Eric Van Ganse

Disease-specific health-related quality of life questionnaires for heart failure: a systematic review with meta-analyses.

BackgroundHeart failure (HF) is an increasingly common condition affecting patients’ health-related quality of life (HRQL). However, there is little literature comparing HF-specific instruments. Our aim was to evaluate and compare data on the conceptual model and metric properties (reliability, validity and responsiveness) of HF-specific HRQL instruments, by performing a systematic review with meta-analyses.Methods and resultsOf 2,541 articles initially identified, 421 were full-text reviewed. Ninety-four reported data on five questionnaires: Minnesota Living with Heart Failure Questionnaire (MLHFQ), Chronic Heart Failure Questionnaire (CHFQ), Quality of Life Questionnaire for Severe Heart Failure (QLQ-SHF), Kansas City Cardiomyopathy Questionnaire (KCCQ) and Left Ventricular Dysfunction (LVD-36) questionnaire. Metric properties (reliability, validity and responsiveness) were summarised using meta-analysis for pools above five estimates. Cronbach’s alpha coefficients were generally high (0.83–0.95) for overall scores and scales measuring physical health. Associations with four validity criteria (New York Heart Association [NYHA] class, six-minute walk test [6MWT] and short form-36 [SF-36] ‘Physical’ and ‘Social Functioning’) were moderate to strong (0.41–0.84), except for those between two CHFQ domains (fatigue and dyspnoea) and the NYHA (0.19 and 0.22). Pooled estimates of change from eight meta-analyses showed the MLHFQ to be highly responsive, with changes in overall score ranging from −9.6 (95% confidence interval [CI]: −4.1; −15.2) for placebo to −17.7 (95% CI: −15.3; −20.2) for pacing devices. The CHFQ and KCCQ also showed good sensitivity to change.ConclusionsMost of the questionnaires studied met minimum psychometric criteria, though current evidence would primarily support the use of the MLHFQ, followed by the KCCQ and CHFQ.

The PAIN Study: Paracetamol, Aspirin and Ibuprofen New Tolerability Study

AbstractObjective: This study aimed to compare directly aspirin (acetylsalicylic acid), ibuprofen and paracetamol (acetaminophen), first-line analgesics which are generally well tolerated, from a safety perspective in general practice. Methods: This was a blinded, multicentre study in general practice of up to 7 days of aspirin, paracetamol (both up to 3g daily) or ibuprofen (up to 1.2g daily), administered for common painful conditions, using patient-generated data with physician assistance. The main outcome was the rate of significant adverse events (serious, severe or moderate events, events resulting in treatment discontinuation or a physician visit). Statistical analysis tested for equivalence between ibuprofen and paracetamol, and for difference with aspirin. Results: 1108 general practitioners included 8677 adults (2900 aspirin, 2886 ibuprofen, 2888 paracetamol; three patients had no code label number). 8633 (99.5%) were evaluable, of whom 8233 (95%) adhered to the study protocol. The main indications were musculoskeletal or back pain (48%), sore throat, the common cold and flu (31%). Rates of significant adverse events were: aspirin 18.7%, ibuprofen 13.7%, and paracetamol 14.5%. Ibuprofen was statistically equivalent to paracetamol. Both were significantly better tolerated than aspirin (p < 0.001). Total gastrointestinal events (including dyspepsia) and abdominal pain were less frequent with ibuprofen (4 and 2.8%, respectively) than with paracetamol (5.3 and 3.9%) or aspirin (7.1 and 6.8%) [all p < 0.035]. There were six cases of non-serious gastrointestinal bleeding, four with paracetamol and two with aspirin, and one case of peptic ulcer with aspirin. Conclusion: The overall tolerability of ibuprofen in this large-scale study was equivalent to that of paracetamol and better than that of aspirin. These findings could lead to a reassessment of the use of first-line analgesics for the short-term management of painful conditions in general practice, recommending ibuprofen first, because of the poor tolerability of aspirin and the potential risks of paracetamol overdose.

Lipid-modifying therapy and attainment of cholesterol goals in Europe: the Return on Expenditure Achieved for Lipid Therapy (REALITY) study

ABSTRACT Background: Few studies have been conducted in actual clinical practice settings to evaluate the ways in which dyslipidemia is managed using lipid-modifying therapies. Objective: To determine lipid-modifying therapy practices and their effects on low-density lipoprotein cholesterol (LDL‐C) and/or total cholesterol (TC) goal attainment in Europeans based on prevailing guidelines at the time of therapy in each country. Methods: Retrospective cohort analysis involving 58 223 patients initiated on lipid-modifying therapies in 10 European countries, with a median patient follow-up on lipid-modifying therapy of 15.3 months. Data on prescriptions of lipid-modifying therapies, laboratory data including LDL‐C and TC, achievement of cholesterol goals for LDL‐C and/or TC, and hospitalizations were obtained from healthcare administrative databases and/or patient chart reviews. Results: Across Europe, statin monotherapy was the initial lipid-modifying treatment in 51 786 (89.3%) of 58 009 patients with available data. In addition, 38 853 (89.5%) of 43 410 patients with available follow-up statin potency data were initiated on statin regimens of medium or lower equipotency. Low-equipotency regimens include atorvastatin 5 mg, simvastatin 10 mg, and pravastatin 20 mg, whereas medium-equipotency regimens include atorvastatin 10 mg, simvastatin 20 mg, and pravastatin 40 mg. Regimens were adjusted to higher equipotency via either up-titration or switches to combination regimens in 16.2% of patients. On average, 40.5% of patients across Europe who were not initially at guideline recommended cholesterol goals (either LDL‐C or TC) and had follow-up data attained recommended cholesterol levels, including < 30% of patients in Spain, Italy, or Hungary. In many countries, the likelihood of goal attainment was inversely associated with baseline cardiovascular risk and/or LDL‐C levels. Conclusions: Lipid management strategies in Europe during the study period were dominated by statin monotherapy. Even after prolonged follow-up on lipid-modifying therapy, approximately 60% of Europeans studied did not achieve guideline recommended cholesterol goals. Future emphasis must be placed on subsequent lipid panel monitoring, as well as the use of more efficacious, well-tolerated lipid-modifying therapies such as dual cholesterol inhibitors to enable more European patients to attain their recommended cholesterol goals.

Ongoing pharmaceutical reforms in France: implications for key stakeholder groups.

The rapid rise in pharmaceutical costs in France has been driven by new technologies and the growing prevalence of chronic diseases as well as considerable prescribing freedom and choice of physician among patients. This has led to the introduction of a number of reforms and initiatives in an attempt to moderate expenditure whilst ensuring universal coverage and rewarding innovation. These reforms include accelerating access to and granting average European prices for new innovative drugs, delisting drugs where there are concerns over their value and instigating rebates for excessive prescribing. Alongside this, ongoing initiatives to improve the quality and efficiency of prescribing include programmes to enhance generic prescribing and dispensing as well as to reduce antibacterial and anxiolytic/hypnotic prescribing. However, there have been few publications documenting the impact of specific reforms on the overall costs and quality of care, which have been exacerbated by compartmentalization of budgets. Estimates suggest savings of over 27 million euro/year by decreasing antibacterial prescribing, 450 million euro/year by not reimbursing ineffective drugs, 670 million euro/year from pharmaceutical company rebates and approximately 1 billion euro/year from increased prescribing and dispensing of generics (year 2003-7 values). Additional savings of at least 1.5 billion euro/year are seen as being possible from increased use of generics such as generic proton pump inhibitors, statins (HMG-CoA reductase inhibitors) and ACE inhibitors instead of current branded products such as angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]). Delisting drugs when there are concerns about their value provides an example to other countries with currently limited demand-side measures. Other possible examples include price : volume agreements and multifaceted campaigns to enhance generic prescribing and dispensing and reduce antibacterial prescribing. Possible future initiatives could include adopting more stringent criteria for categorizing new drugs as innovative as well as further reductions in the prices of generics. Other initiatives could include further enhancement of the quality and efficiency of prescribing, including formal auditing of physician prescribing, as well as increasing efforts to monitor the risk : benefit ratio of new drugs post-launch in real-world practice.

Ongoing pharmaceutical reforms in France

The rapid rise in pharmaceutical costs in France has been driven by new technologies and the growing prevalence of chronic diseases as well as considerable prescribing freedom and choice of physician among patients. This has led to the introduction of a number of reforms and initiatives in an attempt to moderate expenditure whilst ensuring universal coverage and rewarding innovation. These reforms include accelerating access to and granting average European prices for new innovative drugs, delisting drugs where there are concerns over their value and instigating rebates for excessive prescribing. Alongside this, ongoing initiatives to improve the quality and efficiency of prescribing include programmes to enhance generic prescribing and dispensing as well as to reduce antibacterial and anxiolytic/hypnotic prescribing.However, there have been few publications documenting the impact of specific reforms on the overall costs and quality of care, which have been exacerbated by compartmentalization of budgets. Estimates suggest savings of over €27 million/year by decreasing antibacterial prescribing, €450 million/year by not reimbursing ineffective drugs, €670 million/year from pharmaceutical company rebates and approximately €1 billion/year from increased prescribing and dispensing of generics (year 2003–7 values). Additional savings of at least €1.5 billion/year are seen as being possible from increased use of generics such as generic proton pump inhibitors, statins (HMG-CoA reductase inhibitors) and ACE inhibitors instead of current branded products such as angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]).Delisting drugs when there are concerns about their value provides an example to other countries with currently limited demand-side measures. Other possible examples include price : volume agreements and multifaceted campaigns to enhance generic prescribing and dispensing and reduce antibacterial prescribing.Possible future initiatives could include adopting more stringent criteria for categorizing new drugs as innovative as well as further reductions in the prices of generics. Other initiatives could include further enhancement of the quality and efficiency of prescribing, including formal auditing of physician prescribing, as well as increasing efforts to monitor the risk : benefit ratio of new drugs post-launch in real-world practice.

Quality of life during pollen season in patients with seasonal allergic rhinitis with or without asthma

Objectives: We studied the evolution of generic and rhinoconjunctivitis-specific quality of life (QOL) during pollen season in patients with isolated seasonal allergic rhinitis (SAR) and those with asthma and concomitant SAR (AS+SAR). Generic QOL between groups was also compared at pollen peak. Methods: A prospective cohort study was conducted in Southern France in 2002. Outpatients aged 18–60, regularly visiting respiratory physicians for SAR, were recruited before the grass (grass cohort) or ragweed pollination period (ragweed cohort). Before the pollination period (baseline) and at peak pollination, patients completed French versions of the Mini Rhinoconjuctivitis Quality of Life Questionnaire (Mini-RQLQ) and physical and mental Short Form-12 (SF-12) scores (PCS and MCS) to determine rhinoconjunctivitis and generic QOL. Results: Totals of 83 and 52 patients were included in the SAR and AS+SAR groups, respectively (mean age = 35.4; 56.4% females). Mini-RQLQ scores indicated slightly worse QOL in the A+SAR group at inclusion, which significantly deteriorated at the time of pollen peak, both in the SAR (p < 0.0001) and AS+SAR groups (p = 0.003). In univariate analysis, significantly higher SF-12 PCS (meaning better QOL) were observed at pollen peak in the SAR compared with the AS+SAR group (p = 0.0008), while the difference for SF-12 MCS was more limited (p = 0.05). Results were confirmed in multivariable analyses adjusting for gender, allergy medication use at pollen peak, cohort of inclusion (grass/ragweed) and comorbid conditions. Conclusions: Significant deterioration in rhinoconjunctivitis-specific QOL was observed through the pollination period in patients with SAR and AS+SAR. At pollen peak, AS+SAR patients experienced significantly worse physical functioning than patients with SAR alone.

Adherence to treatment regimen in depressed patients treated with amitriptyline or fluoxetine

OBJECTIVE Non-compliance presents a constant challenge to effective therapy. Many studies only investigate early treatment discontinuation and not other measures like adherence to treatment regimen. We compared adherence in depressed patients using either a selective serotonin reuptake inhibitor (fluoxetine) or a tricyclic antidepressant (amitriptyline), and examined its clinical relevance through adverse events, drop-out rates, and outcome. Adherence was measured electronically with the MEMS (Medication Event Monitoring System). DESIGN Nine-week double blind, randomized controlled trial. SETTING Ambulatory psychiatric care. PATIENTS Random sample of 66 depressed (DSM-III-R criteria) patients. INTERVENTION Fluoxetine 20 mg or amitriptyline 150 mg. MAIN OUTCOME MEASURES Time course of adherence and its relation to severe adverse events, drop-outs and outcome. RESULTS Non-adherence to the treatment regimen occurred frequently in both treatment groups: 31% of patients had at least one 3-day drug holiday, and 34% of patients had at least one episode of three pills in a 24-h period. Over-consumption occurred more frequently during the early phases of treatment while under-consumption occurred more frequently during the later phases. Patients on amitriptyline (P=0.03) and patients with a higher pill intake (P=0.01) experienced more severe adverse events. Patients on amitriptyline (P=0.009) and patients with a lower adherence to the treatment regimen (P=0.004) discontinued from treatment more frequently. The final Hamilton score was significantly predicted by a longer duration of treatment and by a better adherence, but only in amitriptyline users. CONCLUSIONS Non-adherence to the treatment regimen has important clinical consequences. Pharmacodynamics and human behavior predict risk for severe adverse events and drop-outs. Moreover, in amitriptyline users but not in fluoxetine users, better adherence predicts a better outcome.

Level of Control and Hospital Contacts in Persistent Asthma

The purpose of this study was to estimate relationships between asthma control and hospital contacts (visits to emergency rooms and hospitalizations) in a group of patients suffering from persistent asthma, after adjustment for prior use of inhaled corticosteroids. A computerized family practice database was used to identify patients (aged 6–50 years) with persistent asthma who received asthma therapy from January 1995. The database provided information on patient demographics and drug therapy. Asthma control was estimated by a survey of patients at the end of a 12-month study period. Frequency of hospital contacts during the study period was related to demographics, asthma control, and prescribed doses of inhaled corticosteroids during a prestudy period. Review of computerized medical files of 497 family practice physicians identified 1966 patients with persistent asthma who met the study criteria. Of these patients, 1251 completed the survey (63.6%). Asthma control was assessed in 1130 patients; it was moderate or poor in 42% of the cases. During the 12-month study period, 14.8% of patients reported at least one hospital contact. The level of asthma control was significantly p < 0.001) associated with hospital contacts. The odds ratio (OR) for hospital contact for good and poor asthma control was 0.5 (95% confidence interval [CI] 0.2–0.7) and 2.2 (95% CI 1.2–4.4), respectively. Asthma control was related to hospital contacts independently of use of inhaled corticosteroids before the study period. Overall, control of asthma was not optimal in this population. The occurrence of hospital contacts was closely related with the level of control. This association was independent of the dose of inhaled corticosteroids prescribed before the study, suggesting that in asthma, hospital contacts are primarily related to the level of control experienced by the patients.

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.

Evidence on the global measurement model of the Minnesota Living with Heart Failure Questionnaire

PurposeThe Minnesota Living with Heart Failure Questionnaire (MLHFQ) is the most widely used health-related quality of life measure in both clinical and research settings. Nevertheless, its measurement model has never been confirmed. This study aims to fill that gap with a large international sample.MethodsData from eight studies (3,847 patients with heart failure) from 21 countries were merged and analysed. Common variables included MLHFQ scores, functional capacity, cardiovascular risk factors and the socio-demographic characteristics of the patient. The measurement model of the MLHFQ was assessed by means of exploratory and confirmatory factor analyses (EFA-CFA). The reliability of MLHFQ scores was evaluated using Cronbach’s alpha coefficient and the MLHFQ’s ability to differentiate among known groups was assessed through severity levels.ResultsFindings from the EFA and CFA suggest that the MLHFQ total and domain-specific scores fall within a bifactor model. The physical and emotional scores were supported within the sample, as was the original total score. Furthermore, a third factor was revealed regarding social environment. The reliability coefficient reached 0.9 for almost all physical and total scores. All the MLHFQ mean scores showed the ability to differentiate among functional capacity groups, with most of the effect size coefficients reaching 0.8.ConclusionsBeyond the suitable degree of reliability and validity displayed by the MLHFQ scores in the different country-specific versions, our results confirmed for the first time the unidimensionality of the most commonly used score in HF patients: the total MLHFQ score. Moreover, the social environment domain identified in this study can now be considered when assessing these patients’ HRQL, especially as a relevant outcome with regard to disease management.