Relationship between use of antidepressants and risk of fractures: a meta-analysis.

UNLABELLED: It has been shown that antidepressants would have a direct action on bone metabolism and would be associated with increased fracture risk. Results from this large meta-analysis show that both SSRIs and TCAs are associated with a moderate and clinically significant increase in the risk of fractures of all types. INTRODUCTION: This study seeks to investigate the relationship between use of antidepressants and the risk of fracture. METHODS: An exhaustive systematic research of case-control and cohort studies published or performed between 1966 and April 2011 that reported risk estimates of fracture associated with use of antidepressants was performed using MEDLINE, PsycINFO, and the Cochrane Systematic Review Database, manual review of the literature, and congressional abstracts. Inclusion, quality scoring, and data abstraction were performed systematically by three independent reviewers. RESULTS: A total of 34 studies (n = 1,217,464 individuals) were identified. Compared with non-users, the random effects pooled RR of fractures of all types, among antidepressant users, were 1.39 (95%CI 1.32-1.47). Use of antidepressants were associated with a 42 %, 47 %, and 38 % risk increase in non-vertebral, hip, and spine fractures, respectively ([For non-vertebral fractures: RR = 1.42, 95%CI 1.34-1.51]; [For hip fractures: RR = 1.47, 95%CI 1.36-1.58]; [For spine fractures: RR = 1.38, 95%CI 1.19-1.61]). Studies examining SSRI use showed systematically a higher increase in the risk of fractures of all types, non-vertebral, and hip fractures than studies evaluating TCA use. CONCLUSIONS: Results from this large meta-analysis show that both SSRIs and TCAs are associated with a moderate and clinically significant increase in the risk of fractures of all types.

Perception, knowledge, and use by general practitioners of Belgium of a new WHO tool (FRAX) to assess the 10-year probability of fracture.

The FRAX tool that calculates the 10-year probability of having a fracture has recently been validated for Belgium. Little is known about the perception and knowledge that GPs have about this tool in their daily practice. A survey has been conducted as part of a screening campaign for various diseases. The primary objective of the present study was to assess the perception and the knowledge of the FRAX tool by GPs. The secondary objective was to assess the impact of an information brochure about the FRAX tool on these outcomes. The survey was sent to a sample of 700 GPs after only half of them had received the information brochure. The survey results show that, out of the 193 doctors who responded to the survey, one-third know the FRAX tool but less than 20 % use it in their daily clinical practice. Among those who use it, the FRAX tool is largely seen as a complementary but not as an essential tool in the diagnosis or in the management of osteoporosis. It appears that the brochure could improve the knowledge of the FRAX tool but it would not be more efficient on its use in daily practice than the other sources of information. At present, the use of the FRAX tool in Belgium is limited but an information brochure could have a positive impact on the knowledge of the FRAX tool.

Relationship between bone mineral density changes and risk of fractures among patients receiving calcium with or without vitamin D supplementation: a meta-regression.

UNLABELLED: Surrogate measures of fracture risk, such as effects on bone mineral density, may be of great interest to assess the efficacy of available osteoporosis treatments.Our results suggest that bone mineral density (BMD)changes cannot be used as a surrogate of anti-fracture efficacy, among patients receiving calcium, with or without vitamin D. INTRODUCTION: The purpose of this study is to examine the association between changes in bone mineral density with reduction in the risk of fractures in patients receiving calcium with or without vitamin D. METHODS: We selected all randomized placebo-controlled clinical trials of calcium with or without vitamin D supplementation. To be included in this analysis, the studies were required to report both BMD (hip/proximal femur and/or lumbar spine) and the incidence of fractures. Meta-regression analyses were used to examine the associations of changes in BMD with reduction in risk of fracture over the duration of each study. The change in BMD was the difference between changes (from baseline) observed in the active treatment group and placebo group. RESULTS: A total of 15 randomized trials (n=47,365) were identified, most of whom (77%) came from the Women's Health Initiative trial. Results show that larger increases in BMD at the lumbar spine were not associated with greater reduction in fracture risk. Concerning hip BMD changes,we found a statistically significant relationship between hip BMD changes and reduction in risk. However, results were not quite significant after excluding the both largest studies, in which BMD changes were measured in very small subset of patients. These points may have largely biased our results. CONCLUSIONS: In conclusion, there was no evidence of a relationship between BMD changes and reduction in risk of fractures among patients receiving calcium with or without vitamin D supplementation. Calcium and/or Vitamin D may reduce fracture rates through a mechanism independent of bone density.

Partial adherence: a new perspective on health economic assessment in osteoporosis.

UNLABELLED: Partial adherence in osteoporosis increases the risk for fragility fracture and has considerable impact on cost-effectiveness. This review highlights a number of avenues for further research, such as improved definition of thresholds of compliance and persistence, as well as gap length, offset times, and fraction of benefit. INTRODUCTION: A number of economic models have been developed to evaluate osteoporosis therapies and support decisions regarding efficient allocation of health care resources. Adherence to treatment is seldom incorporated in these models, which may reduce their validity for decision-making since adherence is poor in real-world clinical practice. METHODS: An ad hoc working group of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis met to review key issues concerning the incorporation of partial adherence in health economic models. RESULTS: Observational data have shown that poor adherence is associated with an increase in the risk for fragility fracture. Health economic modelling indicates that full adherence is associated with more quality-adjusted life years gained than partial adherence, as well as higher treatment costs and lower fracture-related costs. Although adherence appears as an important driver of cost-effectiveness, the effect is dependent on a range of other variables, such as offset time, fraction of benefit, fracture risk, fracture efficacy, fracture-related costs, and drug cost, some of which are poorly defined. Current models used to evaluate cost-effectiveness in osteoporosis may oversimplify the contributions of compliance and persistence. CONCLUSION: Partial adherence has a significant impact on cost-effectiveness. Further research is required to optimise thresholds of compliance and persistence, the impact of gap length, offset times, and fraction of benefit.

Positive impact of compliance to strontium ranelate on the risk of nonvertebral osteoporotic fractures.

SUMMARY: Adherence is now one of the major issues in the management of osteoporosis. This paper relates the relationship existing between adherence to strontium ranelate and the risk of subsequent nonvertebral fracture among postmenopausal women with osteoporosis. INTRODUCTION: The aim of this study is to investigate compliance to strontium ranelate (SR) therapy and the impact of compliance on the risk of nonvertebral fractures among women with osteoporosis. METHODS: This study was a post-hoc analysis of pooled data from two international, phase III, randomized, placebo-controlled, double-blind studies (the Spinal Osteoporosis Therapeutic Intervention and Treatment Of Peripheral Osteoporosis). A nested case-control study was performed in the strontium ranelate-treated population. Compliance was quantified using the medication possession ratio (MPR). RESULTS: Two hundred eighty-five nonvertebral fracture cases (hip fx n = 70; major nonvertebral fx n = 213) were identified and matched to 1,425 controls. The mean MPR was 86.8% for controls and 82.6% for cases (p < 0.001). Women who were compliant to SR had a 38% reduction in all nonvertebral fractures compared with those who were not (OR = 0.62; 95%CI[0.47-0.81; p < 0.001). Considering hip fractures only, the risk was reduced by 50% for compliant patients compared to noncompliant patients (OR = 0.50; 95%CI[0.28-0.88]; p < 0.05). CONCLUSION: Our analyses emphasize the importance of good compliance to treatment in order to reduce the risk of osteoporotic fractures. In particular, there was a greater reduction in the risk of nonvertebral and hip fractures with increase compliance.

[Prevention and treatment of osteoporosis: avoiding clinical inertia and promoting therapeutic adherence]. / Prévention et traitement de l'ostéoporose: eviter l'inertie clinique et motiver l'adhésion au traitement.

Given the ageing of the population and the socio-economic burden of osteoporotic fractures, prevention and treatment of osteoporosis are a priority. A number of effective therapeutic agents have been developed, allowing a better management of postmenopausal osteoporosis. Despite the availability of these agents, osteoporosis remains underdiagnosed and a significant proportion of patients receive no treatment. The prevention of the first fracture constitutes one of the major concerns. Moreover, adherence to anti-osteoporosis medications remains poor. Long-term adherence to therapy is required for optimal therapeutic benefit for patients with osteoporosis. Adequate adherence to anti-osteoporotic treatment leads to abetter increase in bone mineral density and a significant reduction in risk of both vertebral and nonvertebral fractures. Consequently, therapeutic adherence must be a major concern for physicians managing osteoporosis. The extension of dosing intervals may be an element, among others, allowing to improve therapeutic adherence. The once monthly oral, quaterly or annual intravenous (bisphosphonates), or else subcutaneous, every 6 months (denosumab) formulations may potentially improve adherence.

Effects of Protein, Essential Amino Acids, B-Hydroxy B-Methylbutyrate, Creatine, Dehydroepiandrosterone and Fatty Acid Supplementation on Muscle Mass, Muscle Strength and Physical Performance in Older People Aged 60 Years and Over. A Systematic Review on the Literature.

OBJECTIVES: The objective of this study was to perform a systematic review to investigate the effects protein, essential amino acids (EAA), ß-hydroxy ß-methylbutyrate (HMB), creatine, dehydroepiandrosterone (DHEA) and fatty acid supplementation on muscle mass, muscle strength and physical performance of elderly subjects. METHODS: Using the electronic databases MEDLINE and EMBASE we identified RCTs published until February 2016 which assessed the effects of these nutrient supplementation on muscle strength, muscle mass or physical performance. Study selection and data extraction were performed by two independent reviewers. RESULTS: Search strategy allowed us to identify 23 RCTs. Among them, four used proteins as nutritional supplement, seven EAAs, six creatine, four DHEA and finally, two HMB. From our systematic review, it seems that the effects of these supplementations on muscle health are rather limited. Only consistent effects of EAA supplementation on physical performance (3 out of the 4 RCTs using EAA supplementation found significant effect of this supplementation on physical performance) and HMB supplementation on muscle mass (all the 2 identified RCTs using HMB supplementation found significant effect of this supplementation on muscle mass) have been found across studies. No consistent effects were found for the other types of dietary supplementation. Because of the important limitations in study design, inconsistency and lack of directness, the overall quality of the evidence was judged to be low or very low using the GRADE system. CONCLUSION: This systematic review showed a limited effect of nutritional supplementation on muscle mass, muscle power and physical function. Inconsistent positive effects were observed for some specific supplementations but the results only concerned one aspect of the muscle. Well designed and appropriately powered RCTs are needed to provide evidence for appropriate clinical recommendations.

Adherence, patient preference and dosing frequency: understanding the relationship.

Adherence to treatment among patients with chronic diseases is currently suboptimal. Poor adherence leads to reduced clinical benefit, a raised incidence of secondary complications and therefore increased healthcare costs. For patients with osteoporosis, long-term adherence to therapy is further complicated by the asymptomatic nature of the disease and the lack of options for patient self-monitoring. Bone densitometry and biochemical markers of bone turnover are assessments that could be used by physicians to provide feedback to patients on the effectiveness of medication. However, these feedback systems are costly and not readily available. Oral bisphosphonates are currently the first-line therapy for postmenopausal osteoporosis. However, they are associated with stringent dosing procedures, and some patients may experience upper gastrointestinal side-effects following administration. Alarmingly, approximately 50% of patients discontinue daily bisphosphonate therapy within 1 year, which negatively impacts upon treatment outcomes, leading to a reduced antifracture effect. Thus, there is a need for an effective therapy that enhances patient adherence. The impact of reducing bisphosphonate dosing frequency on therapeutic adherence has been documented in several studies. Data have shown that, although weekly dosing improves adherence compared with daily administration, levels are still suboptimal. Results from two recent studies that have assessed patient preference for a once-monthly compared with a weekly dosing schedule have demonstrated that patients prefer a monthly regimen (67-71%). Their reasons for preferring once-monthly dosing were that it would fit better with their lifestyle (49-77%) and would be more convenient (75%). A novel once-monthly bisphosphonate regimen, such as the ibandronate regimen, may therefore help patients to follow dosing guidelines and encourage them to stay on therapy longer, thereby improving overall therapy effectiveness.

[Adherence to treatment in osteoporosis influence on efficiency]. / Observance et persistance: impact sur l'efficience des traitements de l'ostéoporose.

Low adherence to therapies has been repeatedly described as a major determinant of poor clinical outcomes in chronic disorders. Bisphosphonates, the most widely prescribed drugs in this field, have been linked to a 12-month persistence lower than 40%. The situation is improved when using the weekly formulation compared to the daily intake of the drug. Low compliance results in lesser increase in bone mineral density and decreased anti-fracture efficacy. New medications, currently developed for the management of osteoporosis, will be user-friendly, allowing to an improvement of compliance and persistence.

[Numerus clausus at the end of the third year of medical school]. / Numerus clausus en fin de troisième candidature en médecine: mort annoncée d'une hérésie?

Owing to the establishment of a procedure aiming at a reduction of the medical supply (numerus clausus), the French Community of Belgium had decided to introduce, at the end of the third year of medical studies (third candidature), a procedure of selective attribution of the certificate allowing for a unlimited medical practice. We assessed the predictive value of the results obtained during and at the end of the first candidature (first year of medicine) for the attribution of this certificate. We studied the results of the 225 students enrolled in the first candidature in medicine at the University of Liège during the academic year 1997-1998, and we correlated them to the subsequent attribution (1999-2000- and 2000-2001) of the certificate. The success of the first candidature in the first or second session is an important predicting factor towards the reception of the certificate. A non-authorization to continue the studies in medicine in case of failure in the first session or a non-authorization to repeat the first candidature in case of failure in the second session would have, respectively, a negative predictive value (NPV) of 91.9% and 97.4% and would allow to restream 111 students at the end of the first session or 39 students at the end of the first candidature. The results of the preliminary assessments mode during the month of January are also highly predictive of the chances to get the certificate. Among the 160 students who have not successfully passed a minimum of 3 exams, only 14 students obtained the certificate. The restreaming of those students would correspond to a NPV of 91.2%. Students who were not successful in a minimum of 2 exams would have less than 5% chance to obtain the certificate. In this case, 109 students would be restreamed (NPV = 95.4%). In conclusion, the selection of the students who will obtain, at the end of the third year of medicine, the certificate allowing them for an unlimited medical practice is obtained, in a large proportion, during the first candidature and especially after the session of January. In view of those results and considering the decree abolishing the selection at the end of the third year of medical studies, one could argue about the appropriateness of the current procedure, chosen by the French Community of Belgium, compared to other solutions prioritising an earlier selection of the future doctors.

Effect of collagen hydrolysate in articular pain: a 6-month randomized, double-blind, placebo controlled study.

OBJECTIVE: Evaluation of the efficacy and safety of a food supplement made of collagen hydrolysate 1200 mg/day versus placebo during 6 months, in subjects with joint pain at the lower or upper limbs or at the lumbar spine. DESIGN: Comparative double-blind randomized multicenter study in parallel groups. SETTING: 200 patients of both genders of at least 50 years old with joint pain assessed as ≥30 mm on a visual analogical scale (VAS). INTERVENTION: Collagen hydrolysate 1200 mg/day or placebo during 6 months. MAIN OUTCOME MEASURE: Comparison of the percentage of clinical responder between the active collagen hydrolysate group and the placebo group after 6 months of study. A responder subject was defined as a subject experiencing a clinically significant improvement (i.e. by 20% or more) in the most painful joint using the VAS score. All analyses were performed using an intent-to-treat procedure. RESULTS: At 6 months, the proportion of clinical responders to the treatment, according to VAS scores, was significantly higher in the collagen hydrolysate (CH) group 51.6%, compared to the placebo group 36.5% (p<0.05). However, there was no significant difference between groups at 3 months (44.1% vs. 39.6%, p=0.53). No significant difference in terms of security and tolerability was observed between the two groups. CONCLUSIONS: This study suggests that collagen hydrolysate 1200 mg/day could increase the number of clinical responders (i.e. improvement of at least 20% on the VAS) compared to placebo. More studies are needed to confirm the clinical interest of this food supplement.

Antidepressant medications and osteoporosis.

Use of antidepressant medications that act on the serotonin system has been linked to detrimental impacts on bone mineral density (BMD), and to osteoporosis. This article reviews current evidence for such effects, and identifies themes for future research. Serotonin receptors are found in all major types of bone cell (osteoblasts, osteocytes, and osteoclasts), indicating an important role of the neuroendocrine system in bone. Observational studies indicate a complex relationship between depression, antidepressants, and fracture. First, the presence of depression itself increases fracture risk, in relation with decreased BMD and an increase in falls. A range of aspects of depression may operate, including behavioral factors (e.g., smoking and nutrition), biological changes, and confounders (e.g., comorbidities and concomitant medications). A substantial proportion of depressed patients receive antidepressants, mostly selective serotonin reuptake inhibitors (SSRIs). Some of these have been linked to decreased BMD (SSRIs) and increased fracture risk (SSRIs and tricyclic agents). Current use of SSRIs and tricyclics increases fracture risk by as much as twofold versus nonusers, even after adjustment for potential confounders. While there is a dose-response relationship for SSRIs, the effect does not appear to be homogeneous across the whole class of drugs and may be linked to affinity for the serotonin transporter system. The increase in risk is the greatest in the early stages of treatment, with a dramatic increase after initiation, reaching a peak within 1 month for tricyclics and 8 months for SSRIs. Treatment-associated increased risk diminishes towards baseline in the year following discontinuation. The body of evidence suggests that SSRIs should be considered in the list of medications that are risk factors for osteoporotic fractures.

Adherence to bisphosphonates therapy and hip fracture risk in osteoporotic women.

UNLABELLED: Adherence is now one of the major issues in the management of osteoporosis and several papers have suggested that vertebral fractures might be increased in patients who do not follow appropriately their prescriptions. This paper relates the strong relationship existing between adherence to anti-osteoporosis treatment and the risk of subsequent hip fracture. INTRODUCTION: A study was performed to investigate adherence to bisphosphonate (BP) therapy and the impact of adherence on the risk of hip fracture (Fx). METHODS: An exhaustive search of the Belgian national social security database was conducted. Patients enrolled in the study were postmenopausal women, naive to BP, who received a first prescription of alendronate. Compliance at 12 months was quantified using the medication possession ratio (MPR). Persistence was calculated as the number of days from the initial prescription to a gap of more than 5 weeks after completion of the previous refill. A logistic regression model was used to estimate the impact of compliance on the risk of hip fracture. The impact of persistence on hip fracture risk was analysed using the Cox proportional hazards model. RESULTS: The mean MPR at 12 months was significantly higher among patients receiving weekly (n = 15.021) compared to daily alendronate (n = 14,136) (daily = 58.6%; weekly = 70.5%; p < 0.001). At 12 months, the rate of persistence was 39.45%. For each decrease of the MPR by 1%, the risk of hip Fx increased by 0.4% (OR: 0.996; CI 95%: 0.994-0.998; p < 0.001). The relative risk reduction for hip Fx was 60% (HR: 0.404; CI 95%: 0.357-0.457; p < 0.0001) for persistent compared to non-persistent patients. CONCLUSION: These results confirm that adherence to current therapeutic regimens remains suboptimal.

Flurbiprofen in the symptomatic management of rheumatoid arthritis: a valuable alternative.

BACKGROUND: The withdrawal of certain cyclooxygenase-2 selective drugs and the availability of over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs) have increased the pressure for researching and prescribing conventional NSAIDs with a favourable efficacy/tolerance ratio in inflammatory diseases, particularly rheumatoid arthritis. The aim of this comprehensive meta-analysis was to evaluate the absolute and relative efficacy and safety of flurbiprofen in the management of rheumatoid arthritis. METHODS: A systematic and exhaustive bibliographic research of published literature has been performed. The inclusion criteria are summarised as follows: randomised trial and rheumatoid arthritis and flurbiprofen and oral administration and anti-inflammatory doses from 100 to 300 mg and (placebo or aspirin or indomethacin or naproxen or ibuprofen or ketoprofen) and (articular pain or stiffness or swelling or mobility or patient/physician reported efficacy or tolerance or gastrointestinal (GI) tolerance). Studies were conducted from January 1975 to January 2006. Analyses have been stratified by comparisons and outcomes. Publication bias and robustness have been extensively investigated. RESULTS: Fourteen studies, accounting for 1103 patient-years, have been included in the quantitative review. The mean daily doses administrated were 200 mg flurbiprofen, 4000 mg aspirin, 150 indomethacin, 750 mg naproxen and 1800 mg ibuprofen. Flurbiprofen was superior to placebo for all outcomes, and superior to three of four other NSAIDs in terms of formal symptomatic measures (pain, stiffness and swelling). Several patients or physicians reported the efficacy of flurbiprofen as superior to indomethacin and naproxen, while its safety, and particularly its GI tolerance were better compared with aspirin and indomethacin. Sensitivity analyses have reported a sufficient robustness against systematic publication bias assumptions. CONCLUSION: This meta-analysis has shown that flurbiprofen is an interesting alternative to commonly prescribed NSAIDs in the symptomatic management of rheumatoid arthritis, especially given its favourable efficacy/tolerance ratio.

Adherence to treatment of osteoporosis: a need for study.

UNLABELLED: Adherence to anti-osteoporosis medications is currently low and is associated with poor anti-fracture efficacy. This manuscript reviews the potential design of clinical studies that aim to demonstrate improved adherence, with new chemical entities to be used in the management of osteoporosis. INTRODUCTION: Several medications have been unequivocally shown to decrease fracture rates in clinical trials. However, in real life settings, long-term persistence and compliance to anti-osteoporosis medication is poor, hence decreasing the clinical benefits for patients. METHODS: An extensive search of Medline from 1985 to 2006 retrieved all trials including the keywords osteoporosis, compliance, persistence or adherence followed by a critical appraisal of the data obtained through a consensus expert meeting. RESULTS: The impact of non-adherence on the clinical development of interventions is reviewed, so that clinicians, regulatory agencies and reimbursement agencies might be better informed of the problem, in order to stimulate the necessary research to document adherence. CONCLUSION: Adherence to therapy is a major problem in the treatment of osteoporosis. Both patients and medication factors are involved. Adherence studies are an important aspect of outcomes studies, but study methodologies are not well developed at the moment and should be improved. Performing adherence studies will be stimulated when registration authorities accept the result of these studies and include the relevant information in Sect. 5.1 of the summary of product characteristics. Reimbursement authorities might also consider such studies as important information for decisions on reimbursement.

Determinants of gastro-protective drugs co-prescription during treatment with nonselective NSAIDs: a prospective survey of 2197 patients recruited in primary care.

OBJECTIVE: Our goal was to identify the magnitude of gastro-protective drugs (GPDs) co-prescription and the profile of patients who received GPD co-prescription, during nonsteroidal anti-inflammatory drugs (NSAIDs) treatment in a "real life setting" of primary care practice. METHODS: A pragmatic prospective 6-month survey of 2197 new takers of nonselective NSAIDs, selected and followed by general practitioners (GPs) on the bias of their usual standards of care. RESULTS: Forty-seven percent of our survey population used at least one GPD during the 6-month follow-up. No difference was identified between piroxicam, diclofenac, ibuprofen, meloxicam and nimesulid for the GPD co-prescription. Besides the presence of gastro-intestinal (GI) symptoms, previous use of GPD, previous occurrence of GI disorders and increase in age are the most prominent predictive factors of GPD use during NSAID treatment. When adjusted for other risk factors, co-prescription of GPD was significantly increased in patients aged 55 years and above (odds ratio (OR): 1.29, 95% confidence interval (CI): 1.01-1.64) with no further increase in the co-prescription in older subjects. CONCLUSION: Patients above 55 years with previous history of GI symptoms or GPD use are more likely to benefit from cytoprotective medications.

The direct and indirect costs of the chronic management of osteoporosis: a prospective follow-up of 3440 active subjects.

INTRODUCTION: The objective of this study was to estimate the direct and indirect costs attributable to osteoporosis (OP) from a societal and a payer's perspective among active subjects living in Belgium and employed in the public workforce. MATERIALS AND METHODS: A cohort of 3440 subjects employed by the Liege City Council was followed for 6 months. The City Council employees were invited to fill a monthly log of the data related to their utilization of health resources (contacts with health professionals, medical examinations, drug use,...) due to OP. Information on work disability (number of days of sick leave) and on informal care (number of days off work incurred by active subjects in helping relatives or friends suffering from OP) was also collected. RESULTS: Of those asked to participate in the study, 1,811 subjects filled in at least one questionnaire. The mean duration of follow-up was 3.46 months. Self-reported prevalence of OP at inclusion was 5.3%. OP subjects were significantly older (52.7+/-6.1 years) than normal subjects (45.5+/-9.8 years) (p<0.05) and included more women (85.3 vs. 55.9%). Direct costs came to 44.6 euros per OP patient-month: 10.9 euros was spent on contact with health professionals, 19.0 euros on medical examinations, 12.1 euros on drugs and 2.6 euros on hospitalizations. During this 6-month study, a total of 140 days of sick leave was recorded (mean: 0.4 per OP patient-month). From a payer's perspective, this loss in productivity yielded a mean cost of 34.05 euros per OP patient-month. A mean number of days off work of 0.018 per active subject-month, attributable to informal care, was recorded. These days of inactivity represented, for the employer, a mean cost of 1.8 euros per active subject-month. CONCLUSION: The results of this survey of a large sample of active subjects confirm that OP-related expenditures, both for medical care and for loss of productivity, are significant.

A naturalistic study of the determinants of health related quality of life improvement in osteoarthritic patients treated with non-specific non-steroidal anti-inflammatory drugs.

OBJECTIVES: To capture changes in the quality of life (QoL) occurring in patients with osteoarthritis (OA) during treatment with non-specific non-steroidal anti-inflammatory drugs (NSAIDs) and to identify factors that predict such changes. METHODS: A naturalistic, prospective follow up of 783 patients with OA in whom primary care physicians decided to start treatment with non-selective NSAIDs. Short Form-36 (SF-36) and the Western Ontario and McMaster Universities OA index (WOMAC) were assessed at baseline and after 3 months. Baseline results were compared with QoL values in 4800 subjects randomly selected from the general population. Multiple regression analysis was performed to identify determinants of QoL at baseline and measures influencing changes in SF-36 or WOMAC during follow up. RESULTS: All QoL dimensions were significantly (p<0.01) decreased in patients with OA compared with controls. Significant improvement (p<0.05) in four dimensions of the SF-36 (vitality, role emotional, role physical, bodily pain) and in all components of the WOMAC was seen between baseline and month 3. Older age, female sex, longer duration of OA, and a higher number of comorbidities were the major determinants of a poor QoL at baseline. Maximal benefit from non-specific NSAIDs was seen in patients with the most severe impairment in QoL and the shortest duration of OA. CONCLUSION: OA negatively impacts all dimensions of the QoL. Non-specific NSAIDs improve the QoL in patients with OA treated in a "real life setting". The profile of patients receiving maximal benefit from such treatment may be of interest for health providers, enabling them to decide who should preferentially be given cytoprotective treatments or coxibs.

Time dependent risk of gastrointestinal complications induced by non-steroidal anti-inflammatory drug use: a consensus statement using a meta-analytic approach.

OBJECTIVES: To provide an updated document assessing the global, NSAID-specific, and time dependent risk of gastrointestinal (GI) complications through meta-analyses of high quality studies. METHODS: An exhaustive systematic search was performed. Inclusion criteria were: RCT or controlled study, duration of 5 days at least, inactive control, assessment of minor or major NSAID adverse effects, publication range January 1985 to January 2003. The publications retrieved were assessed during a specifically dedicated WHO meeting including leading experts in all related fields. Statistics were performed conservatively. Meta-regression was performed by regressing NSAID adjusted estimates against study duration categories. RESULTS: Among RCT data, indolic derivates provided a significantly higher risk of GI complications related to NSAID use than for non-users: RR = 2.25 (1.00; 5.08) than did other compounds: naproxen: RR = 1.83 (1.25; 2.68); diclofenac: RR = 1.73 (1.21; 2.46); piroxicam: RR = 1.66 (1.14; 2.44); tenoxicam: RR = 1.43 (0.40; 5.14); meloxicam: RR = 1.24 (0.98; 1.56), and ibuprofen: RR = 1.19 (0.93; 1.54). Indometacin users had a maximum relative risk for complication at 14 days. The other compounds presented a better profile, with a maximum risk at 50 days. Significant additional risk factors included age, dose, and underlying disease. The controlled cohort studies provided higher estimates: RR = 2.22 (1.7; 2.9). Publication bias testing was significant, towards a selective publication of deleterious effects of NSAIDs from small sized studies. CONCLUSION: This meta-analysis characterised the "compound" and "time" aspects of the GI toxicity of non-selective NSAIDs. The risk/benefit ratio of such compounds should thus be carefully and individually evaluated at the start of long term treatment.