Interventions to Improve Adherence in Patients with Immune-Mediated Inflammatory Disorders: A Systematic Review.

BACKGROUND: In patients with immune-mediated inflammatory disorders, poor adherence to medication is associated with increased healthcare costs, decreased patient satisfaction, reduced quality of life and unfavorable treatment outcomes. OBJECTIVE: To determine the impact of different interventions on medication adherence in patients with immune-mediated inflammatory disorders. DESIGN: Systematic review. DATA SOURCES: MEDLINE, EMBASE and Cochrane Library. STUDY ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Included studies were clinical trials and observational studies in adult outpatients treated for psoriasis, Crohn's disease, ulcerative colitis, rheumatoid arthritis, spondyloarthritis, psoriatic arthritis or multiple sclerosis. STUDY APPRAISAL AND SYNTHESIS METHODS: Intervention approaches were classified into four categories: educational, behavioral, cognitive behavioral, and multicomponent interventions. The risk of bias/study limitations of each study was assessed using the GRADE system. RESULTS: Fifteen studies (14 clinical trials and one observational study) met eligibility criteria and enrolled a total of 1958 patients. Forty percent of the studies (6/15) was conducted in patients with inflammatory bowel disease, half (7/15) in rheumatoid arthritis patients, one in psoriasis patients and one in multiple sclerosis patients. Seven out of 15 interventions were classified as multicomponent, four as educational, two as behavioral and two as cognitive behavioral. Nine studies, of which five were multicomponent interventions, had no serious limitations according to GRADE criteria. Nine out of 15 interventions showed an improvement of adherence: three multicomponent interventions in inflammatory bowel disease; one intervention of each category in rheumatoid arthritis; one multicomponent in psoriasis and one multicomponent in multiple sclerosis. CONCLUSION: The assessment of interventions designed for increasing medication adherence in IMID is rare in the literature and their methodological quality may be improved in upcoming studies. Nonetheless, multicomponent interventions showed the strongest evidence for promoting adherence in patients with IMID.

Concordance between prescriber- and patient-reported previous medical history and NSAID indication in the CADEUS cohort.

PURPOSE: Various data sources may be used in pharmacoepidemiological studies. When they cannot be obtained from valid databases, medical data must be obtained from physicians or patients. In the CADEUS study, both patients and their prescribers reported medical data allowing investigation of the concordance between these sources. METHODS: CADEUS is a French national cohort study of traditional non-steroidal anti-inflammatory drug (NSAID) and coxib users conducted between September 2003 and August 2004 in France that employed self-administered questionnaires to obtain medical data from patients and their prescribers. The Kappa statistic (kappa) was used to measure concordance between patients and prescribers in 18 530 pairs with regard to previous medical history and index NSAID indication. RESULTS: For previous medical history, the proportion of agreement ranged from 70.7 to 99.2% and concordance was: substantial (kappa = 0.61-0.80) for hypertension, myocardial infarction, stroke and diabetes; moderate (kappa = 0.41-0.60) for angina pectoris, peripheral arterial disease and hypercholesterolaemia; fair (kappa = 0.21-0.40) for unstable angina, cardiac insufficiency, dyspepsia, gastroesophageal reflux and gastric ulcer; slight (kappa < 0.21) for upper gastrointestinal haemorrhage. For index NSAID indication, the proportion of agreement ranged from 84.3 to 99.4% and concordance was almost perfect (kappa = 0.81-1.00) for inflammatory rheumatism, flu-like symptoms, dysmenorrhoea and dental pain; substantial for arthritis, back pain and headache; moderate for osteoarticular pain. CONCLUSIONS: Concordance was better for specific or serious conditions both regarding previous medical history and indication. Prescriber or patient perception and understanding may reduce concordance for certain items.

Hospitalizations for gastrointestinal and cardiovascular events in the CADEUS cohort of traditional or Coxib NSAID users.

AIMS: To assess hospital admission rates for gastrointestinal (GI) or cardiovascular (CV) events in real-life use of nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: CADEUS is a real-life population-based cohort study of 23 535 coxib (celecoxib or rofecoxib) and 22 919 traditional NSAID (tNSAID) users. Each hospitalization reported between index day (NSAID delivery) and questionnaire submission (median = 75 days) was explored using hospital discharge summaries. An expert committee validated blindly serious GI and CV events according to predefined criteria. RESULTS: Coxib users were older and had more GI history than tNSAID users. There were 21 hospitalizations for GI events, 12 in the coxib cohort and nine in the tNSAID cohort (respectively one and three upper GI haemorrhages and no ulcer perforations). Rates of GI events were 0.39 per 1000 patients [95% confidence interval (CI) 0.18, 0.75] for tNSAID users and 0.51 per 1000 patients (95% CI 0.26, 0.89) for coxib users. There were 21 hospitalizations for CV events, 13 in the coxib cohort and eight in the tNSAID cohort. None was fatal. Rates of CV events were, respectively, 0.59 (95% CI 0.24, 1.22), 0.51 (95% CI 0.19, 1.11) and 0.35 (95% CI 0.15, 0.69) per 1000 patients for celecoxib, rofecoxib and tNSAIDs. GI or CV event rates were not different between products even for patients >60 years old. CONCLUSIONS: Hospitalization rates for GI bleeding were 10-20 times lower than expected from published randomized clinical trials, probably because of differences in drug usage and concomitant gastroprotection. CV event rates conformed to those expected from general population data. These results emphasize the necessity of developing population healthcare databases to explore such low event rates.

Medical and non-medical direct costs of chronic low back pain in patients consulting primary care physicians in France.

A retrospective, observational, cohort study in primary care. To determine the total direct medical and non-medical cost of chronic low back pain (LBP) in France and its associated factors. Chronic LBP affects 5-10% of the population its burden in France is unknown. Ninety-eight randomly selected general practitioners included 796 adult patients with chronic LBP between October 2001 and December 2002. Direct costs due to physician visits, investigations, medications, hospitalizations, and other medical and non-medical resource use were collected for the 6 months prior to study visit. Costs both reimbursed and not by the French health insurance system were considered. Quality of life (QoL) and disease severity were measured using Short Form (SF)-8 and Roland-Morris disability questionnaire (RMDQ), respectively. Costs were updated to represent 2007 prices. Men represented 50.6% of the 796 patients, mean age was 53 +/- 11.3 years, and the duration of LBP was more than 1 year in 80.9% of patients. The total mean cost per patient over six months was 715.6 euro (95% CI: 644.2-797.8). Of these costs, 22.9% related to care provided by physiotherapists and allied specialists, 19.5% to medications, 17.4% to hospitalizations, 9.6% to investigations, and 12.5% to physician fees. In multivariate analysis, the factors associated with the cost of chronic LBP were disease severity (RMDQ score) and age of the patients. LBP is a disease that is both common and costly.

The CADEUS study: burden of nonsteroidal anti-inflammatory drug (NSAID) utilization for musculoskeletal disorders in blue collar workers.

AIM: The aim of this study was to compare patterns of utilization of NSAIDs for musculoskeletal disorders (MSD) by occupation in a general employed population. METHODS: This was a secondary analysis of the CADEUS cohort study on 5651 actively employed patients, who submitted at least one claim for the reimbursement of a NSAID dispensation for a MSD between August 2003 and July 2004, in the French National Healthcare Insurance database. Questionnaires were sent to prescribing physicians to obtain diagnoses and the medical history, and to patients for their occupation, height and weight and smoking status. Multivariate logistic regression was used to study the determinants of a heavy use of NSAIDs defined as 'over four dispensations in one year with less than two months between any two'. RESULTS: Factors associated with heavy use of NSAIDs were age (Odds ratio (OR): 1.8 (ten years), 95% confidence interval (CI): 1.6-1.9), osteoarthritis (versus back pain) (OR: 1.8, 95% CI: 1.5-2.1), body mass index (superior to 30) (OR: 1.8, 95% CI: 1.5-2.2), and occupation (blue collar versus white collar workers) (OR: 1.4, 95% CI: 1.2-1.6). Blue collar workers also had a 20% higher prevalence of 5-year history of dyspepsia. No difference was observed between sexes or in the use of COX-2 selective inhibitors between occupations. CONCLUSION: Factors associated with occupational constraints that contribute to the severity of MSDs, may explain the heavier use of NSAIDs among blue collar workers in spite of a concurrent and past medical history of adverse reactions to this type of medication.

Impact of prescriber nonresponse on patient representativeness.

BACKGROUND: In pharmacoepidemiology studies where patients are selected by prescribers, there is concern that the patients of responding prescribers are not necessarily an unbiased sample of all patients. However, this usually cannot be explored. In the CADEUS study, patients and prescribers were independently contacted so that data are available for patients irrespective of whether their prescriber responded or not. Our objective was to compare the characteristics of patients whose prescriber did or did not respond. METHODS: The CADEUS study included patients treated with COX-2 inhibitors (celecoxib, rofecoxib) or traditional NSAIDs from September 2003 to August 2004. Redeemed prescriptions were randomly sampled on a monthly basis within the database of the French national healthcare insurance system for salaried persons during 1 year. Patients and prescribers were questioned independently. Data from patients and from the database were used to compare patients whose prescriber responded and those whose prescriber did not. RESULTS: Of 45,217 patients, 26,618 had prescriber data. Patients whose prescriber responded were similar to patients whose prescriber did not respond for the main study outcomes: age (56.8 +/- 16.3 years vs. 56.1 +/- 16.3 years), sex (66.0% female vs. 64.8%), cardiovascular disease history (52.2% vs. 52.0%), gastrointestinal disease history (39.5% vs. 39.4%), concomitant prescription of gastroprotective agents (22.4% vs. 23.7%), and NSAID indication, prescription type, use, and duration. CONCLUSIONS: We found no evidence for a difference between patients whose prescriber responded and patients whose prescriber did not participate in the study.

Drug-drug interactions with systemic antifungals in clinical practice.

PURPOSE: We describe drug-drug interactions (DDIs) encountered with antifungals in clinical practice. METHODS: Retrospective observational study of hospitalized adults receiving systemic antifungal treatment in the intensive care unit (ICU) and in the infectious diseases unit (IDU) of the University Hospital of Bordeaux, France between 1996 and 2001. All treatment episodes with antifungal agent were examined and all prescribed concomitant medication identified for potential drug-drug interactions (PDDI)-serious events occurring during treatment were adjudicated for clinical DDI. RESULTS: There were 150 treatment episodes with antifungal agent in 105 patients. Fluconazole was used in 48% of the treatment episodes, amphotericin B in 46%, itraconazole in 4.7% and flucytosine in 1.3%. One hundred and sixteen PDDIs were identified related to the use of amphotericin B (81.0%), fluconazole (17.2%) or itraconazole (1.7%). Of these, 22 were associated with a clinical evidence of adverse interaction (hypokalemia, increased creatininemia or nephrotoxicity). All these clinical drug-drug interactions (CDDIs) were with amphotericin B. They were due to furosemide (36.4%), cyclosporine (31.8%) and hydrocortisone (18.2%). PDDIs were mostly associated with leukaemia (40.4%), HIV infection (24.6%) and cancer (10.5%). CONCLUSIONS: In ICU and IDU, systemic antifungal treatments lead to many PDDIs, mainly related to the type of antifungal used and to the pathology treated. Clinical DDI seem more common with amphotericin.

Less use of NSAIDs in long-term than in recent chondroitin sulphate users in osteoarthritis: a pharmacy-based observational study in France.

In clinical trials, long-term use of a specific chondroitin sulphate, Chondrosult 400 (CS400) has demonstrated symptomatic efficacy in osteoarthritis comparable to that of nonsteroidal anti-inflammatory drugs (NSAIDs) with significantly fewer side-effects. CS400 could therefore reduce the use of and risks associated with NSAIDs. A cross-sectional observational study was therefore devised in 199 randomly selected pharmacies in France to verify the concomitant use of analgesic and NSAIDs medication in patients prescribed CS400. Consecutive patients filling a prescription for CS400 were prospectively recruited and classified into recent users (3 months or less of continuous use) and long-term users (more than 3 months of continuous use) of CS400. The main outcome measure was current and long-term use of analgesics and NSAIDs. The 844 participating patients included 623 (73.8%) women and 221 (26.2%) men. Mean age was 65.9 years. Ninety eight (11.6%) patients did not use any analgesic or NSAIDs for osteoarthritis: 746 (88.4%) reported the use of at least one of these drugs. Compared to recent users, long-term users of CS400 had a significantly lower current (44.4 versus 52.5%, p < 0.05) and long-term use of NSAIDs (11.8% versus 18.5%, p < 0.05), and of analgesics (70.3 versus 79.3%, p < 0.01).

Effects of armagnac or vodka on platelet aggregation in healthy volunteers: a randomized controlled clinical trial.

BACKGROUND: Cardiovascular mortality is especially low in southwest France (the French Paradox). In previous experimental studies, we found that alcohol-free extracts of armagnac could inhibit human platelet function in vitro and experimental thrombosis in vivo. To test the possible relevance of these findings, we tested the effects of daily use of small quantities of armagnac against same alcohol strength, polyphenol-free vodka in healthy volunteers. METHOD: Randomized controlled trial comparing 5-year old armagnac (30 ml/day for 2 weeks) to same alcoholic strength vodka, in 20 healthy volunteers, on platelet aggregation induced by ADP, collagen, and thrombin, as well as bleeding time, partial thromboplastin time (pTT), and plasma lipids during and after consumption. Platelet testing was done blind. RESULTS: After 14 days, ADP-induced platelet aggregation was inhibited more in armagnac (-31+/-3.2% compared to pretreatment values, p<.01) than in vodka (-11.0+/-6.8%, NS) users (p<.05, armagnac vs. vodka). A rebound increase of aggregation was found 2 weeks later in vodka but not in armagnac users. The same pattern was found for thrombin-induced aggregation, including post-treatment rebound. No effect was found on collagen-induced aggregation, bleeding time, pTT, or plasma lipids. CONCLUSION: The chronic ingestion of moderate quantities of armagnac modified platelet aggregation to ADP in healthy volunteers. The difference with the effects of same alcohol degree vodka is in favour of an effect of the nonalcoholic fraction in the effects of armagnac, rather than just alcohol. All spirits may not be equal for cardioprotection.

Patterns and correlates of benzodiazepine use in the French general population.

OBJECTIVE: To investigate the prevalence of current use of benzodiazepines (BZDs) and related drugs in the French general population and factors associated with this use. METHODS: National cross-sectional telephone survey conducted between 25 April 2001 and 8 May 2001 in a representative sample of non-institutionalized adults of BZD use and duration, prescriber specialty, socio-demographic data and mood and anxiety disorders, using a structured diagnostic interview. RESULTS: The prevalence of current use of BZD was 7.5%. It was higher among women (9.7%) than men (5.2%). It increased with age and was higher in the jobless (10.9). Duration of BZD use was more than 6 months in 75.9% of users and increased with age. Of the 711 (17.7%) subjects with at least one mood or anxiety disorder, 122 (17%) used BZD compared with 180 (5.5%) of the 3296 subjects without mood or anxiety disorders. In multivariate analysis, factors associated with BZD use were age [odds ratio (OR): 3.6; 95% confidence interval (CI) 2.0-5.6], 6.5 (4.1-10.3) and 10.9 (6.9-17.1), respectively, for ages 35-44 years, 45-59 years and over 60 years compared with below 34 years, female gender (OR: 1.7; 95% CI 1.3-2.1), anxiety only (OR: 2.2; 95% CI 1.5-3.2), mood disorder only (OR: 4.4; 95% CI 2.7-7.1) or both mood and anxiety disorders (OR: 8.8; 95% CI 5.9-12.6). CONCLUSION: Despite precautions, warnings and attempts to limit use, there remains a high proportion of long-term BZD users in the general French population, especially in the elderly. Our findings add to the weight of opinion that messages concerning proper use of BZDs certainly need to be clarified and amplified.

[Real-life use of inhaler devices for chronic obstructive pulmonary disease in primary care]. / Utilisation des systèmes d'inhalation dans la bronchopneumopathie chronique obstructive.

The correct use of inhalation devices is an inclusion criterion in many comparative studies. However, patients can make errors, thus compromising the effectiveness of their own inhaler. The aim of the study is to evaluate inhaler use by patients with chronic obstructive pulmonary disease (COPD) [n = 984]. General practitioners assessed inhalation technique, using a specific checklist previously established for each inhaler model (Aerolizer, Autohaler, Diskus, a pressurised metered-dose inhaler (pMDI) or a Turbuhaler). A total of 24% of the patients using a pMDI did not make an error compared with 34-40% of those using breath-actuated devices. The frequency of critical errors varied according to the device: 11.5-14.9% of the subjects using an Aerolizer, Autohaler or Diskus versus 37.4% and 38.1% of the patients using a pMDI and a Turbuhaler, respectively. The proper use of the Turbuhaler is often overestimated (24.7%) compared with the pMDI (2.1%). The development of educational programmes for patients and prescribers is needed to improve the management of COPD.