2% of the continuous heavy users. | Exposure of patients to long-term use of NSAIDs and upper gastrointestinal bleeding should be reduced by regular analysis of patient's pain and consideration of other treatment options. |
3,126 | 28,277 | Quadriceps femoris muscle strengthening is a common rehabilitation exercise for knee osteoarthritis (OA). More information is needed to determine whether targeting muscle power is a useful adjunct to strengthening for people with knee OA.
The purpose of this study was to identify the predictive ability of knee extensor strength and knee extensor power in the performance of physical tasks in adults with knee OA.
This study used a cross-sectional design.
Fifty-five participants with clinical knee OA were included (43 women; mean [SD] age=60.9 [6.9] years). Dependent variables were: timed stair ascent, timed stair descent, and the Six-Minute Walk Test (6MWT). Independent variables were: peak knee extensor strength and mean peak knee extensor power. Covariates were: age, body mass index, and self-efficacy. Multiple regression analyses were run for each dependent variable with just covariates, then a second model including strength, and then a third model including power. The R(2) values were compared between models.
Power explained greater variance than strength in all models. Over and above the covariates, power explained an additional 6% of the variance in the 6MWT, increasing the R(2) value from .33 to .39; 8% in the stair ascent test, increasing the R(2) value from .52 to .60; and 3% in the stair descent test, increasing the R(2) value from .44 to .47.
The sample demonstrated very good mobility and muscle function scores and may not be indicative of those with severe knee OA. | In adults with knee OA, knee extensor power was a stronger determinant of walking and stair performance when compared with knee extensor strength. Clinicians should consider these results when advising patients on exercise to maintain or improve mobility. |
3,127 | 627 | Stair climbing test (SCT) has been suggested as the first task affected in individuals with symptomatic knee osteoarthritis (KOA). However, there are environmental barriers for the execution of the 9- to 12-step SCT. Thus, we developed a feasible one-step SCT that could be completed in 15s.
To check the clinimetric properties of the 15s Step Up and Down (StUD) test in individuals with KOA.
Prospective validity study.
Eighty-two individuals with KOA participated in this study. The test-retest reliability of the StUD test was measured with a 1-week interval. The construct validity and responsiveness were assessed by testing predefined hypotheses. For this, the 30s Chair Stand Test (30CS), Timed Up and Go Test (TUG), quadriceps strength, Knee Injury and Osteoarthritis Outcome Score (KOOS), and Lequesne Algofunctional Index were used as comparator instruments.
The StUD test presented good test-retest reliability (ICC = 0.87; 95% CI = 0.79-0.91) and showed a moderate to good correlation with the 30CS (r = 0.65), TUG (r = -0.56), and quadriceps strength (r = 0.41). We found a higher correlation between the StUD test and the performance-based tests than the patient-reported outcome measures. The StUD test was responsive, with five out of the six (83.3%) hypotheses confirmed. | StUD test showed good reliability, adequate validity and responsiveness. Our findings suggest that StUD is a useful performance-based test for individuals with KOA. |
3,128 | 3,989 | Fibromyalgia is a functional pain disorder in which patients suffer from widespread pain and poor quality of life. Fibromyalgia pain and its impact on quality of life are not effectively managed with current therapeutics. Previously, in a preclinical rat study, we demonstrated that exposure to green light-emitting diodes (GLED) for 8 hours/day for 5 days resulted in antinociception and reversal of thermal and mechanical hypersensitivity associated with models of injury-related pain. Given the safety of GLED and the ease of its use, our objective is to administer GLED as a potential therapy to patients with fibromyalgia.
One-way crossover clinical trial.
United States.
We enrolled 21 adult patients with fibromyalgia recruited from the University of Arizona chronic pain clinic who were initially exposed to white light-emitting diodes and then were crossed over to GLED for 1 to 2 hours daily for 10 weeks. Data were collected by using paper surveys.
When patients were exposed to GLED, but not white light-emitting diodes, they reported a significant reduction in average pain intensity on the 10-point numeric pain scale. Secondary outcomes were assessed by using the EQ-5D-5L survey, Short-Form McGill Pain Questionnaire, and Fibromyalgia Impact Questionnaire and were also significantly improved in patients exposed to GLED. GLED therapy was not associated with any measured side effects in these patients. | Although the mechanism by which GLED elicits pain reduction is currently being studied, these results supporting its efficacy and safety merit a larger clinical trial. |
3,129 | 31,885 | Economic evaluation typically is conducted using health state utilities to estimate treatment benefits. However, such outcomes are often missing from studies of clinical effectiveness. This study aims to bridge that gap by providing appropriate methods to link values from the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) to the EQ-5D utility instrument.
Patients from a large registry of Spanish patients (n = 7072 observations) with knee or hip osteoarthritis who completed both WOMAC and EQ-5D was used. A mixture model approach was used based on distributions bespoke to the EQ-5D UK value set to estimate EQ-5D as a function of WOMAC pain, stiffness and function subscores.
A five class mixture model provides very close fit to the observed data at all levels of disease severity. The overall mean (0.542 vs 0.542), median (0.620 vs 0.636) and the percentage of observations at full health (15 vs 14.8) were very similar between the observed data and the estimated model respectively. Stiffness has limited relationship to EQ-5D, whereas functional disability and pain are strong predictors. | EQ-5D can be reliably estimated from WOMAC subscale scores without any systematic bias using these results. |
3,130 | 2,601 | Detailed kinematics of floor-sitting activities after total knee arthroplasty (TKA) have not been well explored. Knee kinematics of cross-legged sitting, seiza-sitting, and side-sitting after TKA were examined to clarify the differences in tibiofemoral kinematics of each activity.
Subjects were 40 knees in 20 osteoarthritic patients who underwent bilateral TKA with a high-flexion fixed-bearing posterior-stabilized prosthesis. Dynamic radiographs of floor-sitting activities were taken, and the knee kinematics were compared among the three activities. The patients were also divided into two groups (possible/easy group and impossible/no-try group) for each activity, and group comparisons were conducted.
The maximum implant flexion angle was significantly greater in seiza-sitting. In valgus/varus rotation, seiza-sitting demonstrated neutral rotation, while cross-legged sitting showed varus of about 10°, and side-sitting exhibited valgus. In tibial internal/external rotation, seiza-sitting demonstrated a constant rotational angle, while cross-legged sitting showed tibial internal rotation with flexion, and side-sitting exhibited tibial external rotation with flexion. The kinematic pathway during deep flexion illustrated the medial pivot pattern in cross-legged sitting, a small amount of bicondylar rollback in seiza-sitting, and the weak lateral pivot pattern in side-sitting. A greater flexion angle was the important factor for the performance of each floor-sitting activity followed by varus laxity at 10° knee flexion. | This study successfully revealed characteristic kinematic patterns of TKA knees in three floor-sitting activities. Obtaining a greater knee flexion with adequate lateral laxity is the key to enhancing postoperative floor-sitting activities. |
3,131 | 13,672 | Mast cells (MCs) are involved in the pathogenesis of rheumatoid arthritis (RA). However, their contribution remains controversial. To establish their role in RA, we analysed their presence in the synovium of treatment-naïve patients with early RA and their association and functional relationship with histological features of synovitis.
Synovial tissue was obtained by ultrasound-guided biopsy from treatment-naïve patients with early RA (n=99). Immune cells (CD3/CD20/CD138/CD68) and their relationship with CD117
High synovial MC counts are associated with local and systemic inflammation, autoantibody positivity and high disease activity. IHC/IF showed that MCs reside at the outer border of lymphoid aggregates. Furthermore, human MCs promote the activation and differentiation of naïve B cells and induce the production of ACPA, mainly via contact-dependent interactions. In AIA, synovial MC numbers increase in IL27 | Synovial MCs identify early RA patients with a severe clinical form of synovitis characterised by the presence of ELS. |
3,132 | 50,055 | The optimal therapeutic trial duration of anti-TNF-alpha therapy is currently unknown. The British Society for Rheumatology (BSR) guidance states that non-response at 3 months warrants re-evaluation of treatment and recommends not to persist beyond 6 months. The National Institute for Health and Clinical Excellence (NICE) specifies treatment continuation if response is achieved by 6 months, yet the European League against Rheumatism (EULAR) and the American College of Rheumatology (ACR) maintain a 3 month cut-off. No evidence exists to support a 6 month therapeutic trial over 3 months. Thus, we undertook a study to evaluate the proportion of patients who failed to meet NICE response criteria at 3 months but obtained this by 6 months, and to identify predictive factors for this.
Patients who commenced anti-TNF-alpha therapy for RA were studied, counting those who switched to a second or third agent separately for each instigation of therapy (n = 244). Response at 3 and 6 months was defined according to NICE criteria as a >or=1.2 reduction in Disease Activity Score (DAS28).
Of the 189 patients with available 3 month DAS28 responses, 149 fulfilled response criteria. Of the 40 who failed, 27 continued treatment, of whom 21 were available for follow-up at 6 months. Out of the 21 patients, 12 (57%; 95% CI 36, 78) achieved a response at this time. This data set was too small to investigate predictors of response at 6 months. | A substantial proportion of patients who fail NICE response criteria at 3 months and continue on treatment to 6 months achieve a response. These results support a 6 month therapeutic trial over 3 months. |
3,133 | 10,596 | Few studies in the literature show results with more than 20 years of follow-up after anterior cruciate ligament reconstruction (ACLR). The main purpose of this retrospective study was to describe knee-specific quality of life, functional results and prevalence of osteoarthritis (OA) of the knee in patients with ACLR using bone-patellar tendon-bone (BPTB) autograft with ultra-long-term follow-up.
Prospective analyzed data included demographics, meniscus status, radiographic OA, KT-1000 arthrometer measurements and physical examinations. KOOS, Lysholm and IKDC subjective surveys were conducted. Multivariate and univariate logistic models were used to determine the effect of potential predictors of OA and symptomatic knees.
Seventy-two knees were included at a median follow-up of 22 (IQR 21-25) years postoperatively. Radiographic scores were normal in 15%, nearly normal in 57%, abnormal in 18% and severely abnormal in 10%. Multivariate analysis showed that the predictive factor for the presence of OA in the long-term was an associated meniscal lesion; patients with meniscal lesions were 3.9 times as likely to develop OA in comparison with those without meniscal injury. The subjective scores were progressively and significantly lower as the level of OA was greater.
Level IV; case series. | At a median of 22 years of follow-up, this study shows that patellar tendon autograft ACL reconstruction provides good clinical outcomes, with clinically objective knee stability and a 28% prevalence of OA. Additionally, we identified that meniscal injury at time of surgery was an independent predictor of OA. |
3,134 | 16,843 | After the diagnosis of immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA), the incidence of psychiatric comorbidity is increased relative to the general population. We aimed to determine whether the incidence of psychiatric disorders is increased in the 5 years before the diagnosis of IMID as compared with the general population.
Using population-based administrative health data from the Canadian province of Manitoba, we identified all persons with incident IBD, MS and RA between 1989 and 2012, and cohorts from the general population matched 5 : 1 on year of birth, sex and region to each disease cohort. We identified members of these groups with at least 5 years of residency before and after the IMID diagnosis date. We applied validated algorithms for depression, anxiety disorders, bipolar disorder, schizophrenia, and any psychiatric disorder to determine the annual incidence of these conditions in the 5-year periods before and after the diagnosis year.
We identified 12 141 incident cases of IMID (3766 IBD, 2190 MS, 6350 RA) and 65 424 matched individuals. As early as 5 years before diagnosis, the incidence of depression [incidence rate ratio (IRR) 1.54; 95% CI 1.30-1.84) and anxiety disorders (IRR 1.30; 95% CI 1.12-1.51) were elevated in the IMID cohort as compared with the matched cohort. Similar results were obtained for each of the IBD, MS and RA cohorts. The incidence of bipolar disorder was elevated beginning 3 years before IMID diagnosis (IRR 1.63; 95% CI 1.10-2.40). | The incidence of psychiatric comorbidity is elevated in the IMID population as compared with a matched population as early as 5 years before diagnosis. Future studies should elucidate whether this reflects shared risk factors for psychiatric disorders and IMID, a shared final common inflammatory pathway or other aetiology. |
3,135 | 20,261 | To evaluate the incidence, prevalence, characteristics, disease associations, risk factors, and outcome of clinical enthesitis in patients with psoriatic arthritis (PsA).
The study included patients with PsA followed prospectively. Enthesitis was defined as the presence of at least 1 tender enthesis at 1 of the 18 entheseal sites of the Spondyloarthritis Research Consortium of Canada enthesitis index.
Between 2008 and 2014, 281 of 803 patients had enthesitis, providing a prevalence of 35%. A total of 192 patients developed enthesitis during the course of followup, with an annual incidence of 0.9%. Most of the patients had 1 (48.4%) or 2 (32.2%) tender entheseal sites, and the mean ± SD number of sites per visit was 2.03 ± 1.6. The 3 most common sites were at the insertions of the Achilles tendon, plantar fascia on the calcaneus, and the lateral epicondyles (24.2%, 20.8%, and 17.2%, respectively). More active disease (higher actively inflamed joint count, tenosynovitis, and dactylitis), more pain, and less clinical damage were associated with enthesitis. Higher body mass index, more actively inflamed joints, and younger age were risk factors for developing this condition. Enthesitis resolved in most patients without changing treatment. | Clinical enthesitis is common, with a period prevalence of 35% of PsA patients. It usually involves only 1 or 2 sites simultaneously. The most common tender sites are at the insertions of the Achilles tendon, plantar fascia, and the lateral epicondyles. More active disease and more pain are associated with enthesitis. |
3,136 | 60,656 | To evaluate the feasibility of the phase difference-based post-processing water-fat imaging method for fat suppression at low-field in imaging of arthritic joints.
Thirty joints (wrist, 10; elbow, 10; knee, 10) in 30 patients with rheumatoid arthritis were imaged using a 0.23T MRI unit. Contrast-enhanced T1-weighted (T1w) three-dimensional (3D) gradient-echo (GRE) images with and without fat suppression along with short inversion time inversion-recovery (STIR) images were evaluated by two radiologists. Contrast-enhanced T1w 3D GRE images and corresponding post-processed fat-suppressed images were scored for conspicuity and delineation of enhancing synovial hypertrophy. The uniformity of fat suppression was evaluated between T1w 3D GRE fat-suppressed images and STIR images, and general image quality was estimated for all of the three techniques by consensus. For a quantitative analysis, the enhancing synovial hypertrophy-to-fat contrast-to-noise (CNR) values for the T1W 3D GRE images with and without fat suppression were measured. For comparison, synovial bright signal-to-fat CNR values for the STIR images were measured.
The post-processing water-fat imaging technique for fat suppression was successfully applied in all examinations. Conspicuity and delineation of enhancing tissue were superior in fat-suppressed T1w 3D GRE images compared to non-fat-suppressed images (P < 0.0001). As expected, the enhancing synovial hypertrophy tissue-to-fat CNRs were significantly higher in fat-suppressed T1w 3D GRE images compared to non-fat-suppressed images (P < 0.0001). General image quality was assessed to be best in non-fat-suppressed images, and the difference was significant compared to fat-suppressed images (P < 0.05) and STIR images (P < 0.05). | The phase difference-based post-processing water-fat imaging technique for fat suppression can be successfully used at low-field, and it provides high-quality fat suppression images in imaging of arthritic joints. |
3,137 | 31,491 | To estimate the incremental cost-effectiveness of infliximab versus conventional combination treatment over 21 months in patients with methotrexate-refractory early rheumatoid arthritis.
In this multicentre, two-arm, parallel, randomised, active-controlled, open-label trial, rheumatoid arthritis patients with <1 year symptom duration were recruited from 15 rheumatology clinics in Sweden between October 2002 and December 2005. After 3-4 months of methotrexate monotherapy, patients not achieving low disease activity were randomised to addition of infliximab or sulfasalazine+hydroxychloroquine (conventional treatment group). Costs of drugs, healthcare use, and productivity losses were retrieved from nationwide registers, while EuroQol 5-Dimensions utility was collected quarterly.
Of 487 patients initially enrolled, 128 and 130 were randomised to infliximab and conventional treatment, respectively. The infliximab group accumulated higher drug and healthcare costs (€27,487 vs €10,364; adjusted mean difference €16,956 (95% CI 14,647 to 19,162)), while productivity losses did not differ (€33,804 vs €29,220; €3961 (95% CI -3986 to 11,850)), resulting in higher societal cost compared to the conventional group (€61,291 vs €39,584; €20,916 (95% CI 12,800 to 28,660)). Mean accumulated quality-adjusted life-years (QALYs) did not differ (1.10 vs 1.12; adjusted mean difference favouring infliximab treatment 0.01 (95% CI -0.07 to 0.08)). The incremental cost-effectiveness ratios for the infliximab versus conventional treatment strategy were €2,404,197/QALY from the societal perspective and €1,948,919/QALY from the healthcare perspective.
NCT00764725. | In early, methotrexate-refractory rheumatoid arthritis, a treatment strategy commencing with addition of infliximab, as compared to sulfasalazine+hydroxychloroquine, was not cost-effective over 21 months at willingness to pay levels generally considered acceptable. |
3,138 | 48,292 | Dysregulated Wnt signaling appears to modulate chondrocyte fate and joint disorders. Dickkopf-1 (DKK1) regulates the pathogenesis of skeletal tissue by inhibiting Wnt actions. This study examined whether DKK1 expression is linked to chondrocyte fate in osteoarthritis (OA).
Articular cartilage specimens harvested from nine patients with knee OA and from six controls with femoral neck fracture were assessed for DKK1, interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), Bad, Bax, Bcl2 and caspase-3 expression by real time-polymerase chain reaction (RT-PCR) and immunohistochemistry. Apoptotic chondrocytes were detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labelling (TUNEL) and 4', 6-dianidino-2-phenylindole dihydrochloride (DAPI) staining. Human chondrocyte cultures were treated with recombinant IL-1beta and monoclonal DKK1 antibody to determine whether DKK1 impairs chondrocyte survival.
Expression of DKK1 correlated with inflammatory cytokine levels (IL-1beta and TNF-alpha expressions), proapoptosis regulators (Bad and caspase-3 expressions) and TUNEL staining in OA cartilage tissues. The IL-1beta induced expressions of DKK1, Bax, Bad and caspase-3-dependent apoptosis of chondrocyte cultures. Neutralization of DKK1 by monoclonal DKK1 antibody significantly abrogated IL-1beta-mediated caspase-3 cleavage and apoptosis and reversed chondrocyte proliferation. Recombinant DKK1 treatment impaired chondrocyte growth and promoted apoptosis. By suppressing nuclear beta-catenin accumulation and Akt phosphorylation, DKK1 mediated IL-1beta promotion of chondrocyte apoptosis. | Chondrocyte apoptosis correlates with joint OA. Expression of DKK1 contributes to cartilage deterioration and is a potent factor in OA pathogenesis. Attenuating DKK1 may reduce cartilage deterioration in OA. |
3,139 | 51,340 | To estimate the population pharmacokinetics of low-dose methotrexate (MTX) in Japanese patients using nonmem, a computer program designed for analysing drug pharmacokinetics in study populations through pooling of data.
A total of 153 serum concentration measurements obtained from the 17 healthy volunteers and 17 patients with rheumatoid arthritis were collected. Analysis of the pharmacokinetics of MTX was accomplished using a two-compartment pharmacokinetic model with first-order absorption. The effect of a variety of developmental and demographic factors on MTX disposition was investigated.
The final pharmacokinetic parameters were CL/F (L/kg/h) = 0.177 x 0.394MULT, V1/F (L/kg) = 0.0501, Q/F (L/kg/h) = 0.056, V2/F (L/kg) = 0.368, ka (h-1) = 0.503, where CL is total body clearance, V1 and V2 is apparent volume of distribution in the central and peripheral compartments, k(a) is absorption rate constant, Q is intercompartmental clearance and MULT = 1 for patients received multiple dosing and zero otherwise. The interindividual variabilities in CL, Q and V1 were 25.7%, 22.3% and 217.9%, respectively, and the residual variability was 17.8% as a coefficient of variation. Because of the lake of information on data set we were unable to characterize the interindividual variability for V2 and ka. | Clinical application of the model to patient care may permit selection of an appropriate dosage to achieve target MTX concentrations, thus enabling the clinician to achieve the desired therapeutic effect in Japanese patients. However, the MTX dosage regimen for the individual patient should be based on a careful appraisal of their clinical need for the drug. |
3,140 | 23,748 | Unintentional weight loss is important and can be predictive of long-term outcomes in patients with rheumatoid arthritis (RA). This study was undertaken to assess how primary therapies for RA may influence changes in body mass index (BMI) in RA patients from a large administrative database.
Unique dispensing episodes of methotrexate, prednisone, leflunomide, and tumor necrosis factor inhibitors (TNFi) administered to RA patients were identified from the US Department of Veterans Affairs pharmacy databases. Values for C-reactive protein (CRP) level and BMI closest to the time point within 30 days of the treatment course start date and at follow-up time points were linked. Missing laboratory values were imputed. Weight loss was defined as a decrease in BMI of >1 kg/m(2) . Regression models were used to evaluate changes in BMI during each drug treatment as compared to treatment with methotrexate. To assess the impact of confounding by indication, propensity scores for use of each drug were incorporated in analyses using matched-weighting techniques.
In total, 52,662 treatment courses in 32,859 RA patients were identified. At 6 months from the date of prescription fill, weight gain was seen among patients taking methotrexate, those taking prednisone, and those taking TNFi. On average, compared to methotrexate-treated patients, prednisone-treated patients had significantly more weight gain, while leflunomide-treated patients demonstrated weight loss. In multivariable models, more weight loss (β = -0.41 kg/m(2) , 95% confidence interval [95% CI] -0.46, -0.36; P < 0.001) and a greater risk of weight loss (odds ratio 1.73, 95% CI 1.55, 1.79; P < 0.001) were evident among those receiving leflunomide compared to those receiving methotrexate. Treatment with prednisone was associated with greater weight gain (β = 0.072 kg/m(2) , 95% CI 0.042, 0.10; P < 0.001). These associations persisted in analyses adjusted for propensity scores and in sensitivity analyses. | Leflunomide is associated with significantly more, but modest, weight loss, while prednisone is associated with greater weight gain compared to other therapies for RA. |
3,141 | 13,574 | Primary Sjögren's syndrome (pSS) is a complex chronic systemic disorder, for which specific and effective therapeutic interventions are still lacking. In this era of precision medicine, there is a clear need for a better definition of disease phenotypes to foster the research of novel specific biomarkers and new therapeutic targets. The main objectives of this work are: 1) to compare Auto Contractive Map (AutoCM), a data mining tool based on an artificial neural network (ANN) versus conventional Principal Component Analysis (PCA) in discriminating different pSS subsets and 2) to specifically focus on variables predictive of MALT-NHL development, assessing the previsional gain of the predictive models developed.
Out of a historic cohort of 850 patients, we selected 542 cases of pSS fulfilling the AECG criteria 2002. Thirty-seven variables were analysed including: patient demographics, glandular symptoms, systemic features, biological abnormalities and MALT-NHLs. AutoCM was used to compute the association of strength of each variable with all other variables in the dataset. PCA was applied to the same data set.
Both PCA and AutoCM confirmed the associations between autoantibody positivity and several pSS clinical manifestations, highlighting the importance of serological biomarkers in pSS phenotyping. However, AutoCM allowed us to clearly distinguish pSS patients presenting with predominant glandular manifestations and no or mild extra-glandular features from those with a more severe clinical presentation. Out of 542 patients, we had 27 cases of MALT-NHLs. The AutoCM highlighted that, besides other traditional lymphoproliferative risk factors (i.e. salivary gland enlargement, low C4, leukocytopenia, cryoglobulins, monoclonal gammopathy, disease duration), rheumatoid factor was strongly associated to MALT-NHLs development. By applying data mining analysis, we obtained a predictive model characterised by a sensitivity of 92.5% and a specificity of 98%. If we restricted the analysis to the seven most significant variables, the sensitivity of the model was 96.2% and its specificity 96%. | Our study has shed new light on the possibility of using novel tools to extract hidden, previously unknown and potentially useful information in complex diseases like pSS, facing the challenge of disease phenotyping as a prerequisite for discovering novel specific biomarkers and new therapeutic targets. |
3,142 | 34,447 | Earlier studies have found a positive effect of alcohol consumption, with a reduced disease activity in rheumatoid arthritis (RA). The aim of this study was to assess alcohol consumption and its association with disease activity and health related quality of life (HRQL) in Swedish RA patients.
Between 1992 and 2005, 2,800 adult patients were included in the BARFOT study of early RA in Sweden. In 2010 a self-completion postal questionnaire was sent to all 2,102 prevalent patients in the BARFOT study enquiring about disease severity, HRQL, and lifestyle factors. Alcohol consumption was assessed using the validated AUDIT-C questionnaire.
A total of 1,238 out of 1,460 patients answering the questionnaire had data on alcohol consumption: 11% were non-drinkers, 67% had a non-hazardous drinking, and 21% were classified as hazardous drinkers. Women who drank alcohol reported lower disease activity and better HRQL, but there were no association between alcohol consumption and disease activity in men. For current smokers, alcohol use was only associated with fewer patient-reported swollen joints. The outcome was not affected by kind of alcohol consumed. | There was an association between alcohol consumption and both lower self-reported disease activity and higher HRQL in female, but not in male, RA patients. |
3,143 | 57,976 | Multiple independent juvenile oligoarthritis susceptibility loci have been identified within the major histocompatibility complex (MHC), including HLA-A, HLA-DRB1 and an as yet unlocalized effect in the centromeric class I region. The discoidin domain receptor 1 (DDR1) gene resides within this region and codes for a receptor tyrosine kinase that plays an important role in regulating cell attachment to collagen, chemotaxis, proliferation and matrix metalloproteinase (MMP) production. DDR1 expression in chondrocytes has not been investigated. The objectives of this study were to investigate expression of DDR1 in healthy chondrocytes and to identify linkage and association of this candidate gene with juvenile oligoarthritis.
A set of 135 simplex juvenile idiopathic arthritis families consisting of one affected child and healthy parent(s) and 199 healthy unrelated individuals were genotyped for six single nucleotide polymorphisms (SNPs) within the DDR1 gene using the primer extension SNaPshot trade mark method. Single-point and multipoint transmission disequilibrium tests were carried out with the ETDT and TDTPHASE packages. Allele frequency comparisons between cases and controls were carried out with the chi(2) test. DDR1 expression was investigated in normal articular cartilage by RT-PCR and immunofluorescence methods.
No linkage and association with any of the six SNPs or their haplotypic combinations were observed in the families studied. No significant differences were observed in allele frequencies between patients and controls. DDR1 expression was found in normal articular cartilage by RT-PCR and by immunofluorescence. | The DDR1 SNPs examined are not involved in susceptibility to juvenile oligoarthritis. |
3,144 | 63,809 | To investigate the pathogenic role of macrophage lineage (CD68+) cells in synovial proliferation in patients with human T cell leukemia virus I (HTLV-I) associated arthropathy (HAAP).
Synovial tissues obtained from 3 patients with HAAP and 3 patients with osteoarthritis (OA) were examined for the expression of tumor necrosis factor-alpha (TNF-alpha) mRNA, HTLV-I tax/rex mRNA, and number of CD68 by in situ reverse transcription assay and immunohistochemistry. Western blot and flow cytometric analyses were used to determine TNF-alpha production in HTLV-I infected synoviocytes. Changes in CD68+ cell population were examined by flow cytometric analysis. Proliferative effects of supernatants of HTLV-I infected synoviocytes on normal synoviocytes were also determined.
TNF-alpha and HTLV-I tax/rex mRNA were preferentially expressed in CD68+ cells in HAAP synovia. Infection of OA synoviocytes by HTLV-I resulted in preferential expression in CD68+ cells, and these cells produced TNF-alpha. Supernatants of HTLV-I infected synoviocytes significantly enhanced the proliferation of normal synoviocytes through a TNF-alpha dependent pathway. | Our results suggest HTLV-I viral tropism for CD68+ cells, and that HTLV-I infected synoviocytes were induced to produce TNF-alpha, which enhances synovial proliferation in HAAP. |
3,145 | 65,490 | To assess the contribution of radiological osteoarthritis of the hips and knees to disabilities in the activities of daily living related to lower limb function.
During a home interview 1156 men and 1739 women, randomly chosen from the source population of all independently living residents aged 55 years and over living in a district of Rotterdam (the Rotterdam Study) were asked about locomotor disability by six questions of the Health Assessment Questionnaire (HAQ) and about pain in the hips and knees in the past month. Radiographs of hips and knees were scored according to the Kellgren grading system for osteoarthritis.
The prevalence of locomotor disability, defined as at least some difficulty with three or more out of six lower limb functions, was 20.2% for men and 31.9% for women; hip pain was present in 8.3% of the men and 16.6% of the women; knee pain in 12.6% of the men and 22.3% of the women. The prevalence of radiological osteoarthritis grade 2+ of the hip was 14.1% for men and 15.9% for women, and of the knee 16.3% and 29.1% respectively. The odds ratio (OR) (95% confidence intervals) of hip radiological osteoarthritis for locomotor disability adjusted for age and all other variables was for men: 1.4 (0.9, 2.1) and for women: 2.2 (1.6, 2.9). The ORs of knee radiological osteoarthritis adjusted for age and all other variables were 1.1 (0.9, 2.1) and 1.4 (1.1, 1.8) respectively. Severe radiological osteoarthritis (grade 3+) was stronger associated. The ORs of pain in the hips or knees and morning stiffness were much higher (between 2.7 and 5.5 for men and between 2.1 and 5.1 for women). | Radiological osteoarthritis of the hip and knee are only weak independent predictors of locomotor disability in women, and not at all independently associated with locomotor disability in men. Age, pain of the hips and knees, and morning stiffness seem to be the most important independent determinants of locomotor disability. |
3,146 | 68,330 | As disturbed nociception may be relevant to the pathogenesis of fibromyalgia, nonnoxious electrocutaneous stimulation was used as a tool to investigate nociceptive status.
Perception threshold and pain tolerance were studied in the upper limbs of 10 patients with fibromyalgia and 10 healthy volunteers.
Perception threshold did not differ between the groups but the marked reduction in pain tolerance found in patients with fibromyalgia was accompanied by spread and persistence of dysesthesiae. | The upper limbs of patients with fibromyalgia resembled regions of secondary hyperalgesia, which may imply that perturbation of central nociceptive mechanisms is involved in the pathogenesis of this syndrome. |
3,147 | 32,776 | The purposes of this study were to assess the presence of cam and pincer morphology in asymptomatic individuals with a negative femoroacetabular impingement test, and to determine and compare the ranges of alpha angle using two measurement methods.
In total, 68 consecutive patients who underwent abdominopelvic computed tomography (CT) for reasons other than hip problems were the patient population. Patients who had a positive femoroacetabular impingement test were excluded. Alpha angle measurements from axial oblique (AN) and radial reformat-based images (AR) from the anterior through the superior portion of the femoral head-neck junction, as well as femoral head-neck offset, center-edge angle, acetabular version angle measurements, and acetabular crossover sign assessment, were made.
Overall prevalences of cam (increased alpha angle, decreased femoral head-neck offset) and pincer morphology (increased center-edge angle, decreased acetabular version) were 20.0%, 26.8%, 25.8%, and 10.2% of the hips, respectively. The mean AR ranged from 41.64° ± 4.23° to 48.13° ± 4.63°, whereas AN was 41.10° ± 4.44°. The values of AR were higher than AN, and the difference was statistically significant (P <0.001). The highest AR values were measured on images from the anterosuperior section of femoral head-neck junction. | In asymptomatic subjects, higher alpha angle values were obtained from radial reformatted images, specifically from the anterosuperior portion of the femoral head-neck junction compared with the axial oblique CT images. Other measurements used for the assessment of cam and pincer morphology can also be beyond the ranges that are considered normal in the general population. |
3,148 | 40,711 | To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States.
This international, multicenter, double-blind, placebo-controlled trial randomly assigned 747 patients with FM to placebo or 300, 450, or 600 mg/day pregabalin twice daily for 14 weeks. Primary efficacy measures were endpoint mean pain scores and Patient Global Impression of Change (PGIC). Secondary outcomes included assessments of sleep and function.
Patients in the 450 mg/day pregabalin group showed significant improvements versus placebo in endpoint mean pain score (-0.56; p = 0.0132), PGIC (73% improved vs 56% placebo; p = 0.0017), and function [Fibromyalgia Impact Questionnaire (FIQ) total score -5.85; p = 0.0012]. PGIC was also significant for 600 mg/day pregabalin (69% improved; p = 0.0227). Results for these endpoints were nonsignificant for pregabalin at 300 mg/day and for pain and FIQ score at 600 mg/day. Early onset of pain relief was seen, with separation from placebo detected by Week 1 in all pregabalin groups. All pregabalin doses demonstrated superiority to placebo on the Medical Outcomes Study-Sleep Scale Sleep Disturbance subscale and the Sleep Quality diary. Dizziness and somnolence were the most frequently reported adverse events. | Pregabalin demonstrated modest efficacy in pain, global assessment, and function in FM at 450 mg/day, and improved sleep across all dose levels, but it did not provide consistent evidence of benefit at 300 and 600 mg/day in this study. Pregabalin was generally well tolerated for the treatment of FM. (Clinical trial registry NCT00333866). |
3,149 | 67,717 | Bone sialoprotein (BSP) was quantified in synovial fluids and sera from rheumatoid arthritis (RA) patients to elucidate whether its release from bone relates to the degree of joint tissue destruction. Osteocalcin was assayed for comparison.
BSP and osteocalcin levels were determined by immunoassays of knee synovial fluids and of sera from RA patients who were selected on the basis of radiographic knee joint tissue damage.
Synovial fluid concentrations of BSP increased with increasing degrees of knee joint damage (rs = 0.6848, P < 0.001). Synovial fluid concentrations of osteocalcin did not relate to the degree of joint damage. Serum concentrations of BSP were increased, but did not relate to the degree of joint damage. Serum concentrations of osteocalcin were normal, but increased within the range of normal during progression of joint destruction (rs = 0.4567, P < 0.001). | Quantification of BSP in synovial fluid holds promise as a useful means of assessing the degree of tissue damage at the molecular level in patients with RA. |
3,150 | 8,432 | To examine medication satisfaction and adherence and their relationships to disease variables and health-related quality of life (HRQoL) in adults with juvenile idiopathic arthritis (JIA).
Patients (n = 96, mean age 25 years, 67% female) completed questionnaires about their health status 19 years after disease onset. Patients receiving biologic disease-modifying antirheumatic drugs (bDMARDs) or methotrexate (MTX) were assessed with the 8-item Morisky Medication Adherence Scale (MMAS-8) and the Treatment Satisfaction Questionnaire for Medication (TSQM), including dimensions of effectiveness, side effects, convenience, and global satisfaction.
DMARDs were received by 52 patients (54%) (mean age 25 years, 75% female), of which 28 received MTX and 37 received bDMARDs. Patients receiving combination therapy of MTX and bDMARDs (n = 15) reported higher satisfaction with bDMARDs than MTX in the dimensions of side effects and global satisfaction (mean ± SD 92.9 ± 15.5 versus 56.2 ± 30.9, and mean ± SD 67.6 ± 19.8 versus 47.1 ± 21.7; P < 0.001 and P = 0.016, respectively). Patients receiving either bDMARDs (n = 22) or MTX (n = 13) reported higher satisfaction with bDMARDs than MTX for the dimensions of effectiveness and global satisfaction (mean ± SD 78.7 ± 15.4 versus 60.2 ± 19.9, and mean ± SD 73.6 ± 17.7 versus 52.3 ± 23.9; P = 0.004 and P = 0.005, respectively). Nearly one-half of patients (46%) reported low adherence (MMAS-8 score <6) and 25% high adherence (MMAS-8 score = 8). Higher levels of pain, psychological distress, more active joints, and current MTX use were the strongest correlates of lower medication satisfaction. Perceived medication effectiveness and global satisfaction correlated positively with physical and mental HRQoL. | Patients with JIA were more satisfied with bDMARDs than MTX, and 46% reported low adherence. Higher medication satisfaction was associated with better HRQoL. |
3,151 | 32,939 | Health-related utility measures overall health status and quality of life and is commonly incorporated into cost-effectiveness analyses. This study investigates whether attainment of federal physical activity guidelines translates into better health-related utility in adults with or at risk for knee osteoarthritis (OA).
Cross-sectional data from 1,908 adults with or at risk for knee OA participating in the accelerometer ancillary study of the Osteoarthritis Initiative were assessed. Physical activity was measured using 7 days of accelerometer monitoring and was classified as 1) meeting guidelines (≥150 bouted moderate-to-vigorous [MV] minutes per week); 2) insufficiently active (≥1 MV bout[s] per week but below guidelines); or 3) inactive (zero MV bouts per week). A Short Form 6D health-related utility score was derived from patient-reported health status. Relationship of physical activity levels to median health-related utility adjusted for socioeconomic and health factors was tested using quantile regression.
Only 13% of participants met physical activity guidelines, and 45% were inactive. Relative to the inactive group, median health-related utility scores were significantly greater for the meeting guidelines group (0.063; 95% confidence interval [95% CI] 0.055, 0.071) and the insufficiently active group (0.059; 95% CI 0.054, 0.064). These differences showed a statistically significant linear trend and strong cross-sectional relationship with physical activity level even after adjusting for socioeconomic and health factors. | We found a significant positive relationship between physical activity level and health-related utility. Interventions that encourage adults, including persons with knee OA, to increase physical activity even if recommended levels are not attained may improve their quality of life. |
3,152 | 34,740 | Rheumatologic diseases may cause neurologic disorders that mimic multiple sclerosis (MS). A panel of serum autoantibodies is often obtained as part of the evaluation of patients suspected of having MS.
To determine, in light of recently revised diagnostic criteria for MS, neuromyelitis optica, and Sjogren's Syndrome, if testing for autoantibodies in patients with a confirmed diagnosis of MS would reveal a frequency or demonstrate a clinical utility divergent from previous reports or lead to identification of undiagnosed cases of Sjogren's Syndrome.
Convenience sample cross-sectional study of MS patients recruited from the OHSU Multiple Sclerosis Center.
Autoantibodies were detected in 38% (35/91) of patients with MS and were not significantly associated with disease characteristics or severity. While four patients had SSA antibodies, none met diagnostic criteria for Sjogren's Syndrome. | Rheumatologic autoantibodies are frequently found in MS patients and are not associated with disease severity or systemic rheumatologic disease. Our demonstration of the low specificity of these autoantibodies suggests that the diagnostic utility and cost-effectiveness of testing is not supported when there is strong clinical suspicion of MS and low clinical suspicion of rheumatologic disease. |
3,153 | 8,882 | Narrow femoral implants were developed to improve fit and prevent overhang in primary total knee arthroplasty (TKA). We compared intraoperative soft tissue balance between standard and narrow implants in posterior-stabilized (PS) TKA.
We enrolled 30 consecutive patients with varus osteoarthritis undergoing PS TKA using an image-free navigation system. Standard and narrow femoral trial implants were inserted, and their soft tissue balance was measured. Subgroup analysis, based on the actual implanted femoral implant, was performed to assess the influence of narrow implants on soft tissue balance.
Narrow trial group had significantly larger joint component gaps than standard trial group at all measured flexion angles, except at 60° (P < .05). For the standard implant cohort, narrow trial group had significantly larger joint component gaps than standard trial group at 30°, 120°, and 135° flexion (P < .05). For the narrow implant cohort, narrow trial group had significantly larger joint component gaps than standard trial group at all measured flexion angles, except at 0° and 60° (P < .05). Narrow trial group had significantly larger varus ligament balance than standard trial group at 45° and 60° flexion (P < .05). The varus angles for standard implants were comparable between groups; however, narrow trial group had significantly larger varus angles for narrow implants than standard trial group at 45°, 60°, and 120° flexion (P < .05). | The medial-lateral dimension and volume of the femoral component may influence intraoperative soft tissue balance in PS TKA. The effects may be greater when narrow implants are selected to avoid component overhang. |
3,154 | 57,624 | To evaluate the gastrointestinal safety and efficacy of the COX inhibiting nitric oxide donator AZD3582 in patients with hip or knee osteoarthritis.
970 patients were randomised (7:7:2) to AZD3582 750 mg twice daily, naproxen 500 mg twice daily, or placebo twice daily in a double blind study. The primary end point was the six week incidence of endoscopic gastroduodenal ulcers (diameter > or =3 mm). Overall damage measured on the Lanza scale was a secondary end point. Safety and tolerability assessments included endoscopic upper gastrointestinal erosions and the gastrointestinal symptom rating scale (GSRS). Efficacy was primarily assessed by WOMAC.
The incidence of ulcers with AZD3582 was 9.7% and with naproxen 13.7% (p = 0.07, NS), v 0% on placebo. The incidence of Lanza scores >2 was higher with naproxen (43.7%) than with AZD3582 (32.2%) (p<0.001). Compared with baseline, significantly fewer ulcers and erosions developed in stomach and stomach/duodenum combined, and fewer erosions developed in stomach, duodenum, and both combined on AZD3582 than on naproxen. GSRS reflux and abdominal pain subscale scores were lower for AZD3582 than for naproxen but there was no difference for indigestion, constipation, and diarrhoea. AZD3582 was as effective as naproxen at improving WOMAC scores. Both agents were well tolerated, with no significant effects on blood pressure. | At doses with similar efficacy in relieving osteoarthritis symptoms, the primary end point of six week endoscopic gastroduodenal ulcer incidence was not significantly different between AZD3582 and naproxen. Most secondary endoscopic gastrointestinal end points favoured AZD3582. |
3,155 | 44,048 | Juvenile idiopathic arthritis (JIA) is the most common chronic pediatric rheumatic disease and can have long-term effects leading to disability in adulthood. Biologics are a new class of drugs increasingly used to treat JIA. The primary study objective was to determine the incremental costs of biologics per additional responder compared to conventional treatment (methotrexate).
A separate decision model was created for etanercept, infliximab, adalimumab, and abatacept. The study population consisted of polyarticular-course JIA patients with a prior inadequate response or intolerance to disease-modifying antirheumatic drugs (DMARDs). The effectiveness measure was the proportion of patients who had a treatment response at 1 year according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) improvement criteria. Direct and indirect costs were calculated in 2008 Canadian dollars. Incremental cost-effectiveness ratios and 95% confidence intervals (95% CIs) were calculated for each biologic agent using probabilistic sensitivity analyses.
The additional costs per additional ACR Pedi 30 responder at 1 year were $26,061 (95% CI $17,070, $41,834), $46,711 (95% CI $30,042, $75,787), $16,204 (95% CI $11,393, $22,608), and $31,209 (95% CI $16,659, $66,220) for etanercept, adalimumab, abatacept, and infliximab, respectively. | Biologics are more effective than methotrexate in achieving a short-term response in JIA patients with prior inadequate responses to DMARDs; however, this comes at a high annual cost. Adequate long-term data with respect to both safety and effectiveness are not currently available, nor are utility estimates. Such data will be important to estimate value for money for treating JIA with biologic drugs over the long term. |
3,156 | 1,875 | While considered a satisfactory solution, unicompartmental knee arthroplasty (UKA) still raises concerns in regard to its durability. These concerns particularly focus on the tibial component. This study aims to compare two different cemented tibial components belonging to the same UKA design: all polyethylene (AP) versus metal backed (MB), at a long-term follow-up.
We retrospectively reviewed 143 successive patients, 83 of which underwent surgery with AP tibial component UKA (37 males, 46 females), and 67 with MB ones (17 males, 50 females). All implants had the same prosthetic design (Accuris UKA, Smith e Nephew) with identical femoral oxinium component but different tibial component, AP or MB. The KSS and KOOS were assessed at a mean of 11.5-year follow-up and compared to pre-operative, post-operative, and one year evaluation. Statistical analysis was performed with SPSS for Mac (version 17.0). To assess potential statistically significant differences, t test was used and significance was set at P < 0.05.
Final KSS at a mean of 11.5-year follow-up was 94.27 for the AP group and 96.12 for the MB ones. The final KOOS was 87 for AP components and 89.67 for the MB group. These results demonstrated, in all cases, statistically significant better results for MB tibial components compared to AP regarding KSS (P = 0.048), KOOS (P = 0.000), and pain (P = 0.014) at the 11.5-year follow-up. Survivorship for AP tibial component implants was 97.6%, while it was 89.5% for MB ones. | While the survivorship rate has been found to be greater for AP implants compared to MB tibial components, this study reveals statistically better functional results according to KSS and KOOS, and pain, at a long-term follow-up for MB implants. |
3,157 | 54,097 | To examine the economic burden of illness of gout in an employed population, quantifying the impact on employers annual health benefit costs for medical and prescription claims, sick leave, short- and long-term disability, and workers' compensation.
Adjudicated claims data from 300000 employees from 2001 through 2004 were utilized. T-tests were used to compare demographic data and medical costs and services by Agency for Healthcare Research and Quality (AHRQ) diagnostic categories. Two-part models were used to determine average annual health benefit costs overall and medical costs by place of delivery. A risk stratification quintile analysis was also performed utilizing gout-specific medical and pharmaceutical costs.
There were 1171 employees with gout identified (total n = 249 038). All demographic variables between the two groups were statistically different (p <or= 0.05). The total annual cost for the employee with gout versus without gout was $6870 versus $3705, respectively, with significantly higher costs for medical claims, prescription claims, sick leave, short-term disability, and workers' compensation benefits. Costs were significantly higher by location of service for office, outpatient hospital or clinic, inpatient hospital, and laboratory. For the gout cohort, the top major diagnostic category in average cost was 'circulatory system' and in average services was 'endocrine, nutritional, metabolic, and immunologic systems'. Only 0.9% of employees with gout generated 20% of the total gout-specific medical and prescription costs. | Gout inflicts a substantial burden of illness upon employers in terms of medical and prescription costs, as well as other work-related benefits. |
3,158 | 19,855 | To compare the efficacy of abatacept to that of placebo for the treatment of Takayasu arteritis (TAK).
In this multicenter trial, patients with newly diagnosed or relapsing TAK were treated with abatacept 10 mg/kg intravenously on days 1, 15, and 29 and week 8, together with prednisone administered daily. At week 12, patients in remission underwent a double-blinded randomization to continue to receive abatacept monthly or switch to placebo. Patients in both study arms received a standardized prednisone taper, reaching a dosage of 20 mg daily at week 12, with discontinuation of prednisone at week 28. All patients remained on their randomized assignment until meeting criteria for early termination or until 12 months after enrollment of the last patient. The primary end point was duration of remission (relapse-free survival).
Thirty-four eligible patients with TAK were enrolled and treated with prednisone and abatacept; of these, 26 reached the week 12 randomization and underwent a blinded randomization to receive either abatacept or placebo. The relapse-free survival rate at 12 months was 22% for those receiving abatacept and 40% for those receiving placebo (P = 0.853). Treatment with abatacept in patients with TAK enrolled in this study was not associated with a longer median duration of remission (median duration 5.5 months for abatacept versus 5.7 months for placebo). There was no difference in the frequency or severity of adverse events, including infection, between the treatment arms. | In patients with TAK, the addition of abatacept to a treatment regimen with prednisone did not reduce the risk of relapse. |
3,159 | 61,793 | To analyse the treatment response to etanercept in patients with polyarticular course juvenile idiopathic arthritis (JIA).
22 patients with polyarticular course JIA (19 females, three males; mean age 13.9 years; mean disease duration 6.3 years; 15 with polyarticular onset, seven with systemic onset, one with residual systemic activity; eight rheumatoid factor positive; eight with erosive disease) were treated with etanercept for up to 24 months. Etanercept was given subcutaneously at 0.4 mg/kg twice a week. Treatment response was ascertained in an open prospective study.
All patients showed impressive clinical improvement, with a decrease in swollen joint count by an average of 10.1 joints (mean of 49% decrease), a decrease in tender joint count by 9.3 joints (mean of 94%), and decrease in total joint count by 11.2 joints (mean of 48%). Duration of morning stiffness decreased to less than 10 minutes. Furthermore, haemoglobin concentration increased on average by 14 g/l (mean of 15.3%) and packed cell volume increased by 0.035 (mean increase of 12%), and erythrocyte sedimentation rate decreased on average by 42.8 mm/1st h (mean decrease of 64%). No major side effects were noted. | Etanercept continues to be clinically effective and well tolerated in patients with polyarticular course JIA over a two year period. |
3,160 | 35,628 | To reduce fusion nonunion, autogenous bone graft is often incorporated into foot and ankle fusion procedures. B2A peptide-coated ceramic granules, with encouraging results in pilot studies of transforaminal lumbar interbody fusion, were here reformulated into Amplex with a coating concentration of 225 μg B2A/cm(3) ceramic granules (B2A-granule) with the goal of eliminating autogenous bone graft in foot and ankle arthrodesis. The purpose of this study was to perform a multicenter prospective randomized pilot clinical trial designed to compare the safety and effectiveness of B2A-granule to autogenous bone graft in patients undergoing foot and ankle arthrodesis surgery.
This study was a multicenter, prospective, randomized, pilot clinical trial designed to compare safety and effectiveness of B2A-granule to autogenous bone graft in patients undergoing foot and ankle arthrodesis surgery. Twenty-four patients were enrolled and randomized (1:1) into 2 groups: autogenous bone graft control and B2A-granule. Primary outcome measures at 6 months (with follow-up at 9 and 12 months) included radiographic fusion assessed by computerized tomography and Ankle Osteoarthritis Scale scores for pain and disability.
Radiographic fusion success rates were similar in both groups (100% in the B2A-granule group, 92% autograft). Both the B2A-granule group and the autograft group had improvements in the pain and disability scores over the course of the study. Graft harvest-site pain affected only autograft-treated patients. There were no adverse events attributed to the graft material in either the B2A-granule or autograft group.
Level II, prospective comparative study. | The results of this pilot study are supportive of a larger clinical trial to assess the safety and efficacy of B2A-granule as a bone graft substitute in foot and ankle fusions. |
3,161 | 32,914 | This study aimed to quantify and compare conjunctival epithelial tumor necrosis factor (NF) α mRNA expression in Sjögren syndrome (SS), non-Sjögren syndrome aqueous-deficient dry eye (non-SS DE), and non-dry eye (NDE) control subjects.
A total of 76 subjects were recruited for this study: 25 SS (confirmed via American-European Consensus Criteria 2002), 25 non-SS DE (confirmed by symptoms and Schirmer scores ≤ 10 mm), and 26 NDE. Superior and temporal bulbar conjunctival epithelial cells were collected via impression cytology. Epithelial RNA was extracted, and TNF-α mRNA expression was quantified by real-time quantitative polymerase chain reaction.
The expression of TNF-α mRNA was found to be significantly higher in the SS group (2.48 ± 1.79) compared to both non-SS DE (0.95 ± 1.18; p < 0.05) and NDE (0.84 ± 0.51; p < 0.05) groups. No difference in TNF-α mRNA expression was found between the non-SS DE and NDE groups (p = 0.67). | These results demonstrate that SS-associated aqueous-deficient dry eye is associated with a significant upregulation of conjunctival epithelial TNF-α mRNA relative to both non-SS DE and control groups. The degree to which TNF-α mRNA is upregulated in SS may contribute to the severe ocular surface damage observed in these patients. |
3,162 | 25,157 | Cardiac events are a major cause of death in patients with idiopathic inflammatory myopathies. The study objective was in a controlled setting to describe cardiac abnormalities by noninvasive methods in a cohort of patients with polymyositis (PM) or dermatomyositis (DM) and to identify predictors for cardiac dysfunction.
In a cross-sectional study, 76 patients with PM/DM and 48 matched healthy controls (HCs) were assessed by serum levels of cardiac troponin I, electrocardiography, Holter monitoring, echocardiography with tissue Doppler imaging, and quantitative cardiac (99m) Tc-pyrophosphate ((99m) Tc-PYP) scintigraphy.
Compared to HCs, patients with PM/DM more frequently had left ventricular diastolic dysfunction (LVDD) (12% versus 0%; P = 0.02) and longer QRS and QT intervals (P = 0.007 and P < 0.0001, respectively). In multivariate analysis, factors associated with LVDD were age (P = 0.001), disease duration (P = 0.004), presence of myositis-specific or -associated autoantibodies (P = 0.05), and high cardiac (99m) Tc-PYP uptake (P = 0.006). In multivariate analysis of the pooled data for patients and HCs, a diagnosis of PM/DM (P < 0.0001) was associated with LVDD. | Patients with PM or DM had an increased prevalence of cardiac abnormalities compared to HCs. LVDD was a common occurrence in PM/DM patients and correlated to disease duration. In addition, the association of LVDD with myositis-specific or -associated autoantibodies and high cardiac (99m) Tc-PYP uptake supports the notion of underlying autoimmunity and myocardial inflammation in patients with PM/DM. |
3,163 | 65,247 | To distinguish potential autoimmune and nonautoimmune mechanisms underlying the salivary gland inflammation seen in Sjögren's syndrome and normal aging.
Immunohistochemical studies were conducted on the lacrimal and salivary glands of 2- and 5-month-old C3H.MRL-Faslpr autoimmune strain mice and age-matched C3H/HeJ nonautoimmune controls.
Glandular inflammatory foci, interstitial areas, and vasculature were stained for immunoglobulin G (IgG), immunoglobulin A (IgA), and complement to determine differences in their local immune parameter. Differences between the two strains were compared for immune changes attributable to autoimmune disease and between the two normal groups for normal aging changes.
Greater staining of IgG, IgA, and complement occurred in the inflammatory foci and interstitial areas of 5-month-old C3H.MRL-Faslpr lacrimal and submandibular glands compared with 5-month-old controls. Normal mice showed some increased immunoglobulin staining with aging, but little or no complement in any glands. | These differential findings suggest that the systemic autoimmune disease plays a more direct role in focal glandular inflammation in Sjögren's syndrome, whereas less severe immune mechanisms are involved in the inflammation of normal glands. |
3,164 | 52,680 | Acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) is increasingly recognized as a relatively common and highly morbid clinical event. However, clinical data on AE in non-IPF interstitial pneumonia are sparse. This study was performed to find the frequency, clinical features, and outcome of AE in non-IPF interstitial pneumonia.
Retrospective analysis of 10 patients who satisfied the modified Akira criteria for AE during follow-up of 74 patients with surgical lung biopsy-confirmed idiopathic nonspecific interstitial pneumonia (I-NSIP) and 93 patients with biopsy-confirmed interstitial pneumonia associated with collagen vascular disease (CVD-IP).
AE occurred in six patients with I-NSIP (1-year frequency, 4.2%) and in four patients with CVD-IP (rheumatoid arthritis [RA], n = 3; scleroderma, n = 1), with 1-year frequency of 3.3%. Median age was 58 years (range, 47 to 75); six patients were female. AE occurred in two patients immediately after surgical biopsy. Median duration of acute symptom before hospital admission was 10 days (range, 1 to 30). Median ratio of Pao(2) to the fraction of inspired oxygen (Fio(2)) was 172 (range, 107 to 273), and Pao(2)/Fio(2) ratio was < 200 in six patients. Surgical lung biopsy performed at the time of AE in two patients revealed diffuse alveolar damage superimposed on nonspecific interstitial pneumonia pattern. Four patients with I-NSIP survived to discharge and were followed up for 24 months (range, 6 to 121). | AE occurred in the patients with I-NSIP with apparently better prognosis. In patients with CVD-IP, AE occurred mostly with RA-usual interstitial pneumonia in our small series with poor outcome. |
3,165 | 41,023 | To investigate the role of hepcidin as an inducer of anemia of inflammation in patients with rheumatoid arthritis (RA), and its correlation to coronary artery atherosclerosis.
Our study included 60 patients with RA and 20 healthy controls. Anemic RA patients with serum transferrin receptors/log ferritin (sTfR-F) index value < 1.5 were classified as having pure anemia of chronic disease (ACD), and patients with sTfR-F index value > 1.5 were classified as having anemia of chronic disease with coexistent iron deficiency anemia (ACD+IDA). Measurements were taken for Disease Activity Score for 28 joints (DAS28), Modified Health Assessment Questionnaire (MHAQ), erythrocyte sedimentation rate (ESR), high sensitivity C-reactive protein (hsCRP), rheumatoid factor (RF), lipid profile, serum interleukin 6 (IL-6), tumor necrosis factor-α, iron studies, and serum hepcidin. Coronary calcium score (CCS) was measured using multislice spiral computed tomography as a marker of atherosclerosis.
Serum hepcidin was found to be higher in anemic patients with RA than in controls (p < 0.001), and higher in the pure ACD subgroup than in the ACD+IDA subgroup (p < 0.001). Hepcidin concentration was positively correlated with disease duration, ESR, hsCRP, RF, DAS28, MHAQ, serum ferritin, IL-6, and mean CCS and inversely correlated with hemoglobin, sTfR, and the sTfR-F index. | Hepcidin can be considered a key inducer of anemia of inflammation in patients with RA. This inflammation was proved to be directly linked to coronary artery atherosclerosis. The correlations between serum hepcidin with disease activity and IL-6 raise the possibility of using it as a surrogate marker for disease activity. |
3,166 | 20,181 | To evaluate the clinical outcome in 108 total knee arthroplasty (TKA) patients with a medial-lateral balanced versus unbalanced gap after a mean follow-up of 34 months.
64 women and 44 men (mean age, 69.5 years) underwent computer-assisted TKA for osteoarthritis using a cemented fixed-bearing cruciate-retaining prosthesis. The medial-lateral gap difference (measured with the prosthesis in situ and the patella reduced) was balanced (≤2 mm) in 81 patients and unbalanced (>2 mm) in 27 patients. After a mean follow-up of 34 months, patients were assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire for pain, stiffness, and physical function. Scores were normalised to 0% (worst) to 100% (best).
The balanced and unbalanced gap groups were comparable in terms of age, severity of osteoarthritis, and proportion of pre- and post-operative mechanical alignment. Compared with the balanced gap group, the unbalanced gap group had a larger medial-lateral extension gap difference (0.75±0.57 vs. 2.02±1.15 mm, p=0.001) and medial-lateral flexion gap difference (0.79±0.63 vs. 2.98±2.13 mm, p=0.001) and lower normalised total WOMAC score (84.9±18 vs. 74.8±20.8, p=0.017). | WOMAC score is better in TKAs with a medial-lateral balanced (<2 mm) gap. |
3,167 | 18,380 | To update our earlier systematic reviews which evaluated all published randomized controlled trials (RCTs) evaluating pharmacological and non-pharmacological therapies in patients with hand osteoarthritis (OA). Surgical therapies were not evaluated.
RCTs published between March 2008 and December 2015 were added to the previous systematic reviews.
A total of 95 RCTs evaluating various pharmacological and non-pharmacological therapies in hand OA were analyzed in this update. Generally, the methodological quality of these RCTs has improved since the last update, with more studies describing their methods for randomization, blinding, and allocation concealment. However, RCTs continue to be weakened by a lack of consistent case definition and a lack of standardized outcome assessments specific to hand OA. The number and location of evaluated hand joints continues to be underreported, and only 25% of RCTs adequately described the method used to ensure allocation concealment. These remain major weaknesses of published RCTs. A meta-analysis could not be performed because of marked study heterogeneity, insufficient statistical data available in the published RCTs, and a small number of identical comparators. | Hand OA is a complex area in which to study the efficacy of therapies. There has been an improvement in the overall design and conduct of RCTs, however, additional large RCTs with a more robust methodological approach specific to hand OA are needed in order to make clinically relevant conclusions about the efficacy of the diverse treatment options available. |
3,168 | 50,465 | Increased wait times for total joint arthroplasty (TJA) are a concern nationally and provincially. Additionally, the number of patients requiring revision of their initial TJA is increasing. The purpose of this study was to evaluate the wait times and impact of waiting for revision TJA.
We followed 127 revision hip arthroplasty patients (mean age 68 y) prospectively while they waited for surgery. We collected Western Ontario and McMaster Universities Osteoarthritis Index (pain, stiffness and physical function) data at the decision for surgery and at 6-month intervals until surgery.
The mean wait time for surgery was 123.8 days (mean wait times for individual surgeons ranged from 7 to 213 d). Of the patients, 106 waited < 6 months, 12 waited 6-12 months and 9 waited > 12 months. Wait times evaluated up to 6 months, 6-12 months or > 12 months demonstrated significant increases in pain (F = 7.12, p = 0.01), with a mean change of 2.6 points when patients waited > 6 months. Physical disability increased (F = 4.61, p = 0.01), with a mean change of 5.1 points when the wait time was 6-12 months and 8.8 points when the wait time was > 12 months. | Waiting > 6 months for revision hip arthroplasty resulted in significant increases in pain and physical disability. |
3,169 | 26,950 | This multi-center study (Cabuenes Hospital and Santa Lucia University Hospital) assessed the results of a retrospective and ongoing series of 135 total hip arthroplasties (THA) in which a latest generation dual-mobility cup was implanted.
A total of 135 THAs performed between 2005 and 2008 were analyzed. Mean follow-up was 32 months. The causes of surgery were: coxarthrosis in 31.8% and hip fracture in 68.1%. Mean age was 82.1 years. All patients were seen at regular follow-up visits for clinical and radiological assessments.
The follow-up lasted over 24 months in 121 THAs (14 patients died). In the most recent follow-up, in May 2011, 119 cups did not show any loosening. Complications were as follows: 2 postoperative dislocations; 4 DVTs; 3 infections; 5 periprosthetic fractures; 2 loosened cups, and one subsided stem. The mean preoperative Harris Hip Score (HHS) was 45, 83; the mean postoperative HHS was 80.03. Only two of the 135 cups analyzed had radiographic modifications without clinical signs. Isolated cup survival at 12 months was 97.03% (87.3-99.2) with a 95% confidence interval; survival at 5 years was 96.7% (85.4-98.8).
In our study, the new dual-mobility cup showed good results for the following indications: primary coxarthrosis and femur neck fractures. | The complication rate in our series was similar to the one reported in other series in the literature, except for dislocation. The latter was considerably less frequent (1.48%) in our series compared to the rates reported by the classical series, especially in patients with neuromuscular or cognitive problems (one third of patients). |
3,170 | 8,405 | Previously, the authors modified the surgical technique to preserve tibial bone mass for Oxford unicompartmental knee arthroplasty (UKA). The purpose of this study was to determine the clinical outcomes and values of this modified technique.
Clinical data of 34 consecutive patients who underwent the unilateral modified UKA technique (modified group, 34 knees) were retrospectively analyzed. To compare the outcome, a match-paired control group (conventional group, 34 knees) of an equal number of patients using the conventional technique system in the same period were selected and matched with respect to diagnosis, age, pre-operative range of motion (ROM), and radiological grade of knee arthrosis. Clinical outcomes including knee Hospital for Special Surgery (HSS) score, ROM, and complications were compared between the two groups. Post-operative radiographic assessments included hip-knee-ankle angle (HKA), joint line change, implant position, and alignment.
The mean follow-up time was 38.2 ± 6.3 months. There was no difference in baseline between the two groups. The amount of proximal tibial bone cut in the modified group was significantly less than that of the conventional group (4.7 ± 1.1 mm vs. 6.7 ± 1.3 mm, t = 6.45, P < 0.001). Joint line was elevated by 2.1 ± 1.0 mm in the modified group compared with -0.5 ± 1.7 mm in the conventional group (t = -7.46, P < 0.001). No significant differences were observed between the two groups after UKA with respect to HSS score, VAS score, ROM, and HKA. Additionally, the accuracy of the post-operative implant position and alignment was similar in both groups. As for implant size, the tibial implant size in the modified group was larger than that in the conventional group (χ = 4.95, P = 0.035). | The modified technique for tibial bone sparing was comparable with the conventional technique in terms of clinical outcomes and radiographic assessments. It can preserve tibial bone mass and achieve a larger cement surface on the tibial side. |
3,171 | 26,496 | Patient-reported outcomes (PROs) reflect treatment efficacy from the patients' perspective. The objective was to assess PROs improvement with rituximab in rheumatoid arthritis.
Patients with long-standing rheumatoid arthritis received rituximab 1000mg twice at 2 weeks interval, and were assessed over 6 months. PROs including physical PROs (pain, functional assessment, physical quality of life) and mental or mixed aspects (fatigue, sleep and mental quality of life) were assessed. Standardized response means were calculated. Early improvement in PROs was used to predict EULAR response at 6 months.
For the 175 patients (mean age 54.6±10.6 years, mean disease duration 12.9±9.3 years), the plateau of efficacy of rituximab on PROs was reached at week 12, and the effect was more prominent on physical PROs (e.g., pain standardized response means -0.75 [95% confidence interval -0.91; -0.60]), than on sleep (-0.43; [-0.56; -0.29]). It was not possible to accurately predict 6-month EULAR response by early improvement in PROs. | Rituximab was effective on PROs with an early effect. PROs reflecting physical aspects were more modulated by this biologic than other PROs (fatigue, sleep or mental quality of life). Links between sleep difficulties, fatigue and RA should be further studied. |
3,172 | 60,599 | To determine whether the biochemical presentation and urinary physicochemical environment of patients with hyperuricosuria presenting with calcium stones (hyperuricosuric calcium urolithiasis [HUCU]) differs from those of patients with gouty diathesis (GD) or idiopathic uric acid urolithiasis.
A total of 122 patients with HUCU and 68 patients with GD were identified from our "stone registry" of patients who underwent a full ambulatory evaluation. All patients with HUCU had urinary uric acid greater than 800 mg/day in men and greater than 750 mg/day in women and presented with calcium stones. Those with GD had pure uric acid stones or mixed uric acid-calcium stones and did not have secondary causes of uric acid urolithiasis. Data derived from the fasting serum and 24-hour urine samples collected on a random diet and on a diet restricted in calcium, sodium, and oxalate were compared between the two groups.
Compared with patients with HUCU, those with GD had significantly higher serum uric acid and lower urinary uric acid and pH levels (mean value 5.38 and 5.35 on random and restricted diets versus 6.09 and 6.14, respectively). The fractional excretion of urate and the discriminant score of the relationship between urinary pH and the fractional excretion of urate were significantly lower in those with GD than in those with HUCU. Patients with HUCU displayed a greater urinary saturation of sodium urate and calcium oxalate compared with those with GD, and those with GD had a higher urinary content of undissociated uric acid and lower urinary saturation of brushite (calcium phosphate). | Patients with HUCU presented with normal urinary pH and hyperuricosuria, accompanied sometimes by hypercalciuria, which produced increased urinary saturation of sodium urate and calcium oxalate. In contrast, those with GD had a low fractional excretion of urate (that contributed to hyperuricemia) and low urinary pH (that led to increased amount of undissociated uric acid). The varying biochemical and physicochemical presentations of the two conditions can be ascribed to overindulgence with purine-rich foods in those with HUCU and underlying primary gout in those with GD. |
3,173 | 34,802 | Recent neurophysiological evidence attests to the validity of fibromyalgia (FM), a chronic pain condition that affects >2% of the population.
To present the evidence-based guidelines for the diagnosis, management and patient trajectory of individuals with FM.
A needs assessment following consultation with diverse health care professionals identified questions pertinent to various aspects of FM. A literature search identified the evidence available to address these questions; evidence was graded according to the standards of the Oxford Centre for Evidence-Based Medicine. Drafted recommendations were appraised by an advisory panel to reflect meaningful clinical practice.
The present recommendations incorporate the new clinical concepts of FM as a clinical construct without any defining physical abnormality or biological marker, characterized by fluctuating, diffuse body pain and the frequent symptoms of sleep disturbance, fatigue, mood and cognitive changes. In the absence of a defining cause or cure, treatment objectives should be patient-tailored and symptom-based, aimed at reducing global complaints and enhancing function. Healthy lifestyle practices with active patient participation in health care forms the cornerstone of care. Multimodal management may include nonpharmacological and pharmacological strategies, although it must be acknowledged that pharmacological treatments provide only modest benefit. Maintenance of function and retention in the workforce is encouraged. | The new Canadian guidelines for the treatment of FM should provide health professionals with confidence in the complete care of these patients and improve clinical outcomes. |
3,174 | 62,235 | To study whether patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) differ from healthy individuals in their immune responses to acute psychological stress.
The phenotype and function of peripheral blood lymphocytes were analysed before and after stress exposure in patients and healthy subjects.
Natural killer (NK) cell numbers increased transiently in all groups under stress. NK activity, however, increased in healthy controls only. We observed a stress-induced increase in interleukin (IL)-4-producing (IL-4(+)) cells in SLE patients only, whereas interferon (IFN) gamma(+) cell numbers increased due to stress in all three groups. An analysis of supernatants from phytohaemagglutinin (PHA) cultures revealed increased IFN gamma and IL-10 levels in healthy subjects but not in SLE or RA patients after stress exposure. | These data demonstrate that RA and SLE patients differ in their immune response to stress from healthy controls. Changes in cytokine patterns might be responsible for stress-induced exacerbation of disease activity in RA and SLE patients. |
3,175 | 20,490 | Based on a novel approach suggesting a role of adipose tissue in osteoarthritis (OA), we aimed to determine whether the infrapatellar fat pad (IFP) may affect joint cell functions through adipokines.
The conditioned media of IFP and subcutaneous adipose tissue from OA patients were used to determine the production of leptin and adiponectin, and to stimulate chondrocytes and fibroblast-like synoviocytes (FLS). Blocking experiments were carried out to evaluate the contribution of adipokines to IFP effects. The gene expression of inflammatory and degradative proteins, growth factors and components of the extracellular matrix, and the production of inflammatory mediators and metalloproteases were determined to evaluate cell response to fat-conditioned media.
IFP releases elevated amounts of leptin and adiponectin independently of the body mass index and the gender. The conditioned media from IFP strongly induce the expression of inflammatory genes in both articular cells and the expression of degradative genes in chondrocytes, but remain ineffective in regulating the expression of aggrecan, type 2 collagen or growth factors. Blocking leptin or adiponectin does not change the cell response to IFP. A great variability between patients is found when compared the inflammatory activity of paired samples of IFP and subcutaneous adipose tissue. | IFP may trigger both cartilage destruction and inflammation of the synovium, but not through leptin or adiponectin. The data suggest also that IFP may have specific inflammatory phenotypic features independent from the general phenotype found in obesity. |
3,176 | 51,451 | To assess the effects of tumour necrosis factor (TNF) antagonist therapy on B lymphocyte stimulator (BLyS) expression in patients with rheumatoid arthritis (RA).
Blood from 38 patients with RA from a single centre was collected prior to and following initiation of TNF antagonist therapy. Plasma BLyS protein levels, blood leukocyte BLyS mRNA levels and disease activity were longitudinally monitored. Twelve patients with RA who either refused or were felt not to be candidates for TNF antagonist therapy and five normal healthy volunteers served as TNF antagonist-naïve controls.
Baseline plasma BLyS protein levels, but not blood leukocyte BLyS mRNA levels, were elevated in patients with RA. Plasma BLyS protein levels declined following initiation of TNF antagonist therapy in good responders (GR) to TNF antagonist therapy but not in poor responders (PR). By contrast, the erythrocyte sedimentation rate (ESR) declined in response to TNF antagonist therapy in GR and PR. TNF antagonist therapy did not promote change in blood leukocyte BLyS mRNA levels in either GR or PR, suggesting that the TNF antagonist-associated changes in circulating BLyS protein levels reflected changes in local BLyS production in the affected joints rather than changes in systemic BLyS production. BLyS expression did not change over time in either the normal or RA control groups. | A good clinical response to TNF antagonist therapy in patients with RA is associated with a decline in plasma BLyS protein levels. Increased BLyS expression in affected joints may contribute to ongoing disease activity, and reduction of such expression may help promote a favourable clinical response to TNF antagonist therapy. |
3,177 | 20,400 | Rheumatic diseases, irrespective of etiology and clinical course, influence different areas of a patient's life. Adapting to disability and limitations caused by an illness is very difficult for many patients. The main goal of a therapeutic procedure should be improvement of health-related quality of life (QoL).
Evaluation of the factors that influence the QoL that are conditioned by the state of health of patients with osteoarthritis (OA) and rheumatoid arthritis (RA).
The study group consisted of 198 patients diagnosed with OA, according to the American College of Rheumatology criteria (1988), and 100 patients diagnosed with RA, according to the American College of Rheumatology criteria (2010). A diagnostic survey using visual analog scale of pain, health assessment questionnaire disability index, and 36-item short form health survey were used in this study.
The average age of patients with OA was 59.16 (±15.87) years and patients with RA was 55.22 (±14.87) years. The average duration of illness examined for OA was 5.5 (±4.32) years, whereas for RA, it was slightly more at 6.8 (±5.21) years. Overall the QoL in both study groups was of medium level. Among patients with OA and RA, lower evaluation of QoL was mainly affected by age (OA - physical sphere [PCS] | Patients with OA, despite their average older age, had a higher evaluated QoL than patients with RA. Overall QoL in terms of mental functioning in both rheumatic diseases was assessed at a higher level than in the area of physical functioning. |
3,178 | 60,718 | To investigate whether osteoarthritis (OA) of the knee or bandaging of the knee affects movement detection.
Movement detection levels were determined in 10 women aged > 65 years with moderate to severe knee OA and 10 healthy women matched for age, body mass index, and activity levels. Movements were imposed at 0.5 degrees /second, 1.0 degrees /second, and 2.5 degrees /second. Additionally, detection levels were compared with and without the knee bandaged at a single velocity, (0.5 degrees /second).
Controls perceived significantly smaller movements than OA subjects at all test velocities (P < 0.01). However, the bandage did not affect movement detection (P > 0.05). | Detection of movement at the knee was impaired in subjects with severe knee OA, and a bandage did not improve detection. Thus, considering previous findings that position sense is impaired, a generalized proprioceptive deficit appears to be associated with OA. This deficit could result from loss of receptors, altered muscle function, or the consequent joint instability. |
3,179 | 56,175 | To demonstrate the association between various measures of spinal mobility and radiographic damage of the spine in individual patients with ankylosing spondylitis, and to determine whether the assessment of spinal mobility can be a proxy for the assessment of radiographic damage.
Radiographic damage was assessed by the mSASSS. Cumulative probability plots combined the radiographic damage score of an individual patient with the corresponding score for nine spinal mobility measures. Receiver operating characteristic analysis was performed to determine the cut off level of every spinal mobility measure that discriminates best between the presence and absence of radiographic damage. Three arbitrary cut off levels for radiographic damage were investigated. Likelihood ratios were calculated to explore further the diagnostic properties of the spinal mobility measures.
Cumulative probability plots showed an association between spinal mobility measures and radiographic damage for the individual patient. Irrespective of the chosen cut off level for radiographic progression, lateral spinal flexion and BASMI discriminated best between patients with and those without structural damage. Even the best discriminatory spinal mobility assessments misclassified a considerable proportion of patients (up to 20%). Intermalleolar distance performed worst (up to 30% misclassifications). Lateral spinal flexion best predicted the absence of radiographic damage, and a modified Schober test best predicted the presence of radiographic damage. | This study unequivocally demonstrated a relationship between spinal mobility and radiographic damage. However, spinal mobility cannot be used as a proxy for radiographic evaluation in an individual patient. |
3,180 | 38,887 | The primary purpose of our study was to analyse the long-term outcome of patients treated for anterior cruciate ligament (ACL) tears by anatomical single-bundle ACL reconstruction with patellar tendon autograft. The secondary purpose was to identify predictive factors for good outcome and occurrence of osteoarthritis.
Sixty-three patients (m:f = 54:9; mean age at surgery, 27 ± 7 years) treated by ACL reconstruction were evaluated with a mean follow-up of 16 ± 1 years using IKDC2000, the SF36, Lysholm and Tegner score, Knee Society score, visual analogue scale for pain and satisfaction and KOOS. The femoral tunnel position was evaluated according to Sommer. It was also assessed in percentage of the Blumensaat line and the tibial tunnel position in percentage of the total anterior-posterior plateau length. The extent of osteoarthritis was graded according to the Kellgren-Lawrence score.
The total IKDC2000 was normal in 20 (32 %), nearly normal in 29 (46 %), abnormal in 12 (19 %) and severely abnormal in 3 (5 %) of patients. The mean total SF-36 was 89 ± 13, the Lysholm score 95 ± 12, the Knee Society score 191 ± 16 and the total KOOS 84 ± 19. The Tegner score decreased from pre-injury 7(4-10) to 6 (2-10) at follow-up. The Kellgren-Lawrence score was normal in 17 (27 %), suspected osteoarthritis in 25 (40 %), minimal osteoarthritis in 5 (8 %), moderate osteoarthritis in 9 (14 %) and severe osteoarthritis in 3 patients (5 %). The femoral tunnel was in zone A in 43 patients (68 %), in zone B in 16 (25 %) and in zone C in 4 patients (7 %). The femoral tunnel position in percentage of the Blumensaat line was 49 ± 3 (range, 44-57), and the tibial tunnel position in percentage of the total anterior-posterior plateau length was 32 ± 6 (range, 21-46). Patients with meniscal lesion at the time of ACL tear showed significantly less favourable outcomes than those without. | Patients treated by the proposed ACL reconstruction technique showed on average good to excellent long-term results. A meniscal lesion at the time of ACL tear was highly predictive for less favourable outcome. |
3,181 | 48,852 | The precise anatomical location of pathology associated with inflammatory back pain (IBP) in early spondyloarthropathy (SpA) remains unclear.
To use MRI to study the sacroiliac joint (SIJ) and lumbar spine (LS) and explore the relationship between sites and extent of inflammation and HLA-B27 status over 12 months.
54 patients with IBP; median duration 24 weeks (54% HLA-B27 positive; median Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 5.65) and 22 control subjects (11 with mechanical back pain; 11 volunteers) were recruited and 63% (n = 34) were reassessed at 1 year. Fat saturation and T1-weighted MRI was performed with images being scored for active bone marrow oedema (BMO) lesions representative of inflammation.
At baseline 46/54 (85%) patients had BMO (SIJs and LS) compared with 40% in the control group. The majority of affected patients had inflammation at the SIJ level (96% (n = 44); 23.5% (n = 12) LS) and 28.3% (n = 13) at both sites simultaneously. The SIJ activity score confirmed more severe inflammation (BMO grade 2 or 3: 52.2%) in the IBP group (controls = BMO grade 1: 100%; p<0.001). HLA-B27 was associated with both the severity (p = 0.009) and number of baseline SIJ lesions (p = 0.045) and with persistence (SIJ or LS) at 1 year (p = 0.02). 90% of reattenders fulfilled European Spondyloarthropathy Study Group criteria; 73.5% showed MRI inflammation despite clinical improvement (median BASDAI 5.65 to 3.05; p<0.009). | LS and SIJ involvement may occur simultaneously in very early SpA and may be differentiated from non-inflammatory back pain by the severity of MRI lesions. HLA-B27 is associated with both the severity of osteitis and its persistence. |
3,182 | 50,736 | Previous evidence suggests the role of psychological stress in triggering the onset of autoimmunity. We aimed to investigate whether stress following major and minor life events could precede the onset of primary Sjögren's syndrome (pSS). The role of coping strategies and social support, as compensating buffering mechanisms, was also explored.
47 patients with pSS were compared with two control groups: 35 patients with lymphoma (disease controls, DC) and 120 healthy controls (HC) with disease onset within the previous year. All subjects completed questionnaires assessing the occurrence of major and minor stressful events, coping strategies and social support prior to disease onset. Data analysis was performed by univariate and multivariate logistic regression models.
A higher number of patients with pSS reported the occurrence of negative stressful life events prior to disease onset compared with patients with lymphoma and HC, while the number and impact of daily hassles did not differ between the three groups. Coping strategies were defective and the overall social support was lower in patients with pSS compared with DC and HC groups. In the multivariate model, pSS status was associated with maladaptive coping and lower overall social support relative to DC and HC, as well as with an increased number of negative stressful life events compared with HC but not DC. | Prior to disease onset, patients with pSS experience high psychological stress following major negative life events, without developing satisfactory adaptive coping strategies to confront their stressful life changes. Lack of social support may contribute to the relative risk of disease development. |
3,183 | 48,328 | To compare outcomes in patients with juvenile psoriatic arthritis (PsA) with those in patients with other juvenile idiopathic arthritis (JIA) subtypes, and to evaluate characteristics and genetic markers that may differentiate PsA from other subtypes of JIA.
JIA patients first admitted between 1980 and 1985 were clinically examined after a median of 15 years. Health status was reassessed by the Short Form-36 Health Survey (SF-36) after a median of 23 years. Of 336 JIA patients, 31 (9%) had PsA.
Predictors of PsA were psoriasis in the patient (OR 12.06, p = 0.004) or first-degree relative (OR 30.86, p < 0.001), dactylitis (OR 10.97, p < 0.001), and ankle/toe arthritis (OR 3.04, p = 0.038) within the first 6 months. HLA-DRB1*11/12 status (OR 2.69, p = 0.040) and onset after age 6 years (OR 4.41, p = 0.004) differentiated PsA from either oligoarthritis or polyarthritis. After 15 years, PsA patients had poorer physical health than healthy population controls (p = 0.001). After 23 years, the SF-36 physical scores were poorer in PsA patients than in those with either oligoarthritis or polyarthritis (p < 0.045). The need for disease-modifying antirheumatic drugs and/or anti-tumor necrosis factor agents was present in 33% of PsA versus 8% in oligoarthritis and 13% in either oligoarthritis or polyarthritis patients (p < 0.001 and p = 0.002, respectively). | In addition to a history of psoriasis, dactylitis, ankle or toe arthritis, and DRB1*11/12 in children with JIA indicate the likelihood of PsA, a subtype associated with unfavorable outcome. |
3,184 | 16,119 | We used T2 mapping to quantify the effect of intra-articular hyaluronic acid administration (IAHAA) on cartilage with correlation to clinical symptoms.
One hundred two patients with clinical and MRI diagnosis of hip or knee grade I-III chondropathy were prospectively included. All patients received a standard MRI examination of the affected hip/knee (one joint/patient) and T2-mapping multiecho sequence for cartilage evaluation. T2 values of all slices were averaged and used for analysis. One month after MR evaluation 72 patients (38 males; mean age 51±10 years) underwent IAHAA. As a control group, 30 subjects (15 males; 51 ± 9 years) were not treated. MR and WOMAC evaluation was performed at baseline and after 3, 9, and 15 months in all patients.
T2 mapping in hyaluronic acid (HA) patients showed a significant increase in T2 relaxation times from baseline to the first time point after therapy in knees (40.7 ± 9.8 ms vs. 45.8 ± 8.6 ms) and hips (40.9 ± 9.7 ms; 45.9 ± 9.5 ms) (p < 0.001). At the 9- and 15-month evaluations, T2 relaxation dropped to values similar to the baseline ones (p < 0.001 vs. 3 month). The correlation between T2 increase and pain reduction after IAHAA was statistically significant (r = 0.54, p < 0.01) in patients with grade III chondropathy.
• T2 relaxation times change over time after hyaluronic acid intra-articular administration • T2 relaxation times of the medial femoral condyle correlate with WOMAC variation • T2 relaxation times are different between Outerbridge I and II-III. | T2 mapping can be used to evaluate the effect over time of IAHAA in patients with hip and knee chondropathy. |
3,185 | 50,421 | To gain insight into the determinants of the use of wrist working splints among patients with rheumatoid arthritis (RA).
A qualitative descriptive study was performed among 18 patients with RA who recently received a fabric wrist working splint because of pain due to arthritis of the wrist. Patients were interviewed at home using semistructured in-depth interviews. Interviews were audiotaped and transcribed verbatim and analyzed using the framework approach.
The majority of patients indicated that their splint use was dependent on the seriousness of the symptoms (pain, swelling, or tingling feelings) they perceived. Important reasons to wear the splint were reduction of symptoms, wrist support, and immobilization of the wrist. Important reasons to stop wearing the splint were reduced functional abilities using the splint and the performance of dirty or wet activities. | The reasons for patients to wear and not wear wrist working splints are related to intentional decisions of the patients, which are primarily based on perceived benefits and barriers of splint wearing. The results of this study have been used to develop educational and behavioral strategies to increase adherence to wearing wrist working splints. |
3,186 | 8,756 | The aim of this study was to investigate whether microRNA-421 could participate in the proliferative, migratory and inflammatory changes of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis by targeting SPRY1.
The expressions of microRNA-421 and SPRY1 in synovial tissues and FLS were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. The binding condition between microRNA-421 and SPRY1 was verified by the Dual-Luciferase reporter gene assay. MicroRNA-421 mimics and inhibitor were constructed and transfected. The levels of extracellular interleukin-1 (IL-1), IL-6, and COX2 in FLS after microRNA-421 mimics or inhibitor transfection were detected by enzyme-linked immunosorbent assay (ELISA). The regulatory effect of microRNA-421 on the proliferation and migration of FLS was detected using cell counting kit-8 (CCK-8) and transwell assay, respectively. Furthermore, collagen-induced RA mouse model was constructed to confirm the specific effect of microRNA-421 on regulating RA development.
MicroRNA-421 was highly expressed in the synovial tissues of RA patients. SPRY1 expression in FLS was negatively regulated by microRNA-421. Moreover, the overexpression of microRNA-421 significantly promoted proliferative, invasive potentials and inflammatory response of FLS. In vivo, RA mouse model indicated that downregulated microRNA-421 and upregulated SPRY1 were observed in mice injected with cortisone and microRNA-421 inhibitor when compared with those of controls. | MicroRNA-421 promotes the inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis by downregulating the SPRY1 expression. |
3,187 | 26,135 | We aimed to evaluate interobserver agreement in the definition of spine instability among spine neuroradiologists with or without experience in dynamic magnetic resonance imaging (MRI).
Two expert neuroradiologists and two residents retrospectively evaluated the pre-operative dynamic MRI examinations of patients with vertebral instability. Segmental motion, defined as excessive (more than 3 mm) translational motion from supine to upright, was investigated in 103 subjects (309 segments) using kinetic MRI. Radiographic parameters which can help indicate segmental instability include disc degeneration, facet joint osteoarthritis, and ligament flavum hypertrophy. These three radiographic parameters were simultaneously evaluated, and the combinations corresponding to significant segmental instability at each level were determined. The agreement among the neuroradiologists was calculated using the kappa coefficient. All patients had neurosurgical intervention to stabilize the spine.
Agreement was high among experienced and non-experienced neuroradiologists. Agreement was nearly perfect for spinal location of spinal instability. | This study demonstrates that the experience of the evaluator has a low impact on the assessment of spinal instability if correct classification is used. The interobserver agreement confirms the usefulness and safety of kinetic MRI in the correct diagnosis of spinal instability even by less experienced evaluators. |
3,188 | 17,874 | High-heeled shoes (high heels) are frequently worn by many women and form an important part of female gender identity. Issues of explicit and implicit compulsion to wear high heels have been noted. Previous studies and reviews have provided evidence that high heels are detrimental to health. However, the evidence base remains fragmented and no review has covered both the epidemiological and biomechanical literature. In addition, no review has considered the psychosexual benefits that offer essential context in understanding the public health challenge of high heels.
We searched seven major bibliographic databases up to November 2016, in addition to supplementary searches. We initially identified all review articles of any design that assessed either the psychosexual benefits or negative musculoskeletal health effects of high heels, the latter looking at both the epidemiological and biomechanical perspectives. We additionally considered additional primary studies on areas that had not been reviewed before or in which a marked lack of evidence had been noted. Data were extracted onto standardised forms. Proportionate second review was conducted.
A total of 506 unique records were identified, 27 full-text publications were screened and 20 publications (7 reviews and 13 additional studies) were included in our evidence synthesis. The most up-to-date epidemiological review provides clear evidence of an association between high heel wear and hallux valgus, musculoskeletal pain and first-party injury. The body of biomechanical reviews provides clear evidence of changes indicative of increased risk of these outcomes, as well as osteoarthritis, which is not yet evidenced by epidemiological studies. There were no reviews on psychosexual benefits, but all five identified original studies provided evidence of increased attractiveness and/or an impact on men's behaviour associated with high heel wear. With regard to second-party injury, evidence is limited to one descriptive study and eight case reports. | Our evidence synthesis clearly shows that high heels bring psychosexual benefits to women but are detrimental to their health. In light of this dilemma, it is important that women's freedom of choice is respected and that any remaining issues of explicit or implicit compulsion are addressed. |
3,189 | 26,231 | We analyzed the histopathologic findings in end-stage osteoarthritic ankle joint tissue that display increased uptake of bone-seeking radiotracer in single-photon emission computed tomography-computed tomography (SPECT-CT) imaging.
Six consecutive patients with end-stage osteoarthritis undergoing total ankle replacement received preoperative SPECT-CT imaging using (99m)Technetium dicarboxypropane diphosphonate ((99m)Tc-DPD). Using imaging data for stratification, osteochondral tissue sections were prepared from SPECT-positive (+) and -negative (-) areas of tibial and talar resection specimens. Histomorphometric analyses of osteoblast numbers, collagen deposition, and cartilage degeneration were performed on hematoxylin and eosin, van Gieson's and Safranin-O stained tissue sections. Osteoclast activity was visualized using tartrate-resistant acid phosphatase (TRAP) staining.
Increased (99m)Tc-DPD uptake was observed exclusively subjacent to the subchondral bone plate of tibial and talar joint compartments. SPECT(-) tissues displayed typical fatty marrow morphology containing mainly collagen-positive blood vessels and few marrow and bone-lining cells. SPECT(+) tissues were characterized by increased numbers of active bone-lining osteoblasts depositing collagen fibers. Collagen area fraction of subchondral bone marrow was significantly increased in SPECT(+) (0.52 ± 0.21) compared with SPECT(-) (0.29 ± 0.13) tissues (P = .30). Multinucleated TRAP(+) osteoclasts were absent from bone formation sites, but associated with vascular structures invading articular cartilage through the subchondral bone plate. Increased (99m)Tc-DPD uptake was specifically and strongly correlated with increased osteoblast numbers (P = .011), and with collagen area fraction (P = .030) but not with Mankin score (P = .202), or with osteoclast number (P = .576).
Our findings suggest a pathologic bone-remodeling process in end-stage ankle OA areas with increased (99m)Tc-DPD uptake. | Subchondral bone tissues in SPECT(+) areas of end-stage ankle osteoarthritis were histologically characterized by increased osteoblast-mediated bone formation in the absence of functional osteoclasts, and increased cellularity and collagen deposition in marrow tissues. |
3,190 | 45,195 | To evaluate the natural history of radiographic hand osteoarthritis (OA) over 10 years.
We assessed 118 subjects (30 women) twice (X-ray A and B) with mean (SD) follow-up time of 9.6 (0.4) years. Subjects were of mean (SD) age 52 (10) years at X-ray A and had undergone prior knee meniscectomy. Radiographs of the distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints, and the first interphalangeal (IP1) and first carpometacarpal (CMC1) joints of both hands were read for joint space narrowing (JSN) and osteophytes according to the OARSI atlas. Radiographic progression was evaluated both at joint and subject level.
At the time of X-ray A, we found radiographic OA (approximating Kellgren and Lawrence grade 2 or worse) in at least one hand joint in 42 (36%) subjects, and in 62 (53%) at X-ray B (P<0.001). At X-ray A, 21 subjects (18%) were classified as having primary hand OA vs 35 (30%) at X-ray B (P<0.001). Increase in JSN and osteophyte grade occurred most frequently in the DIP joints. OA at X-ray B was most frequently found in subjects' CMC1 (29%), DIP (14-27%), and IP1 joints (19%). Fifty-nine percent of subjects progressed radiographically (increase in total radiographic score by at least 2). However, the progression of the radiographic changes was mostly minor. | In subjects with prior meniscectomy, CMC1, DIP, and IP1 joint OA is common. However, further hand OA progression over 10 years, as detected by plain radiography, is relatively modest. More sensitive imaging techniques may be preferable for clinical trials to evaluate structural hand OA progression. |
3,191 | 24,067 | To describe the methodology, challenges, and baseline characteristics of a prevention development trial entitled "Reducing Pain, Preventing Depression."
A sequential multiple assignment randomized trial (SMART) compared sequences of cognitive behavioral therapy (CBT) and physical therapy for knee pain and prevention of depression and anxiety. Participants were randomized to CBT, physical therapy, or enhanced usual care and followed for 12 months for new-episode depression or anxiety. Participants were age ≥ 60 with knee osteoarthritis and subsyndromal depression, defined as 9-item Patient Health Questionnaire (PHQ-9) score ≥1 (which included the endorsement of one of the cardinal symptoms of depression [low mood or anhedonia]) and no diagnosis of major depressive disorder per the Structured Clinical Interview for DSM-IV. Depression and anxiety severity and characterization of new episodes were assessed with the PHQ-9, Generalized Anxiety Disorder-7, and the PRIME-MD. Knee pain was characterized with the Western Ontario McMaster Arthritis Index. Response was defined as at least "Very Much Better" on a Patient Global Impression of Change.
At baseline there were 99 patients with an average age of 71; 61.62% were women and 81.8% white. The average PHQ-9 was 5.6 and average Generalized Anxiety Disorder-7, was 3.2. Most were satisfied with the interventions and study procedures. The challenges and solutions described here will also be used in a confirmatory clinical trial of efficacy. | A SMART design for depression and anxiety prevention, using both CBT and physical therapy, appears to be feasible and acceptable to participants. The methodologic innovations of this project may advance the field of late-life depression and anxiety prevention. |
3,192 | 52,423 | Treatment-limiting infusion reactions to infliximab have not been fully explained in rheumatoid arthritis patients. Our main objective is to investigate the role of daily oral glucocorticoids use on such reactions.
Forty-three patients with immediate-type infusion reactions were identified in a large registry-based cohort. These patients were then compared with the entire cohort (n = 639) and, in a separate analysis, to a nested matched control group (n = 43). The following base-line variables were compared: use of oral glucocorticoids, health-assessment questionnaire, 28-joint count-based disease activity score, duration of disease and number of failed disease-modifying antirheumatic drugs.
The proportion of infusions associated with infusion reactions decreased significantly during the study period (p = 0.0024). Fifty per cent of the patients in the cohort were treated with daily low-dose glucocorticoids at baseline. 15/326 (4.6%) patients had an infusion reaction as compared with 28/324 (8.6%) of patients without glucocorticoid treatment (p = 0.057). In the matched comparison, 15/43 (35%) of the cases were on low-dose glucocorticoids as compared with 27/43 (64%) of the controls (p = 0.017). The use of low-dose glucocorticoids was associated with a significantly lower risk for a treatment-limiting infusion reactions in a Kaplan-Meier analysis (p = 0.04). The number needed to treat to prevent a treatment-limiting infusion reaction was 25 (95% CI: 13 to 527) in the cohort. | The use of daily low-dose glucocorticoids is associated with a lower risk for treatment-limiting infusion reactions to infliximab. Overall, treatment-limiting infusion reactions have become significantly less common during the past 5 years. |
3,193 | 23,487 | To evaluate whether baseline T1ρ and T2 relaxation times of hip cartilage are associated with magnetic resonance imaging (MRI) based progression of hip osteoarthritis (OA) at 18 months.
3T MRI studies of the hip were obtained at baseline and 18-month follow-up for 54 subjects without evidence of severe OA at baseline [Kellgren-Lawrence (KL) score of 0-3]. 2D fast spin-echo sequences were used for semi-quantitative morphological scoring of cartilage lesions and a combined T1ρ/T2 sequence was used to quantitatively assess cartilage composition. Progression of hip OA was defined based on incident or progression of morphological semi-quantitative grade at 18 months. Baseline T1ρ and T2 relaxation times were compared between progressors and non-progressors using one-way analysis of variance and Mann-Whitney U tests and used to predict progression with binary logistic regression after adjusting for age, gender, body mass index, and KL score. Additionally, a novel voxel-based relaxometry technique was used to compare the spatial distribution of baseline T1ρ and T2 between progressors and non-progressors.
Significantly higher baseline T1ρ and T2 values were observed in hip OA progressors compared to non-progressors, particularly in the posterosuperior and anterior aspects of the femoral cartilage. Logistic regression showed that higher baseline T1ρ or T2 values in the femoral cartilage were significantly associated with progression of femoral cartilage lesions at 18 months. | T1ρ and T2 relaxation parameters are associated with morphological cartilage degeneration at 18 months and may serve as potential imaging biomarkers for progression of cartilage lesions in hip OA. |
3,194 | 4,140 | Non-genetic risk factors for Sjögren's syndrome (SS) are poorly understood. Adherence to a Mediterranean diet has been associated with reduction in other autoimmune diseases. We examined the association of Mediterranean diet with SS.
New patients attending a single centre warranting investigation for primary SS (pSS) were recruited into the Optimising Assessment in Sjögren's Syndrome cohort established in Birmingham, UK (2014-2018). Participants were classified into pSS and non-SS sicca, considered as cases and non-cases, respectively, and asked to complete an optional food frequency questionnaire on their diet before onset of symptoms. A semi-quantitative Mediterranean diet score (MDS) was calculated (possible range=0 to 18). Using multivariate logistic regression, corrected for energy intake, body-mass index, sex, age, symptom duration, and smoking status, we examined the association of MDS with SS.
Dietary data were available for 133/243 (55%) eligible patients (n=82 pSS and n=51 sicca). In the adjusted model, a higher total MDS (mean ± SD, 9.41±2.31 points) was associated with lower odds of pSS (OR 0.81, 95% CI 0.66-0.99; p=0.038) per one unit of MDS. Among MDS components, the strongest association was seen with fish with OR 0.44 (95% CI 0.24-0.83; p=0.01) in the comparison between <1 portion/week and 1 to 2.5 portions/week. Higher galactose, vitamin A-retinol-equivalents and vitamin C showed associations with lower odds of pSS in multivariate analysis, where the association of vitamin C was attenuated when adjusted for MDS. | When adjusted for potential confounders, adherence to the Mediterranean diet was associated with lower likelihood of having pSS. |
3,195 | 5,047 | Current clinical guidelines do not support the use of manual therapy (MT) interventions for Fibromyalgia (FM) patients, despite evidence of positive biochemical, mechanical and psychological effects, and the popularity of hands-on treatments amongst patients. An optimal dose for MT has not been established; this may explain the discrepancies found within the published literature. The aim of this systematic review was to determine whether there is a dose response relationship for MT leading to improvements in core domains of FM symptomology; Pain, Mood, Sleep, Global Measure of Impact (Functional Status & Quality of Life).
We searched six databases from 1990 to January 2018; studies were evaluated using the PEDro scale. Within-group (ESd) and between-group (ESg) Effect Sizes were calculated.
We identified and screened 4012 articles, 12 articles were critically appraised. Overall, there is moderate evidence that MT has positive effects on the four clinical outcomes investigated. However, there was no consistent dose response relationship observed across all studies. | A dose of approximately 45 min MT, three to five times per week, for three to five weeks, totalling 11 h 15 min, should be considered a baseline generic protocol for treatment delivery and research trials. Further research is necessary to confirm domain specific, or patient specific optimal doses. Moderator variables such as treatment time, frequency, duration; and MT type also need to be explored to ensure optimal delivery of MT in future research and clinical care provision. |
3,196 | 47,589 | The aim of this study was to examine seroconversion and the relationship with age and inflammation of autoantibodies in a large group of patients attending an outpatient rheumatology clinic.
Levels of antibodies to citrullinated proteins/peptides (ACPAs) and IgM rheumatoid factor (IgM-RF) were determined in 22,427 samples collected from 18,658 patients. The diagnosis was derived from a diagnosis registration system. The degree of seroconversion in repeated samples and the correlation of levels with age and inflammatory markers were determined for ACPA and IgM-RF in rheumatoid arthritis (RA) and non-RA patients.
Seventy-one percent of RA patients (n = 1,524) were ACPA-positive and 53% were IgM-RF-positive; in non-RA patients (n = 2,245), the corresponding values were 2% and 4%, respectively. In patients with at least two samples (n = 3,769), ACPA status was more stable than IgM-RF status in RA patients. ACPA- or IgM-RF-negative non-RA patients seldom became positive. ACPA positivity was unrelated to age in both RA and non-RA patients. IgM-RF positivity was unrelated to age in RA patients; however, it increased with age in non-RA patients. The correlation between autoantibody levels and inflammatory markers was low in general and was somewhat higher for IgM-RF than for ACPA. | ACPA status is more stable in time and with increasing age than IgM-RF status, further establishing its role as a disease-specific marker. ACPA and IgM-RF levels are only moderately correlated with markers of inflammation. |
3,197 | 65,046 | We review our experience with safety, efficacy, and practicality of self-administration of gold and methotrexate (MTX) in 40 patients.
Between 1992 and 1995, 40 patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) followed in the drug monitoring clinics of the Mary Pack Arthritis Centre were taught to self-administer parenteral gold or MTX. Self-injection education was recommended to patients who were stable and improved taking parenteral gold or MTX, and who had not experienced serious side effects. Charts were reviewed to extract and analyze prospectively collected data regarding safety, efficacy, and compliance.
Sixty-five percent of patients performed self-injection and 35% received injections at home from a partner. Side effects in the self-injection patients are similar to those observed in clinic patients receiving drug by nurse administration. One MTX treated patient required treatment for interstitial pneumonitis, which developed after 22 weeks on self-injection. Side effects of self-injection included superficial irritation at the injection site in 2 patients and dosing error in 2 patients with no adverse effects. Seventy percent of gold and MTX treated patients continued self-injection after a mean of 34 months. Patients surveyed for satisfaction identified time saving and convenience as major benefits. | With basic instruction and close supervision, self-injection of antirheumatic drugs is safe in selected patients. Self-injection reduces utilization of health care services, and is convenient and time and cost-saving to the patient. |
3,198 | 17,221 | To discuss the utility of
IRPF patients diagnosed between September 2011 and June 2016 were included. Retroperitoneal malignancy patients were included as control. The morphological features and FDG uptake of retroperitoneal lesions were measured along with lymph node (LN) mapping.
Seventy-one iRPF patients were included. Fifteen lymphoma patients and 6 retroperitoneal metastatic malignancy patients were included as control. Significant differences in morphological features were observed between iRPF and lymphoma but not retroperitoneal metastatic carcinoma. Compared with malignancy, iRPF displayed a lower frequency of high-FDG-uptake retroperitoneal lesions (P = 0.017) and a lower mean maximum standardized uptake value (SUV | Retroperitoneal malignancy can mimic iRPF morphologically. |
3,199 | 13,407 | Free fatty acids (FAs) may influence cartilage metabolism and osteoarthritis (OA) disease progression. It is not clearly studied which FAs are present in the synovial fluid of knee joints and whether there are differences in FA content between nonsymptomatic and OA knee joints. The aim of this study was to investigate the presence of different types of FAs in synovial fluid of both OA- and nonsymptomatic control joints, and to analyze differences between both groups.
A total of 23 synovial fluid samples were collected from patients with end-stage knee OA undergoing total knee replacement, with approval of the medical ethical committee. As controls, 6 synovial fluid samples were obtained from postmortem donors without any history of joint disease or arthritis. Measurement of free FA concentration was done by mass spectrometry for saturated FAs (SFA), monounsaturated FAs (MUFA), and omega-3 and omega-6 polyunsaturated FAs (n-3 PUFAs and n-6 PUFAs).
Our measurements demonstrated the presence of SFAs, MUFAs, n-3 and n-6 PUFAs in synovial fluid of both nonsymptomatic and OA knee joints. The n-6/n-3 ratio was significantly lower in the OA group ( | Synovial fluid contains a broad spectrum of free FAs. The FAs profile differs between OA and control subjects, including a tendency for less n-6 FAs in OA joints. |
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