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 guidelines for the management of knee osteoarthritis using Appraisal of Guidelines Research and Evaluation criteria

Clinical practice guidelines have been elaborated to summarize evidence related to the management of knee osteoarthritis and to facilitate uptake of evidence-based knowledge by clinicians. The objectives of the present review were summarizing the recommendations of existing guidelines on knee osteoarthritis, and assessing the quality of the guidelines using a standardized and validated instrument--the Appraisal of Guidelines Research and Evaluation (AGREE) tool. Internet medical literature databases from 2001 to 2006 were searched for guidelines, with six guidelines being identified. Thirteen clinician researchers participated in the review. Each reviewer was trained in the AGREE instrument. The guidelines were distributed to four groups of three or four reviewers, each group reviewing one guideline with the exception of one group that reviewed two guidelines. One independent evaluator reviewed all guidelines. All guidelines effectively addressed only a minority of AGREE domains. Clarity/presentation was effectively addressed in three out of six guidelines, scope/purpose and rigour of development in two guidelines, editorial independence in one guideline, and stakeholder involvement and applicability in none. The clinical management recommendation tended to be similar among guidelines, although interventions addressed varied. Acetaminophen was recommended for initial pain treatment, combined with exercise and education. Nonsteroidal anti-inflammatory drugs were recommended if acetaminophen failed to control pain, but cautiously because of gastrointestinal risks. Surgery was recommended in the presence of persistent pain and disability. Education and activity management interventions were superficially addressed in most guidelines. Guideline creators should use the AGREE criteria when developing guidelines. Innovative and effective methods of knowledge translation to health professionals are needed.     

Clinical Practice Guidelines and Consensus Statements in Oncology – An Assessment of Their Methodological Quality

BackgroundConsensus statements and clinical practice guidelines are widely available for enhancing the care of cancer patients. Despite subtle differences in their definition and purpose, these terms are often used interchangeably. We systematically assessed the methodological quality of consensus statements and clinical practice guidelines published in three commonly read, geographically diverse, cancer-specific journals. Methods Consensus statements and clinical practice guidelines published between January 2005 and September 2013 in Current Oncology, European Journal of Cancer and Journal of Clinical Oncology were evaluated. Each publication was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) rigour of development and editorial independence domains. For assessment of transparency of document development, 7 additional items were taken from the Institute of Medicine’s standards for practice guidelines and the Journal of Clinical Oncology guidelines for authors of guidance documents.MethodsConsensus statements and clinical practice guidelines published between January 2005 and September 2013 in Current Oncology, European Journal of Cancer and Journal of Clinical Oncology were evaluated. Each publication was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) rigour of development and editorial independence domains. For assessment of transparency of document development, 7 additional items were taken from the Institute of Medicine''s standards for practice guidelines and the Journal of Clinical Oncology guidelines for authors of guidance documents.FindingsThirty-four consensus statements and 67 clinical practice guidelines were evaluated. The rigour of development score for consensus statements over the three journals was 32% lower than that of clinical practice guidelines. The editorial independence score was 15% lower for consensus statements than clinical practice guidelines. One journal scored consistently lower than the others over both domains. No journals adhered to all the items related to the transparency of document development. One journal’s consensus statements endorsed a product made by the sponsoring pharmaceutical company in 64% of cases.ConclusionGuidance documents are an essential part of oncology care and should be subjected to a rigorous and validated development process. Consensus statements had lower methodological quality than clinical practice guidelines using AGREE II. At a minimum, journals should ensure that that all consensus statements and clinical practice guidelines adhere to AGREE II criteria. Journals should consider explicitly requiring guidelines to declare pharmaceutical company sponsorship and to identify the sponsor’s product to enhance transparency.     

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.     

Microbicides Development Programme: design of a phase III trial to measure the efficacy of the vaginal microbicide PRO 2000/5 for HIV prevention

Background

Non-pharmacological, non-surgical interventions are recommended as the first line of treatment for osteoarthritis (OA) of the hip and knee. There is evidence that exercise therapy is effective for reducing pain and improving function in patients with knee OA, some evidence that exercise therapy is effective for hip OA, and early indications that manual therapy may be efficacious for hip and knee OA. There is little evidence as to which approach is more effective, if benefits endure, or if providing these therapies is cost-effective for the management of this disorder. The MOA Trial (Management of OsteoArthritis) aims to test the effectiveness of two physiotherapy interventions for improving disability and pain in adults with hip or knee OA in New Zealand. Specifically, our primary objectives are to investigate whether: 1. Exercise therapy versus no exercise therapy improves disability at 12 months; 2. Manual physiotherapy versus no manual therapy improves disability at 12 months; 3. Providing physiotherapy programmes in addition to usual care is more cost-effective than usual care alone in the management of osteoarthritis at 24 months.

Methods

This is a 2 × 2 factorial randomised controlled trial. We plan to recruit 224 participants with hip or knee OA. Eligible participants will be randomly allocated to receive either: (a) a supervised multi-modal exercise therapy programme; (b) an individualised manual therapy programme; (c) both exercise therapy and manual therapy; or, (d) no trial physiotherapy. All participants will continue to receive usual medical care. The outcome assessors, orthopaedic surgeons, general medical practitioners, and statistician will be blind to group allocation until the statistical analysis is completed. The trial is funded by Health Research Council of New Zealand Project Grants (Project numbers 07/199, 07/200).

Discussion

The MOA Trial will be the first to investigate the effectiveness and cost-effectiveness of providing physiotherapy programmes of this kind, for the management of pain and disability in adults with hip or knee OA.

Trial registration

Australian New Zealand Clinical Trials Registry ref: ACTRN12608000130369.     

Evaluation of four hematology and a chemistry portable benchtop analyzers using non-human primate blood

Background  Near patient testing (NPT) and point-of-care testing (POCT) using portable benchtop analyzers has become necessary in many areas of the medical community, including biocontainment.
Methods  We evaluated the Beckman AcT diff, Abaxis Vetscan HMII (two instruments), Abbott Cell-Dyn 1800, and Abaxis Vetscan VS2 for within-run precision and correlation to central laboratory instruments using non-human primates blood.
Results  Compared with the central laboratory instruments, the Beckman AcT diff correlated on 80%; the HMII instruments on 31% and 44%, the CD1800 on 31%, and the VS2 on 71% of assays. For assays with published manufacturers precision guidelines, the AcT diff met all nine, the HMII instruments met one and six of six, and the CD 1800 met one of six.
Conclusions  Laboratories using NPT/POCT must test their individual instruments for precision and correlation, identify assays that are reliable, and exclude or develop supplemental procedures for assays that are not.     

Postoperative use of radioiodine (131-I): review of recommendations and guidelines

In the management of large number of patients with differentiated thyroid cancer, the radioactive iodine (131-I) administration plays an important role. The guidelines of numerous international and national medical societies regarding the issue of postoperative 131-I administration have been published and updated in the last few years. The guidelines differ in the shape and content, and contain some specific features. The different methods for evaluation and analysis of clinical evidence level and resulting grades of recommendations have been used in line with the very guidelines. The postoperative 131-I administration refers to the radioiodine ablation as a form of adjuvant treatment and radioiodine therapy in the management of patients with recurrent cancer, persistent disease and regional or distant metastases. According to the indications for the postoperative 131-I administration, the patients could be divided into the three risk groups: the very low risk group in which there is no indication for the postoperative 131-I administration, the low risk group in which the indication could be considered, and the high risk group in which there is a clear indication for the 131-I administration. The different criteria for distribution of patients into these three groups are expressed in a certain guidelines. There are different opinions about the necessary dosage of 131-I for the efficient ablation in the low risk group. Moreover, the opinions are also divided regarding the conduction of postoperative (preablative or pretherapeutic) scintigraphy with 131-I. As regards the instructions on preparation of patients for the radioiodine ablation and therapy, all the guidelines recommend the low iodine diet and endogenous or exogenous stimulation of TSH. The endogenous stimulation is accomplished by the withdrawal of thyroid hormones, whereas the recombinant human TSH (rhTSH) is used for exogenous stimulation. For conducting the therapy with 131-I the level of TSH has to be > 25-30 mU/L.     

Hyperthyroidism and Other Causes of Thyrotoxicosis: Management Guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists

ObjectiveThyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This article describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspeciality physicians and others providing care for patients with this condition.MethodsThe development of these guidelines was commissioned by the American Thyroid Association in association with the American Association of Clinical Endocrinologists. The American Thyroid Association and American Association of Clinical Endocrinologists assembled a task force of expert clinicians who authored this report. The task force examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to develop the text and a series of specific recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group.ResultsClinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves’ hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves’ disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves’ ophthalmopathy; and management of other miscellaneous causes of thyrotoxicosis.ConclusionsOne hundred evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.     

Is there any scientific evidence for the use of glucosamine in the management of human osteoarthritis?

Glucosamine in its acetylated form is a natural constituent of some glycosaminoglycans (for example, hyaluronic acid and keratan sulfate) in the proteoglycans found in articular cartilage, intervertebral disc and synovial fluid. Glucosamine can be extracted and stabilized by chemical modification and used as a drug or a nutraceutical. It has been approved for the treatment of osteoarthritis (OA) in Europe to promote cartilage and joint health and is sold over the counter as a dietary supplement in the United States. Various formulations of glucosamine have been tested, including glucosamine sulfate and glucosamine hydrochloride. In vitro and in vivo studies have uncovered glucosamine's mechanisms of action on articular tissues (cartilage, synovial membrane and subchondral bone) and justified its efficacy by demonstrating structure-modifying and anti-inflammatory effects at high concentrations. However, results from clinical trials have raised many concerns. Pharmacokinetic studies have shown that glucosamine is easily absorbed, but the current treatment doses (for example, 1,500 mg/day) barely reach the required therapeutic concentration in plasma and tissue. The symptomatic effect size of glucosamine varies greatly depending on the formulation used and the quality of clinical trials. Importantly, the effect size reduces when evidence is accumulated chronologically and evidence for the structure-modifying effects of glucosamine are sparse. Hence, glucosamine was at first recommended by EULAR and OARSI for the management of knee pain and structure improvement in OA patients, but not in the most recent NICE guidelines. Consequently, the published recommendations for the management of OA require revision. Glucosamine is generally safe and although there are concerns about potential allergic and salt-related side effects of some formulations, no major adverse events have been reported so far. This paper examines all the in vitro and in vivo evidence for the mechanism of action of glucosamine as well as reviews the results of clinical trials. The pharmacokinetics, side effects and differences observed with different formulations of glucosamine and combination therapies are also considered. Finally, the importance of study design and criteria of evaluation are highlighted as new compounds represent new interesting options for the management of OA.     

Using provenance to manage knowledge of in silico experiments

This article offers a briefing in one of the knowledge management issues of in silico experimentation in bioinformatics. Recording of the provenance of an experiment-what was done; where, how and why, etc. is an important aspect of scientific best practice that should be extended to in silico experimentation. We will do this in the context of eScience which has been part of the move of bioinformatics towards an industrial setting. Despite the computational nature of bioinformatics, these analyses are scientific and thus necessitate their own versions of typical scientific rigour. Just as recording who, what, why, when, where and how of an experiment is central to the scientific process in laboratory science, so it should be in silico science. The generation and recording of these aspects, or provenance, of an experiment are necessary knowledge management goals if we are to introduce scientific rigour into routine bioinformatics. In Silico experimental protocols should themselves be a form of managing the knowledge of how to perform bioinformatics analyses. Several systems now exist that offer support for the generation and collection of provenance information about how a particular in silico experiment was run, what results were generated, how they were generated, etc. In reviewing provenance support, we will review one of the important knowledge management issues in bioinformatics.     

New horizons and perspectives in the treatment of osteoarthritis

Osteoarthritis (OA) is increasingly prevalent worldwide and is associated with a significant economic burden. Despite the increasing number of patients with OA, treatments to manage the condition remain symptomatic, designed to control pain, and improve function and quality of life while limiting adverse events. Both the EULAR (European League Against Rheumatism) and the OARSI (Osteoarthritis Research Society International) issued new guidelines in 2007 and 2008 recommending a combination of nonpharmacological and pharmacological modalities to manage OA effectively. Because of gastrointestinal risks (including ulcer complications) and cardiovascular risks (including hypertension and thrombotic events associated with nonsteroidal anti-inflammatory drugs [NSAIDs]), these guidelines propose acetaminophen as the first choice anti-inflammatory agents. However, NSAIDs are considered to be more effective than acetaminophen for relief of pain. Given the efficacy, safety, and tolerability issues associated with NSAIDs, development of new agents to manage the pain associated with arthritis but without the cardiovascular and gastrointestinal adverse events remains a priority. This review considers current recommendations for the treatment of OA, the most recent evidence on the cardiovascular risks associated with current NSAID treatments, and the potential of newer anti-inflammatory agents with improved benefit-risk profiles.     

How attractive does a new technology have to be to warrant adoption and utilization? Tentative guidelines for using clinical and economic evaluations.

Because economic evaluations of health care services are being published with increasing frequency it is important to (a) evaluate them rigorously and (b) compare the net benefit of the application of one technology with that of others. Four "levels of evidence" that rate economic evaluations on the basis of their methodologic rigour are proposed. They are based on the quality of the methods used to estimate clinical effectiveness, quality of life and costs. With the use of the magnitude of the incremental net benefit of a technology, therapies can also be classified into five "grades of recommendation." A grade A technology is both more effective and cheaper than the existing one, whereas a grade E technology is less or equally effective and more costly. Those of grades B through D are more effective and more costly. A grade B technology costs less than $20,000 per quality-adjusted life-year (QALY), a grade C one $20,000 to $100,000/QALY and a grade D one more than $100,000/QALY. Many issues other than cost effectiveness, such as ethical and political considerations, affect the implementation of a new technology. However, it is hoped that these guidelines will provide a framework with which to interpret economic evaluations and to identify additional information that will be useful in making sound decisions on the adoption and utilization of health care services.     

Update on the american urological association guidelines for the treatment of benign prostatic hyperplasia

The updated 2003 American Urological Association (AUA) Guidelines for the treatment of benign prostatic hyperplasia (BPH) are the culmination of an exhaustive effort predicated on scientifically accepted methods of reviewing the medical literature. In this second publication of the guidelines, a multidisciplinary panel reviewed a new meta-analysis of outcome data from the BPH literature from before and after 1994. The major differences between the 2 guidelines are the changes in our understanding of the biology of the prostate and the introduction of new therapies. The vast majority of randomized controlled trials, particularly with respect to minimally invasive therapies and progression of BPH, were performed after the release of the 1994 guidelines. Also, the most recent AUA panel carefully reviewed unpublished data to make the guidelines as timely as possible. Studies that were subsequently published included those on the value of combination medical therapy for BPH. The panel agreed on updated recommendations for the treatment of moderate-to-severe lower urinary tract symptoms associated with BPH, and diagnostic algorithms were revised. The durability and utility of the present guidelines should exceed that of its predecessor.     

Outcome of Arthroscopy in Patients with Advanced Osteoarthritis of the Hip

Hip arthroscopy has continued to expand its horizons in treating many conditions other than femoroacetabular impingement (FAI). However, the results of hip arthroscopy are known to be poor if the degree of articular cartilage damage is significant. We wanted to assess, whether the procedure might have a role in the management of young and active patients with advanced osteoarthritis (OA) and whether it should be offered as a treatment modality. 77 consecutive patients with Tönnis grade 2 and 3 osteoarthritis of the hip who had undergone hip arthroscopy were included in the study. Patients'' medical notes, plain radiographs and outcome scores (modified Harris hip score (mHHS), non-arthritic hip score (NAHS)) preoperatively and postoperatively at six weeks, six months, one year and annually thereafter, were analysed. 77 patients consisted of 63 men and 14 women with mean follow-up of 2.8 years (2.2 to 4.2) and mean age at surgery of 43 years (19 to 64). The mean preoperative mHHS and NAHS scores were 58 (28 to 87) and 64 (27 to 93) respectively. The mean improvements in both the mHHS and NAHS scores were significant (p = 0.003 and p = 0.0001 for mHHS at one and two years, p = 0.002 and p = 0.0003 for NAHS at one and two years, respectively). There were 34 patients (44%) who required a total hip replacement at mean of 18 months (6 to 48) after hip arthroscopy. We conclude that hip arthroscopy improves outcome scores in 56% of patients with severe OA of the hip (Tönnis grade 2 and 3) for at least two years after surgery. We thus consider the procedure to be a reasonable option for patients with hip OA, although success of the procedure will be less than if undertaken for certain other conditions.     

关节腔内注射细胞制剂治疗骨关节炎的临床研究进展

关节腔内注射细胞制剂是治疗骨关节炎(OA)的新趋势,且展现了良好的临床效果、安全性及可行性。细胞制剂有多种类型,包括血小板、干细胞和单个核细胞(MNCs)。血小板制剂倾向于基层医疗机构应用和早期OA患者的治疗;MNCs较适用于不具备干细胞培养条件的医疗机构和中期OA患者应用;而干细胞制剂较适合高级别医疗机构和晚期OA患者应用。虽然腔内注射细胞产品治疗OA进行了大量临床研究,但亦有不足;因此制定腔内注射治疗OA不同细胞制剂的质量控制标准、临床应用标准和进行大样本多中心随机对照临床试验势在必行。探索外泌体、外周血MNCs治疗OA的临床研究及其分子机制,是研究的新切入点。     

Appraisal of WHO Guidelines in Maternal Health Using the AGREE II Assessment Tool

In 2007, the World Health Organization (WHO) received a criticism for a lack of transparency and systematic methods in the development of guidelines, which were at that time perceived as substantially driven by expert opinion. In this paper we assessed the quality of maternal and perinatal health guidelines developed since then. We used the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool to evaluate the quality of methodological rigour and transparency of four different WHO guidelines published between 2007 and 2011. Our findings showed high scores among the most recent guidelines on maternal and perinatal health suggesting higher quality. However, there is still potential for improvement, especially in including different stakeholder views, transparency of guidelines regarding the role of the funding body and presentation of the guideline document.     

Progress in the use of mesenchymal stromal cells for osteoarthritis treatment

Literature review of MSCs in the treatment of osteoarthritis in the past five yearsOsteoarthritis (OA) is one of the most common chronic joint diseases, with prominent symptoms caused by many factors. However, current medical interventions for OA have resulted in poor clinical outcomes, demonstrating that there are huge unmet medical needs in this area. Cell therapy has opened new avenues of OA treatment. Different sources of mesenchymal stromal cells (MSCs) may have different phenotypes and cellular functions. Pre-clinical and clinical studies have demonstrated the feasibility, safety and efficacy of MSC therapy. Mitogen-activated protein kinase, Wnt and Notch signaling pathways are involved in the chondrogenesis of MSC-mediated treatments. MSCs may also exert effective immunoregulatory and paracrine effects to stimulate tissue repair. Therapy with extracellular vesicles containing cytokines, which are secreted by MSCs, might be a potential treatment for OA.     

Photosynthesis of six barley genotypes as affected by water stress

The effect of water stress on plant water status and net photosynthetic gas exchange (PN) in six barley genotypes (Hordeum vulgare L.) differing in productivity and drought tolerance was studied in a controlled growth chamber. Osmotic adjustment (OA), PN, stomatal conductance (gs), and the ratio intercellular/ambient. CO2 concentration (Ci/Ca) were evaluated at four different levels of soil water availability, corresponding to 75, 35, 25 and 15 % of total available water. Variability in OA capacity was observed between genotypes: the drought tolerant genotypes Albacete and Alpha showed higher OA than drought susceptible genotypes Express and Mogador. The genotype Albacete exhibited also higher PN than the others at low water potential (Ψ). The ratios of PN/gs and Ci/Ca showed that differences in photosynthetic inhibition between genotypes at low Ψ were probably due to nonstomatal effects. In Tichedrett, a landrace genotype with a very extensive root development, OA was not observed, however, it exhibited a capacity to maintain its photosynthetic activity under water stress. This revised version was published online in June 2006 with corrections to the Cover Date.