Biomedical subjects

G Wells

Publications and source records attributed to G Wells.

At least 91 records · Page 5Linked to original sources

PubMed2000

Sulfasalazine for rheumatoid arthritis.

OBJECTIVES: To estimate the short-term efficacy and toxicity of sulfasalazine for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to July 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing sulfasalazine against placebo in patients with RA. DATA COLLECTION AND ANALYSIS: Two reviewers determined the studies to be included based on inclusion and exclusion criteria (GW, MSA). Data were independently abstracted by two reviewers (EB, MSA), and checked by a third reviewer (BS) using a pre-developed form for the rheumatoid arthritis sub-group of the Cochrane Musculoskeletal Group. The same two reviewers, using a validated scale (Jadad 1996) assessed the methodological quality of the RCTs and CCTs independently. Rheumatoid arthritis outcome measures were extracted from the publications. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts, pain, and global and functional assessments. Weighted mean differences (WMDs) were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios (OR) for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout and random effects for outcomes showing heterogeneity. MAIN RESULTS: Six trials, including 468 patients were included. A statistically significant benefit was observed for sulfasalazine when compared to placebo for tender and swollen joint scores, pain and ESR. The standardized weighted mean difference between treatment and placebo was -0.49 for tender and swollen joint scores, and -0.42 for pain. The difference for ESR was -17.6mm. Withdrawals from adverse reactions were significantly higher in the sulfasalazine group (OR=3.0). Patients receiving placebo were four times more likely to discontinue treatment because of lack of efficacy than patients receiving sulfasalazine. REVIEWER'S CONCLUSIONS: Sulfasalazine appears to have a clinically and statistically significant benefit on the disease activity of patients with RA. Its effects on overall health status and radiological progression are not clear at this time, but would appear to be modest.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

Antimalarials for rheumatoid arthritis.

OBJECTIVES: To estimate the short-term efficacy and toxicity of antimalarials for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register, Medline and Embase up to and including July 1997. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing antimalarials against placebo in patients with RA DATA COLLECTION AND ANALYSIS: Data abstraction was carried out independently by two reviewers. The same two reviewers using Jadad's scale (Jadad 1995) assessed the methodological quality of the RCTs and CCTs. Rheumatoid arthritis outcome measures were extracted from the publications for the 6-month endpoint. The pooled analysis was performed using standardized mean differences for joint counts, pain and global assessments. Weighted mean differences were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout. MAIN RESULTS: We found four trials, with 300 patients randomized to hydrochloroquine and 292 to placebo. Only trials evaluating hydroxychloroquine could be pooled in the analysis. A statistically significant benefit was observed when hydroxychloroquine was compared to placebo. The standardized mean differences for the various outcome measures ranged from -0.33 to -0. 52, and were statistically significant. Statistically significant differences were also observed for ESR. Overall withdrawals and withdrawals due to lack of efficacy were significantly more frequent in the placebo group. No differences were observed in withdrawals due to toxicity. REVIEWER'S CONCLUSIONS: Hydroxychloroquine appears to be efficacious for the treatment of RA. Its overall effect appears to be moderate, but its low toxicity profile should be considered when treating patients with RA.

Antimalarials↗

PubMed2000

Cyclosporine for rheumatoid arthritis.

OBJECTIVES: To estimate the short-term (up to one year) effects of cyclosporine for rheumatoid arthritis. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group trials register, and Medline, up to 1997, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). The search was complemented with bibliography searching of the reference list of the trials retrieved from the electronic search. Key experts in the area were contacted for further published and unpublished articles. SELECTION CRITERIA: All randomized clinical trials (RCTs) and controlled clinical trials (CCTs) comparing cyclosporine against placebo in patients with rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: Two reviewers determined the trials to be included based on inclusion and exclusion criteria (GW, MSA). Data were independently abstracted by two reviewers (DH, GW),and checked by a third reviewer (BS) using a pre-developed form for the rheumatoid arthritis sub-group of the Cochrane Musculoskeletal Group. Methodological quality of the RCTs and CCTs was assessed by two reviewers (BS, DH). Rheumatoid arthritis outcome measures were extracted from the publications for change from baseline endpoints. Sufficient data were obtained to include in the pooled analysis the number of swollen joints, physician global assessment, patient global assessment and erythrocyte sedimentation rate (ESR). MAIN RESULTS: Three trials and 318 patients were included. A statistically significant decrease in the number of tender and swollen joints was observed for cyclosporine when compared to placebo. The standardized mean difference (SMD) for the change in the number of swollen joints was -0.969. Significant improvements in pain and the functional index were also found for cyclosporine. More side effects occurred in the cyclosporine group compared to placebo. REVIEWER'S CONCLUSIONS: Cyclosporine has an important clinical benefit int the short-term (up to one year) treatment of patients with progressive rheumatoid arthritis.

Antirheumatic Agents↗

PubMed2000

Pharmacotherapy for Behcet's syndrome.

OBJECTIVES: To determine the effects of available pharmacological interventions in treating the different clinical features of Behcet's syndrome. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register, and Medline up to January 1998. The computer search was complemented by a hand search of all bibliographic references from the reference lists of included trials. Principal investigators were contacted to seek unpublished literature. All languages were included. SELECTION CRITERIA: Studies were eligible if they fulfilled all of the four following criteria: 1. Randomized controlled trials, single or double-blind; 2. Participants were patients with Behcet's Syndrome as defined by the International Study Group, 1990 (Int Study Group, 1990); 3. Interventions included any pharmacological therapy compared to placebo or some other pharmacological intervention for the treatment of Behcet's syndrome. 4. Outcome measures included active ocular inflammatory processes, arthritis, mucocutaneous manifestations (oral ulcer, genital ulcer, erythema nodosum), laboratory changes and major events such as adverse effects and death. DATA COLLECTION AND ANALYSIS: The 32 potentially relevant references were assessed by two independent reviewers (MA, AS) according to the inclusion criteria. Ten trials fit the inclusion criteria and were included in this review. From the 10 included trials, data were independently extracted by the same two observers and crosschecked. The quality of the included trials was assessed independently by two observers (MA, AS) using a validated scale (Jadad 1996). For dichotomous measures, the treatment effect for each trial was calculated using a fixed effect model [Peto model (Petitti 1994)]. The weighted mean differences were based, if available, on end-of-trial results. The analysis was conducted separately for each different intervention. Since the trials could not be pooled it was not possible to carry out a sensitivity analysis by quality scores or a subgroup analysis by drug dosages. Because of this lack of comparability across trials and the small number of trials, we could not conduct a heterogeneity test or a funnel plot. MAIN RESULTS: Ten trials and 679 patients were included. The main results were the lack of efficacy of some of the classic treatments for Behcet's syndrome, including colchicine, cyclophosphamide and steroids for eye involvement, azapropazone and colchicine for arthritis and acyclovir, colchicine and topical interpheron for aphthas. The results confirm the protective effects of cyclosporine and azathioprine for eye involvement and benzathine-penicillin for arthritis. REVIEWER'S CONCLUSIONS: We conclude that further randomized, placebo-controlled, double-blind trials should be carried out to compare cyclosporine, azathioprine and benzathine-penicillin versus placebo in order to make the results generalizable and comparable.

Acyclovir↗

PubMed2000

Cyclophosphamide for rheumatoid arthritis.

OBJECTIVES: To estimate the short-term effects of cyclophosphamide for the treatment of rheumatoid arthritis. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's Register, the Cochrane Controlled Trials Register, Medline and Embase up to and including July 1997. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing oral cyclophosphamide against placebo (or an active drug at a dosage considered to be ineffective) in patients with rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: Data abstraction was carried out independently by two reviewers. The same two reviewers using Jadad's scale (Jadad 1995) assessed the methodological quality of the RCTs and CCTs. Rheumatoid arthritis outcome measures were extracted from the publications for baseline and end-of-study. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts. Weighted mean differences (WMDs) were used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout. MAIN RESULTS: A total of 70 patients were included in the pooled analysis of two trials, 31 receiving cyclophosphamide. A statistically significant benefit was observed for cyclophosphamide when compared to placebo for tender and swollen joint scores: SMDs were -0.57 and -0.59 respectively. The difference in ESR also favoured the active drug but did not reach statistical significance (-12 mm, 95%CI: -26 to 2.5). One trial reported the number of patients developing new or worse erosions: the OR for cyclophosphamide compared to placebo was 0.17 (95% CI: 0.05 to 0.57). Patients receiving placebo were six times more likely to discontinue treatment because of lack of efficacy than patients receiving cyclophosphamide. Withdrawals from adverse reactions were higher in the cyclophosphamide group (Odds ratio=2.9), although this difference was not statistically significant. Side effects from cyclophosphamide included hemorrhagic cystitis, nausea, vomiting, leucopenia, thrombocytopenia, alopecia, amenorrhea and herpes zoster infections. REVIEWER'S CONCLUSIONS: Cyclophosphamide appears to have a clinically and statistically significant benefit on the disease activity of patients with RA, similar to some disease modifying antirheumatic drugs (DMARDs) such as antimalarials or sulfasalazine, but lower than methotrexate. Toxicity however is severe, limiting its use given the low benefit-risk ratio compared to other antirheumatic agents.

Antirheumatic Agents↗

PubMed2000

Moderate-term, low-dose corticosteroids for rheumatoid arthritis.

OBJECTIVES: To perform a systematic review of low-dose corticosteroid efficacy in the moderate term for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We conducted a search in MEDLINE from 1966 to 1998, using the keywords "corticosteroids" and "rheumatoid arthritis". We also handsearched all issues of Arthritis and Rheumatism and the Scandinavian Journal of Rheumatology from their dates of first publication to 1994. Furthermore, we examined all Arthritis and Rheumatism abstracts over the 15 year period preceding 1994. References of all identified studies were searched for relevant trials. Authors of unpublished manuscripts were contacted. SELECTION CRITERIA: Studies were selected by two independent reviewers (LC, KS) using a set of predetermined criteria. Specifically, we required that trials be randomized or cross-over and report at least one of the following outcome measures in a quantitative manner: joint tenderness, joint swelling, grip strength, or erythrocyte sedimentation rate (ESR). We also required that trials be of at least three months duration and use prednisone (or a comparable corticosteroid preparation) at a mean dosage of less than or equal to 15 mg/day. We included studies that used either placebo or active drug controls (i.e., comparative studies). DATA COLLECTION AND ANALYSIS: We compared the effectiveness of prednisone to placebo and/or active controls using a fixed effects model for continuous data. A chi square test for homogeneity was performed, and where heterogeneity existed a random effects model was used. We reported results for all available outcomes recommended by the Outcome Measures for Rheumatology Trials (OMERACT) group. These included the number of tender and swollen joints, pain, functional status and ESR. Grip strength was also evaluated. Standardized mean differences (SMD) were used for outcomes assessing the same concept with different scales (eg. swollen joint counts). MAIN RESULTS: Very few studies directly assessed the effectiveness of corticosteroids for RA treatment and many were of poor methodologic quality. Only seven of 34 studies identified by our search met criteria for inclusion. Our results indicated that corticosteroids were significantly more effective than placebo controls for four of six outcomes assessed [standardized mean difference for tender joints = -0.37 (95%CI: -0. 59, -0.14), swollen joints = -0.41 (-0.67, -0.16), pain = -0.43 (-0. 74, -0.12), and functional status = -0.57 (-0.92, -0.22)]. The results for grip strength and ESR were not significant [GS = +0.30 (-0.19, +0.80), weighted mean difference (WMD) for ESR = -7.03 (-18. 06, +4.01)]. The single trial that compared prednisone to aspirin indicated no statistically significant difference between these groups for joint tenderness (0.10 (-0.35, +0.55) and for ESR [0.00 (-11.09, +11.09]. Overall, the four outcomes assessed in the single trial that compared prednisone to chloroquine suggested that the effectiveness of these two agents is similar [SMD for joint tenderness = +0.23 (-0.30, +0.75), swollen joints = +0.43 (-0.11, +0. 96), functional status = -0.27 (-0.80, +0.26), and WMD for ESR = -16. 00 (-30.58, -1.42)]. REVIEWER'S CONCLUSIONS: Based on the limited data available, moderate-term prednisone treatment of RA appears to be superior to placebo and comparable to treatment with aspirin or chloroquine in improving several common rheumatoid arthritis disease activity measures.

Arthritis, Rheumatoid↗

PubMed2000

Bisphosphonates for steroid induced osteoporosis.

OBJECTIVES: To assess the effects of bisphosphonates for the prevention and treatment of corticosteroid-induced osteoporosis. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group trials register, Medline up to 1997 and Embase1988-1997), and selected hand searching of reference lists was conducted. Hand searching of scientific abstracts from relevant meetings for the last five years was also done. An electronic search in Current Contents was done for the last six months. The Cochrane Controlled Trials Register (CCTR) will be searched for future updates. All languages were included in the search. For practical reasons only those in English were included, but all languages will be retrieved and translated for future updates. SELECTION CRITERIA: All controlled clinical trials (CCTs) dealing with prevention or treatment of corticosteroid-induced osteoporosis with bisphosphonates of any type and reporting the outcomes of interest were assessed. Trials had to involve adults only, and subjects had to be taking a mean steroid dose of 7.5 mg/day or more. DATA COLLECTION AND ANALYSIS: All data extraction was performed by two independent reviewers. Outcomes of interest included change in bone mineral density (BMD) at the lumbar spine and femoral neck at six and 12 months. If present, data on number of new fractures and withdrawals due to adverse effects were also extracted. All data extraction was performed by two independent reviewers. Both continuous and dichotomous data were analyzed using fixed effects models. When significant heterogeneity was present, a random effects model was used. MAIN RESULTS: A total of 13 trials, including 842 patients are included in this meta-analysis. Results are reported as a weighted mean difference of the percent change in BMD between the treatment and placebo groups, with trials being weighted by the inverse of their variance. The 95% confidence intervals (95% CI) are presented. At the lumbar spine, the weighted mean difference of BMD between the treatment and placebo groups was 4.3% (95% CI 2.7, 5.9). At the femoral neck, the weighted mean difference was 2.1% (95%CI 0. 01, 3.8). Although there was a 24% reduction in odds of spinal fractures [OR 0.76 (95%CI 0.37, 1.53)], this result was not statistically significant. REVIEWER'S CONCLUSIONS: Bisphosphonates are effective at preventing and treating corticosteroid-induced bone loss at the lumbar spine and femoral neck. Efficacy regarding fracture prevention cannot be concluded from this analysis, although bone density changes are correlated with fracture risk.

Diphosphonates↗

PubMed2000

Calcitonin for the treatment and prevention of corticosteroid-induced osteoporosis.

BACKGROUND: Corticosteroid-induced osteoporosis is a cause of morbidity in patients with chronic obstructive lung disease, asthma, and rheumatologic disorders. Corticosteroid treatment causes bone loss by a variety of complex mechanisms. It has been shown that bone mineral loss at the hip averages 14% in the first year after starting corticosteroid therapy. OBJECTIVES: To review the efficacy of calcitonin (subcutaneous or nasal) for the treatment and prevention of corticosteroid-induced osteoporosis. SEARCH STRATEGY: We conducted a search of Medline, the Cochrane Controlled Trials Register and Embase using the Cochrane Musculoskeletal Group search strategy for randomized controlled trials (RCTs) up to May 1998. We also searched bibliographic references and consulted content experts. SELECTION CRITERIA: Two independent reviewers selected RCTs which met predetermined inclusion criteria. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data using predetermined forms and assessed methodological quality of randomization, blinding and dropouts. For dichotomous outcomes, relative risks (RR) were calculated. For continuous data, weighted mean differences (WMD) of the percent change from baseline were calculated. We decided a priori to use random effects models for all outcomes, because of uncertainty about whether a consistent true effect exists in such different populations. MAIN RESULTS: Nine trials met the inclusion criteria, including 221 patients randomized to calcitonin and 220 to placebo. The median methodologic quality was two out of a maximum of five points. Calcitonin was more effective than placebo at preserving bone mass at the lumbar spine after six and 12 months of therapy with a WMD of 2.8% (95% CI: 1.4 to 4.3) and 3.2% (95% CI: 0.3 to 6.1). At 24 months, lumbar spine BMD was not statistically different between groups: WMD 4.5% (95% CI: -0.6 to 9.5)]. Bone density at the distal radius was also higher with calcitonin after six months of therapy, but bone density at the femoral neck was not different between placebo and calcitonin treated groups. The relative risk of fractures was not significantly different between calcitonin and placebo with a relative risk (RR) of 0.71 (95% CI: 0.26 to 1.89) for vertebral and 0.52 (95% CI: 0.14 to 1.96) for nonvertebral fractures. The subgroup analyses of methodological quality and duration of corticosteroid therapy were confounded. Trials of patients who had been taking steroids for greater than three months (which were of low methodologic quality) demonstrated a larger effect of calcitonin on spine bone density (about 6%) than prevention trials (about 1%). There was no consistent effect of different dosages (50-100 IU compared to 200-400 IU). However, subcutaneous calcitonin showed substantially greater prevention of bone loss. Withdrawals due to side effects were higher in the calcitonin-treated groups: RR 3.19 (95%CI: 0.66 to 15.47). Important side effects included nausea and facial flushing. REVIEWER'S CONCLUSIONS: Calcitonin appears to preserve bone mass in the first year of glucocorticoid therapy at the lumbar spine by about 3% compared to placebo, but not at the femoral neck. Our analysis suggests that the protective effect on bone mass may be greater for the treatment of patients who have been taking corticosteroids for more than three months. Efficacy of calcitonin for fracture prevention in steroid-induced osteoporosis remains to be established.

Calcitonin↗

PubMed2000

Low level laser therapy (classes I, II and III) for the treatment of osteoarthritis.

BACKGROUND: Osteoarthritis (OA) affects a large proportion of the population. Low Level Laser Therapy (LLLT) is a light source that generates extremely pure light, of a single wavelength. The effect is not thermal, but rather related to photochemical reactions in the cells. LLLT was introduced as an alternative non-invasive treatment for OA about 10 years ago, but its effectiveness is still controversial. OBJECTIVES: To assess the effectiveness of LLLT in the treatment of OA. SEARCH STRATEGY: We searched MEDLINE, EMBASE, the Cochrane Musculoskeletal registry, the registry of the Rehabilitation and Related Thereapies field and the Cochrane Controlled Trials Register up to January 30, 2000. SELECTION CRITERIA: Following an a priori protocol, only controlled clinical trials of LLLT for the treatment of patients with a clinical diagnosis of OA were eligible. Abstracts were excluded unless further data could be obtained from the authors. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials and abstracted data using predetermined forms. Heterogeneity was tested with Cochran's Q test. A fixed effects model was used throughout for continuous variables, except where heterogeneity existed, in which case, a random effects model was used. Results were analyzed as weighted mean differences (WMD) with 95% confidence intervals (CI), where the difference between the treated and control groups was weighted by the inverse of the variance. Standardized mean differences (SMD) were calculated by dividing the difference between treated and control by the baseline variance. SMD were used when different scales were used to measure the same concept (e.g. pain). Dichotomous outcomes were analyzed with odds ratios. MAIN RESULTS: Five trials were included, with 112 patients randomized to laser, 85 patients to placebo laser. Treatment duration ranged from 4 to 10 weeks. Pain was assessed by four trials. The pooled estimate (random effects) of three trials showed no effect on pain measured using a scale (SMD: -0.2, 95% CI: -1.0, +0.6), but there was statistically significant heterogeneity (p>0,05). Two of the trials showed no effect and one demonstrated very beneficial effects with laser. In another trial, with no scale-based pain outcome, significantly more patients reported pain relief (yes/no) with laser with an odds ratio of 0.05, (95% CI: 0.0 to 1.56). Other outcomes of joint tenderness, joint mobility and strength were not significant. REVIEWER'S CONCLUSIONS: For OA, the results are conflicting in different studies and may depend on the method of application and other features of the LLLT application. Clinicians and researchers should consistently report the characteristics of the LLLT device and the application techniques used. New trials on LLLT should make use of standardized, validated outcomes. Despite some positive findings, this meta-analysis lacked data on how LLLT effectiveness is affected by four important factors: wavelength, treatment duration of LLLT, dosage and site of application over nerves instead of joints. There is clearly a need to investigate the effects of these factors on LLLT effectiveness for OA in randomized controlled clinical trials.

Humans↗

PubMed2000

Low level laser therapy (classes I, II and III) in the treatment of rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) affects a large proportion of the population. Low Level Laser Therapy (LLLT) was introduced as an alternative non-invasive treatment for RA about 10 years ago. LLLT is a light source that generates extremely pure light, of a single wavelength. The effect is not thermal, but rather related to photochemical reactions in the cells. The effectiveness of LLLT for rheumatoid arthritis is still controversial. OBJECTIVES: To assess the effectiveness of LLLT in the treatment of RA. SEARCH STRATEGY: We searched MEDLINE, EMBASE, the registries of the Cochrane Musculoskeletal group and the field of Rehabilitation and Related Therapies as well as the Cochrane Controlled Trials Register up to January 30, 2000. SELECTION CRITERIA: Following an a priori protocol, we selected only randomized controlled trials of LLLT for the treatment of patients with a clinical diagnosis of RA were eligible. Abstracts were excluded unless further data could be obtained from the authors. DATA COLLECTION AND ANALYSIS: Two reviewers independently select trials for inclusion, then extracted data and assessed quality using predetermined forms. Heterogeneity was tested with Cochran's Q test. A fixed effects model was used throughout for continuous variables, except where heterogeneity existed, in which case, a random effects model was used. Results were analyzed as weighted mean differences (WMD) with 95% confidence intervals (CI), where the difference between the treated and control groups was weighted by the inverse of the variance. Standardized mean differences (SMD) were calculated by dividing the difference between treated and control by the baseline variance. SMD were used when different scales were used to measure the same concept (e.g. pain). Dichotomous outcomes were analyzed with odds ratios. MAIN RESULTS: A total of 204 patients were included in the five placebo-controlled trials, with 112 randomized to laser therapy. Relative to a separate control group, LLLT reduced pain by 70% relative to placebo and reduced morning stiffness duration by 27.5 minutes (95%CI: 2.9 to 52 minutes) and increased tip to palm flexibility by 1.3 cm (95% CI: 0. 8 to 1.7 cm). Other outcomes such as functional assessment, range of motion and local swelling did not differ between groups. There were no significant differences between subgroups based on LLLT dosage, wavelength, site of application or treatment length. For RA, relative to a control group using the opposite hand, there was no difference between the control and treatment hand, but all hands improved in terms of pain relief and disease activity. REVIEWER'S CONCLUSIONS: In summary, LLLT for RA is beneficial as a minimum of a four-week treatment with reductions in pain and morning stiffness. On the one hand, this meta-analysis found that pooled data gave some evidence of a clinical effect, but the outcomes were in conflict, and it must therefore be concluded that firm documentation of the application of LLLT in RA is not possible. Clinicians and researchers should consistently report the characteristics of the LLLT device and the application techniques used. New trials on LLLT should make use of standardized, validated outcomes. Despite some positive findings, this meta-analysis lacked data on how LLLT effectiveness is affected by four important factors: wavelength, treatment duration of LLLT, dosage and site of application over nerves instead of joints.

Arthritis, Rheumatoid↗

PubMed2000

Prevention of chronic NSAID induced upper gastrointestinal toxicity.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are important agents in the management of arthritic and inflammatory conditions, and are among the most frequently prescribed medications in North America and Europe. However, there is overwhelming evidence linking these agents to a variety of gastrointestinal (GI) toxicities. OBJECTIVES: To review the effectiveness of common interventions for the prevention of NSAID induced upper GI toxicity. SEARCH STRATEGY: A literature search was conducted, according to the Cochrane methodology for identification of randomized controlled trials in electronic databases, including MEDLINE from 1966 to January 2000, Current Contents for 6 months prior to January 2000, Embase to Febuary 1999, and a search of the Cochrane Controlled Trials Register from 1973 to 1999. Recent conference proceedings were reviewed and content experts and companies were contacted. SELECTION CRITERIA: Randomized controlled clinical trials (RCTs) of prostaglandin analogues (PA), H2-receptor antagonists (H2RA) or proton pump inhibitors (PPI) for the prevention of chronic NSAID induced upper GI toxicity were included. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data regarding population characteristics, study design, methodological quality and number of patients with endoscopic ulcers, ulcer complications, symptoms, overall drop-outs, drop outs due to symptoms. Dichotomous data was pooled using Revman V3.1. Heterogeneity was evaluated using a chi square test. MAIN RESULTS: Thirty-three RCTs met the inclusion criteria. All doses of misoprostol significantly reduced the risk of endoscopic ulcers. Misoprostol 800 ug/day was superior to 400 ug/day for the prevention of endoscopic gastric ulcers (RR=0.18, and RR=0. 38 respectively, p=0.0055). A dose response relationship was not seen with duodenal ulcers. Misoprostol caused diarrhea at all doses, although significantly more at 800ug/day than 400ug/day (p=0.0012). Misoprostol was the only prophylactic agent documented to reduce ulcer complications. Standard doses of H2RAs were effective at reducing the risk of endoscopic duodenal (RR=0.24; 95% CI: 0.10-0. 57) but not gastric ulcers(RR=0.73; 95% CI:0.50-1.09). Both double dose H2RAs and PPIs were effective at reducing the risk of endoscopic duodenal and gastric ulcers (RR=0.44; 95% CI:0.26-0.74 and RR=0.37;95% CI;0.27-0.51 respectively for gastric ulcer), and were better tolerated than misoprostol. REVIEWER'S CONCLUSIONS: Misoprostol, PPIs, and double dose H2RAs are effective at preventing chronic NSAID related endoscopic gastric and duodenal ulcers. Lower doses of misoprostol are less effective and are still associated with diarrhea. Only Misoprostol 800ug/day has been directly shown to reduce the risk of ulcer complications.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

Transcutaneous electrical nerve stimulation for knee osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a disease that affects synovial joints, which mainly causes degeneration and destruction of hyaline cartilage. To date, no curative treatment for OA exists. The primary goals for OA therapy are to relieve pain, maintain or improve functional status, and minimize deformity. Transcutaneous electrical nerve stimulation (TENS) is a noninvasive modality in physiotherapy that is commonly used to control both acute and chronic pain arising from several conditions. A number of trials evaluating the efficacy of TENS in OA have been published. OBJECTIVES: To assess the effectiveness of TENS in the treatment of knee OA. The primary outcomes of interest were those described by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) 3, which included pain relief, functional status, patient global assessment, and change in joint imaging for studies of one year or longer. The secondary objective was to determine the most effective mode of TENS application in pain control. SEARCH STRATEGY: We searched MEDLINE, EMBASE, CINAHL, HEALTHSTAR, PEDro, Current Contents and the Cochrane Controlled Trial Register using the Cochrane Musculoskeletal Group search strategy for trials up to and including December 1999. We also hand-searched reference lists and consulted content experts. SELECTION CRITERIA: Two independent reviewers selected the trials that met predetermined inclusion criteria. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted the data using standardized forms and assessed the quality of randomization, blinding and dropouts. A third reviewer was consulted to resolve any differences. For dichotomous outcomes, relative risks (RR) were calculated. For continuous data, weighted mean differences (WMD) or standardized mean difference (SMD) of the change from baseline were calculated. A fixed effects model was used unless heterogeneity of the populations existed. In this case, a random effects model was used. MAIN RESULTS: Seven trials were eligible to be included in this review. Six used TENS as the active treatment while one study used acupuncture-like TENS (AL-TENS). A number of 148 and 146 patients were involved in the active TENS treatment and placebo, respectively. Three studies were cross-over studies and the others were parallel group, randomized controlled trials (RCTs). Median methodological quality of these studies was two. Pain relief from active TENS and AL-TENS treatment was significantly better than placebo treatment. Knee stiffness also improved significantly in active treatment group compared to placebo. Different modes of TENS setting (High Rate and Strong Burst Mode TENS) demonstrated a significant benefit in pain relief of the knee OA over placebo. Subgroup analyses showed a heterogeneity in the studies with methodological quality of three or more and those with repeated TENS applications. REVIEWER'S CONCLUSIONS: TENS and AL-TENS are shown to be effective in pain control over placebo in this review. Heterogeneity of the included studies was observed, which might be due to the different study designs and outcomes used. More well designed studies with a standardized protocol and adequate number of participants are needed to conclude the effectiveness of TENS in the treatment of OA of the knee.

Humans↗

PubMed2000

Fluoride for treating postmenopausal osteoporosis.

OBJECTIVES: To assess the efficacy of fluoride therapy on bone loss, vertebral and non-vertebral fractures and side effects in postmenopausal women. SEARCH STRATEGY: We searched Medline, Current Contents and the Cochrane Controlled Trial Registry up to December 1998. SELECTION CRITERIA: Two independent reviewers selected RCTs which met predetermined inclusion criteria. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data using predetermined forms and assessed the methodological quality of the trials using a validated scale. For dichotomous outcomes, relative risks (RR) were calculated and for continuous outcomes, weighted mean differences (WMD) of percentage change from baseline were calculated. Where heterogeneity existed (determined by a chi-square test) a random effects model was used. MAIN RESULTS: Eleven studies (1429 subjects) met the inclusion criteria. The increase in lumbar spine bone mineral density (BMD) was found to be higher in the treatment group than in the control group with a WMD 8.1% (95%CI: 7.15,9.09) after two years of treatment and 16.1%(95%CI: 14.65,17.5) after four years. The RR for new vertebral fractures was not significant at two years [0.87 (95%CI: 0.51,1.46)] or at four years [0.9(95%CI: 0.71,1.14)]. The RR for new non-vertebral fractures was not significant at two years 1.2(95%CI: 0.68,2.1) but was increased at four years in the treated group 1.85(95%CI: 1.36,2.5), especially if used at high doses and in a non slow release form. The RR for gastrointestinal side effects was not significant at two years 2.18(95%CI: 0.86,1.21) but was increased at four years in the treated group 2.18(95%CI: 1.69,4.57) especially if fluoride was used at high doses and in a non slow release form. The number of withdrawals and dropouts was not different between treated and control groups at two and four years. REVIEWER'S CONCLUSIONS: Although fluoride has an ability to increase BMD at lumbar spine, it does not result in a reduction of vertebral fractures. In increasing the dose of fluoride, one increases the risk of non-vertebral fracture and gastrointestinal side effects without any effect on the vertebral fracture rate.

Bone Density↗

PubMed2000

Thermotherapy for treating rheumatoid arthritis.

BACKGROUND: Heat and cold therapy are often used as adjuncts in the treatment of rheumatoid arthritis by rehabilitation specialists. OBJECTIVES: To evaluate the effects of heat and cold on objective and subjective measures of disease activity in patients with rheumatoid arthritis. SEARCH STRATEGY: We searched Medline, Embase, PEDro, Current Contents, Sports Discus and CINAHL up to June 2000. The Cochrane Field of Rehabilitation and related therapies and the Cochrane Musculoskeletal Review Group were also contacted for a search of their specialized registers. Handsearching was conducted on all retrieved articles for additional articles. SELECTION CRITERIA: Randomized or controlled clinical trials of ice or heat compared to placebo or active interventions in patients with rheumatoid arthritis and case-control and cohort studies were eligible. No language restrictions were applied. Abstracts were accepted. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified potential articles from the literature search. These reviewers extracted data using pre-defined extraction forms. Consensus was reached on all data extraction. Quality was assessed by two reviewers using a 5 point scale that measured the quality of randomization, double-blinding and description of withdrawals. MAIN RESULTS: Three studies (79 subjects) met the inclusion criteria. There was no effect on objective measures of disease activity (including inflammation, pain and x-ray measured joint destruction) of either ice versus control or heat versus control. Patients reported that they preferred heat therapy to no therapy (94% like heat therapy better than no therapy). There was no difference in patient preference for heat or ice. No harmful effects of ice or heat were reported. REVIEWER'S CONCLUSIONS: Since patients enjoy thermotherapy, and there are no harmful effects, thermotherapy should be recommended as a therapy which can be applied at home as needed to relieve pain. There is no need for further research on the effects of heat or cold for RA.

Arthritis, Rheumatoid↗

PubMed2000

Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration.

OBJECTIVE: To use individual patient data from rheumatoid arthritis (RA) clinical trials to identify factors that affect the response to treatment as defined by the American College of Rheumatology (ACR) criteria for improvement (the "ACR response"). METHODS: Primary trial data from 14 diverse, randomized, controlled trials of second-line drugs or devices in RA were analyzed. The trials included 11 methotrexate (MTX) trials (5 placebo controlled and 6 comparative, of which 2 were unpublished), 1 combination trial of cyclosporine plus MTX, 1 induction trial of a combination treatment in early RA (the COBRA trial), and 1 placebo-controlled trial of a new device (Prosorba). Both patient factors and disease activity measures (primarily, items from the ACR core criteria set) were available. RESULTS: A total of 1,435 patients (549 in placebo-controlled trials, 886 in comparative trials) were studied. In both active treatment and placebo groups, disease duration had a strong effect on the likelihood of patient response (e.g., with any active treatment, the response rate was 53% for patients with < or =1 year of disease, 43% for 1-2 years' disease duration, 44% for 2-5 years, 38% for 5-10 years, and 35% for > 10 years; P = 0.001). Decreasing response with greater disease duration was seen during treatment with most of the individual active drugs, as well as with placebo. Other factors decreasing the rate of response to treatment included any prior use of a disease-modifying antirheumatic drug (DMARD), higher disease functional class (according to the Steinbrocker criteria), low disease activity (according to patient's global assessment), and female sex. Each ACR core set variable exhibited a diminished response to treatment in patients with long-standing disease. The difference between active treatment and placebo response rates was not affected by disease duration nor by other factors associated with the ACR response. CONCLUSION: RA patients with longer disease duration do not respond as well to treatment compared with patients with early disease, and female sex, prior DMARD use, disease functional class, and disease activity also have effects on the likelihood of patient response to treatment. This has implications for trial interpretation and for the clinical expectations of RA patients.

Antirheumatic Agents↗

PubMed2000

Clinical improvement as reflected in measures of function and health-related quality of life following treatment with leflunomide compared with methotrexate in patients with rheumatoid arthritis: sensitivity and relative efficiency to detect a treatment effect in a twelve-month, placebo-controlled trial. Leflunomide Rheumatoid Arthritis Investigators Group.

OBJECTIVE: To examine correlations between clinical improvement as defined by the American College of Rheumatology (ACR) responder analysis and clinical improvement as determined by 4 function and/or health-related quality of life measures, and to estimate the sensitivity and relative efficiency of these measures compared with changes in the tender joint count in patients with rheumatoid arthritis (RA). METHODS: A 52-week, multicenter, double-blind controlled trial was conducted to compare treatment with leflunomide (n = 182), methotrexate (n = 180), or placebo (n = 118) in patients with active RA. ACR response rates and improvement in scores on the Health Assessment Questionnaire (HAQ), Problem Elicitation Technique (PET), and Medical Outcomes Survey Short Form 36 (SF-36) were compared in 438 of the patients. RESULTS: In comparing leflunomide with placebo, the patient global assessment, HAQ disability index, and SF-36 bodily pain scale were most responsive to treatment group differences. The modified HAQ (M-HAQ), PET Top 5, SF-36 physical component score, physician global assessment, pain intensity scale, and SF-36 physical functioning scale were more responsive to treatment group differences than was the tender joint count. In comparing methotrexate with placebo, the patient and physician global assessments were most responsive. These 2 measures, as well as the pain intensity scale and the C-reactive protein level, were more responsive to treatment group differences than was the tender joint count, while the SF-36 mental health component score was least responsive. A close correlation between changes in the M-HAQ and HAQ scores indicated that the M-HAQ was similarly responsive to change over time. Improvements in the PET, SF-36 physical component score, bodily pain, and physical functioning scales correlated with the ACR responder status. CONCLUSION: Both disease-specific and generic measures of function and health-related quality of life detect improvements in RA patients. Using both types of measures for evaluating therapies will identify discernible changes that are important to patients, and will facilitate comparisons across different disease states.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

Fluoride for the treatment of postmenopausal osteoporotic fractures: a meta-analysis.

We conducted an effectiveness meta-analysis to determine the efficacy of fluoride therapy on bone loss, vertebral and nonvertebral fractures and side effects in postmenopausal women. A literature search was conducted on MEDLINE, Current Contents and the Cochrane Controlled Trial Registry. Two independent reviewers selected randomized controlled trials which met predetermined inclusion criteria. They independently extracted data using predetermined forms and assessed the methodologic quality of the trials using a validated scale. For dichotomous outcomes, the relative risk (RR) was calculated, and for continuous outcomes, the weighted mean difference (WMD) of percentage change from baseline was calculated. Where heterogeneity existed (determined by a chi-square test) a random effects model was used. Eleven studies (1429 subjects) met the inclusion criteria. The increase in lumbar spine bone mineral density (BMD) was found to be higher in the treatment group than in the control group with a WMD 8.1% (95% CI: 7.15, 9.09) after 2 years of treatment and 16.1% (95% CI: 14.65, 17.5) after 4 years. The RR for new vertebral fractures was not significant at 2 years [0.87 (95% CI: 0.51, 1.46)] or at 4 years [0.9 (95% CI: 0.71, 1.14)]. The RR for new nonvertebral fractures was not significant at 2 years [1.2 (95% CI: 0.68, 2.10)] but was increased at 4 years in the treated group [1.85 (95% CI: 1.36, 2.50)], especially if used at high doses and in a non-slow-release form. The RR for gastrointestinal side effects was not significant at 2 years [2.18 (95% CI: 0.86, 1.21)] but was increased at 4 years in the treated group [2.18 (95% CI: 1.69, 4.57)], especially if fluoride was used at high doses and in a non-slow-release form. The number of withdrawals and dropouts was not different between treated and control groups at 2 and 4 years. Thus, although fluoride has an ability to increase bone mineral density at the lumbar spine, it does not result in a reduction in vertebral fractures. Increasing the dose of fluoride increases the risk of nonvertebral fractures and gastrointestinal side effects without any effect on the vertebral fracture rate.

Aged↗

PubMed2000

Preventing perineal trauma during childbirth: a systematic review.

OBJECTIVE: To review systematically techniques proposed to prevent perineal trauma during childbirth and meta-analyze the evidence of their efficacy from randomized controlled trials. DATA SOURCES: MEDLINE (1966-1999), the Cochrane Library (1999 Issue 1), and the Cochrane Collaboration: Pregnancy and Childbirth Database (1995); and reference lists from articles identified. Search terms included childbirth or pregnancy or delivery, and perineum, episiotomy, perineal massage, obstetric forceps, vacuum extraction, labor stage-second. No language or study-type constraints were imposed. STUDY SELECTION: Randomized controlled trials (RCTs) of interventions affecting perineal trauma were reviewed. If no RCTs were available, nonrandomized research designs such as cohort studies were included. Studies were selected by examination of titles and abstracts of more than 1,500 articles, followed by analysis of the methods sections of studies that appeared to be RCTs. INTEGRATION AND RESULTS: Eligible studies used random or quasirandom allocation of an intervention of interest and reported perineal outcomes. Further exclusions were based on failure to report results by intention to treat, or incomplete or internally inconsistent reporting of perineal outcomes. Final selection of studies and data extraction was by consensus of the first two authors. Data from trials that evaluated similar interventions were combined using a random effects model to determine weighted estimate of risk difference and number needed to treat. Effects of sensitivity analysis and quality scoring were examined. Results indicated good evidence that avoiding episiotomy decreased perineal trauma (absolute risk difference -0.23, 95% confidence interval [CI] -0.35, -0.11). In nulliparas, perineal massage during the weeks before giving birth also protected against perineal trauma (risk difference -0.08, CI -0.12, -0.04). Vacuum extraction (risk difference -0.06, CI -0.10, -0.02) and spontaneous birth (-0.11, 95% CI -0.18, -0.04) caused less anal sphincter trauma than forceps delivery. The mother's position during the second stage has little influence on perineal trauma (supported upright versus recumbent: risk difference 0.02, 95% CI -0.05, 0.09). CONCLUSION: Factors shown to increase perineal integrity include avoiding episiotomy, spontaneous or vacuum-assisted rather than forceps birth, and in nulliparas, perineal massage during the weeks before childbirth. Second-stage position has little effect. Further information on techniques to protect the perineum during spontaneous delivery is sorely needed.

Delivery, Obstetric↗