Biomedical subjects

M G Judd

Publications and source records attributed to M G Judd.

4 recordsLinked to original sources

PubMed2006

Acetaminophen for osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis. Published guidelines and expert opinion are divided over the relative role of acetaminophen (also called paracetamol or Tylenol) and non-steroidal anti-inflammatory drugs (NSAIDs) as first-line pharmacologic therapy. The comparative safety of acetaminophen and NSAIDs is also important to consider. This update to the original 2003 review includes nine additional RCTs. OBJECTIVES: To assess the efficacy and safety of acetaminophen versus placebo and versus NSAIDs (ibuprofen, diclofenac, arthrotec, celecoxib, naproxen, rofecoxib) for treating OA. SEARCH STRATEGY: We searched MEDLINE (up to July 2005), EMBASE (2002-July 2005), Cochrane Central Register of Controlled Trials (CENTRAL), ACP Journal Club, DARE, Cochrane Database of Systematic Reviews (all from 1994 to July 2005). Reference lists of identified RCTs and pertinent review articles were also hand searched. SELECTION CRITERIA: Published randomized controlled trials (RCTs) evaluating the efficacy and safety of acetaminophen alone in OA were considered for inclusion. DATA COLLECTION AND ANALYSIS: Pain, physical function and global assessment outcomes were reported. Results for continuous outcome measures were expressed as standardized mean differences (SMD). Dichotomous outcome measures were pooled using relative risk (RR) and the number needed to treat (NNT) was calculated. MAIN RESULTS: Fifteen RCTs involving 5986 participants were included in this review. Seven RCTs compared acetaminophen to placebo and ten RCTs compared acetaminophen to NSAIDs. In the placebo-controlled RCTs, acetaminophen was superior to placebo in five of the seven RCTs and had a similar safety profile. Compared to placebo, a pooled analysis of five trials of overall pain using multiple methods demonstrated a statistically significant reduction in pain (SMD -0.13, 95% CI -0.22 to -0.04), which is of questionable clinical significance. The relative percent improvement from baseline was 5% with an absolute change of 4 points on a 0 to 100 scale. The NNT to achieve an improvement in pain ranged from 4 to 16. In the comparator-controlled RCTs, acetaminophen was less effective overall than NSAIDs in terms of pain reduction, global assessments and in terms of improvements in functional status. No significant difference was found overall between the safety of acetaminophen and NSAIDs, although patients taking traditional NSAIDS were more likely to experience an adverse GI event (RR 1.47, (95% CI 1.08 to 2.00). 19% of patients in the traditional NSAID group versus 13% in the acetaminophen group experienced an adverse GI event. However, the median trial duration was only 6 weeks and it is difficult to assess adverse outcomes in a relatively short time period. AUTHORS' CONCLUSIONS: The evidence to date suggests that NSAIDs are superior to acetaminophen for improving knee and hip pain in people with OA. The size of the treatment effect was modest, and the median trial duration was only six weeks, therefore, additional considerations need to be factored in when making the decision between using acetaminophen or NSAIDs. In OA subjects with moderate-to-severe levels of pain, NSAIDs appear to be more effective than acetaminophen.

Acetaminophen↗

PubMed2005

Rofecoxib for rheumatoid arthritis.

BACKGROUND: Editor's note: The anti-inflammatory drug rofecoxib (Vioxx) was withdrawn from the market at the end of September 2004 after it was shown that long-term use (greater than 18 months) could increase the risk of heart attack and stroke. Further information is available at www.vioxx.com. Rheumatoid arthritis (RA) is a systemic auto-immune disorder, in which the synovial lining of many joints and tendon sheaths are persistently inflamed. OBJECTIVES: To assess the efficacy and toxicity of rofecoxib for treating RA. SEARCH STRATEGY: We searched the following electronic databases up to December 2000: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment database. The bibliographies of retrieved papers were scanned for additional references. The manufacturers of rofecoxib, MSD, were also approached by the UK National Institute for Clinical Excellence to submit additional evidence to inform it's appraisal on the use of cyclo-oxygenase inhibitors for arthritis. SELECTION CRITERIA: We included randomised controlled trials of parallel group design evaluating the efficacy and/or toxicity of rofecoxib in RA, both placebo based and comparative trials were eligible. Relevant outcome criteria had to be available to evaluate efficacy and/or toxicity, such as the OMERACT outcomes. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers and the results were compared for the degree of agreement. A validated tool (Jadad 1996) was used to score the quality of the randomised controlled trials. The planned analysis was to pool, where appropriate, continuous outcome measures using mean or standardized mean differences, and dichotomous outcome measures using relative risk ratios. MAIN RESULTS: Two randomised controlled trials evaluating rofecoxib for the treatment of RA were identified and met the inclusion criteria. One compared rofecoxib to placebo and was designed to assess the safety and efficacy of several doses of rofecoxib. The second trial compared rofecoxib to naproxen and was primarily designed to assess the safety of rofecoxib so did not include all the recommended RA efficacy measures. The overall number of ACR 20 responders who had received 25mg (82/ 171 = 48%) or 50mg (86/161 = 53%) was statistically significantly more than those receiving placebo (58/168 = 35% ) (RR 1.39 CI: 1.07, 1.80 and RR 1.55 CI: 1.20, 1.99 respectively) with no statistically significant differences between the 25 and 50 mg doses. The safety profile of rofecoxib was similar to that of placebo. In the comparative trial, rofecoxib at a dosage of 50 mg/day demonstrated similar efficacy to naproxen at a dosage of 500 mg twice daily. However, the combined rate of clinically significant complicated gastro-intestinal events (GI) (perforations, ulcers, bleeds, or obstructions) was lower with rofecoxib than with naproxen (RR 0.46, 95% CI, 0.34 to 0.63) due to a reduction in the number of ulcers and bleeds. Compared to patients taking naproxen, patients taking rofecoxib had a greater risk of having any cardiovascular event (45/4047 = 1.1% vs 19/4029 =0.47%) (RR 2.36 CI 1.38 to 4.02) and had greater risk of having a non-fatal myocardial infarction (MI) (18/4047 =0 .44% and 4/4029 =0.1%) (RR 4.48, 95% CI, 1.52 to 13.23). AUTHORS' CONCLUSIONS: In patients with RA, rofecoxib demonstrates a greater degree of efficacy than placebo, while having a comparable safety profile. Rofecoxib demonstrates a similar degree of efficacy as naproxen, but with a significantly lower rate of ulceration and gastrointestinal bleeding. Rofecoxib was associated with a greater risk for MI, but the exact significance and pathophysiology of this possible relationship is unclear. Rofecoxib was voluntarily withdrawn from global markets in October 2004. It cannot therefore be prescribed and therefore there are no implications for practice concerning its use. None the less when considering which NSAID to use, it must be borne in mind that the toxicity of NSAIDs is variable amongst patients and drugs and it tends to be dose related and associated with variation in the mode of action, absorption, distribution and metabolism. There remains a number of questions over both the benefits and risks associated with Cox II selective agents and further work is ongoing. It is likely that this issue will not be resolved until research has enabled a fuller understanding of the complex mechanism by which the Cox system operates.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2003

Transcutaneous electrical nerve stimulation (TENS) for the treatment of rheumatoid arthritis in the hand.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory, system disease. It commonly affects the small peripheral joints (such as fingers and wrist). The main goals of intervention for RA are preventing joint deformity, preserving joint function, and reducing inflammation and pain. Transelectrical nerve stimulation (TENS) is a form of electrotherapy and is thought to produce analgesia according to the gate control theory. OBJECTIVES: To determine the efficacy and safety of TENS in the treatment of RA of the hand. The primary outcomes of interest were relief of grip pain and resting pain intensity, relief of joint tenderness, number of tender joints and patient assessment of disease. The secondary objective was to determine the most effective mode of TENS application in pain control. SEARCH STRATEGY: We searched for relevant studies, in English, in the Cochrane field of physical and related therapies, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, HEALTHSTAR, Sports Discus, CINAHL, Current Contents, and the PEDro database, up to October 2002. SELECTION CRITERIA: Two independent reviewers selected the trials that met predetermined inclusion criteria. DATA COLLECTION AND ANALYSIS: Study results were extracted by two independent reviewers. Continuous outcomes were analyzed by weighted mean difference (WMD) using a fixed effects model. MAIN RESULTS: Three RCTs, involving 78 people, were included in this review. AL-TENS and C-TENS were compared to placebo and to each other. Administration of 15 minutes of AL-TENS a week, for 3 weeks, resulted in a significant decrease in rest pain (67% relative benefit, 45 points absolute benefit on 100 mm VAS scale) but not in grip pain compared to placebo. AL-TENS did result in a clinical beneficial improvement in muscle power scores with a relative difference of 55%, and an absolute benefit of 0.98, compared to placebo. No significant difference was found between one 20-minute treatment duration of C-TENS versus AL-TENS, or C-TENS versus placebo on decrease in mean scores for rest pain or grip pain, or on the number of tender joints. Results showed a statistically significant reduction in joint tenderness, but no clinical benefit from C-TENS over placebo in relief of joint tenderness. No statistically significant difference was shown between 15 days of treatment with C-TENS or AL-TENS in relief of joint pain, although there was a clinically important benefit of C-TENS over AL-TENS on patient assessment of change in disease (risk difference 21%, NNT 5). REVIEWER'S CONCLUSIONS: There are conflicting effects of TENS on pain outcomes in patients with RA. AL-TENS is beneficial for reducing pain intensity and improving muscle power scores over placebo while, conversely, C-TENS resulted in no clinical benefit on pain intensity compared with placebo. However C-TENS resulted in a clinical benefit on patient assessment of change in disease over AL-TENS. More well designed studies with a standardized protocol and adequate number of subjects are needed to fully conclude the effect of C-TENS and AL-TENS in the treatment of RA of the hand.

Arthritis, Rheumatoid↗

PubMed1996

Potassium-induced stimulation of glutamate uptake in mouse cerebral astrocytes: the role of intracellular pH.

The Na(+)-glutamate cotransporters are believed to countertransport OH- and K+. Previous evidence that the velocity of glutamate uptake can exceed the acid extrusion capacity of astrocytes raised the question of whether intracellular pH can become rate limiting for glutamate uptake. Cytoplasmic buffering capacity and acid extrusion in astrocytes are partially HCO3- dependent. Also, it was reported recently that raising extracellular [K+] alkalinizes astrocyte cytoplasm by an HCO3- dependent mechanism. Here, we have compared glutamate uptake in HCO3(-)-buffered and HCO3(-)-depleted solutions at varying [K+]. We observed a pronounced stimulation of glutamate uptake by extracellular K+ (3-24 mM) that was substantially HCO3- dependent and affected preferentially the uptake of high concentrations (> 25 microM) of glutamate. Stimulation of uptake by low extracellular [K+] (1.5-3 mM) was less dependent on HCO3-. Potassium-induced stimulation of uptake was weaker in rat astrocyte cultures than in mouse. The effects of Ba2+ and amiloride on glutamate uptake, as well as the HCO3(-)-dependent stimulatory effects of K+ and the species difference, all related consistently to effects on intracellular pH. The effects on uptake, however, were much larger than predicted by the associated changes in electrochemical gradient of OH-. A "bimodal" scheme for glutamate transport can account qualitatively for the observed correlation between intracellular pH and velocity of glutamate uptake.

Animals↗