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Bernard Avouac

Publications and source records attributed to Bernard Avouac.

11 recordsLinked to original sources

Osteoarthritis of the knee and hip and activity: a systematic international review and synthesis (OASIS).

UNLABELLED: The goal of this study was to determine which activities in four domains, daily life, exercises, sports and occupational activities, should be recommended, in favor or against, for the patient suffering from knee or hip OA. METHODS: Scientific literature was searched in Medline, Embase and Cochrane databases for articles in French or English, reporting original data. The articles were evaluated with standardized epidemiological criteria. Seventy-two articles were retained. Recommendations were graded according to the level of scientific evidence (A high, B moderate, C clinical consensus) and were formulated for primary care. CONCLUSIONS AND RECOMMENDATIONS: For activity of daily life (ADL), the OASIS group states with a moderate level of scientific evidence, that ADL are a risk factor for knee OA and that risk increases with intensity and duration of activity. The group concludes that healthy subjects as well as OA patients in general can pursue a high level of physical activity, provided the activity is not painful and does not predispose to trauma (grade B). Radiographic or clinical OA is not a contraindication to promoting activity in patients who have a sedentary lifestyle (grade C). For exercises and other structured activities pursued with a goal of health improvement, the group states with a high level of scientific evidence that they have a favourable effect on pain and function in the sedentary knee OA patient. The OASIS group recommends the practice of exercises and other structured activities for the sedentary patient with knee OA (grade A). Static exercises are not favored over dynamic exercises, availability, preference and tolerance being the criteria for the choice of an exercise (grade A). As results deteriorate when exercises are stopped, they should be performed at a frequency of between one and three times per week (grade B). Professional assistance can be useful in improving initial compliance and perseverance (grade B). There is no scientific argument to support halting exercise in case of an OA flare-up (grade C). For sports and recreational activity, the group states with a high degree of scientific evidence, that these activities are a risk factor for knee and hip OA and that the risk correlates with intensity and duration of exposure. The group also states, with a high degree of scientific evidence, that the risk of OA associated with sport is lesser than that associated with a history of trauma and overweight. No firm conclusion could be drawn about the possible protective role of sports such as cycling, swimming or golf. The OASIS group recommends that athletes should be informed that joint trauma is a greater risk factor than the practice of sport (Grade A). The high level athlete should be informed that the risk of OA is associated with the duration and intensity of exposure (Grade B). The OA patient can continue to engage regularly in recreational sports as long as the activity does not cause pain (Grade C). The OA patient who practices a sport at risk for joint trauma should be encouraged to change sport (Grade C). For occupational activity, the OASIS group states with a high level of scientific evidence that there is a relationship between occupational activity and OA of the knee and hip. The precise nature of biomechanical stresses leading to OA remains unclear but factors such as high loads on the joint, unnatural body position, heavy lifting, climbing and jumping may contribute to knee and hip OA. The group recommends that taking an occupational history should always be part of managing the OA patient (Grade B). In the knee or hip OA patient, work-related activity that produces or maintains pain should be avoided (Grade B). Physicians should be alerted by the early knee and hip signs and symptoms in workers exposed to stresses that are known or supposed to favour knee or hip OA (Grade C).

Activities of Daily Living↗

Assessing chronic pain in general practice: are guidelines relevant? A cluster randomized controlled trial.

OBJECTIVES: To evaluate the impact of using pain assessment scales on the management of musculoskeletal chronic pain. METHODS: Cluster-randomized controlled multicentre trial in French general practice settings. Practices were randomized by region before patient recruitment. The inclusion concerned patients suffering from musculoskeletal chronic pain. General practitioners assigned to the scale group used two validated assessment instruments; those assigned to the control group cared for their patients according to their usual practice. The primary end-point was the level of relief obtained and the secondary changes in prescription of painkilling modalities. RESULTS: A total of 155 general practitioners included 772 successive patients suffering from musculoskeletal chronic pain. The control group reported a mean level of relief of 50.7% compared with one of 41.1% in the scale group (p<0.0001). In the intervention group, physicians decreased significantly their prescription of level two painkillers. CONCLUSIONS: In general practice, the use of pain assessment scales is not associated with greater pain relief. The lesser level of pain relief obtained in the scale group does provide evidence that using pain assessment scales does not enhance the relief of chronic pain in patients in primary care. Guidelines which recommend the systematic use of scales for the assessment and monitoring of chronic pain are not tailored to either the context or the patients encountered in the primary care setting.

Aged↗

[What is the impact of cardiovascular and renal complications on the benefit/risk ratio of the NSAIDs?].

Long-term studies of NSAIDs have demonstrated cardiovascular toxicity which poses a general problem of the benefit risk between the relief of the patient's symptoms and the risk of digestive and cardiovascular toxicity. The digestive complications and the risk factors associated with the ingestion of NSAIDs have been defined by numerous studies but the prevention of this digestive toxicity can be attempted. The benefit-risk ratio caused by the digestive and cardiovascular toxicities of the NSAIDs and COX-2 inhibitors must be evaluated for each individual before starting a treatment. For a treatment of short duration in patients with a low risk of digestive and cardiovascular complications, the risk of digestive toxicity must be taken into consideration first and the COX-2 inhibitors are favoured. For a treatment of long duration the risk must be evaluated with the greatest care. In the case of cardiovascular risk factors, the cardiovascular risk must be evaluated and the treatment must be prescribed at the lowest dose for the shortest duration. In patients with very high risk of digestive and cardiovascular complications, since the digestive and cardiovascular extra-mortality associated with the ingestion of NSAIDs or COX-2 inhibitors is high, it is advised to abandon this type of long-term treatment.

Age Factors↗

Recommendations for an update of the current (2001) regulatory requirements for registration of drugs to be used in the treatment of osteoporosis in postmenopausal women and in men.

Recent advances in the understanding of the epidemiology of osteoporosis suggest that certain parts of the current European guidelines for the registration of drugs in osteoporosis might be no longer substantiated. The object of this review is to provide the European regulatory authorities with an evidence-based working document providing suggestions for the revision of the "Note for guidance for the approval of drugs to be used in postmenopausal osteoporosis" (CPMP/EWP/552/95). Following an extensive review of the literature (1990-2004), the Group for the Respect of Ethics and Excellence in Science (GREES) organized a workshop including European regulators, academic scientists and representatives of the pharmaceutical industry. The outcomes of this meeting reflect the personal views of those who attended and should not, in any case, be seen as an official position paper of any regulatory agency. The group identified a certain number of points that deserve discussion. They mainly relate to the nature of the indication being granted to new chemical entities (treatment of osteoporosis in women at high risk of fracture instead of prevention and treatment of osteoporosis), the requirements of showing an anti-fracture efficacy on all or on major nonvertebral fractures (instead of the hip), the duration of pivotal trials (2 years instead of 3) and the possibility of considering bridging studies for new routes of administration, new doses or new regimens of previously approved drugs. The group also recommends that an indication could be granted for the treatment of osteoporosis in males on the basis of a placebo-controlled study, with bone mineral density changes after 1 year as the primary endpoint, for medications approved in the treatment of osteoporosis in women at high risk of fractures.

Female↗

A randomized, double-blind, placebo controlled triphosphate in study of oral adenosine subacute low back pain.

OBJECTIVE: To assess the efficacy and safety of oral adenosine triphosphate (ATP) in subacute low back pain. METHODS: This was a randomized, double-blind, parallel group, placebo controlled clinical trial. The patients were given either ATP 90 mg once daily (n=81) or placebo (n=80) for one month. The patients were assessed 3 times during the study period, at days 0, 7, and 30. The primary outcome measure was the Roland-Morris Disability Questionnaire (RDQ) at day 30. Secondary measures of efficacy included visual analog scale (VAS) pain, overall assessments of efficacy by both patient and investigator, and number of dextropropoxyphene and acetaminophen combination tablets used as rescue analgesic. RESULTS: Regarding the RDQ, the mean values dropped from 10.3 +/-2.8 at baseline to 7.5 +/-3.8 (day 7) and 5.2 +/-5.2 (day 30) in the ATP group, and from 11.0 +/- 3.5 to 9.1 +/- 4.2 (day 7) and 6.1 +/- 4.3 (day 30) in the placebo group. The difference between the 2 groups was statistically significant at day 7 (p= 0.02) but not at day 30 (p=0.2). In other words, the mean changes from baseline were 2.8 +/- 3.1 and 2.0 +/- 2.6 at day 7 (p=0.06), and 5.1 +/- 3.9 and 5.0 +/- 4.2 at day 30 (p=0.78) in the ATP group and the placebo group, respectively. There were no statistically significant differences in the VAS pain and overall assessments of efficacy between groups at any time point during the study. Conversely, there was a significant difference in the use of the rescue analgesic between groups, in favor of ATP (p=0.04). Oral ATP was well tolerated. CONCLUSION: Oral ATP might have an early acting effect in subacute low back pain.

Adenosine Triphosphate↗

Recommendations for the use of new methods to assess the efficacy of disease-modifying drugs in the treatment of osteoarthritis.

BACKGROUND: Recent innovations in the pharmaceutical drug discovery environment have generated new chemical entities with the potential to become disease modifying drugs for osteoarthritis (DMOAD's). Regulatory agencies acknowledge that such compounds may be granted a DMOAD indication, providing they demonstrate that they can slow down disease progression; progression would be calibrated by a surrogate for structural change, by measuring joint space narrowing (JSN) on plain X-rays with the caveat that this delayed JSN translate into a clinical benefit for the patient. Recently, new technology has been developed to detect a structural change of the OA joint earlier than conventional X-rays. OBJECTIVE: The Group for the Respect of Ethics and Excellence in Science (GREES) organized a working party to assess whether these new technologies may be used as surrogates to plain x-rays for assessment of DMOADs. METHODS: GREES includes academic scientists, members of regulatory authorities and representatives from the pharmaceutical industry. After an extensive search of the international literature, from 1980 to 2002, two experts meetings were organized to prepare a resource document for regulatory authorities. This document includes recommendations for a possible update of guidelines for the registration of new chemical entities in osteoarthritis. RESULTS: Magnetic resonance imaging (MRI) is now used to measure parameters of cartilage morphology and integrity in OA patients. While some data are encouraging, correlation between short-term changes in cartilage structure observed with MRI and long-term radiographic or clinical changes are needed. Hence, the GREES suggests that MRI maybe used as an outcome in phase II studies, but that further data is needed before accepting MRI as a primary end-point in phase III clinical trials. Biochemical markers of bone and cartilage remodelling are being tested to predict OA and measure disease progression. Recently published data are promising but validation as surrogate end-points for OA disease progression requires additional study. The GREES suggests that biochemical markers remain limited to 'proof of concept' studies or as secondary end-points in phase II and III clinical trials. However, the GREES emphasizes the importance of acquiring additional information on biochemical markers in order to help better understand the mode of action of drugs to be used in OA. Regulatory agencies consider that evidence of improvement in clinical outcomes is critical for approval of DMOAD. Time to total joint replacement surgery is probably the most relevant clinical end-point for the evaluation of efficacy of a DMOAD. However, at this time, time to surgery can not be used in clinical trials because of bias by non disease-related factors like patient willingness for surgery or economic factors. At this stage, it appears that DMOAD should demonstrate a significant difference compared to placebo. Benefit should be measured by 3 co-primary end-points: JSN, pain and function. Secondary end-points should include the percentage of patients who are 'responder' (or 'failure'). The definition of a 'failure' patient would be someone with progression of JSN>0.5mm over a period of 2-3 years or who has a significant worsening in pain and/or function, based on validated cut-off values. The definition of the clinically relevant cut-off points for pain and function must be based on data evaluating the natural history of the disease (epidemiological cohorts or placebo groups from long-term studies). These cut-offs points should reflect a high propensity, for an individual patient, to later require joint replacement. CONCLUSION: GREES has outlined a set of guidelines for the development of a DMOAD for OA. Although these guidelines are subject to change as new information becomes available, the information above is based on the present knowledge in the field with the addition of expert opinion.

Anthraquinones↗

[Prescription of NSAIDs in patients treatment with platelet inhibitors or anticoagulants].

PLATELET INHIBITION: Conventional NSAIDs and aspirin have platelet-inhibiting properties via platelet cyclo-oxygenase-1 (Cox-1) isoenzyme inhibition. Among the NSAIDs which induce reversible inhibition of Cox-1, naproxen seems to have a potent platelet-inhibiting action associated with a decrease in cardiovascular clinical events in secondary prevention. Flurbiprofen is indicated in the secondary prevention after myocardial infarction. Conversely, no conventional NSAID is indicated and none have demonstrated efficacy in primary prevention. GI BLEEDING: The platelet-inhibiting action of conventional NSAIDs and aspirin is a key factor in explaining the increased risk of bleeding reported with these medicinal products. Digestive system bleeding is the main risk. Few data are available regarding bleeding other than gastro-intestinal. COX-2 SPECIFIC INHIBITION PROPERTIES: Conversely, Cox-2 specific inhibitors have no platelet-inhibiting properties: the pharmacological profile of Cox-2 SI is therefore different from that of conventional NSAIDs. These medicinal products are anti-inflammatory, analgesic, platelet-inhibiting agents which are not harmful to the GI mucosa and which probably induce less bronchospasms. In patients with cardiovascular risks, Cox-2 SI can and should be used in combination with platelet-inhibiting agents, in particular aspirin, because they do not alter the aspirin effect on platelets, contrary to what is observed with conventional NSAIDs. PRESCRIPTION WITH ANTI-COAGULANTS: The concomitant prescription of conventional NSAIDs with anti-coagulants is not recommended because, in addition to the possible potentiation of oral anti-coagulants, NSAIDs increase the risk of serious bleeding adverse events due to their irritative effect on the GI mucosa and their platelet-inhibiting effect. This risk might be lower with Cox-2 specific inhibitors.

Administration, Oral↗

[Justification and indications for coxib therapy combined with gastro-protective agents].

UNLABELLED: IN THEORY: Combination use of a coxib with a gastro-protective agent does not appear justified since results of studies conducted on patients of all types demonstrated that the upper-digestive tract safety and tolerability profile of coxibs is good. IN SUMMARY: On the other hand, prescription-related descriptive data demonstrate that in real-life situations such a combination occurs in approximately 25% of cases. Two cases should be differentiated: in about half of cases, patients are receiving long-term therapy with a proton pump inhibitor (PPI) (for reflux oesophagitis, oesophagitis or dyspepsia) and when an NSAID is necessary, the prescribing physician logically turns to a coxib; in the other half of cases, it involves a true simultaneous co-prescription of a coxib and a gastro-protective agent (most often by far a PPI). Thus, it is only in 10-15% of patients that prescription of a coxib leads to prescription of a PPI. A SAFETY ATTITUDE: This approach can be justified by the physician's desire to be as cautious as possible in dealing a patient at high risk of GI disorders (elderly patients, previous history of digestive bleeding, co-prescription of aspirin and/or a steroid, co-morbidity) or in patients for whom the occurrence of GI bleeding would be very serious (i.e. a patient in poor condition due to multiple disorders, treatment with an oral anti-coagulant or heparin). In both cases, if the prescription of an NSAID cannot be avoided, it is therefore logical first to choose a coxib and second to prescribe simultaneously a gastro-protective agent.

Age Factors↗

[Guidelines for the development of anti-osteoporosis medications].

Osteoporosis is a general disorder of the skeleton characterised by a decrease in bone mass, with damage to the microarchitecture leading to an increase in bone fragility and fracture risk. The incidence of this illness will increase in the future because of the aging of the population and increasing risk factors. Many guidelines have been proposed by qualified authorities--those of the European Agency for the Evaluation of Medicinal Products (EMEA) being the latest published. The aim of treatment of the osteoporosis is to increase, maintain or improve bone mass as well as its strength, with a view to decreasing the incidence of bone fractures. With regard to preclinical studies, in vitro studies--such as those using osteoblast or osteoclast cultures--allow a better understanding of the mechanism of action of drug treatment. The evaluation of bone quality should be performed in two species, such as the ovariectomised female rat model and larger animals (ewe, sow, primate etc.). Phase I studies are designed to enable determinations of pharmacokinetic profiles and bone diffusion and to offer indications of the putative clinical relevance of the dosages. For phase II studies (double-blind controlled studies versus placebo, ideally with a duration of 24 or sometimes 12 months), tests of three dosages are recommended, and the bone mass is considered as a relevant substitution criterion. The aim of secondary osteoporosis prevention studies (randomised double-blind and comparative controlled design versus placebo) is to avoid the occurrence of new bone fractures, and the main evaluation criterion is the number of patients with new fractures. The study length should not be less than 3 years. For evaluation of primary osteoporosis prevention, efficacy in the prevention of bone fracture is the prerequisite--before the use of bone mass as the main evaluation criterion. This criterion can be evaluated by alterations in bone mineral density at the rachis level. Reference drugs such as estrogens can be an alternative to placebo comparison. The tolerability of drugs for the treatment of osteoporosis requires evaluation in long-term studies and the collection of postmarketing data. The International Conference on Harmonisation (ICH) could lead to uniform guidelines for the US, Europe and Japan.

Animals↗