Risk of angioedema associated with levetiracetam compared with phenytoin: Findings of the observational health data sciences and informatics research network.

Recent adverse event reports have raised the question of increased angioedema risk associated with exposure to levetiracetam. To help address this question, the Observational Health Data Sciences and Informatics research network conducted a retrospective observational new-user cohort study of seizure patients exposed to levetiracetam (n = 276,665) across 10 databases. With phenytoin users (n = 74,682) as a comparator group, propensity score-matching was conducted and hazard ratios computed for angioedema events by per-protocol and intent-to-treat analyses. Angioedema events were rare in both the levetiracetam and phenytoin groups (54 vs. 71 in per-protocol and 248 vs. 435 in intent-to-treat). No significant increase in angioedema risk with levetiracetam was seen in any individual database (hazard ratios ranging from 0.43 to 1.31). Meta-analysis showed a summary hazard ratio of 0.72 (95% confidence interval [CI] 0.39-1.31) and 0.64 (95% CI 0.52-0.79) for the per-protocol and intent-to-treat analyses, respectively. The results suggest that levetiracetam has the same or lower risk for angioedema than phenytoin, which does not currently carry a labeled warning for angioedema. Further studies are warranted to evaluate angioedema risk across all antiepileptic drugs.

Underutilization of gastroprotective drugs in patients receiving non-steroidal anti-inflammatory drugs.

AIM: To assess the prevalence of gastroprotective agent prescription in patients treated with non-steroidal anti-inflammatory drugs in France and to analyze the determinants of this prescription. METHODS: A cross-sectional observational study was performed in 2576 patients treated with non-steroidal anti-inflammatory drugs recruited prospectively in the French primary care system. RESULTS: Thirty-nine percent of the patients (n=1002) received gastroprotective agents, mostly proton pump inhibitors (99.5%). In patients with a single risk factor, the gastroprotection rates were: 50% for age>65, 67% for concurrent use of corticosteroids or antithrombotics, and 87% and 100% for history of uncomplicated and complicated gastroduodenal ulcers. In patients without risk factors, gastroprotective agents were prescribed in 31.8%. Among them, two thirds had symptoms of gastro-oesophageal reflux or history of non-steroidal anti-inflammatory drug intolerance or dyspepsia. Conversely, 40% (n=256) of at-risk non-steroidal anti-inflammatory drug users did not receive gastroprotective agents. Gastroprotection was significantly associated with history of gastroduodenal ulcer (OR: 8.2; 95%CI: 4.3-15.6) or history of non-steroidal anti-inflammatory drug intolerance (OR: 6; 95%CI: 4.5-8.1), gastro-oesophageal reflux (OR: 6; 95%CI: 4.4-8.2), dyspepsia (OR: 5.2; 95%CI: 3.7-7.5), concurrent gastrotoxic treatment (OR: 3.3; 95%CI: 1.9-5.6) and age>65 (OR: 3; 95%CI: 2.3-4.1). CONCLUSIONS: Despite widespread recommendations, gastroprotection is still largely underprescribed in patients at risk of gastrointestinal non-steroidal anti-inflammatory drug complications in France. Only half of non-steroidal anti-inflammatory drug users above 65 years are prescribed gastroprotective agents.

Asthma patients' perception of their ability to influence disease control and management.

BACKGROUND: Patients' perception of their ability to influence their asthma symptoms has not been sufficiently addressed. OBJECTIVE: To study the relationship between patients' perceived ability to self-care, as approached by internal locus of control (LOC) orientation, and concomitant level of asthma control. METHODS: A cross-sectional study was conducted from May 19, 2004, through July 7, 2005. Asthma patients receiving inhaled corticosteroids and supervised in primary care were identified. Asthma control was measured with the Asthma Control Test. Patients reported their LOC orientation on a 100-mm visual analog scale (0%, "I have absolutely no influence on asthma change," to 100%, "this change only depends on me"). Asthma therapy was obtained from a prescription database. The risk of an internal LOC of less than 50% was studied. RESULTS: Among the 163 patients with documented LOC (mean age, 52 years; 58% female), 72 (44.2%) had an internal LOC of less than 50%. Asthma control was inadequate for 65 of the 157 patients with available data on the global score of the Asthma Control Test (41.4%). Patients with inadequately controlled asthma had a higher risk of a LOC of less than 50% (odds ratio, 2.68; 95% confidence interval, 1.23-5.81). A 3-fold increased risk also appeared for patients older than 65 years compared with those younger than 45 years. Conversely, no association was identified with sex, asthma severity markers, or therapy. CONCLUSIONS: Asthma control was related to internal LOC orientation (ie, perceived ability to self-care). Improved self-care efficiency is a target for adequate disease management.

Asthma patients' self-reported behaviours toward inhaled corticosteroids.

BACKGROUND: Patient adherence to recommended use of ICS is questionable in asthma, with irregular use or interruptions occurring frequently. Factors explaining discontinuation of controller therapy could orientate interventions. The characteristics of patients with interruptions of inhaled corticosteroids (ICSs), intentional or accidental, were investigated. METHODS: Asthma patients regularly prescribed ICS by GPs (Cegedim network) were included. Patients' characteristics and behaviours toward ICS (accidental/intentional interruptions, less frequent use of ICS and change in dosing) were identified from self-report questionnaires, and linked to data prescription database. Interrelations between declared behaviours toward ICS were studied with a Multiple Component Analysis (MCA) and the correlates of ICS interruptions were identified. RESULTS: During the past 3 months, 31.6% of 204 patients (mean age: 53.8 years, females: 59.3%) intentionally interrupted ICS when feeling better, 25.4% forgot ICS and 18.3% deliberately changed the doses. A quarter of patients considered constant use of respiratory medicines as unhealthy. MCA revealed that intentional, accidental interruptions and less frequent use of ICS were closely correlated. Risk of intentional interruption was increased when patients considered constant use of respiratory therapy to be unhealthy (OR=3.36, 95%CI=[1.47-7.66]). Conversely, risk was significantly lower when ICS was associated or combined with another controller (OR=0.24, 95%CI=[0.08-0.73]), compared to ICS in monotherapy. Less frequent interruptions were observed in patients older than 65 (OR=0.35, 95%CI=[0.13-0.89]). CONCLUSIONS: Our study suggests that discontinuation of use of controllers is associated with other inadequate behaviours or beliefs about inhaled controllers. Efforts should be targeted at patients' perceptions and behaviours toward controller therapy.

Prevalence of low high-density lipoprotein cholesterol and hypertriglyceridaemia in patients treated with hypolipidaemic drugs.

AIM: To estimate the prevalence of triglyceride and/or high density lipoprotein cholesterol (HDL-C) disorders and their relationships with other cardiovascular risk factors among patients with dyslipidaemia on lipid-lowering therapy. METHODS: In this cross-sectional study in dyslipidaemic patients receiving lipid-lowering therapy, lipid disorders were defined as triglyceride greater than 1.5 g/L, HDL-C lesser than 0.4 g/L and low-density lipoprotein cholesterol (LDL-C) above the recommended concentration according to French guidelines. Based on these disorders, patients were classified into four groups: group 1, no lipid disorders; group 2, low HDL-C and/or high triglyceride concentration with normal LDL-C; group 3, isolated elevated LDL-C; and group 4, elevated LDL-C and low HDL-C and/or high triglyceride. Patients' cardiovascular risk levels were compared across groups. RESULTS: Among the 2727 patients (mean age 64.7 years, 46.7% women), 28% did not reach the target LDL-C concentration as defined by French guidelines. Prevalence rates of high triglyceride and low HDL-C were 27.2 and 10.3%, respectively. Over half (51.2%) of the patients were in group 1, 20.5% were in group 2, 16.2% in group 3 and 12.1% in group 4. Among patients meeting the target LDL-C, those with high triglyceride and/or low HDL-C exhibited a significantly higher number of risk factors (1.83 vs 1.68, p<0.001). Smoking, diabetes and hypertension were associated separately with low HDL-C and/or high triglyceride (p=0.01, p<0.0001, p=0.03, respectively). Conversely, these associations were not observed in patients who did not achieve the target LDL-C, with the exception of smoking (p<0.0001). CONCLUSION: HDL-C and triglyceride disorders are relatively frequent among treated patients, particularly when cardiovascular risk level increased.

Correlates of LDL-cholesterol goal attainment in patients under lipid lowering therapy.

BACKGROUND: LDL-cholesterol therapeutic objectives attainment under lipid lowering therapy remains inadequate. The correlates of LDL-cholesterol therapeutic objective attainment have not been thoroughly explored in an observational setting. METHODS: Patients under lipid lowering therapy and managed by general practitioners were included. LDL-cholesterol therapeutic objective was defined according to the number of cardiovascular risk factors associated with dyslipidemia (AFSSAPS-2005 guidelines). RESULTS: Most of the 2727 patients (mean age: 64.7+/-11.0) received a statin (70.0%) or a fibrate (24.3%) in monotherapy. 58.5% of patients at high cardiovascular risk did not reach therapeutic objective. Compared to simvastatin, patients receiving fibrates were less likely to be at therapeutic objective (OR=0.38, 95% CI=[0.26-0.54]). So were patients receiving fluvastatin (OR=0.41, IC95%=[0.26-0.64]) or pravastatin (OR=0.49, IC95%=[0.35-0.70]) at the dosages used by GPs. No significant difference appeared with atorvastatin (OR=0.99, 95% CI=[0.71-1.39]) or rosuvastatin (OR=1.25, CI95%=[0.77-2.02]). Patients with LDL-cholesterol levels<0.7 g/L tended to be prescribed high doses of lipid lowering therapy. CONCLUSIONS: In real conditions of lipid lowering therapy use, LDL-cholesterol therapeutic objective attainment was inadequate in high-risk patients, and TO differences were observed between drugs at prescribed doses.

Use of margarine enriched in phytosterols by patients at high cardiovascular risk and treated by hypolipidemic drugs.

BACKGROUND AND AIMS: The use of phytosterol-enriched margarines (PEM) in patients at cardiovascular risk has not been thoroughly explored. We determined the proportion of users of PEM in a population at high cardiovascular risk, and their characteristics. In addition, the correlates of using at least 25 g/d of PEM were identified. METHODS AND RESULTS: Patients with at least two cardiovascular risk factors in addition to dyslipidemia (primary prevention) or with past cardiovascular disease (secondary prevention) were recruited by general practitioners (GPs). Baseline characteristics were collected from a computerized GP database linked to a survey. GPs recorded patterns of PEM use. First, users were compared with non-users. Then, analyses were conducted to identify characteristics of patients using PEM at a recommended dose (>or=25 g/d). Among 1631 patients with documented consumption, a minority used PEM (15.2%), and only 36.4% of consumers used it at recommended level. Overall, PEM users did not differ from non-users as to general characteristics, nor as to the level of cardiovascular risk in primary prevention. However, PEM users reported significantly more cardiovascular events among their parents (OR=1.4; 95% CI=[1.0-1.9]). Consumers who used at least 25 g/d of PEM were more likely to be men (OR=3.1; 95% CI=[1.6-5.8]), to be aged 60-74 (OR=3.0; 95% CI=[1.4-6.4]), or 75 or older (OR=4.0; 95% CI=[1.5-10.6]). Again, no difference was observed regarding the level of cardiovascular risk. CONCLUSIONS: The level of use of PEM was low in this population of high cardiovascular risk patients. In addition, only a third of users consumed margarine at the recommended level. Our data suggest that pattern of use of PEM is not related to the level of cardiovascular risk.

Discrepancies between patient-reported outcomes and clinician-reported outcomes in chronic venous disease, irritable bowel syndrome, and peripheral arterial occlusive disease.

OBJECTIVE: To explore the degree of agreement between patient- and clinician-reported outcomes (PROs and CROs, respectively) in three chronic diseases. METHODS: Respectively, 120, 131, and 61 French general practitioners (GPs) included 291, 307, and 90 patients with chronic venous disease (CVD), irritable bowel syndrome (IBS), and peripheral arterial occlusive disease (PAOD), in a cross-sectional survey. Patients completed a specific Health-Related Quality of Life (QoL) questionnaire (Chronic Venous Insufficiency Questionnaire [CIVIQ], Functional Digestive Disorders Quality of Life [FDDQL], and Claudication Scale [CLAU-S], respectively) and scored their pain (visual analog scale, pain-free walking distance). GPs were concomitantly asked to estimate patients' pain and QoL. RESULTS: Although correlated (CVD and IBS: Kw = 0.27 and Kw = 0.31, respectively; PAOD: r = 0.64, P < 0.01), pain intensity estimated by GPs was lower than as estimated by patients with CVD and IBS (e.g., 39.0 +/- 24.9 vs. 30.4 +/- 21.0 for IBS), and pain-free walking distance was greater as estimated by GPs than by patients with PAOD. Pain estimated by patients only partially reflected their QoL (r between 0.30 and 0.78; P between 0.02 and <0.01). Global QoL scores estimated by patients and GPs were moderately correlated (Kw between 0.17 and 0.28). GPs underestimated QoL impairment in CVD (global score: 72 +/- 19 vs. 61 +/- 20) and in most dimensions of the IBS questionnaire (in six of eight dimensions), and overestimated QoL impairment in PAOD (54 +/- 21 vs. 66 +/- 23). CONCLUSIONS: Although correlated, PROs and CROs differed. In addition, their relationship was not consistent across diseases. PROs are therefore essential to take account of all the aspects of diseases.