A critical appraisal of clinical practice guidelines for the treatment of lower-limb osteoarthritis

Clinical practice guidelines are important tools to assist clinical decision-making. Recently, several guidelines addressing the management of osteoarthritis (OA) have been published. Clinicians treating patients with OA must ensure that these guidelines are developed with consistency and methodological rigour. We undertook a qualitative summary and critical appraisal of six medical treatment guidelines for the management of lower-limb OA published in the medical literature within the past 5 years. A review of these six guidelines revealed that each possesses strengths and weakness. While most described the scope and intended patient populations, the guidelines varied considerably in the rigour of their development, coverage of implementation issues, and disclosure of conflicts of interest.     

A critical appraisal of clinical practice guidelines for the treatment of lower-limb osteoarthritis

Clinical practice guidelines are important tools to assist clinical decision-making. Recently, several guidelines addressing the management of osteoarthritis (OA) have been published. Clinicians treating patients with OA must ensure that these guidelines are developed with consistency and methodological rigour. We undertook a qualitative summary and critical appraisal of six medical treatment guidelines for the management of lower-limb OA published in the medical literature within the past 5 years. A review of these six guidelines revealed that each possesses strengths and weakness. While most described the scope and intended patient populations, the guidelines varied considerably in the rigour of their development, coverage of implementation issues, and disclosure of conflicts of interest.     

A Systematic Critical Appraisal for Non-Pharmacological Management of Osteoarthritis Using the Appraisal of Guidelines Research and Evaluation II Instrument

Clinical practice CPGs (CPGs) have been developed to summarize evidence related to the management of osteoarthritis (OA). CPGs facilitate uptake of evidence-based knowledge by consumers, health professionals, health administrators and policy makers. The objectives of the present review were: 1) to assess the quality of the CPGs on non-pharmacological management of OA; using a standardized and validated instrument - the Appraisal of Guidelines Research and Evaluation (AGREE II) tool - by three pairs of trained appraisers; and 2) to summarize the recommendations based on only high-quality existing CPGs. Scientific literature databases from 2001 to 2013 were systematically searched for the state of evidence, with 17 CPGs for OA being identified. Most CPGs effectively addressed only a minority of AGREE II domains. Scope and purpose was effectively addressed in 10 CPGs on the management of OA, stakeholder involvement in 12 CPGs, rigour of development in 10 CPGs, clarity/presentation in 17 CPGs, editorial independence in 2 CPGs, and applicability in none of the OA CPGs. The overall quality of the included CPGs, according to the 7-point AGREE II scoring system, is 4.8±0.41 for OA. Therapeutic exercises, patient education, transcutaneous electrical nerve stimulation, acupuncture, orthoses and insoles, heat and cryotherapy, patellar tapping, and weight control are commonly recommended for the non-pharmacological management of OA by the high-quality CPGs. The general clinical management recommendations tended to be similar among high-quality CPGs, although interventions addressed varied. Non-pharmacological management interventions were superficially addressed in more than half of the selected CPGs. For CPGs to be standardized uniform creators should use the AGREE II criteria when developing CPGs. Innovative and effective methods of CPG implementation to users are needed to ultimately enhance the quality of life of arthritic individuals.     

A Systematic Critical Appraisal of Non-Pharmacological Management of Rheumatoid Arthritis with Appraisal of Guidelines for Research and Evaluation II

Clinical practice guidelines (CPGs) have been developed to summarize evidence about the management of rheumatoid arthritis (RA) and facilitate the uptake of evidence-based knowledge by consumers, health professionals, health administrators and policy makers. The objectives of this review was to assess the quality of CPGS on non-pharmacological management of RA with a standardized and validated instrument - the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool and summarize the key recommendations from these CPGs. Scientific literature databases from 2001 to 2013 were systematically searched and a total of 13 CPGs for RA was identified. Only a minority of AGREE II domains were effectively addressed by the CPGS. Scope and purpose was effectively addressed in 10 out of 13 CPGs, stakeholder involvement in 11 CPGs, rigor of development in 6 CPGs, clarity/presentation in 9 CPGs, editorial independence in 1 CPGs, and applicability in none of the CPGs. The overall quality of the included CPGs according to the 7-point AGREE II scoring system was 4.8±1.04. Patient education/self-management, aerobic, dynamic and stretching exercises were the commonly recommended for the non-pharmacological management of RA by the high-quality CPGs. The general clinical management recommendations tended to be similar among high-quality CPGs. Non-pharmacological management interventions were superficially addressed in more than half of the selected CPGs. CPGs creators should use the AGREE II criteria when developing guidelines. Innovative and effective methods of CPGs implementation to users are needed to ultimately enhance the quality of life of arthritic individuals. In addition, it was difficult to establish between strongly recommended, recommended and weakly recommended, as there is no consensus between the strength of the recommendations between the appraised CPGs.     

A Systematic Critical Appraisal of Clinical Practice Guidelines in Juvenile Idiopathic Arthritis Using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) Instrument

Objectives

The objectives of this review are to: 1) appraise the methodological quality of clinical practice guidelines (CPGs) in juvenile idiopathic arthritis (JIA) providing pharmacological and/or non-pharmacological intervention recommendations, and 2) summarize the recommendations provided by the included CPGs and compare them where possible.

Methods

A systematic search was performed. Three trained appraisers independently evaluated the methodological quality of the CPGs using a validated and reliable instrument, the Appraisal of Guidelines in Research and Evaluation II. Six domains were considered: 1) score and purpose; 2) stakeholder involvement; 3) rigor of development; 4) clarity of presentation; 5) applicability; and 6) editorial independence. The domains consist of a total of 23 items each scored on a 7-point scale. High quality CPGs were identified if they had a domain score above 60% in rigor of development, and two other domains.

Results

Of the three included CPGs, the Royal Australian College of General Practitioners (RACGP) and American College of Rheumatology (ACR) CPGs were considered to be of high quality, but the German Society for Pediatric Rheumatology was of lower quality. Domains one to four had high domain scores across the guidelines (mean (standard deviation)): 72.76 (13.80); 66.67 (9.81); 64.67 (7.77); and 87.00 (9.64), respectively. Lower scores were obtained for applicability (14.00 (5.57)) and editorial independence (43.44 (7.02)). Recommendations varied across CPGs due to differences in context, target audience (general practitioners, rheumatologists, and other multidisciplinary healthcare professionals) and patients’ disease presentations. Despite this variability, progression of pharmacological treatment did not conflict between CPGs. Recommendations for non-pharmacological interventions were vague and the interventions considered varied between CPGs.

Conclusions

Overall, recommendations were based on a paucity of evidence and weak study designs. Further research is needed on interventions in JIA, as well as higher quality CPGs to facilitate implementation of the best evidence-based recommendations in clinical practice.     

Prevention of injury-related knee osteoarthritis: opportunities for the primary and secondary prevention of knee osteoarthritis

Where risk factors have been identified in knee and hip osteoarthritis (OA), with few exceptions, no prevention strategies have proven beneficial. The major risk factors for knee OA are advanced age, injury and obesity. However, there is limited or no evidence that they are modifiable or to what degree modifying them is effective in preventing development of knee OA or in preventing symptoms and progressive disease in persons with early OA. The notable exception is the growing epidemic of (sports) injury related knee OA. This review details the biological and clinical data indicating the efficacy of interventions targeting neuromuscular and biomechanical factors that make this subset of OA an attractive public health target, and highlights research opportunities for the future.     

A critical appraisal of the mitochondrial coenzyme Q pool.

The function of the coenzyme Q (CoQ) pool in the inner mitochondrial membrane is reviewed in view of recent findings suggesting a supramolecular organization of the mitochondrial respiratory complexes. In spite of the structural evidence for preferential aggregations of the inner membrane components, most kinetic evidence is in favor of a dispersed organization based on random collisions of the small connecting redox components, in particular CoQ, with the individual complexes. The shape of the CoQ molecule in the pool, suggested to be a folded one, is in agreement with its very rapid lateral diffusion mobility in the membrane midplane. Since the structural evidence in favor of specific supercomplexes is rather strong, it cannot be excluded that electron transfer may follow either pool behavior or preferential channeling depending on the physiological conditions. Another function ascribed to the CoQ pool is the antioxidant action of the reduced CoQ molecules; although it cannot be excluded that protein-bound ubisemiquinones may be a source of oxygen radicals, particularly at the level of complex III, the available evidence suggests that the mitochondrial pool only behaves as an antioxidant under physiological conditions.     

A functional difficulty and functional pain instrument for hip and knee osteoarthritis

Introduction  

The objectives of this study were to develop a functional outcome instrument for hip and knee osteoarthritis research (OA-FUNCTION-CAT) using item response theory (IRT) and computer adaptive test (CAT) methods and to assess its psychometric performance compared to the current standard in the field.     

Stem cell application for osteoarthritis in the knee joint: A minireview

Knee osteoarthritis is a chronic, indolent disease that will affect an ever increasing number of patients, especially the elderly and the obese. It is characterized by degeneration of the cartilage substance inside the knee which leads to pain, stiffness and tenderness. By some estimations in 2030, only in the United States, this medical condition will burden 67 million people. While conventional treatments like physiotherapy or drugs offer temporary relief of clinical symptoms, restoration of normal cartilage function has been difficult to achieve. Moreover, in severe cases of knee osteoarthritis total knee replacement may be required. Total knee replacements come together with high effort and costs and are not always successful. The aim of this review is to outline the latest advances in stem cell therapy for knee osteoarthritis as well as highlight some of the advantages of stem cell therapy over traditional approaches aimed at restoration of cartilage function in the knee. In addition to the latest advances in the field, challenges associated with stem cell therapy regarding knee cartilage regeneration and chondrogenesis in vitro and in vivo are also outlined and analyzed. Furthermore, based on their critical assessment of the present academic literature the authors of this review share their vision about the future of stem cell applications in the treatment of knee osteoarthritis.     

Relationship between radiographic grading of osteoarthritis and the biochemical markers for arthritis in knee osteoarthritis

The aim of this study was to investigate the relationship between the biochemical markers of arthritis and the radiographic grading of osteoarthritis (OA) in knees. Seventy-one women aged 49-85 years with knee OA were studied. Anterior-posterior knee radiographs and hand radiographs were taken in all patients. The radiographic grading of OA in the knee was performed by using the Kellgren-Lawrence criteria and the joint space width. The 71 patients with knee OA were divided into two groups: 37 patients exhibiting generalized osteoarthritis (GOA) and 34 non-GOA patients, according to the grading of their hand radiograph. C-reactive protein (CRP), urinary pyridinoline, YKL-40, plasma matrix metalloproteinase (MMP)-3, MMP-9 and tissue inhibitor of metalloproteinases (TIMP)-1 were measured as the biochemical markers of arthritis. The radiographic grading with the Kellgren-Lawrence scale revealed a significant relationship to the joint space width (P = 0.003): the joint space width decreased with increasing Kellgren-Lawrence grade. All biochemical markers had negative correlations with the joint space width, but only urinary pyridinoline had a significant correlation (P = 0.039). Pyridinoline (P = 0.034) and TIMP-1 (P = 0.017) also exhibited a significant relationship to the Kellgren-Lawrence grade. In GOA evaluations, the joint space width did not differ between GOA and non-GOA patients. CRP, pyridinoline, YKL-40 and MMP-3 levels were significantly greater in GOA patients than in non-GOA patients. CRP, pyridinoline, YKL-40, MMP-3 and TIMP-1 levels each related to at least one of the radiographic gradings. Furthermore, pyridinoline related to every type of radiographic grading examined in the present study.     

A critical appraisal of the association between energy charge and cell damage

The association between the energy charge and cellular damage caused by metabolic inhibitors was investigated in a cellular system of quiescent fibroblasts. The cell damage was assessed by the release of lactate dehydrogenase (LDH) which indicates a severe change of membrane integrity. Inhibition of glycolysis resulted in release of LDH when the energy charge decreased below 0.5 at an ATP level of 10% of the original level. If oxidative phosphorylation was inhibited, the energy charge decreased to 0.1-0.35 (dependent on the type of inhibitor) a long time before release of LDH, and no change occurred in the energy charge when release of LDH started. The ATP level was 0.5-2% of the original at this time. Even a decrease of the energy charge to 0.1 could be reversed to a normal level, and at the same time the morphological cellular changes were fully reversed and no release of LDH occurred. The conclusion is that no simple correlation between energy charge and cell survival exists. The different levels of ATP at which release of LDH started after inhibition of glycolysis and oxidative phosphorylation indicate a special role of glycolysis in maintaining the membrane function and integrity. This was emphasized by measuring the potassium loss of the cells which was much more marked after inhibition of glycolysis.     

Vitamin D supplementation in the management of knee osteoarthritis: study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: Osteoarthritis (OA) is a common health issue worldwide in the aging population who are also commonly deficient in vitamin D. Our previous study suggested that higher serum 25-(OH)D levels were associated with reduced knee cartilage loss, implying that vitamin D supplementation may prevent the progression of knee OA. The aim of the VItamin D Effects on OA (VIDEO) study is to compare, over a 2- year period, the effects of vitamin D supplementation versus placebo on knee structural changes, knee pain, and lower limb muscle strength in patients with symptomatic knee OA. Methods/design: Randomised, placebo-controlled, and double-blind clinical trial aiming to recruit 400 subjects (200 from Tasmania and 200 from Victoria) with both symptomatic knee OA and vitamin D deficiency (serum [25-(OH)D] level of >12.5 nmol/liter and <60 nmol/liter). Participants will be randomly allocated to vitamin D supplementation (50,000 IU compounded vitamin D3 capsule monthly) or identical inert placebo group for 2 years. The primary endpoint is loss of knee cartilage volume measured by magnetic resonance imaging (MRI) and Western Ontario and McMaster Universities Index of OA (WOMAC) knee pain score. The secondary endpoints will be other knee structural changes, and lower limb muscle strength. Several other outcome measures including core muscle images and central blood pressure will be recorded. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modeling analyses. Both intention to treat and per protocol analyses will be utilized. DISCUSSION: The trial is designed to test if vitamin D supplementation will reduce loss of knee cartilage volume, prevent the progression of other knee structural abnormalities, reduce knee pain and strengthen lower limb muscle strength, thus modify disease progression in knee OA. Trial Registration: ClinicalTrials.gov identifier: NCT01176344; Australian New Zealand Clinical Trials Registry: ACTRN12610000495022.     

Begomovirus research in India: A critical appraisal and the way ahead

Begomoviruses are a large group of whitefly-transmitted plant viruses containing single-stranded circular DNA encapsidated in geminate particles. They are responsible for significant yield losses in a wide variety of crops in India. Research on begomoviruses has focussed on the molecular characterization of the viruses, their phylogenetic analyses, infectivities on host plants, DNA replication, transgenic resistance, promoter analysis and development of virus-based gene silencing vectors. There have been a number of reports of satellite molecules associated with begomoviruses. This article aims to summarize the major developments in begomoviral research in India in the last approximately 15 years and identifies future areas that need more attention.