Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers

BACKGROUND: Helicobacter pylori infection is common in patients with peptic ulcers caused by the use of non-steroidal anti-inflammatory drugs (NSAIDs). But the pathogenic role of H pylori in this disease is controversial. We studied the efficacy of eradication of H pylori in the prevention of NSAID-induced peptic ulcers. METHODS: We recruited patients with musculoskeletal pain who required NSAID treatment. None of the patients had previous exposure to NSAID therapy. Patients who had H pylori infection but no pre-existing ulcers on endoscopy were randomly allocated naproxen alone (750 mg daily) for 8 weeks or a 1-week course of triple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 400 mg, each given orally four times daily) before administration of naproxen (750 mg daily). Endoscopy was repeated after 8 weeks of naproxen treatment or when naproxen treatment was stopped early because of bleeding or intractable dyspepsia. All endoscopic examinations were done by one endoscopist who was unaware of treatment assignment. The primary endpoint was the cumulative rate of gastric and duodenal ulcers. FINDINGS: 202 patients underwent endoscopic screening for enrolment in the trial, and 100 eligible patients were randomly assigned treatment. 92 patients completed the trial (47 in the naproxen group, 45 in the triple-therapy group). At 8 weeks, H pylori had been eradicated from no patients in the naproxen group and 40 (89%) in the triple-therapy group (p < 0.001). 12 (26%) naproxen-group patients developed ulcers: five had ulcer pain and one developed ulcer bleeding. Only three (7%) patients on triple therapy had ulcers, and two of these patients had failure of H pylori eradication (p = 0.01). Thus, 12 (26%) patients with persistent H pylori infection but only one (3%) with successful H pylori eradication developed ulcers with naproxen (p = 0.002). INTERPRETATION: Eradication of H pylori before NSAID therapy reduces the occurrence of NSAID-induced peptic ulcers.     

Tramadol (Tramal) in the treatment of rheumatic diseases-- comparative study

In order to evaluate the efficacy of centrally acting analgesics. In treating rheumatic diseases, tramadol hydrochloride (Tramal Grunental) has been administered to a group of 68 patients (36 women and 32 men), who received 100 mg twice a day during a 10-day treatment. The testing comprised 14 female patients with rheumatoid arthritis, 20 patients (7 women and 13 men) with degenerative (OA) hip and knee diseases and 34 patients (15 women and 19 men) affected by the vertebrogen painful syndrome of lumbar spine. The control group comprised 12 patients (9 women and 3 men) with rheumatoid arthritis using non-steroidal antiinflammatory drugs only, 22 patients (12 women and 10 men) with the OA of the hip and knee, using paracetamol only, and 30 patients (15 women and 15 men) affected by the vertebrogen painful syndrome of lumbar spine, also using paracetamol only. The visual analogue scale has been used in following the pain relief assessments during the therapy. It has thus been observed that the intensity of pain has not been significantly relieved with the acute rheumatic diseases (p > 0.05) in the control group either; that the significant pain relief has occurred with the degenerative (OA) rheumatic diseases (p < 0.05) but not in the control group; while the best analgetic effect of tramadol has been proved on the patients affected by the vertebrogen painful syndrome of lumbar spine (p < 0.01) but was not significant in the control group. During the therapeutic treatment 13 patients (19%), mostly the elderly, experienced side effects, manifested as nausea and the dry mouth.     

Altered expression of membrane inhibitors of complement in human gastric epithelium during Helicobacter-associated gastritis

Tramadol hydrochloride is a novel, centrally acting analgesic with two complementary mechanisms of action: opioid and aminergic. Relative to codeine, tramadol has similar analgesic properties but may have fewer constipating, euphoric, and respiratory depressant effects. A two-center randomized double-blind controlled clinical trial was performed to assess the analgesic efficacy and reported side effects of tramadol 100 mg, tramadol 50 mg, codeine 60 mg, aspirin (ASA) 650 mg with codeine 60 mg, and placebo. Using a third molar extraction pain model, 200 healthy subjects were enrolled in a 6-hour evaluation after a single dose of drug. Of the 200 patients enrolled, seven provided incomplete efficacy data or discontinued prematurely and one was lost to follow-up. Using standard measures of analgesia, including total pain relief score (TOTPAR), maximum pain relief score (MaxPAR), sum of pain intensity difference scores (SPID), peak pain intensity difference (Peak PID), remedication, and global evaluations, all active treatments were found to be numerically superior to placebo. ASA/codeine was found to be statistically superior to placebo for all measures of efficacy. Tramadol 100 mg was statistically superior to placebo for TOTPAR, SPID, and time of remedication, whereas tramadol 50 mg was statistically superior to placebo onlyfor remedication time. Codeine was not found to be statistically superior to placebo for any efficacy measure. A greater TOTPAR response compared with all other active measures was seen for ASA/codeine during the first 3 hours of study. The 6-hour TOTPAR scores for the tramadol groups and ASA/ codeine group were not significantly different. Gastrointestinal side effects (nausea, dysphagia, vomiting) were reported more frequently with tramadol 100 mg, ASA/ codeine, and codeine 60 mg than with placebo.     

Effect of a nonsteroidal antiinflammatory drug on synovial fluid in osteoarthritis

OBJECTIVE: The use of nonsteroidal antiinflammatory drug (NSAID) therapy in osteoarthritis (OA) is controversial because of suggestions that pure analgesics can be as effective as NSAID for pain relief. In addition, there is incomplete information whether antiinflammatory effects have any longterm benefit in OA. NSAID have been known to affect synovial fluid (SF) prostaglandins in rheumatoid arthritis. We describe the first examination of the effect of an NSAID, etodolac, on SF prostaglandins, cytokines, and cells in OA. METHODS: Joint fluids were studied before and 2 weeks after initiation of therapy with etodolac 400 mg tid. Leukocyte counts, prostaglandin, interleukin 6, and tumor necrosis factor were measured. RESULTS: Pretreatment features of SF did not predict clinical response. We found no change in the relatively low leukocyte counts. However, SF prostaglandin levels and interleukin 6 levels were significantly decreased and tumor necrosis factor alpha levels were increased after therapy with NSAID. CONCLUSION: This NSAID had potentially important local effects that could be either beneficial or deleterious. Further studies on effects of this and other NSAID on a broader variety of SF and synovial cytokines may help predict longterm effects of NSAID on progression of OA.     

Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia

OBJECTIVE: Although opioid analgesics are used in the management of neuropathic pain syndromes, evidence of their efficacy remains to be established. We evaluated the clinical efficacy and safety of oxycodone in neuropathic pain using postherpetic neuralgia as a model. METHODS: Patients with postherpetic neuralgia of at least moderate intensity were randomized to controlled-release oxycodone 10 mg or placebo every 12 hours, each for 4 weeks, using a double-blind, crossover design. The dose was increased weekly up to a possible maximum of 30 mg every 12 hours. Pain intensity and pain relief were assessed daily, and steady (ongoing) pain, brief (paroxysmal) pain, skin pain (allodynia), and pain relief were recorded at weekly visits. Clinical effectiveness, disability, and treatment preference were also assessed. RESULTS: Fifty patients were enrolled and 38 completed the study (16 men, 22 women, age 70+/-11 years, onset of postherpetic neuralgia 31+/-29 months, duration of pain 18+/-5 hours per day). The oxycodone dose during the final week was 45+/-17 mg per day. Compared with placebo, oxycodone resulted in pain relief (2.9+/-1.2 versus 1.8+/-1.1, p=0.0001) and reductions in steady pain (34+/-26 versus 55+/-27 mm, p=0.0001), allodynia (32+/-26 versus 50+/-30 mm, p=0.0004), and paroxysmal spontaneous pain (22+/-24 versus 42+/-32 mm, p=0.0001). Global effectiveness, disability, and masked patient preference all showed superior scores with oxycodone relative to placebo (1.8+/-1.1 versus 0.7+/-1.0, p=0.0001; 0.3+/-0.8 versus 0.7+/-1.0, p=0.041; 67% versus 11%, p=0.001, respectively). CONCLUSIONS: Controlled-release oxycodone is an effective analgesic for the management of steady pain, paroxysmal spontaneous pain, and allodynia, which frequently characterize postherpetic neuralgia.     

Effects of surgical anaesthesia on the viability of nigral grafts in the rat striatum

OBJECTIVE: To compare betamethasone with placebo as an adjuvant to antibiotic therapy in the treatment of acute exudative pharyngitis. METHODS: The study was a randomized, doubled-blind, placebo-controlled, single-center, parallel, outpatient clinical trial. After consent was obtained, each patient was asked to rate his or her pain on a 10-cm numbered visual analog scale (VAS; 0-10). All of the patients received injectable benzathine penicillin. If allergic to penicillin, they were started on a 10-day course of polyenteric-coated erythromycin (PCE). Each patient was randomized to receive either i.m. betamethasone or i.m. placebo. All patients were contacted by telephone at 24 and 48 hours by one of the study investigators and asked to rate their pain based on another VAS. If their pain was not resolved by 48 hours, they were called again daily between the third and seventh days after the initial visit to determine the time of pain resolution. RESULTS: A total of 92 patients were enrolled in the study, with 46 randomized to receive placebo and 46 to receive betamethasone. Eight patients were excluded from the statistical analysis because of inability to obtain follow-up. Demographic comparison showed that gender distributions, ages, mean initial pain scores, mean times to the first and second follow-up calls, and treatment regimens were similar in the 2 groups. There were significantly better pain scores for the betamethasone group at first follow-up (p = 0.0005), at second follow-up (p = 0.004), and in number of hours until relief of pain (p = 0.004). When only those patients with a positive culture for a streptococcus species were analyzed, there also were significant reductions in pain score at the first (p = 0.006) and second (p = 0.02) follow-up visits. CONCLUSION: Pain relief was greater and more rapid in patients treated with betamethasone as an adjuvant therapy in acute exudative pharyngitis.     

A double-masked comparison of Naprelan and nabumetone in osteoarthritis of the knee. Naprelan Study Group

The efficacy and safety of Naprelan (naproxen sodium) 1000 mg once daily (QD) and nabumetone 1500 mg QD were compared in a multicenter, randomized, parallel-group, placebo-controlled, double-masked, 4-week study of adult outpatients with active osteoarthritis (OA) of the knee. Nabumetone 1500 mg was chosen for comparison because it is commonly prescribed in a QD dosing regimen for OA. After a washout period free of nonsteroidal anti-inflammatory drugs, 279 patients were enrolled and assigned randomly to treatment with either Naprelan 1000 mg QD (n = 92), nabumetone 1500 mg QD (n = 93), or placebo (n = 94). All treatments were evaluated for efficacy and safety at baseline and at weeks 2 and 4 of the treatment period or at discontinuation. Demographic characteristics were comparable among all treatment groups. As might be expected in a study of OA of the knee, a majority of patients enrolled were women (68.8%), and many were obese (mean weight, 195.6 lb; mean height, 66 in). Significantly fewer patients (13) treated with Naprelan prematurely discontinued the study than did patients treated with placebo (27); there was a lower rate of discontinuation for insufficient therapeutic effect in the Naprelan group compared with the nabumetone and placebo groups. Using an intent-to-treat model, the overall distribution of scores in all three primary efficacy assessments (investigator's global assessment of OA, patient's global assessment of OA, and walking pain) at week 2 and at the last visit was significantly better for the Naprelan group compared with both the nabumetone and placebo groups. The mean improvement from baseline was also significant for Naprelan compared with the nabumetone and placebo groups for all three assessments at week 2 and for investigator's global assessment of OA and walking pain at the last visit. The nabumetone-treated group showed significant improvement over the placebo-treated group in only one primary assessment: mean change from baseline in patient's global assessment of OA at week 2. At week 2, significant differences favoring Naprelan versus nabumetone and placebo were measured in overall distribution of scores for joint tenderness and nighttime pain. Distribution of quality of sleep and inactivity stiffness scores also improved relative to placebo at week 2. At the last visit, nighttime pain scores were still significantly better for patients receiving Naprelan versus nabumetone and placebo. Patients receiving nabumetone had statistically significant improvement from baseline in inactivity stiffness compared with placebo at week 2. There were no clinically important differences among treatment groups in the occurrence of adverse events or laboratory abnormalities. The results of this 4-week study of Naprelan 1000 mg QD compared with nabumetone 1500 mg QD demonstrate at least equal efficacy (superior efficacy was demonstrated for several parameters) and equal safety in adult outpatients with active OA of the knee.     

Non-verbal communication: evaluation of a computer-assisted learning package

To assess the effect of 4 weeks' therapy with ranitidine 150 mg twice daily on the healing of symptomatic NSAID-associated gastric and duodenal ulcers, 149 arthritic patients were randomly allocated to one of three treatment groups: ranitidine with NSAID continued, ranitidine with NSAID discontinued, and placebo with NSAID discontinued. The healing frequency in patients with gastric ulceration was 67, 68 and 47%, and in those with duodenal ulceration 61, 81 and 42%, respectively. Only the difference between the duodenal ulcer healing rates for ranitidine with NSAID discontinued and placebo was statistically significant (P = 0.02). Healing rates were uninfluenced by gender, age, smoking habits, alcohol consumption, ulcer frequency or size, arthritic disease, or participating country.     

The impact of ibuprofen on the efficacy of antihypertensive treatment with hydrochlorothiazide in elderly persons

BACKGROUND: Nonsteroidal antiinflammatory drugs (NSAIDs) may alter blood pressure through their inhibitory effects on prostaglandin biosynthesis. Such potential hypertensive effects of NSAIDs have not been adequately examined in the elderly, who are the largest group of NSAID users. METHODS: We performed a randomized, double-blind, two-period crossover trial of ibuprofen (1800 mg per day) vs placebo treatment in patients older than 60 years of age with hypertension controlled with hydrochlorothiazide. While continuing their usual thiazide dosage, subjects were randomized to a 4-week treatment period (ibuprofen or placebo) followed by a 2-week placebo wash-out period and a second 4-week treatment period with the alternative therapy. Supine and standing systolic and diastolic blood pressures were measured weekly. RESULTS: Of 25 randomized subjects, 22 completed the study protocol (mean age = 73 +/- 6.7 years). Supine systolic blood pressure and standing systolic blood pressure were increased significantly with ibuprofen treatment, compared with placebo. Mean supine systolic blood pressures were 143.8 +/- 21.0 and 139.6 +/- 15.9 mmHg on ibuprofen and placebo, respectively (p = .004). Mean standing systolic blood pressures were 148.1 +/- 19.9 and 143.4 +/- 17.9 mmHg on ibuprofen and placebo, respectively (p = .002). CONCLUSION: We conclude that 1800 mg per day of ibuprofen does induce a significant increase in systolic blood pressure in older hypertensive patients treated with hydrochlorothiazide. NSAID therapy may negatively impact the control of hypertension in elderly patients.     

Wuchereria bancrofti recombinant antigen-derived poly- and monoclonal antibodies for the detection of circulating antigen(s) in the sera of lymphatic filarial patients

Manipulative therapy is frequently used in the management of musculoskeletal pain. A frequently reported clinical feature of this treatment is the immediacy with which it appears to initiate improvement in pain and function. A randomised, double blind, placebo controlled, repeated measures design was employed to study the initial effects of a cervical spine treatment technique in a group of 15 patients with lateral epicondylalgia. Pressure pain threshold, pain-free grip strength, upper limb neurodynamics, pain and function were assessed prior to and following application of either a treatment, placebo or control condition. All subjects received all three conditions. Differences between the pre-post measures were used as indicators of change in subject's symptom profiles. The treatment condition produced significant improvement in pressure pain threshold, pain-free grip strength, neurodynamics and pain scores relative to placebo and control conditions (P < 0.05). In summary, this study demonstrates that manipulative therapy is capable of eliciting a rapid hypoalgesic effect.     

The role of prenatal diagnosis in the decreasing incidence of congenital defects in the pediatric population of the Czech Republic from 1989 to 1995

CONCLUSION: A dosage of 300 mg/d of allopurinol was not effective in reducing pain or improving activities of daily living in chronic pancreatitis. BACKGROUND: Allopurinol prevents the generation of oxygen-derived free radicals by inhibiting xanthine oxidase. The purpose of this study was to determine whether allopurinol is effective in reducing pain of chronic pancreatitis. METHODS: Thirteen patients with chronic pancreatitis who were experiencing abdominal pain requiring medication at least three times each week entered a randomized, double-blind, two-period crossover clinical trial. Patients evaluated their pain daily using a categorical pain intensity scale, numeric pain intensity scale, and a visual analog scale, and weekly completed a McGill Pain Questionnaire and activities of daily living (ADL) questionnaire. RESULTS: The mean baseline score of pain was approx 50% of most severe pain in all scoring systems. There was no significant decrease in pain associated with allopurinol compared to the placebo (p = 0.24-0.75). In addition, there was no benefit in terms of ADL score associated with allopurinol compared with placebo (p = 0.32). Mean uric acid level was decreased by 1.15 mg/dL while patients were taking allopurinol, compared to when they were taking placebo (p = 0.007).     

Analgesic efficacy of paracetamol and its combination with codeine and caffeine in surgical pain--a meta-analysis

The objective of this study was to quantify the analgesic efficacy of paracetamol and its combination with codeine or caffeine through a systematic overview and meta-analysis of relevant randomized controlled trials (RCTs). Systematic retrieval of relevant clinical trials was carried out using computerized searches, historical searches and communication with manufacturers. The results of RCTs were pooled to estimate (i) the difference in percentage improvement of total pain relief (TOTPAR%) and the sum of pain intensity difference (SPID%); (ii) the proportions of patients obtaining moderate to excellent pain relief relative to placebo (ResRR) and (iii) the ratio of patients requiring analgesic re-medication (RemRR). Head-to-head comparisons were also undertaken for paracetamol versus its combination with codeine or caffeine. A total of 80 RCT reports describing 103 placebo comparisons and 26 head-to-head comparisons were identified. The total pain relief score in the single dose studies increased by 38 percentage points for paracetamol and by 24 points for placebo. The difference (d) in TOTPAR% between the two was highly significant (d = 14, 95% CI: 12, 16). For the difference in SPID%, d = 12, 95% CI: 11, 13. Patients were more than twice as likely to obtain moderate to excellent pain relief on paracetamol than on placebo (ResRR = 2.39, 95% CI: 1.89, 3.02), and less likely to require re-medication (RemRR = 0.78, 95% CI: 0.69, 0.88). There was no significant (P > 0.05) dose-response relationship. The analgesic efficacy of paracetamol 600 mg was enhanced with the addition of codeine 60 mg (using TOTPAR% as outcome) in both indirect and head-to-head comparisons. SPID%, but not ResRR and RemRR, data supported this conclusion. Much weaker effects were observed with the caffeine combination. Adverse effects were mild. Surprisingly, drowsiness was seen more often with paracetamol and paracetamol-codeine combinations than with placebo. The relative risks (95% CI) were 1.83 (1.29, 2.59) and 2.39 (1.58, 3.57), respectively. In conclusion paracetamol is an effective analgesic for post-surgical pain. Caffeine adds little to the analgesic effect of paracetamol. However, there is some evidence that codeine 60 mg adds to the analgesic effects of paracetamol 600 mg, using pain relief or pain intensity scores as outcomes, but this is not necessarily translated into an increase in number of patients who obtain moderate to excellent pain relief.     

Lack of interaction between tramadol and coumarins

The objective of this study was to investigate whether the central analgesic tramadol influences the effects of the coumarin anticoagulant phenprocoumon during multiple-dose administration. Nineteen patients receiving long-term anticoagulant therapy who had been in a stable hypothrombinemic state for at least 3 months completed a double-blind, placebo-controlled, crossover study. Tramadol was administered in the usual therapeutic dose of 50 mg three times daily. The average daily phenprocoumon dose was identical for individual patients in both treatment periods. The equivalence ratio (tramadol/placebo) of the international normalized ratio (INR) values was 0.99 (90% confidence interval 0.89-1.10), thus fulfilling predetermined bioequivalence criteria (0.70-1.43). Therefore, tramadol does not affect INR in patients being treated with phenprocoumon. These data suggest a lack of interaction between tramadol and coumarin anticoagulants.     

The treatment of osteoarthritis of the knee with pulsed electrical stimulation

OBJECTIVE: The safety and effectiveness of pulsed electrical stimulation was evaluated for the treatment of osteoarthritis (OA) of the knee. METHODS: A multicenter, double blind, randomized, placebo controlled trial that enrolled 78 patients with OA of the knee incorporated 3 primary efficacy variables of patients' pain, patients' function, and physician global evaluation of patients' condition, and 6 secondary variables that included duration of morning stiffness, range of motion, knee tenderness, joint swelling, joint circumference, and walking time. Measurements were recorded at baseline and during the 4 week treatment period. RESULTS: Patients treated with the active devices showed significantly greater improvement than the placebo group for all primary efficacy variables in comparisons of mean change from baseline to the end of treatment (p < 0.05). Improvement of > or = 50% from baseline was demonstrated in at least one primary efficacy variable in 50% of the active device group, in 2 variables in 32%, and in all 3 variables in 24%. In the placebo group improvement of > or = 50% occurred in 36% for one, 6% for 2, and 6% for 3 variables. Mean morning stiffness decreased 20 min in the active device group and increased 2 min in the placebo group (p < 0.05). No statistically significant differences were observed for tenderness, swelling, or walking time. CONCLUSION: The improvements in clinical measures for pain and function found in this study suggest that pulsed electrical stimulation is effective for treating OA of the knee. Studies for longterm effects are warranted.     

Bipolar disorder: dominant or recessive on chromosome 5?

Rizatriptan (MK-462) is a potent 5HTID receptor agonist. This multicenter, double-blind, placebo-controlled, outpatient study investigated the clinical efficacy, safety, and tolerability of rizatriptan (2.5, 5, and 10 mg) as a function of dose for acute migraine. Patients with moderate or severe migraine (n = 417) were treated with placebo (n = 67), rizatriptan 2.5 mg (n = 75), 5 mg (n = 130), or rizatriptan 10 mg (n = 145). Headache severity, functional disability, and migraine symptoms were measured immediately before dosing (0) and at 0.5, 1, 1.5, 2, 3, and 4 h post-dose. Patients were permitted to take a second dose of test drug at 2 h if their headache pain was moderate or severe (i.e., placebo initially-->rizatriptan 10 mg as optional second dose; rizatriptan 2.5 mg, 5 mg, or 10 mg initially-->placebo as optional second dose). An upward dose-response relationship was observed among placebo, rizatriptan 2.5 mg, 5 mg, and 10 mg in the primary efficacy measure of proportion of patients reporting pain relief, i.e., a change in headache severity to "no pain or mild pain" at 2 h post-dose. The relationship was evident even at the first recorded timepoint, 30 min, and was statistically significant at 1.5 h and beyond. At the primary timepoint of 2 h after the initial dose, the proportion of patients reporting pain relief was 47.6% for rizatriptan 10 mg; 45.4% for rizatriptan 5 mg; 21.3% for rizatriptan 2.5 mg; and 17.9% for placebo. Seventy percent of patients on rizatriptan 10 mg reported pain relief at 4 h. Patients who took rizatriptan 5 mg and 10 mg were significantly less functionally disabled than those who took placebo at 1.5 and 2 h post-dose. Rizatriptan 10 mg was consistently more effective than 5 mg, although the differences were not statistically significant. The most frequent clinical adverse events were dizziness, somnolence, and asthenia/fatigue. No patients were discontinued for any adverse experiences and there were no serious adverse experiences.     

A systematic review of randomized controlled trials of pharmacological therapy in osteoarthritis of the knee, with an emphasis on trial methodology

We systematically reviewed randomized controlled trials (RCTs) of pharmacological therapy in knee osteoarthritis (OA), published between 1966 and August 1994. RCTs were identified by MEDLINE, supplemented by a manual search of reference lists. Qualitative assessment of RCTs was performed using Gotzsche's method; design and analysis features were rated on a scale of 0 (worst) to 8 (best). Heller et al's method was used to compare efficacy of nonsteroidal antiinflammatory drugs (NSAIDs) in comparative trials. A total of 80 RCTs were analyzed (45 involved NSAIDs, 3 analgesics, 5 intraarticular [IA] steroids, 9 biological agents, including IA hyaluronic acid, and 18 mixed modalities, including topical capsaicin). The median design and analysis scores for all 80 RCTs were 2 and 5, respectively. NSAIDs were superior to placebo in all short-term trials, but in the 32 comparative NSAID trials, only five (16%) found significant differences in efficacy. Heller et al's method identified differences in 14 NSAID comparisons; etodolac (600 mg/day) was superior in five of its nine comparisons. Indomethacin and aspirin were the most toxic NSAIDs. IA steroids were superior to placebo in short-term efficacy (< 1 month). Biological agents were superior to placebo and generally well tolerated over a mean follow-up of 48 weeks. Acetaminophen was superior to placebo and was comparably efficacious to low-dose naproxen and ibuprofen (< 2,400 mg/day). The data support the use of acetaminophen, topical capsaicin, IA steroids, IA hyaluronic acid, and NSAIDs in the treatment of patients with knee OA.     

Ranitidine controls nocturnal gastric acid breakthrough on omeprazole: a controlled study in normal subjects

BACKGROUND & AIMS: Proton pump inhibitors administered twice daily do not provide complete nocturnal acid suppression. Acid breakthrough, or decrease in intragastric pH to <4 for an hour or longer, occurs in three quarters of normal subjects and patients at night. We compared the effect of a third dose of omeprazole at bedtime with that of a dose of ranitidine at bedtime on residual nocturnal acid secretion in patients receiving omeprazole twice daily. METHODS: Twelve volunteers underwent overnight intragastric pH monitoring after 7 days of treatment with omeprazole, 20 mg twice daily, followed by different treatment supplements at bedtime: placebo; additional omeprazole, 20 mg; ranitidine, 150 mg; and ranitidine, 300 mg. RESULTS: Additional omeprazole at bedtime reduced the percentage of time with intragastric pH of <4 from 48% to 31% (P < 0.005) compared with omeprazole twice daily with placebo at bedtime. Ranitidine at bedtime reduced this parameter more, 5% with 150 mg and 6% with 300 mg (P <0.01 vs. omeprazole twice daily plus bedtime). Results for percentage of time with intragastric pH <3 were similar. Eleven subjects had acid breakthrough with placebo at bedtime; 7 with omeprazole at bedtime (P = NS); 4 with ranitidine, 150 mg at bedtime; and 3 with ranitidine, 300 mg at bedtime (P < 0. 05, ranitidine vs. placebo). CONCLUSIONS: Bedtime ranitidine is more effective than bedtime omeprazole on residual nocturnal acid secretion in patients receiving omeprazole twice daily. This finding suggests that fasting breakthrough nocturnal acid secretion in patients receiving omeprazole twice daily is most likely histamine related.     

Musculoskeletal complaints and fibromyalgia in patients attending a respiratory sleep disorders clinic

OBJECTIVE: To determine the frequency of fibromyalgia (FM) syndrome and reporting of pain in an unselected group of patients attending a respiratory sleep disorders clinic, and to examine the association of physical activity and levels of reported pain. METHODS: 108 consecutive patients attending a respiratory sleep disorders clinic were interviewed and examined, blind to sleep disorder status. Assessment of musculoskeletal pain symptoms included patient history of pain, painful sites marked on a mannequin, visual analog scale (VAS) pain score, and tender point count. Daily physical activity was recorded, and all patients underwent nocturnal polysomnography, blind to clinical status. RESULTS: FM was identified in 3 patients (2.7%). Pain reporting was more strongly associated with reduced physical activity than with a specific sleep disorder. Patients with reduced physical activity were more likely to have pain symptoms than physically active patients: tender point count > or = 6 (p = 0.002), > or = 3 sites marked on mannequin (p = 0.008), axial pain (p = 0.003), and VAS pain score (p = 0.008). CONCLUSION: FM by defined criteria was uncommon in patients with a primary complaint of disturbed sleep, and in particular, patients with sleep apnea. Reduced physical activity was strongly associated with reported pain symptoms.     

Oral tramadol and buprenorphine in tumour pain. An Italian multicentre trial

In this multicentre trial tramadol and buprenorphine were compared for the treatment of neoplastic pain no longer responsive to non-steroidal antiinflammatory drugs. A total of 131 adults (86 M, 45F) were treated with tramadol (one 100-mg slow-release tablet every 8-12 h), or buprenorphine (one sublingual 0.2-mg tablet every 6-8 h). The trial was to continue for up to six months. Most patients started treatment with 2-3 tablets/day in both groups, and the mean treatment period was 58 days for tramadol and 51 for buprenorphine. Almost all dose changes needed were made in the first fortnight in both treatment groups, and the largest number of patients dropped out because of inadequate pain relief or progression of the underlying disease. The results achieved in the first two weeks persisted throughout the rest of the trial, and the investigator's assessments on each patient's clinical chart corresponded closely with those that patients made in their own daily diaries. In the four hours after the first dose both drugs virtually halved the severity of pain (measured using a visual analogue scale), and this relief lasted throughout treatment. By the end of the first week the proportion of patients with strong/unbearable pain in the tramadol group had fallen significantly (from 98.4% to 48.1%, p < 0.05), as compared to a drop from 92% to 66.7% for buprenorphine. The quality of sleep also tended to improve in the tramadol group, with the proportion of patients enjoying good or deep sleep rising from 37% to 50%, as compared to 33% to 40-44% with buprenorphine. Karnofsky's and Spitzer's indices reflecting the quality of life did not change in the tramadol group; in the buprenorphine group the Karnofsky index dropped slightly after a fortnight (p < 0.05 between treatments). In the first two months of the trial the number of patients with no/moderate pain rose continuously in the tramadol group (71% and 80% after one and two months); the rise was less marked in the buprenorphine group (number of patients with mild/moderate pain, 45% and 65%). In both the short term and in the longer term, it was found that the levels of efficacy and acceptability were always significantly better in the tramadol group than in the buprenorphine group. General and biological safety in both drugs was good. The most typical side-effects were those characteristic of opioids (nausea and/or vomiting, drowsiness). Adverse reactions were reported in 17 patients taking tramadol (25%) and in 16 taking buprenorphine (26%). There were six drop-outs in the first group (9%) and seven in the second (11%). Serious symptoms arose more frequently in the buprenorphine group (19% cf. 10%). No signs of dependence or tolerance were noted.