Intramuscular NSAIDS reduce post-operative pain after minor outpatient anaesthesia. Efficacy and safety of a topical diclofenac solution (pennsaid) in the treatment of primary osteoarthritis of the knee: a randomized, double-blind, vehicle-controlled clinical trial. The comparative analgesic efficacy of transcutaneous electrical nerve stimulation and a non-steroidal anti-inflammatory drug for painful osteoarthritis. A study of co-treatment of nonsteroidal anti-inflammatory drugs (NSAIDs) with misoprostol for cervical priming before suction termination of first trimester pregnancy. Non-steroidal anti-inflammatory drugs as the first step in cancer pain therapy: double-blind, within-patient study comparing nine drugs. Effects of post-operative pain treatment using non-steroidal anti-inflammatory analgesics, opioids or epidural blockade on systemic and local immune responses in children. Non-steroidal anti-inflammatory drugs in treatment of postoperative pain after cardiac surgery. Soft tissue trauma: a randomised controlled trial of the topical application of felbinac, a new NSAID. Effect of a topical diclofenac solution for relieving symptoms of primary osteoarthritis of the knee: a randomized controlled trial. Comparison of diflunisal and naproxen in the treatment of tennis elbow. Local NSAID gel (eltenac) in the treatment of osteoarthritis of the knee. A double blind study comparing eltenac with oral diclofenac and placebo gel. Transcutaneous electrical nerve stimulation for pain management in patients with uncomplicated minor rib fractures. Multicenter clinical trial of ibuprofen and acetaminophen in the treatment of postoperative dental pain. Single dose and multidose analgesic study of ibuprofen and meclofenamate sodium after third molar surgery. Intraindividual differences in pain relief and functional improvement in osteoarthritis with diclofenac or tramadol. Transdermal fentanyl for improvement of pain and functioning in osteoarthritis: a randomized, placebo-controlled trial. Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial. A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer's disease. Safety and efficacy of topical diclofenac sodium gel for knee osteoarthritis in elderly and younger patients: pooled data from three randomized, double-blind, parallel-group, placebo-controlled, multicentre trials. Treatment of osteoarthritis of the knee with a topical diclofenac solution: a randomised controlled, 6-week trial [ISRCTN53366886]. [Reduced diclofenac administration by B vitamins: results of a randomized double-blind study with reduced daily doses of diclofenac (75 mg diclofenac versus 75 mg diclofenac plus B vitamins) in acute lumbar vertebral syndromes]. Guidelines and educational outreach visits from community pharmacists to improve prescribing in general practice: a randomised controlled trial. Efficacy and safety of topical nimesulide in the treatment of knee osteoarthritis. Choosing between NSAID and arnica for topical treatment of hand osteoarthritis in a randomised, double-blind study. A group randomized trial to improve safe use of nonsteroidal anti-inflammatory drugs.
Two hundred healthy patients scheduled for elective minor gynaecological surgery under general anaesthesia were randomly allocated to one of four groups who received either diclofenac 75 mg intramuscularly (i.m.), ketorolac 30 mg i.m., diclofenac 50 mg orally, or 2 mL NaCl i.m. The drugs were administered 10-20 min prior to a standard anaesthetic. All surgery was uneventful. The patients were discharged after a mean of 110 +/- 30 min with no differences between the groups. Complaints about pain and need for post-operative analgesics were significantly less frequent in the two groups of patients receiving an intramuscular non-steroidal anti-inflammatory drug (NSAID), as compared to placebo. The patients who received 50 mg diclofenac orally, administered shortly before the procedure, had the same pain course as the placebo patients. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to relieve the symptoms of osteoarthritis (OA) but can produce harmful systemic effects and end-organ damage. A topical NSAID formulation may provide symptom relief with fewer adverse effects. A new topical diclofenac sodium solution-containing the absorption enhancer dimethyl sulfoxide-was evaluated for the relief of the symptoms of primary OA of the knee.
                A total of 326 patients met entry criteria (including abnormal radiographic findings and flare of pain) and were randomized to receive 40 drops of topical diclofenac solution or a vehicle-control solution, 4 times daily, for 12 weeks. We evaluated 3 primary outcome measures, the Western Ontario McMaster Universities LK3.1 OA Index (WOMAC) pain and physical function subscales and a patient global assessment, and 2 other measures, stiffness and pain on walking, at baseline and after final application. We assessed safety by evaluation of adverse events, vital signs, and irritation at the application site.
                Topical diclofenac solution was significantly more effective than the vehicle-control solution for all outcome measures; pain, P = .001; physical function, P = .002; patient global assessment, P = .003; stiffness, P = .005; and pain on walking, P = .004. Among patients receiving topical diclofenac, self-limiting minor skin irritation occurred in 68 (41.5%) of 164 patients, including dryness in 60 (36.6%), rash in 18 (11.0%), and paresthesia, pruritus, and vesiculobullous rash in 1 (0.6%) each. There was no significant difference between groups in NSAID-related gastrointestinal tract complaints or in dropouts due to study-related adverse effects.
                Topical diclofenac is effective in the treatment of the symptoms of primary OA of the knee, with only minor local irritation and no significant systemic adverse events. Thirty-six non-hospitalized subjects with chronic pain from OA of the knee participated in an evaluation of transcutaneous electrical nerve stimulation (TENS) and naproxen, an NSAID. All pre-experiment treatment was withdrawn. Each subject experienced in some order three 3-week treatment phases: NSAID plus placebo TENS; TENS plus placebo drug; and double placebo. A broad range of pain measures was used, including daily diary ratings, and four-times-per-day ratings entered into a small electronic data logger (the PIPER) worn by the subject. A substantial placebo response occurred across all conditions, which may have masked treatment differences. Broad comparisons across subjects, combining the four main measures of pain, found no significant differences among the three experimental treatments. Analysis of diary and PIPER data for individuals suggested that, in a small minority of subjects, the NSAID plus placebo TENS combination may be more effective than double placebo. The PIPER ratings seemed to tap aspects of the pain experience different from those captured by conventional measures, suggesting the value of very frequent pain assessments, such as those entered by a subject into the PIPER, in the study of chronic pain. This double-blind randomized control study was conducted to evaluate whether a nonsteroidal anti-inflammatory drug (NSAID) could act as an effective pain control method during first trimester suction abortion, and whether co-treatment of NSAID with misoprostol will decrease the efficacy of the cervical ripening effect of misoprostol. Subjects were randomized to receive misoprostol alone or misoprostol together with diclofenac sodium. Both groups of subjects suffered from similar incidence of preoperative side effects. Co-treatment of NSAID with misoprostol did not attenuate the cervical ripening efficacy of misoprostol. There was no significant pain reduction in the group treated with NSAID, except that a marginal benefit was found in the subgroup of multiparous women. About two thirds of the subjects in both treatment groups found that this was a satisfactory pain relief method during the procedure. The efficacy and tolerability of acetylsalicylic acid, paracetamol, diclofenac, ibuprofen, indomethacin, pirprofen, sulindac, naproxen and suprofen were compared in the treatment of cancer pain. In a double-blind, within-patient randomized study, each drug was given for 1 week to eight patients and for another week to a further eight patients. A total of 65 patients were effectively treated; only 48 completed week 1 and 41 completed week 2. Naproxen, diclofenac and indomethacin were highly effective in pain relief (tested by means of a 100 mm visual analogue scale) and were relatively well tolerated. It is concluded that these non-steroidal anti-inflammatory drugs can be considered as first choice in the treatment of cancer pain. Many studies have been carried out on the effects of anaesthetic drugs and methods on the immune response, but pain and its relief also affect the immune response. We measured systemic immune responses in the blood circulation and local responses in the surgical wound when non-steroidal anti-inflammatory analgesics (NSAIDs), opioids or epidural blockade was used in the peri-operative treatment of pain.
                Responses were measured in 51 children, aged from 2 to 12 years and undergoing major surgery under balanced anaesthesia. Bolus doses of diclofenac intravenously (i.v.) and rectally (NSAID group), continuous i.v. infusion of oxycodone (opioid group) or continuous epidural infusion of bupivacaine + fentanyl (epidural group) were used peri-operatively for pain relief.
                The only difference related to the analgesic method was shorter duration of post-operative leucocytosis and lower phytohaemagglutinin (PHA)-induced lymphocyte proliferative responses in peripheral blood in the opioid group than in the NSAID or epidural groups. By contrast, time-related alterations were seen overall in leucocyte and differential counts, lymphocyte and their subset counts, lymphocyte proliferative responses, and in serum cortisol, C-reactive protein, plasma interleukin-6 and group II phospholipase A2 concentrations and in the appearance of different cell types in the wound.
                Post-operative pain treatments using diclofenac (NSAID), oxycodone (opioid) and epidural blockade have basically similar effects on systemic and local immune responses with only slight, probably clinically unimportant differences in children undergoing surgery under general anaesthesia.
                Copyright 2004 Acta Anaesthesiologica Scandinavica Non-steroidal anti-inflammatory drugs (NSAIDs) are used as analgesic in postoperative pain to reduce opioid side effects, such as drowsiness and nausea. However, NSAIDs have not been used extensively in cardiac surgical patients due to the fear of untoward effects on gastric, renal, and coagulation parameters. This study will evaluate the efficacy and safety of three NSAIDs for pain control in CABG patients.
                One hundred and twenty patients scheduled for elective CABG surgery were enrolled in randomized, double blind, controlled study. Standardized fast track cardiac anesthesia was used. One dose of drug (75 mg diclofenac, 100 mg ketoprofen, 100 mg indomethacin, or placebo) was given pr one hour before tracheal extubation and a second dose 12 hr later. Pain was treated with morphine iv and acetaminophen po. Visual analogue pain scores were recorded at baseline, 3, 6, 12 and 24 hr after the first dose of drug.
                There were no differences among the groups in pain scores. Only patients who received diclofenac required less morphine than patients in the control group (P < 0.05). When the total amounts of pain medications were computed to morphine equivalents, only patients in the diclofenac group received less pain medications than the placebo group (P < 0.05). Proportion of patients with postoperative increase of creatinine level (20% and over) did not differ between placebo and drug groups.
                Non-steroidal anti-inflammatory drugs may be used for analgesia management post CABG surgery in selected patients. Diclofenac appears to have the best analgesic effects by reducing the morphine and other analgesic requirement postoperatively. Two hundred and thirty-one patients with acute soft tissue injuries were treated in a double-blind placebo-controlled study of felbinac (biphenylacetic acid) gel applied three times daily to the injured site. Those treated with felbinac had significantly greater improvement at Day 4 (p less than 0.001) and Day 7 (p less than 0.02) than those who received placebo. Patients' self-assessment diary cards confirmed superiority of the active treatment as early as Day 2 of the study. Local skin reactions were few (three per cent), mild and recovered spontaneously. Felbinac is an effective management for acute soft tissue injuries and because of its topical application may be safer than oral non-steroidal anti-inflammatory drugs for the treatment of these conditions. Treatment of osteoarthritis with oral NSAID therapy provides pain relief but carries a substantial risk of adverse effects. Topical NSAID therapy offers an alternative to oral treatment, with the potential for a reduced risk of side effects. The objective of this trial was to assess the safety and efficacy of a topical diclofenac solution in relieving the symptoms of primary osteoarthritis of the knee.
                We identified 248 men and women from southern Ontario with primary osteoarthritis of the knee and at least moderate pain. The patients were randomly assigned to apply 1 of 3 solutions to their painful knee for 4 weeks: a topical diclofenac solution (1.5% wt/wt diclofenac sodium in a carrier containing dimethyl sulfoxide [DMSO]); a vehicle-control solution (the carrier containing DMSO but no diclofenac); and a placebo solution (a modified carrier with a token amount of DMSO for blinding purposes but no diclofenac). The primary efficacy end point was pain relief, measured by the Western Ontario and McMaster Universities (WOMAC) LK3.0 Osteoarthritis Index pain subscale. Secondary end points were improved physical function and reduced stiffness (measured by the WOMAC subscales), reduced pain on walking and patient global assessment (PGA). Safety was evaluated with clinical and laboratory assessments.
                In the intent-to-treat group the mean change (and 95% confidence interval [CI]) in pain score from baseline to final assessment was significantly greater for the patients who applied the topical diclofenac solution (-3.9 [- 4.8 to -2.9]) than for those who applied the vehicle-control solution (-2.5 [- 3.3 to -1.7]; p = 0.023) or the placebo solution (-2.5 [-3.3 to -1.7]; p = 0.016). For the secondary variables the topical diclofenac solution also revealed superiority to the vehicle-control and placebo solutions, leading to mean changes (and 95% CIs) of -11.6 (-14.7 to -8.4; p = 0.002 and 0.014, respectively) in physical function, -1.5 (-1.9 to -1.1; p = 0.015 and 0.002, respectively) in stiffness and -0.8 (-1.1 to -0.6; p = 0.003 and 0.015, respectively) in pain on walking. The PGA scores were significantly better for the patients who applied the topical diclofenac solution than for those who applied the other 2 solutions (p = 0.039 and 0.025, respectively). The topical diclofenac solution caused some skin irritation, mostly minor local skin dryness, in 30 (36%) of the 84 patients, but this led to discontinuation of treatment in only 5 (6%) of the cases. The incidence of gastrointestinal events did not differ between the treatment groups. No serious gastrointestinal or renal adverse events were reported or detected by means of laboratory testing.
                This topical diclofenac solution can provide safe, site-specific treatment for osteoarthritic pain, with only minor local skin irritation and minimal systemic side effects. The authors favor conservative treatment of tennis elbow, starting with cessation of the offending activity and prescription of a nonsteroidal anti-inflammatory drug (NSAID) and followed by isometric and isotonic exercises when pain and inflammation have subsided. Two NSAIDs, diflunisal and naproxen, were evaluated in 38 patients with mild-to-moderate pain associated with tennis elbow. The physicians' assessments found no statistically significant differences between the two drugs; both provided effective reduction of pain and swelling. Patients' assessments of pain relief achieved with their respective drugs significantly (P = 0.019) favored diflunisal. Prompt and effective relief of pain and swelling hastens the patient's progression to physical therapy and return to normal activities. In a randomized, double blind, multicentre study with 4 weeks follow-up of 290 patients with osteoarthritis of the knee joint, a topical NSAID (eltenac) was compared with oral diclofenac and placebo. The main outcome, Lequesne's Index and pain by VAS showed no statistically significant differences between neither of the active treatments and placebo for the total study population. However, in patients with more severe symptoms, both active groups showed statistically significant differences to placebo. No severe adverse drug reactions were seen but the number of GI reactions were three times higher in the diclofenac group compared to the topical treatment. Local skin reactions were twice as frequent in the eltenac than in the placebo group. Taking into account the nature of the treatment for a chronic disease like OA, our results indicate that eltenac gel could be a safe alternative to oral NSAIDs. Few non-surgical conditions are more painful than rib fractures. There are a few methods for pain relief in patients with minor rib fractures.
                We used a non-steroidal anti-inflammatory drug (NSAID, Naproxen sodium) and transcutaneous electrical nerve stimulator (TENS) to control pain of the patients with uncomplicated minor rib fractures. One hundred consecutive patients admitted to Kartal Education and Research Hospital Emergency Service, were randomized into four groups. The patients were assigned to one of the following pain treatments: NSAID, TENS, NSAID plus inactive TENS or placebo. The patients used NSAIDs and placebo four times a day and TENS twice a day for 3 days. All patients were asked to assess their pain level with a scoring system on days 0, 1 and 3.
                The most effective treatment was TENS on days 1 and 3 (P<0.05). Although NSAID and NSAID plus inactive TENS controlled pain better than placebo on day 1 (P<0.05), this superiority did not continue to day 3 (P>0.05). There was no difference between NSAID and NSAID plus inactive TENS in controlling pain on either days 1 or 3.
                We conclude that TENS was more effective than NSAID or placebo in patients with uncomplicated minor rib fractures, because of its prominent and admirable efficacy in reduction of pain. Pharmacological management of pain for acute and chronic conditions has been guided by a scientific understanding of peripheral and central acting mechanisms for the control of inflammation as well as pain. Oral surgery pain is a reliable model to reference the effectiveness of commonly used analgesics such as ibuprofen and acetaminophen. A total of 706 patients who were experiencing moderate to severe pain received a single dose of ibuprofen, acetaminophen, or placebo. After 6 hours, the degree of pain relief and tolerance was assessed. Ibuprofen has important implications for postoperative pain in clinical practice. The purpose of this study was to compare the analgesic efficacy and safety of meclofenamate sodium with ibuprofen after dental impaction surgery. This study was double-blind and used a unique methodology. Patients (N = 254) were first randomized into the single dose phase of the study that included placebo, meclofenamate 50 mg, meclofenamate 100 mg, ibuprofen 200 mg, and ibuprofen 400 mg, followed by a 7-day multidose phase in which patients in the placebo group were rerandomized into one of the active treatment cells. In the single dose phase, all active treatments were significantly more efficacious than placebo for every summary analgesic measure. A positive dose-response was seen for both active drugs with meclofenamate 100 mg and ibuprofen 400 mg exhibiting the greatest efficacy for pain relief, pain reduction, time to remedication, and overall evaluation. Side effects were reported by 26 patients. They were evenly distributed among treatment groups with headache and drowsiness being the most common. During the multidose phase, there were only small differences in efficacy measures among active treatment groups. However, meclofenamate produced a higher incidence of stomach cramps and diarrhea than did ibuprofen (8.8% and 7.2% versus 0.8% and 0.8%). This study indicates that higher doses of nonsteroidal anti-inflammatory drugs are most effective immediately after surgery and that lower doses of these drugs can be used after the first postoperative day. The side effect profile of nonsteroidal anti-inflammatory analgesics is best observed with the use of a multidose study design. To investigate how individual patients with painful osteoarthritis (OA) respond to the non-steroidal anti-inflammatory drug (NSAID) diclofenac and the centrally acting analgesic tramadol when individual on-demand dose titration is allowed. In addition, we studied whether the differences in the mode of action of the different analgesics were important for functional outcome in OA patients.
                This was performed as a double-blind, crossover, randomised study in 60 patients with OA of the hip (19 patients) or knee (41 patients) without clinical joint inflammation. Patients received either tramadol (50 to 100mg up to three times daily, on demand) for 4 weeks, followed by diclofenac (25 to 50mg up to three times daily, on demand) for 4 weeks, or vice versa. The multidimensional 'Western Ontario and McMaster Universities Osteoarthritis Index' (WOMAC) questionnaire (pain, stiffness and functional impairment) was used to assess the effect of the drugs on pain and functional capability.
                54 patients completed both study periods. The mean (+/- SD) daily dose of tramadol consumed was 164.8mg (+/- 54.1mg) and that of diclofenac was 86.9mg (+/- 21.4mg). Both treatments modestly improved median pain intensity, paralleled by an improvement in functional parameters, and there were no statistically significant differences between the groups. However, individual treatment effects varied greatly, and within individual patients there were considerable variations in analgesic effectiveness between the two treatments. Consistently, pain relief correlated linearly with functional improvement. More patients reported adverse events with tramadol than with diclofenac (20 vs 3%, p = 0.0056), but there was no difference in adverse event-related withdrawals (p = 0.69).
                OA patients' response to analgesic treatment was highly individual and the response to one drug was not predictive of that to another drug. A significant proportion of patients were not treated satisfactorily with diclofenac or tramadol alone. The results obtained from a descriptive analysis of group effects (means, medians) were inappropriate for drawing conclusions on individual treatment benefits. Improvement of functional capability apparently was a consequence of pain relief. Effective pain relief should therefore be the main therapeutic goal in patients with OA where inflammation is less prominent. Although common treatments for osteoarthritis (OA) pain, such as nonsteroidal antiinflammatory drugs (NSAIDs), simple analgesics, and weak opioids, provide relief in some cases, they fail to control pain or are poorly tolerated in many cases. Strong opioids have been used to successfully treat several types of noncancer pain but have rarely been tested in controlled studies. Therefore, we tested the effects of transdermal fentanyl (TDF) in patients with moderate-to-severe OA pain, in a placebo-controlled study.
                The cohort comprised patients with radiologically confirmed OA of the hip or knee (meeting the American College of Rheumatology criteria) requiring joint replacement and with moderate-to-severe pain that had been inadequately controlled by weak opioids. The patients were randomized to receive TDF or placebo for 6 weeks after a 1-week pretreatment run-in phase. During study treatment, previously prescribed NSAIDs and simple analgesics were continued, but weak opioids were discontinued. All patients had access to paracetamol and metoclopramide. Pain was recorded on a visual analog scale (VAS), and function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).
                Data were available for 399 patients (202 receiving TDF, 197 receiving placebo), of whom 199 (50%) completed the study. TDF provided significantly better pain relief than placebo, as demonstrated by the primary outcome measure (area under the curve for VAS scores -20 in the TDF group versus -14.6 in the placebo group; P = 0.007). TDF was also associated with significantly better overall WOMAC scores and pain scores. The most common adverse events were nausea, vomiting, and somnolence, and these occurred more often in the TDF group.
                TDF can reduce pain and improve function in patients with knee or hip OA. A double-blind, placebo-controlled study was carried out to see whether the synthetic E prostaglandin, misoprostol, would prevent gastric ulcer induced by non-steroidal anti-inflammatory drugs (NSAIDs). 420 patients with osteoarthritis and NSAID-associated abdominal pain were studied; they were receiving ibuprofen, piroxicam, or naproxen. Endoscopy was done at entry and after 1, 2, and 3 months of continuous treatment with 100 micrograms or 200 micrograms misoprostol or placebo, given four times daily with meals and at bedtime, concurrently with the NSAID. Abdominal pain was rated independently by patients and physicians. A treatment failure was defined as development of a gastric ulcer. Gastric ulcers (0.3 cm in diameter or greater) occurred less frequently (p less than 0.001) in both misoprostol treatment groups (5.6% 100 micrograms and 1.4% 200 micrograms) than in the placebo group (21.7%). The significant difference in ulcer formation between the placebo and the misoprostol treatment groups remained when comparisons were restricted to ulcers greater than 0.5 cm in diameter (12.3% placebo, 4.2% 100 micrograms misoprostol, and 0.7% 200 micrograms misoprostol). Mild to moderate, self-limiting diarrhoea was the most frequently reported adverse effect attributed to misoprostol. These results provide the first clear indication that NSAID-induced ulcers are preventable. Previous studies suggest a potential benefit from nonsteroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease (AD). Prescribing NSAIDs, however, carries the risk of significant gastrointestinal adverse events.
                To study whether treatment with an NSAID prevents expected decline in AD patients and evaluate whether co-administration of the gastro-protective agent, misoprostol, with an NSAID is safe in AD.
                The efficacy and safety of diclofenac in combination with misoprostol (D/M) was evaluated in 41 patients with mild-moderate AD in a prospective 25-week, randomized, double-blind placebo-controlled trial. Efficacy measures comprised the Alzheimer's Disease Assessment Scale cognitive and noncognitive subsections, Global Deterioration Scale, Clinical Global Impression of Change, Mini-Mental State Examination, Instrumental Activities of Daily Living, Physical Self-Maintenance Scale, and a caregiver-rated Global Impression of Change.
                There were no group differences with any of the outcome measures in an intent-to-treat analysis. There were some nonsignificant trends for the placebo group to have deteriorated more than the D/M-treated patients. Withdrawal rates were 12 of 24 in the D/M group and 2 of 17 in the placebo group. There were no serious drug-related adverse events.
                This pilot study, with small treatment numbers, did not demonstrate a significant effect of NSAID treatment in AD, but the trends observed justify further investigations with a larger number of participants. D/M is safe in AD patients, but its tolerability is not optimal. NSAIDs used for the treatment of osteoarthritis (OA) have dose-related risks for gastrointestinal, cardiovascular and renal adverse events (AEs), particularly in elderly patients. Topical NSAIDs reduce systemic NSAID exposure and may mitigate these risks.
                To evaluate the safety and efficacy of topical diclofenac sodium 1% gel (DSG) versus vehicle in patients aged 25-64 or ≥65 years who have been diagnosed with knee OA.
                Pooled data from three 12-week, randomized, double-blind, parallel-group, multicentre trials.
                US primary care, internal medicine, orthopaedic and rheumatology practices.
                Aged ≥25 years with mild to moderate (Kellgren-Lawrence grade 1-3) knee OA.
                After a 1-week analgesic washout, patients applied 4 g of DSG or vehicle four times daily to one knee. Rescue paracetamol (acetaminophen) up to 4 g/day was allowed.
                Key efficacy outcomes common to the three trials were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (0-20) and physical function (0-68) subscales, global rating of disease (GRD; 100-mm visual analogue scale [VAS]) and pain on movement (POM; 100-mm VAS). ANOVA was used to compare efficacy outcome differences (DSG vs vehicle) by age (25-64 or ≥65 years). A flare design was used that defined a subset of patients who experienced increased pain during the washout period (modified efficacy subpopulation [MES]).
                The MES included both patients aged 25-64 (n = 602) and ≥65 (n = 374) years. Patients in each age group applied >90% of scheduled doses. Among patients aged 25-64 years, the improvement from baseline to week 12 (least squares mean [standard error]) was greater for DSG versus vehicle for WOMAC pain (-5.8 [0.3] vs -4.7 [0.3], p = 0.007), WOMAC physical function (-17.9 [0.9] vs -14.2 [0.9], p = 0.002), GRD (-29.5 [1.6] vs -23.8 [1.6], p = 0.01) and POM (-37.3 [1.8] vs -29.0 [1.8], p < 0.001). Among patients aged ≥65 years, the improvements from baseline for most efficacy outcome scores were significantly greater with DSG versus vehicle: WOMAC pain (-5.3 [0.3] vs -4.1 [0.4], p = 0.02), WOMAC physical function (-15.5 [1.1] vs -11.0 [1.1], p = 0.004) and POM (-33.7 [2.2] vs -26.4 [2.2], p = 0.02). The efficacy of DSG did not differ significantly between patients aged 25-64 years and ≥65 years: WOMAC pain (p = 0.85), WOMAC physical function (p = 0.70), GRD (p = 0.86) and POM (p = 0.81). The incidence of any AE was greater with DSG than with vehicle among patients aged 25-64 years (56.6% vs 50.8%) and ≥65 years (55.8% vs 43.9%). Treatment-related application site dermatitis was more common with DSG compared with vehicle in both younger (4.0% vs 0.7%, respectively) and older (5.8% vs 0.4%, respectively) patients and was the main reason for the difference in treatment-related AEs between the DSG and vehicle groups. Gastrointestinal AEs were infrequent among patients treated with DSG and similar to incidence rates with vehicle in both age groups.
                DSG was effective and generally well tolerated in adults regardless of age. These data support the topical application of DSG for relief of OA knee pain in elderly and younger patients. Clinicaltrials.gov registration numbers NCT00171626, NCT00171678, NCT00426621. Topical NSAIDs have been proven to relieve the symptoms of osteoarthritis (OA) in short-term studies (2 weeks). To justify its chronic use, efficacy of a topical NSAID over a longer term of study should be demonstrated. The efficacy and safety of a topical diclofenac solution over a 6-week treatment course in symptomatic primary OA of the knee was investigated.
                216 men and women, age 40-85 years, with radiologically confirmed primary OA of the knee and a flare of pain at baseline following discontinuation of prior therapy were enrolled into this double-blind study. Participants applied either a topical diclofenac solution (Pennsaid) or vehicle control solution (carrier with no diclofenac); 40 drops 4 times daily directly to the painful knee(s), without massage, for 6 weeks. Pre-planned primary efficacy outcome measures included the core continuous variables pain relief and improved physical function measured by the Western Ontario and McMaster Universities (WOMAC) LK3.1 OA Index, and improved patient global assessment (PGA). Secondary efficacy measure was reduced stiffness. Safety assessments included adverse events and vital signs.
                The topical diclofenac group had a significantly greater mean change in score (final minus baseline) compared to the vehicle control group for pain (-5.2 vs. -3.3, p = 0.003), physical function (-13.4 vs. -6.9, p = 0.001), PGA (-1.3 vs. -0.7, p = 0.0001) and stiffness (-1.8 vs. -0.9, p = 0.002). The mean difference between treatment arms (95% confidence interval [CI]) was 1.9 (0.7 to 3.2), 6.5 (2.5 to 10.5), 0.6 (0.2 to 0.9), and 0.9 (0.3 to 1.4), respectively. Safety analyses showed that topical diclofenac caused skin irritation, mostly minor local skin dryness, in 42/107 (39%), leading to discontinuation of treatment in 5/107 (5%) participants.
                This topical diclofenac solution demonstrated relief at 6 weeks of the symptoms of primary osteoarthritis of the knee. Pain syndromes of the lumbar spine are one of the main problems in orthopedic practice. The therapeutic effect of NSAIDs is not subject to doubt in this connection. But considering that the application of NSAIDs is frequently associated with side effects, a reduction of dosage would be to the patient's benefit. Clinical studies have shown that concomitant treatment with vitamins B1, B6, B12 and diclofenac leads to a more efficient pain relief than treatment using diclofenac alone and thus provides the possibility of saving NSAIDs. This clinical trial was carried out in order to determine whether these results can also be achieved when a reduced dosage of diclofenac (75 mg daily) is used. 123 patients with acute pain syndromes of the lumbar spine were treated with either B-vitamins and diclofenac or diclofenac alone for a maximum of 7 days. There was the option to terminate therapy in the trial after 3-4 days in the case of total pain relief. 45 patients could stop the treatment due to remission of symptoms. 30 patients belonged to the combination therapy group, the other 15 took diclofenac alone; this difference is statistically significant (p less than 0.05). All parameters concerning pain relief and movement of the vertebral column showed statistically significant differences in favour of the B-vitamin-diclofenac-combination, too. The results document the positive influence of B-vitamins on painful vertebral syndromes and indicate that B-vitamins contribute to saving of NSAIDs by shortening the treatment time and reducing daily NSAID-dosage. To evaluate the effectiveness of guidelines with or without one-to-one educational outreach visits by community pharmacists in improving general practice prescribing for non-steroidal anti-inflammatory drugs (NSAIDs).
                Cluster randomised trial of 20 general practices within Avon, England. Practices were randomised to three groups: control; mailed guidelines; mailed guidelines plus educational outreach visits. General practitioners (GPs) in the latter group received two one-to-one outreach visits from community pharmacists. Changes in prescribing were measured using outcomes derived from prescribing analysis and cost (PACT) data. The primary outcome measure was change in the volume of prescribing for ibuprofen, diclofenac and naproxen as a percentage of total NSAID prescribing. Six secondary outcomes included other measures of prescribing quality and volume. A cost-benefit analysis was performed.
                No significant differences were observed for the primary outcome measure: practices receiving outreach visits prescribed only 2.1% [95% confidence interval (CI): -0.8 to 5.0] more of the three recommended NSAIDs than the control practices did and 1.6% (95% CI: -1.4 to 4.7) more than practices that received guidelines only. Following adjustment for multiple comparisons, only one secondary outcome showed a statistically significant difference between the groups: the proportion of prescribing of the five most frequently used drugs was 2.2% (95% CI: 0.9 to 3.6) higher in the educational outreach group compared with the control group. A net increase in costs was shown with both interventions.
                Although good prescribing at baseline in the participating practices limited the capacity for improvement, this trial provides no evidence that guidelines with or without educational outreach visits from community pharmacists lead to substantial improvements in prescribing behaviour. Osteoarthritis (OA) affects mainly older people who are more sensitive to adverse effects of classic nonsteroidal anti-inflammatory drugs. Recent publications indicate that topically applied nonsteroidal anti-inflammatory drugs are effective and much safer than their oral analogues.
                In this double-blind, randomized, placebo-controlled study design, we aimed to investigate whether topical nimesulide treatment has any beneficial effect in knee OA patients.
                Seventy-four adult knee OA outpatients were enrolled. We used Western Ontario and McMaster Universities OA Index (WOMAC), Nottingham Health Profile (NHP), and patient and physician global satisfaction scores. WOMAC and NHP scores were measured at the initial and final visit. Treatment group received topical nimesulide gel 1% on the knee skin 3 times a day whereas placebo group received an identical-appearing gel for 30 days.
                There was a significant improvement in the nimesulide treatment group for all 3 parameters and overall score of WOMAC between pretreatment and posttreatment values. The overall WOMAC scores was significantly better than placebo (P = 0.03), but physical functioning, stiffness, and pain scales did not reach statistical significance. For the NHP scores there was an improvement at "energy level," "pain," "physical motion," and "NHP distress" scores in the treatment group whereas no improvement was found in the placebo group. Between-group differences were not significant. Both patient and physician satisfaction scores were significantly better in the treatment group.
                This study shows that topical nimesulide gel can have beneficial effects and can improve quality of life in patients with knee OA. The use of topical preparations for symptom relief is common in osteoarthritis. The effects of ibuprofen (5%) and arnica (50 g tincture/100 g, DER 1:20), as gel preparations in patients with radiologically confirmed and symptomatically active osteoarthritis of interphalangeal joints of hands, were evaluated in a randomised, double-blind study in 204 patients, to ascertain differences in pain relief and hand function after 21 days' treatment. Diagnosis was according to established criteria; primary endpoints were pain intensity and hand function; statistical design was as per current regulatory guidelines for testing topical preparations. There were no differences between the two groups in pain and hand function improvements, or in any secondary end points evaluated. Adverse events were reported by six patients (6.1%) on ibuprofen and by five patients (4.8%) on arnica. Our results confirm that this preparation of arnica is not inferior to ibuprofen when treating osteoarthritis of hands. To determine whether audit/feedback and educational materials improve adherence to recommendations for laboratory monitoring and cytoprotective agents to detect and prevent adverse events caused by nonsteroidal anti-inflammatory agents (NSAIDs).
                Controlled, cluster-randomized trial.
                Physicians commonly prescribing NSAIDs were identified within a large managed care organization and randomized to a control or an intervention group (audit/feedback with peer-derived benchmarks and continuing medical education). Medical records were examined 10 months before and after the intervention for clinical data and receipt of complete blood count (CBC), creatinine testing, and cytoprotective agents (process measures). Primary analysis compared intervention versus control physicians among those who initially performed below a peer-derived benchmark. General estimating equations accounted for patient clustering.
                Of 101 physicians initially randomized, 85 remained eligible (38 internists, 36 family physicians, 11 rheumatologists) postintervention. Mean percent change in performance between intervention and control physicians for CBC monitoring was 16% versus 10%; for creatinine monitoring, 0% versus 17%; and use of cytoprotective agents, -3% versus -1%. None of these changes were significant. Rheumatology specialty, number of NSAID prescriptions and physician visits, and patient risk factors for NSAID-related toxicity were more strongly associated with improved safety practices than the intervention.
                Audit/feedback and educational materials had no observed effect on improving NSAID-related safety practices. Potentially contributing factors include high baseline performance (ceiling effect), dilution of the intervention effect by case mix and provider factors, nonreceipt of intervention materials, and diverse indications for lab tests.
Topical NSAIDs can provide good levels of pain relief, without the systemic adverse events associated with oral NSAIDs, when used to treat acute musculoskeletal conditions.