A discrete-choice experiment of United Kingdom patients' willingness to risk adverse events for improved function and pain control in osteoarthritis.

OBJECTIVE: To assess patient preferences for treatment-related benefits and risks associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis (OA). DESIGN: Using a chronic-illness panel in the United Kingdom, patients 45 years or older with a self-reported diagnosis of OA were eligible to participate in the study. Patient preferences were assessed using a discrete-choice experiment that compared hypothetical treatment profiles of benefits and risks consistent with NSAID use. Benefit outcomes (ambulatory pain, resting pain, stiffness, and difficulty doing daily activities) were presented on a 0-to-100 mm scale. Risk outcomes (bleeding ulcer, stroke, and myocardial infarction [MI]) were expressed as probabilities over a fixed time period. Each patient answered 10 choice tasks comparing different treatment profiles. Preference weights were estimated using a random-parameters logit model. RESULTS: Final sample included 294 patients. Patients ranked reductions in ambulatory pain and difficulty doing daily activities (both: 6.32; 95% confidence interval [CI]: 5.0-7.6) as the most important benefit outcomes, followed by reductions in resting pain (2.80; 95% CI: 1.8-3.8) and stiffness (2.65; 95% CI: 0.9-4.4). Incremental changes (3%) in the risk of MI or stroke were assessed as the most important risk outcomes (10.00; 95% CI: 8.2-11.8; and 8.90; 95% CI: 7.3-10.5, respectively). CONCLUSION: Patients ranked ambulatory pain as a more important benefit than resting pain; likely due to its impact on ability to do daily activities. For a 25-mm reduction, patients were willing to accept four times the risk of MI in ambulatory pain vs resting pain.

Further assessment of the clinically effective dose range of etoricoxib: a randomized, double-blinded, placebo-controlled trial in rheumatoid arthritis.

OBJECTIVE: To further assess the clinically active dose range of etoricoxib, a COX-2 selective inhibitor, in rheumatoid arthritis (RA). METHODS: RA patients were randomized to etoricoxib 10, 30, 60, or 90 mg or placebo in a double-blind, 12-week study. DMARDs (methotrexate, biologics) or low-dose corticosteroids were allowed in stable doses. The primary endpoint was the proportion of patients completing the study and achieving an American College of Rheumatology 20% (ACR20) response. Secondary endpoints included individual components of the ACR index and Patient Global Assessment of Pain. Safety was assessed by physical exam and adverse experiences (AEs) occurrences. RESULTS: Etoricoxib 90 mg was the only dose to reach a statistically significant difference from placebo (p < 0.001) on the primary endpoint; etoricoxib 60 mg approached significance (p = 0.057). Significant pain improvement vs. placebo was observed with etoricoxib 90 mg (p < 0.001), 60 mg (p = 0.018), and 30 mg (p = 0.017). Despite the use of background biologics and corticosteroids, a dose response was still apparent. A higher proportion of etoricoxib 60 and 90 mg patients had renovascular AEs (i.e., edema and hypertension) compared with placebo, although discontinuations for renovascular AEs were rare. Etoricoxib 90 mg had a higher incidence of serious AEs (n = 5; 1 was considered drug-related) versus placebo (n = 0). LIMITATIONS: The present study was not powered to detect differences in cardiovascular or gastrointestinal safety by dose. Additionally, further research is needed to clarify the role of doses less than the etoricoxib 90 mg dose for pain management in RA patients. CONCLUSION: Etoricoxib 90 mg demonstrated statistically superior efficacy (ACR20) compared with placebo and numerical superiority over the other doses of etoricoxib studied. Etoricoxib 30 and 60 mg demonstrated significant pain improvement versus placebo, suggesting utility for some patients.

Safety issues in the development of treatments for osteoarthritis: recommendations of the Safety Considerations Working Group.

OBJECTIVE: The symptomatic treatment of osteoarthritis (OA) remains to be improved, as many patients do not respond well to current palliative therapies and/or suffer unacceptable adverse events. Given the unmet need for innovative, effective and well-tolerated therapies, it is important to develop the means to estimate the ongoing safety profile of novel therapeutic agents over short- and longer term use. DESIGN: Methods are presented to estimate the number of serious adverse events (SAEs) of interest considered as "acceptable" per 1000 patient-years exposure and to estimate the numbers of patient-years needed in a randomized controlled trial (RCT) to meet objectives. As exposure is increased, more evidence is accrued that the overall risk is within study limits. It is equally important that requirements for delineating the safety of promising new therapies not create barriers that would preclude their development. Therefore, ongoing surveillance of occurrence of SAEs of interest during clinical development is proposed, for example after every incremental 500 patient-years exposure are accrued. RESULTS: This paper and others in this special issue focus on identification of safety signals for symptomatic treatments of OA. Much less information is available for agents aimed at slowing/preventing structural progression but it is expected that a higher risk profile might be considered acceptable in the context of more promising benefit. CONCLUSION: This paper provides a proposal and supporting data for a comprehensive approach for assessing ongoing safety during clinical development of both palliative and disease-modifying therapies for OA.

Responder analysis for pain relief and numbers needed to treat in a meta-analysis of etoricoxib osteoarthritis trials: bridging a gap between clinical trials and clinical practice.

BACKGROUND: Population mean changes from clinical trials are difficult to apply to individuals in clinical practice. Responder analysis may be better, but needs validating for level of response and treatment duration. METHODS: The numbers of patients with pain relief over baseline (> or =15%, > or =30%, > or =50%, > or =70%) at 2, 4, 8 and 12 weeks of treatment were obtained using the WOMAC 100 mm visual analogue pain subscale score for each treatment group in seven randomised placebo-controlled trials of etoricoxib in osteoarthritis lasting > or =6 weeks. Dropouts were assigned 0% improvement from baseline from then on. The numbers needed to treat (NNTs) were calculated at each level of response and time point. RESULTS: 3554 patients were treated with placebo, etoricoxib 30 mg and 60 mg, celecoxib 200 mg, naproxen 1000 mg or ibuprofen 2400 mg daily. Response rates fell with increasing pain relief: 60-80% experienced minimally important pain relief (> or =15%), 50-60% moderate pain relief (> or =30%), 40-50% substantial pain relief (> or =50%) and 20-30% extensive pain relief (> or =70%). NNTs for etoricoxib, celecoxib and naproxen were stable over 2-12 weeks. Ibuprofen showed lessening of effectiveness with time. CONCLUSION: Responder rates and NNTs are reproducible for different levels of response over 12 weeks and have relevance for clinical practice at the individual patient level. An average 10 mm improvement in pain equates to almost one in two patients having substantial benefit.

Once-daily, controlled-release tramadol and sustained-release diclofenac relieve chronic pain due to osteoarthritis: a randomized controlled trial.

OBJECTIVE: The present study was a randomized, parallel, double-blind comparison between controlled-release (CR) tramadol and sustained-release (SR) diclofenac in patients with chronic pain due to osteoarthritis of the hips and/or knees. METHODS: Patients with at least moderate pain intensity, and having received analgesics over the past three months, underwent a two- to seven-day washout of current analgesics before initiation of 200 mg CR tramadol or 75 mg SR diclofenac. During the eight-week study, patients returned to the clinic biweekly. CR tramadol doses were titrated to a maximum of 200 mg, 300 mg or 400 mg per day. SR diclofenac doses were titrated to 75 mg or 100 mg once daily, or 75 mg twice a day based on pain relief and the presence of side effects. For rescue analgesic, patients took acetaminophen as needed, up to 650 mg three times a day. RESULTS: Forty-five patients on CR tramadol and 52 patients on SR diclofenac were evaluable. Significant improvements from prestudy treatment were shown for visual analogue scale pain (P=0.0001), stiffness (P<0.0005) and physical function (P=0.0001) scores for both treatments. There were no significant differences between the two treatments in the Western Ontario and McMaster Universities subscales, overall pain, pain and sleep, or the clinical effectiveness evaluation. Overall incidence of adverse events was similar in both groups, with more opioid-related adverse events with CR tramadol, and two serious adverse events occurring with the use of SR diclofenac. CONCLUSIONS: CR tramadol is as effective as SR diclofenac in the treatment of pain due to knee or hip osteoarthritis, with the potential for fewer of the serious side effects that characterize nonsteroidal anti-inflammatory drug administration.

Exercise for treating fibromyalgia syndrome.

BACKGROUND: Fibromyalgia (FMS) is a syndrome expressed by chronic widespread body pain which leads to reduced physical function and frequent use of health care services. Exercise training is commonly recommended as a treatment. This is an update of a review published in Issue 2, 2002. OBJECTIVES: The primary objective of this systematic review was to evaluate the effects of exercise training including cardiorespiratory (aerobic), muscle strengthening, and/or flexibility exercise on global well-being, selected signs and symptoms, and physical function in individuals with FMS. SEARCH STRATEGY: We searched MEDLINE, EMBASE, CINAHL, SportDiscus, PubMed, PEDro, and the Cochrane Central Register for Controlled Trials (CENTRAL, Issue 3, 2005) up to and including July 2005. We also reviewed reference lists from reviews and meta-analyses of treatment studies. SELECTION CRITERIA: Randomized trials focused on cardiorespiratory endurance, muscle strength and/or flexibility as treatment for FMS were selected. DATA COLLECTION AND ANALYSIS: Two of four reviewers independently extracted data for each study. All discrepancies were rechecked and consensus achieved by discussion. Methodological quality was assessed by two instruments: the van Tulder and the Jadad methodological quality criteria. We used the American College of Sport Medicine (ACSM) guidelines to evaluate whether interventions had provided a training stimulus that would effect changes in physical fitness. Due to significant clinical heterogeneity among the studies we were only able to meta-analyze six aerobic-only studies and two strength-only studies. MAIN RESULTS: There were a total of 2276 subjects across the 34 included studies; 1264 subjects were assigned to exercise interventions. The 34 studies comprised 47 interventions that included exercise. Effects of several disparate interventions on global well-being, selected signs and symptoms, and physical function in individuals with FMS were summarized using standardized mean differences (SMD). There is moderate quality evidence that aerobic-only exercise training at recommended intensity levels has positive effects global well-being (SMD 0.44, 95% confidence interval (CI 0.13 to 0.75) and physical function (SMD 0.68, 95% CI 0.41 to 0.95) and possibly on pain (SMD 0.94, 95% CI -0.15 to 2.03) and tender points (SMD 0.26, 95% CI -0.28 to 0.79). Strength and flexibility remain under-evaluated. AUTHORS' CONCLUSIONS: There is 'gold' level evidence (www.cochranemsk.org) that supervised aerobic exercise training has beneficial effects on physical capacity and FMS symptoms. Strength training may also have benefits on some FMS symptoms. Further studies on muscle strengthening and flexibility are needed. Research on the long-term benefit of exercise for FMS is needed.

Medicinal and injection therapies for mechanical neck disorders.

BACKGROUND: Controversy persists regarding medicinal therapies and injections. OBJECTIVES: To determine the effects of medication and injections on primary outcomes (e.g. pain) for adults with mechanical neck disorders and whiplash. SEARCH STRATEGY: We searched CENTRAL, MANTIS, CINAHL from their start to May 2006; MEDLINE and EMBASE to December 2006. We scrutinised reference lists for other trials. SELECTION CRITERIA: We included randomised controlled trials with adults with neck disorders, with or without associated headache or radicular findings. We considered medicinal and injection therapies, regardless of route of administration. DATA COLLECTION AND ANALYSIS: Two authors independently selected articles, abstracted data and assessed methodological quality. When clinical heterogeneity was absent, we combined studies using random-effects models. MAIN RESULTS: We found 36 trials that examined the effects of oral NSAIDs, psychotropic agents, steroid injections, and anaesthetic agents. Trials had a mean of 3.1 on the Jadad Scale for methodological quality; 70% were high quality. For acute whiplash, administering intravenous methylprednisolone within eight hours of injury reduced pain at one week (SMD -0.90, 95% CI -1.57 to -0.24), and sick leave but not pain at six months compared to placebo in one trial. For chronic neck disorders at short-term follow-up, intramuscular injection of lidocaine was superior to placebo (SMD -1.36, 95% CI -1.93 to -0.80); NNT 3, treatment advantage 45% and dry needling, but similar to ultrasound in one trial each. In chronic neck disorders with radicular findings, epidural methylprednisolone and lidocaine reduced neck pain and improved function more than when given by intramuscular route at one-year follow-up, in one trial. In subacute and chronic neck disorders, muscle relaxants, analgesics and NSAIDs had limited evidence and unclear benefits. In participants with chronic neck disorders with or without radicular findings or headache, there was moderate evidence from five high quality trials that Botulinum toxin A intramuscular injections had similar effects to saline in improving pain (pooled SMD: -0.39, 95%CI -1.25 to 0.47), disability or global perceived effect. AUTHORS' CONCLUSIONS: The major limitations are the lack of replication of the findings and sufficiently large trials. There is moderate evidence for the benefit of intravenous methylprednisolone given within eight hours of acute whiplash, from a single trial. Lidocaine injection into myofascial trigger points appears effective in two trials. There is moderate evidence that Botulinum toxin A is not superior to saline injection for chronic MND. Muscle relaxants, analgesics and NSAIDs had limited evidence and unclear benefits.

WITHDRAWN: Physical medicine modalities for mechanical neck disorders.

BACKGROUND: Twenty-six to 71 percent of the adult population can recall experiencing an episode of neck pain or stiffness in their lifetime. The treatments that patients receive for neck pain are varied, as are the perceptions of the benefits of these treatments. In this age of increasing accountability, governmental agencies, third party payers and patients are demanding evidence-based practice performance. To track down the best estimate of efficacy of the various conservative management strategies for mechanical neck disorders, a four-part systematic review was prepared. Part two investigates and reports on the efficacy of physical medicine modalities. OBJECTIVES: Multiple physical medicine modalities are commonly included as part of therapeutic interventions for mechanical neck disorders (neck pain). The objective of this review was to assess the effects of physical medicine modalities for pain in adults with mechanical neck disorders. SEARCH STRATEGY: We searched Medline, Embase, Chirolars, Index to Chiropractic Literature, Cinahl, Science Citation Index, Conference Proceedings Index, National Technical Information Services and reference lists of the retrieved articles from 1985 to December 1993 and we contacted content experts. SELECTION CRITERIA: Randomised trials and controlled trials of physical medicine modalities in adults with mechanical neck disorder. DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed trial quality and two reviewers independently extracted data. Investigators were contacted to obtain information or data that could not be found in the published reports. MAIN RESULTS: Thirteen trials were included. The overall quality of the included trials was generally good. Two trials using electromagnetic therapy produced a significant reduction in pain (p <0.01) with three to four weeks of daily (eight hours per day) therapy sessions; and three using laser therapy did not differ significantly from a placebo (p=0.20) for six to 10 sessions of treatment. Not enough scientific testing exists to clearly determine the effectiveness of other therapies. This includes treatments such as exercise, traction, acupuncture, heat / cold applications, electrotherapies, cervical orthoses and chronic pain / cognitive behavioural rehabilitation strategies. AUTHORS' CONCLUSIONS: There is little information available from trials to support the use of physical medicine modalities for mechanical neck pain. There is some support for the use of electromagnetic therapy and against the use of laser therapy with respect to pain reduction.

WITHDRAWN: Patient education for mechanical neck disorders.

BACKGROUND: To track down the best estimate of efficacy of the various conservative management strategies for mechanical neck disorders, a four-part systematic review was prepared. Part four investigates the efficacy of patient education strategies as the therapeutic intervention. OBJECTIVES: This review of patient education is one of four reviews of conservative management of mechanical neck disorders. The other reviews address manual, physical and drug therapies. The objective of this review was to assess the effects of patient education for pain in adults with mechanical neck disorders. SEARCH STRATEGY: We searched Medline, Embase, Chirolars, Index to Chiropractic Literature, Cinahl, Science Citation Index, Conference Proceedings Index, National Technical Information Services from 1985 to December 1993, reference lists of the retrieved articles and we contacted experts in the field. SELECTION CRITERIA: Randomised trials or controlled clinical trials of patient educational strategies for adults with mechanical neck disorders. DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed trial quality and two reviewers independently extracted data. Investigators were contacted to obtain data that could not be found in the published reports. MAIN RESULTS: Three trials were included. Their methodological quality varied from weak to strong. One trial did not find a significant reduction in pain using group instructional strategies (neck school) and exercise with or without psychological counselling compared to no treatment (standardised mean difference 0.07, 95% confidence interval -0.51 to 0.66, and -0.37, 95% confidence interval -0.95 to 0.22, respectively). Another trial did not find a significant reduction in pain using individualised patient education (advice), anti-inflammatories and analgesics compared with placebo (standardised mean difference 0.24, 95% confidence interval -0.58 to 1.07). The third trial found that advice which included demonstrated mobilization exercises, verbal and written instruction on posture correction, the use of a collar, heat sources, muscle relaxation and analgesics gave significant pain relief compared with general advice about mobilisation after a period of rest and use of analgesics at 4 weeks of treatment (standardised mean difference -0.62, 95% confidence interval -1.05 to -0.19) but at 6 weeks of treatment there was no longer any difference (s.m.d. -0.37, 95% confidence interval -0.8 to 0.05). The first two trials lacked statistical power and the third was methodologically weak. AUTHORS' CONCLUSIONS: Patient education utilising individualised or group instructional strategies has not been shown to be beneficial in reducing pain for mechanical neck disorders.

The immunogenicity, safety, and efficacy of etanercept liquid administered once weekly in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the immunogenicity, safety, and efficacy of 50 mg/mL liquid etanercept. METHODS: In a multicenter, open-label study, adults with active rheumatoid arthritis (RA) received 50 mg/mL liquid etanercept subcutaneously once weekly for 24 weeks. Immunogenicity was assessed at baseline and weeks 24 and 28, safety at all study visits, and efficacy at baseline and weeks 12 and 24. RESULTS: Of 222 treated patients, 88% completed the study; 81% were women; 84% were white; mean age was 53 years; mean RA duration was 10 years. Antibodies to etanercept, all non-neutralizing, were detected in 12 of 214 patients; 7 of the 12 were borderline positive (antibody titers <1:50). The presence of non-neutralizing anti-etanercept antibodies did not appear to affect clinical safety or efficacy. Few patients reported serious adverse events (6.3%), serious infections (2.3%), or withdrew because of adverse events (4.5%). Most adverse events were mild or moderate. The most common event, injection site reaction, occurred in 29.3% patients. At week 24, 63% of patients achieved an ACR20 response, 36% an ACR50 response, and 14% an ACR70 response. Similar responses were apparent by week 12. Week 24 mean improvement in the Health Assessment Questionnaire disability index scores was 0.6 points; improvement in the Short Form-36 Physical Component Score was 10.0 points. CONCLUSION: The 50 mg/mL liquid etanercept formulation administered once weekly was well tolerated. The incidence of anti-etanercept antibodies, the nature and frequency of adverse events, and improvements in signs and symptoms of RA and patient physical function were similar to those in previous etanercept studies.

Massage for mechanical neck disorders.

BACKGROUND: Mechanical neck disorders (MND) are common, disabling and costly. Massage is a commonly used modality for the treatment of neck pain. OBJECTIVES: To assess the effects of massage on pain, function, patient satisfaction and cost of care in adults with neck pain. To document adverse effects of treatment. SEARCH STRATEGY: Cochrane CENTRAL, MEDLINE, EMBASE, MANTIS, CINAHL, and ICL databases were electronically searched, without language restriction, from their inception to September 2004 SELECTION CRITERIA: Studies using random or quasi-random assignment were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently conducted citation identification, study selection, data abstraction and methodological quality assessment. Using a random-effects model, we calculated the relative risk and standardized mean difference. MAIN RESULTS: Nineteen trials met the inclusion criteria. Overall, the methodological quality was low, with 12/19 assessed as low-quality studies. Trials could not be statistically pooled because of heterogeneity in treatment and control groups. Therefore, a levels-of-evidence approach was used to synthesize results. Assessment of the clinical applicability of the trials showed that the participant characteristics were well reported, but neither the descriptions of the massage intervention nor the credentials or experience of the massage professionals were well reported. Six trials examined massage as a stand-alone treatment. The results were inconsistent. Of the 14 trials that used massage as part of a multimodal intervention, none were designed such that the relative contribution of massage could be ascertained. Therefore, the role of massage in multimodal treatments remains unclear. AUTHORS' CONCLUSIONS: No recommendations for practice can be made at this time because the effectiveness of massage for neck pain remains uncertain. Pilot studies are needed to characterize massage treatment (frequency, duration, number of sessions, and massage technique) and establish the optimal treatment to be used in subsequent larger trials that examine the effect of massage as either a stand-alone treatment or part of a multimodal intervention. For multimodal interventions, factorial designs are needed to determine the relative contribution of massage. Future reports of trials should improve reporting of the concealment of allocation, blinding of outcome assessor, adverse events and massage characteristics. Standards of reporting for massage interventions, similar to CONSORT, are needed. Both short- and long-term follow-up are needed.

Long term safety of etanercept in elderly subjects with rheumatic diseases.

OBJECTIVES: To determine the long term safety profile of the tumour necrosis factor (TNF) antagonist etanercept in subjects with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) aged > or =65 years in comparison with subjects aged <65 years. METHODS: Safety data from an integrated database of 4322 subjects enrolled in 18 RA trials, 2 PsA trials, and 2 AS trials were analysed. Safety end points included subject incidence of all adverse events (AE), serious adverse events (SAE), infectious events (IE), medically important infections (MII), and deaths. Events of particular interest in subjects treated with TNF modulating biological treatments, including demyelinating diseases, tuberculosis, lymphomas, and cardiovascular diseases, were also evaluated. RESULTS: The incidence of AE, SAE, IE, MII, and malignancies was not significantly raised in elderly subjects in comparison with subjects aged <65 years. No cases of tuberculosis were reported in the trials. Demyelinating diseases were seen only in subjects aged <65 years. The incidence and types of death in the elderly subjects were consistent with the expected rates for subjects of comparable age. CONCLUSIONS: Etanercept is a generally safe and well tolerated biological agent for treatment of rheumatological diseases in the elderly, and the risk of AE in these studies was no greater in subjects aged > or =65 years than in younger subjects.

Medicinal and injection therapies for mechanical neck disorders.

BACKGROUND: Medicinal therapies and injections are commonly recommended for neck pain, yet controversy persists over their effectiveness. OBJECTIVES: To determine the effect of medicines and injections on pain, function/disability, patient satisfaction and range of motion in participants with mechanical neck disorders (MND). SEARCH STRATEGY: We searched CENTRAL (Issue 4, 2002), and MEDLINE, EMBASE, MANTIS, CINHAL from their start to March 2003. We scrutinized reference lists for other trials. SELECTION CRITERIA: We included randomized controlled trials with adults with MND, with or without associated headache or radicular findings. We considered medicinal and injection therapies, regardless of route of administration. DATA COLLECTION AND ANALYSIS: Two authors independently selected articles, abstracted data and assessed methodological quality using the Jadad criteria. Consensus was used to resolve disagreements. When clinical heterogeneity was absent, we combined studies using random-effects meta-analysis models. MAIN RESULTS: We found 32 trials that examined the effects of oral NSAIDs, psychotropic agents, injections of steroids, and anaesthetic agents. Overall, methodological quality had a mean of 3.2/5 on the Jadad Scale. For acute whiplash, administering intravenous methylprednisolone within eight hours reduced pain at one week, and sick leave but not pain at six months compared to placebo. For chronic MND at short-term follow-up, intramuscular injection of lidocaine was superior to placebo or dry needling, but similar to ultrasound. In chronic MND with radicular findings, epidural methylprednisolone and lidocaine reduced neck pain and improved function at one-year follow-up compared to the intramuscular route. In subacute/chronic MND, we found conflicting evidence of pain reduction for oral psychotropic agents compared to placebo or control. Single trials of eperison hydrochloride and tetrazepam showed positive results. Results for cyclobenzaprine were mixed. Diazepam did not show benefit. Other treatments including NSAIDS and nerve blocks had unclear or limited evidence of benefit. In participants with chronic MND with or without radicular findings or headache, there was moderate evidence from five high quality trials showing that Botox A intramuscular injections were not better than saline in improving pain (pooled SMD: -0.39 (95%CI: -1.25 to 0.47), disability or global perceived effect. AUTHORS' CONCLUSIONS: Intra-muscular injection of lidocaine for chronic MND and intravenous injection of methylprednisolone for acute whiplash were effective treatments. There was limited evidence of effectiveness of epidural injection of methylprednisolone and lidocaine for chronic MND with radicular findings. Oral psychotropic agents had mixed results. There was moderate evidence that Botox A intramuscular injections for chronic MND were no better than saline. Other medications, including NSAIDs, had contradictory or limited evidence of effectiveness.

Identification of an unusual VanA element in glycopeptide-resistant Enterococcus faecium in Brazil following international transfer of a bone marrow transplant patient.

A vancomycin-resistant Enterococcus (VRE) was isolated from a blood culture of a patient in a Brazilian hospital who had a treatment history of a bone marrow transplant in the USA. The organism was identified as Enterococcus faecium, which exhibited an MIC (minimum inhibitory concentration) >or= 256 microg/mL for vancomycin. This was confirmed by E-test and the vanA gene was detected by PCR. Overlapping PCR revealed a left IR deletion and an additional 1.5 kb fragment between vanSH genes. DdeI digestion of vanRSHAX genes showed the determinant to be a T type variant, and the element was cloned and sequenced. These results revealed an IS1251 downstream of nucleotide 5820 of the VanA element. Insertions like this have not been reported previously in Brazil, but have been detected in the USA. The genotype and association with a patient previously treated in the USA suggest that this VRE was introduced from abroad, probably through inter-hospital strain spread.

The effect of strength training combined with bisphosphonate (etidronate) therapy on bone mineral, lean tissue, and fat mass in postmenopausal women.

The combined and separate effects of exercise training and bisphosphonate (etidronate) therapy on bone mineral in postmenopausal women were compared. Forty-eight postmenopausal women were randomly assigned (double blind) to groups that took intermittent cyclical etidronate; performed strength training (3 d/week) and received matched placebo; combined strength training with etidronate; or took placebo and served as nonexercising controls. Bone mineral, lean tissue, and fat mass were assessed by dual-energy X-ray absorptiometry before and after 12 months of intervention. After removal of outlier results, changes in bone mineral density (BMD) of the lumbar spine and bone mineral content (BMC) of the whole body were greater in the subjects given etidronate (+2.5 and +1.4%, respectively) compared with placebo (-0.32 and 0%, respectively) (p < 0.05), while exercise had no effect. There was no effect of etidronate or exercise on the proximal femur and there was no interaction between exercise and etidronate at any bone site. Exercise training resulted in significantly greater increases in muscular strength and lean tissue mass and greater loss of fat mass compared with controls. We conclude that etidronate significantly increases lumbar spine BMD and whole-body BMC and that strength training has no additional effect. Strength training favourably affects body composition and muscular strength, which may be important for prevention of falls.

Manual therapy for mechanical neck disorders: a systematic review.

Neck disorders are common, disabling and costly. Randomized trials were reviewed using a Cochrane format, to determine if manual therapy improves pain, function and patient satisfaction in adults suffering from neck disorders with and without radicular findings or headache. Sequenced computerized searches ended in December 1997. Two independent reviewers extracted data while three assessed trial quality. Standard mean difference and relative risks were translated to number needed to treat (NNT) and the percent treatment advantage. The 20 selected trials' quality was 2.4 (SD: 1.04) on the 5-point scale described by Jadad. Trials were clinically heterogenous. Manipulation alone, mobilizations alone, manipulation/mobilization and treatments including massage consistently showed similar effects to placebo, wait period or control. Multimodal manual therapy care including exercise were superior to a control, to certain physical medicine methods and to rest for pain and patient satisfaction. The NNT for a clinically important reduction in pain varied from 2 to 11 and treatment advantage from 6% to 41% at the cost of benign transient side-effects. While results remain inconclusive, some clinical themes have emerged. For mechanical neck disorder with or without headache, it appears that to be most beneficial, manual therapies should be done with exercise for improving pain and patient satisfaction. Manipulation and mobilization alone appear to be less effective. Factorial design would help delineate the magnitude of effect for each component of care.

Exercise for treating fibromyalgia syndrome.

BACKGROUND: Fibromyalgia (FMS) is a syndrome expressed by chronic widespread body pain which leads to reduced physical function and frequent use of health care services. Exercise training is commonly recommended as a treatment. OBJECTIVES: The objective of this systematic review was to examine the efficacy of exercise training as an treatment for FMS. SEARCH STRATEGY: We searched 6 electronic bibliographies for studies of exercise training in FMS: MEDLINE (1966-12/2000), CINAHL (1982-12/2000), HealthSTAR (1990-12/2000), Sports Discus (1975-05/2000), EMBASE (1974-05/2000) and the Cochrane Controlled Trials Register (2000, issue 4). We also reviewed the reference lists from identified articles including reviews and meta-analyses of treatment studies. SELECTION CRITERIA: Randomized trials focused on cardiorespiratory endurance, muscle strength and/or flexibility as treatment for FMS were selected. DATA COLLECTION AND ANALYSIS: Two reviewers independently identified trials meeting inclusion criteria, rated the methodologic quality using 2 standardized validated instruments, evaluated the adequacy of the exercise training stimulus using the American College of Sports Medicine (ACSM) criteria and evaluated the results. Disagreements were resolved through active discussion and consensus. High quality training studies had scores of 50% or greater on van Tulder methodologic criteria and met the minimum training standards of ACSM. Outcome variables were grouped into 7 constructs: pain, tender points, physical function, global well being, self efficacy, fatigue & sleep, and psychological function. Two reviewers independently extracted data on study characteristics, results and point estimates for selected variables, and used consensus to address discrepancies. MAIN RESULTS: Sixteen trials involving a total of 724 participants were assigned at random to: exercise intervention groups (n=379), control groups (n=277), or groups receiving an alternate treatment (n=68). Seven studies were high quality training studies: 4 aerobic training, 1 a mixture of aerobic, strength and flexibility training, 1 strength training and 2 with exercise training as part of a composite treatment. Flexibility protocols were never described in sufficient detail to allow evaluation. The four high quality aerobic training studies reported significantly greater improvements in the exercise groups versus control groups in aerobic performance (17.1% increase in aerobic performance with exercise versus 0.5% increase in the control groups), tender point pain pressure threshold (28.1% increase versus 7.0% decrease) and improvements in pain (11.4% decrease in pain versus 1.6% increase). Poor description of exercise protocols was common, with insufficient information on intensity, duration, frequency and mode of exercise. Adverse events were also poorly reported. REVIEWER'S CONCLUSIONS: Supervised aerobic exercise training has beneficial effects on physical capacity and FMS symptoms. Strength training may also have benefits on some FMS symptoms. Further studies on muscle strengthening and flexibility are needed. Research on the long-term benefit of exercise for FMS is needed.

Minimal clinically important difference in radiological progression of joint damage over 1 year in rheumatoid arthritis: preliminary results of a validation study with clinical experts.

To determine the minimal clinically important difference (MCID) between hand and foot films with a 1 year interval assessed with the Sharp/van der Heijde or Larsen/Scott scoring method. Progression scores of the 2 methods were compared with the opinion of an international expert panel on clinical relevance of radiological joint damage in 4 predefined clinical settings. The expert panel consisted of 3 rheumatologists, who evaluated 46 pairs of hand and foot films, taken with 1 year intervals, of patients with early rheumatoid arthritis. Receiver operating characteristics curves analyzed the accuracy of different threshold values (progression scores) of the 2 scoring methods to detect the presence or absence of clinically important difference, as defined by the expert panel as external criterion. The threshold value with the highest accuracy was subsequently chosen as the score representing the MCID. Five Sharp/van der Heijde units and 2 Larsen/Scott units were the best cutoffs. The accompanying sensitivities ranged from 77% to 100% for the Sharp/van der Heijde method and from 73% to 84% for the Larsen/Scott method for the 4 clinical settings. The specificities were between 78% and 84% for the Sharp/van der Heijde method and between 74% and 94% for the Larsen/Scott method. The smallest progression score that can be detected apart from interobserver measurement error, the smallest detectable difference (SDD), was equal to or larger than the calculated MCID, 5 Sharp/van der Heijde units and 6 Larsen/Scott units in our study, if the mean progression scores of the same 2 observers were used. The SDD is a conservative estimate of the MCID; our panel rated progression at or below this level as clinically significant.