Measuring the contribution of pharmacological treatment to advice to stay active in patients with subacute low-back pain: a randomised controlled trial.

PURPOSE: In clinical guidelines for acute and subacute low-back pain, pharmacological treatment is recommended for short-term symptomatic relief. The objective was to study the effect of the guidelines' advise to remain active, alone and with the addition of the drug adenosine tri-phosphate (ATP), in patients with subacute low-back pain. METHODS: A drug-guidelines effectiveness trial was undertaken simultaneously to an experimental drug efficacy placebo controlled trial in subacute (4-12 weeks) non-specific low-back pain patients. The 132 participating primary care physicians across France were randomised to participate to either trial. In the drug-guidelines trial, all physicians received a quick consultation card containing the key elements of the clinical guidelines and a brochure that gave their patients practical tips to remain active. Patients were then randomised to receive Atepadene, containing 90 mg of ATP by mouth daily for 30 days (guidelines plus ATP group), or nothing beside the rescue drug that was made available to all patients (guidelines alone group). The principal outcome was functional improvement on the Roland-Morris Disability Questionnaire (RDQ) at 90 days. RESULTS: In the drug-guidelines effectiveness trial, 157 patients were randomised. The rate of improvement in the RDQ over the 90 days of follow-up was superior in the group guidelines plus ATP (8.3 points, 95% confidence interval (CI): 7.3-9.3) than in the group guidelines alone (6.5 points, 95%CI: 5.3-7.7) (p = 0.02). In terms of probability of improving between two to five points on the RDQ at 90 days this difference translated in a 2 to 13 times higher probability compared to the group guidelines alone (odds ratios ranging from 2.1, 95%CI: 0.9-5.0 to 12.9, 95%CI: 1.6-103.4). Patients in the group guidelines plus ATP were also three times less likely to report a condition that had worsened or remained unimproved at 90 days (p = 0.02). CONCLUSION: This drug-guidelines effectiveness trial showed a modest advantage of combined specific pharmacologic and non-pharmacological treatments on absolute improvement on the RDQ. A threefold reduction in the risk of chronicity was observed, an important goal in low-back pain guidelines.

[Strong opioids for chronic non-cancer pain]. / Les opioïdes forts dans les douleurs chroniques non cancéreuses.

A CHALLENGING SITUATION: A number of patients experiencing chronic noncancer pain are unsatisfied with standard treatment modalities. This raises the question of whether there may be a place for strong opioids in the management of these patients. Randomised placebo-controlled trials of strong opioids generated rather disappointing results in this type of pain. Observational studies have indicated that strong opioids may improve comfort and function in some patients with intractable nociceptive or neuropathic pain. However, opioids may be ineffective in others and intolerable side effects, heightened pain and functional impairment as well as drug addiction may also occur. A PROMISING SOLUTION: Finally, strong opioids do not appear to be the issue to all intractable chronic nonmalignant pain states, but they may be a possible issue to a subset of selected and informed patients who agree on the goals of the treatment and accept regular monitoring.

[Drug-induced and toxic myopathies]. / Myopathies médicamenteuses et toxiques.

A large number of drugs and toxins may induce myopathic changes in several ways, they are probably more common than realized. The clinical and pathological features depend on the causative agent and on individual susceptibility to a given compound. Based on their pathologic mechanisms, there are 6 main categories of toxic myopathies: necrotizing myopathy mainly due to lipid-lowering drugs (fibrates and statines); vacuolar myopathy, usually associated with antimalarial agents; inflammatory myopathy induced by thiol derivatives; mitochondrial myopathy; steroid myopathy, and hypokaliemic myopathy. Toxic myopathies are usually reversible after discontinuation of the offending agent. Their prompt recognition may reduce their damaging effects or prevent a fatal outcome. Muscle biopsy can be very useful for the diagnosis of toxic myopathies.

[Tolerance and dependence on opioid analgesics: experimental and clinical aspects]. / Tolérance et dépendance aux antalgiques opioïdes: aspects expérimentaux et cliniques.

Long-term administration of morphine for chronic non-malignant pain continues to be controversial, mainly because of the fear of opioid addiction and abuse. It is important to distinguish three phenomena: tolerance of the analgesic and side-effects of the drug, physical dependence (which is a pure pharmacological event) and addiction (defined as a compulsive drug-related behaviour). Animal studies suggest that similar mechanisms underlie tolerance and physical dependence. These may result from an imbalance between anti- and pro-nociceptive mechanisms. By contrast, the occurrence of an addictive behaviour depends on both different endogenous mechanisms and environmental factors. Clinical data suggest that the use of stable doses of morphine (or other opiates) is common in patients suffering from chronic non-malignant pain. However, drug addiction might develop in 'at-risk patients' and therefore the decision to start long-term treatment with an opiate should be undertaken very cautiously, and ongoing assessment of aberrant drug-related behaviours should be undertaken repeatedly.

Risk-benefit assessment of opioids in chronic noncancer pain.

Opioids have been accepted as appropriate treatment for acute and cancer pain, but their role in the management of chronic nonmalignant pain is the subject of much debate, mainly due to concerns about waning efficacy, the potential for neuropsychological impairment and the development of drug addiction. Controlled clinical trials demonstrated that opioids may be effective in both nociceptive and neuropathic noncancer pain, although the former responded more consistently than the latter. Gastrointestinal and CNS adverse effects were frequent in most studies. Observational studies have generated contradictory findings regarding efficacy and safety as well as the risk of drug addiction in patients with chronic noncancer pain receiving long term opioid therapy. However, they suggest that opioids may be effective in individual cases, whichever the pathophysiological mechanism of pain. Taken together, the available data indicate that the outcomes associated with opioid therapy vary markedly across patients experiencing chronic nonmalignant pain. The main consensus is that a subset of these patients may gain substantial benefit from opioid analgesics without requiring rapidly escalating doses or developing intolerable adverse effects or drug addiction. Prescribing guidelines have been developed to assist practitioners in selecting the appropriate patients and ensuring an acceptable risk : benefit ratio of opioid therapy. Finally, it must be emphasised that chronic pain is a complex entity wherein analgesics, including opioids, are only part of the treatment.

Chondrosarcoma in a patient with McCune-Albright syndrome. Report of a case.

A case of McCune-Albright syndrome with acromegaly and chrondrosarcoma is reported. The potential role of chronic growth hormone overproduction in the occurrence of malignant transformation and the possible value of bisphosphonates in the treatment of bone fibrous dysplasias are discussed.

[Methotrexate and non-steroidal anti-inflammatory agent combination in rheumatoid arthritis]. / Association méthotrexate et anti-inflammatoire non stéroïdien au cours de la polyarthrite rhumatoïde.

It is well known that methotrexate (MTX), used at high dosage in cancer patients, must not be combined with a non-steroidal anti-inflammatory drug (NSAID) because of high risk of side effects; prescribed at low dosage (< or = 15 mg per week) in rheumatoid arthritis patients, MTX is often combined with an NSAID. Some cases reported in the literature underline the potential toxicity of the association of low dose MTX with an NSAID, but most of the pharmacological studies do not confirm this hypothesis. Except for salicylates, NSAIDs do not affect the absorption, distribution, protein binding, area under the curve, half-life, or the elimination of MTX. Therefore, if necessary, MTX (< or = 15 mg per week) can be combined with an NSAID during the treatment of rheumatoid arthritis.

Chronic immunity-driven polyarthritis in hairy cell leukemia. Report of a case and review of the literature.

Hairy cell leukemia can be responsible for polyarthritis due either to leukemic infiltration or to immunity-drive inflammation. The second variant can antedate or post-date the clinical onset of leukemic symptoms and usually presents as rheumatoid arthritis, more rarely as lupus or scleroderma. The presence of hairy cells in the joint fluid does not rule out autoimmune polyarthritis. The main differential diagnoses are Felty's syndrome and large granular lymphocyte leukemia. We report a case of hairy cell leukemia with seropositive rheumatoid arthritis.

[Side-effects during treatment of rheumatoid arthritis with methotrexate]. / Effets indésirables observés au cours du traitement de la polyarthrite rhumatoïde par le méthotrexate.

Methotrexate is the drug with the highest long-term continuation rate in rheumatoid arthritis patients. However, toxicity is the main reason for methotrexate withdrawal. Most adverse effects are mild abnormalities, such as digestive symptoms, stomatitis, elevations in transaminase levels, and moderate decreases in peripheral blood cell counts. Potentially life-threatening effects include hypersensitivity pneumonitis and pancytopenia. Cirrhosis is less common than in patients with psoriasis. Opportunistic infections and Epstein-Barr virus-related lymphomas have been reported. Neurological disorders, cutaneous reactions and renal lesions have been ascribed to low-dose methotrexate. Prior renal dysfunction and concomitant administration of a number of drugs, including cotrimoxazole, have been shown to increase methotrexate toxicity. However, susceptibility to the toxic effects of methotrexate varies widely across individuals. The effectiveness of folate supplementation in preventing methotrexate toxicity remains controversial.

[Tissue and systemic diffusion of idrocilamide after cutaneous administration]. / Diffusion tissulaire et systémique de l'idrocilamide après application cutanée.

Experimental findings have demonstrated that idrocilamide exhibits antiinflammatory and muscle relaxant properties due at least in part to tissular effects. Percutaneous diffusion of a 10% glycero-alcoholic idrocilamide solution was studied in ten patients scheduled to undergo total knee replacement. Four 200-mg doses of idrocilamide were applied to the suprapatellar area at 12-hour intervals before surgery. Pain was evaluated using a visual analog scale before and after treatment. Surgery was performed 1.75 to 3.5 hours after the last idrocilamide dose. Idrocilamide was assayed using high performance liquid chromatography in tissue, plasma, and joint fluid specimens taken during the surgical procedure. Topical administration of idrocilamide on healthy skin produced significant concentrations of the drug in all the tissue specimens, including subcutaneous fat, muscle, tendon, synovium, and knee capsule. Tissue levels were consistently higher than synovial fluid and plasma levels, indicating that little systemic diffusion occurred. Idrocilamide levels in potential target tissues might influence clinical effects.

Tenoxicam concentrations in synovium and joint cartilage in humans.

Tenoxicam is an NSAID of the oxicam group. Its distribution in articular tissues was investigated in 12 patients who required total arthroplasty of the hip. They were given tenoxicam 20 mg once daily for 8 to 30 days before surgery. Blood, synovium and cartilage samples were taken concurrently during surgery, about 14 hours after the last tenoxicam dose. The tissues were ground using a freeze grinder. Tenoxicam was assayed by HPLC. Tenoxicam concentrations averaged 6.21 +/- 3.81 micrograms/ml in plasma, 7.56 +/- 4.67 micrograms/g in synovium and 2.05 +/- 1.43 micrograms/g in cartilage. The individual synovium/cartilage ratios ranged from 1.9 to 9.7. Finally tenoxicam exhibited more affinity for its target organ (synovial tissue) than for joint cartilage.