Direct cost and predictive factors for treatment in patients with ocular hypertension or early, moderate and advanced primary open-angle glaucoma: the CoGIS study in Germany.

BACKGROUND: The main objectives of this analysis were to assess the treatment costs and to identify major cost drivers and factors predicting direct costs in German patients with ocular hypertension (OHT) or primary open-angle glaucoma (POAG). METHODS: This non-interventional cross-sectional study was conducted in two university hospitals and 13 ophthalmology practices in Germany regions (Bavaria, Rhineland-Palatinate, North Rhine-Westphalia, Hamburg and Mecklenburg-Western Pomerania) between May 2009 and January 2010 to assess resource utilisation in patients with OHT (ICD-10: 40.0) or POAG (ICD-10: 40.1) at early, moderate or advanced stages, according to the European Glaucoma Society classification Guidelines. Treatment patterns and direct costs were evaluated retrospectively for 5 years. Resource utilisation data (medication, hospitalisation, outpatient surgery, visits to ophthalmologists) were abstracted from the charts, and unit costs were applied to estimate direct costs per year (in Euros, 2009), calculated from the perspective of the statutory health insurance in Germany (Gesetzliche Krankenversicherung). Factors predicting costs were assessed in multivariate regression analysis. RESULTS: One hundred and fifty-four patients (17.5% OHT, 27.9% early, 22.7% moderate, and 31.8% advanced POAG), on average 67 years old (SD 11) were included in the study. Average total annual direct costs per patient for OHT were 226 (SD 117), for early POAG 423 (SD 647), moderate 493 (SD 385) and advanced POAG 809 (SD 877). Glaucoma-related medications and hospitalisation represented the two major components of direct costs, increasing with the progression of glaucoma. In addition to treatment switches (p = 0.0001), factors predictive of an increase in total direct costs included the number of hospital interventions (p < 0.0001), disease-state changes since the start of treatment (p = 0.05), and current disease state (p = 0.05). CONCLUSIONS: Direct costs of treatment are higher in glaucoma compared to OHT and further increase in more severe glaucoma states. Additional treatment changes are major contributing factors to the increased treatment costs of glaucoma. If intraocular pressure can be controlled over the long term, progression to moderate and advanced states avoided, and patients remain on initial treatments, treatment costs could decline due to reduced and less expensive healthcare resource utilisation.

Health- and vision-related quality of life in patients with ocular hypertension or primary open-angle glaucoma.

BACKGROUND: The main objective of this analysis was to assess the impact of severity of disease on the quality of life (QoL) of patients with ocular hypertension (OHT) and early, moderate, or advanced primary open-angle glaucoma (POAG). METHODS: This multicenter study was conducted at 2 university hospitals and 13 ophthalmology practices in Germany. QoL data were assessed by the Health Utility Index (HUI3) and the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). RESULTS: 154 patients (17.5% OHT, 27.9% early, 22.7% moderate, and 31.8% advanced POAG) were included. The HUI3 scores for OHT, early, moderate, and advanced POAG were 0.87 ± 0.09, 0.85 ± 0.15, 0.75 ± 0.23, and 0.58 ± 0.32, respectively. Compared to a normal population matched by age and gender, for moderate and severe POAG a difference of -0.06 ± 0.24 and -0.19 ± 0.28, respectively, was observed. NEI-VFQ-25 scores illustrate different dimensions of the impact on QoL; reduced peripheral vision or difficulties to drive a car were more crucial to glaucoma patients than social factors. CONCLUSIONS: The key difference for QoL impairment in glaucoma lies between OHT/early POAG versus moderate/severe POAG, hence every possible effort needs to be made to prevent disease progression over this threshold.

Effects of cardiac resynchronization therapy on long-term quality of life: an analysis from the CArdiac Resynchronisation-Heart Failure (CARE-HF) study.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves quality of life (QoL) when measured 3 to 6 months after implantation, but whether these effects are sustained is unknown. The CArdiac Resynchronisation-Heart Failure study is the only long-term randomized trial of CRT with repeated measures of QoL. METHODS: Quality of life was measured at baseline and 3 months using generic European Quality of Life-5 Dimensions and disease-specific (Minnesota Living with Heart Failure) questionnaires and at 18 months and study-end using the latter instrument. Median follow-up was 29.6 (interquartile range 23.6-34.6) months. RESULTS: At baseline, patients had a substantially impaired QoL (mean European Quality of Life-5 Dimensions score 0.60, 95% confidence interval [CI] 0.58-0.62) compared to an age-matched general population (0.78, 95% CI 0.76-0.80). Quality of life improved to a greater extent in patients assigned to CRT at each time point (P < .0001). By 18 months, the mean difference in disease-specific QoL score was 10.7 (95% CI 7.6-13.8) in favor of CRT, mostly due to improved physical functioning. Differences were sustained thereafter. Quality-adjusted life-years at 18 months increased by 0.13 (95% CI 0.07-0.182) and by 0.23 (95% CI 0.13-0.33) at study-end (both P < .0001). Little heterogeneity of effect across subgroups was observed. CONCLUSION: Cardiac resynchronization therapy improves long-term QoL and survival in patients with moderate to severe heart failure. The effects appear sustained, and therefore, the gain in quality-adjusted life years with CRT should be even greater during longer term follow-up.

Lifetime cost-effectiveness of prophylactic implantation of a cardioverter defibrillator in patients with reduced left ventricular systolic function: results of Markov modelling in a European population.

AIMS: Current European guidelines recommend prophylactic implantation of cardioverter defibrillators (ICDs) in patients with a reduced left ventricular ejection fraction (LVEF) who are not in NYHA class IV and have reasonable life expectancy. Cost and benefit implications of this recommendation have not been reported from a European perspective. METHODS AND RESULTS: Markov modelling estimated lifetime costs and effects [life years (LY) and quality-adjusted LY (QALY) gained] of prophylactic ICD implantation vs. conventional treatment, among patients with a reduced LVEF. Efficacy was estimated from a meta-analysis of mortality rates in the six primary prevention trials with inclusion criteria matching ACC/AHA/ESC Class I or IIa recommendations. Direct medical costs were estimated using Belgian national references. Costs and effects were discounted at 3 and 1.5% per annum, respectively. Probabilistic sensitivity and scenario analyses estimated the uncertainty around the incremental cost-effectiveness ratio. An ICD implantation increased the lifetime direct costs by euro 46,413. Estimated mean LY/QALY gained were 1.88/1.57, respectively. Probabilistic analysis estimated mean lifetime cost per QALY gained as euro 31,717 (95% CI: euro 19,760-euro 61,316). Cost-effectiveness was influenced most by ICD efficacy, time to replacement, utility, and patient age at implantation. CONCLUSION: In a European healthcare setting, prophylactic ICD implantation may be cost-effective if current guidelines for patients with a reduced LVEF are followed.

The role of topical moxifloxacin, a new antibacterial in Europe, in the treatment of bacterial conjunctivitis.

This article discusses current practice in the treatment of conjunctivitis and how the use of topical moxifloxacin can increase therapeutic effectiveness, reduce treatment failures and, consequently, be cost effective and reduce the societal burden of the disorder. Current practice and effectiveness data were derived from the literature. Data on healthcare utilization as a result of treatment failure were collected by survey and the cost of treatment was defined using national costings. A decision-analytic model to assess cost effectiveness was developed and the impact on the healthcare budget was calculated to define the health economic impact. Bacterial conjunctivitis represents a significant health problem and accounts for an estimated 1-1.5% of primary-care consultations. The disorder is highly contagious and causes a substantial healthcare and societal burden. Bacterial conjunctivitis is generally self-limiting, resolving within 1-2 weeks. However, the use of antibacterials significantly improves clinical and microbiological remission, shortens symptom duration, and enables more effective use of healthcare resources, compared with placebo. From a health economic perspective this benefits the healthcare system and society, since fewer healthcare resources are needed and the adult affected, or the parent/caregiver of the child affected, can return to full work capacity sooner, reducing loss of productivity. Treatment strategies vary significantly between countries. Most patients are first seen in primary care, where 'wait-and-see', lubrification and antiseptic or antibacterial treatment is provided. In Europe, when antibacterials are prescribed most general practitioners (GPs) prescribe a broad-spectrum topical antibacterial. The most commonly used drugs are chloramphenicol and fusidic acid, with fluoroquinolones rarely reported as first-line treatment by GPs. At the specialist (ophthalmologist) level, or for second-line treatment at the GP level, topical antibacterials are frequently used. However, in most countries, topical fluoroquinolones, particularly those recently approved by the European Medicines Agency, such as topical levofloxacin and topical moxifloxacin, are rarely used and instead are reserved for use as a last resort. In other parts of the world topical lomefloxacin, gatifloxacin and/or besifloxacin are also available. The strategy of using novel topical fluoroquinolones as a last resort reflects a belief that the use of topical fluoroquinolones may enhance the development of resistance, jeopardizing future availability of antibacterial treatment for ocular infections. In fact, most cases of bacterial resistance arise as a result of systemic treatment. Thus, this concern should not be extrapolated to topical use of fluoroquinolones, which results in antibacterial concentrations at the ocular surface that can significantly exceed mutant prevention concentrations. In addition, with products such as topical moxifloxacin, a dual-step mutation is required for resistance to emerge. Moxifloxacin restricts the selection of resistant mutants, meaning that emergence of resistance is unlikely. The strategy of not using the most effective fluoroquinolones such as topical moxifloxacin may lead to more patients with no improvement or worsening of symptoms, requiring re-intervention, additional examination and new treatment; these outcomes are defined as 'treatment failures'. Treatment failures cause an extra societal burden and increased costs due to the extra healthcare resources required (additional GP/specialist visits, laboratory tests, additional treatment, etc.). Compared with non-fluoroquinolones, topical moxifloxacin has a higher potency and faster in vitro 'speed-to-kill'. It has also been shown that, within the fluoroquinolone class, topical moxifloxacin and besifloxacin achieve the highest mean concentrations in conjunctival tissue, have the longest residence times and display favourable area under the concentration-time curve from time zero to 24 hours (AUC(24))/minimum inhibitory concentration ratio required to inhibit the growth of 90% of organisms (MIC(90)) and thus favourable pharmacokinetic/pharmacodynamic characteristics. This can result in reduced time-to-cure and a lower number of treatment failures, leading to better disease management and a healthcare-economic benefit arising from the associated reduction in utilization of healthcare resources. The high potency and mean concentration in conjunctival tissue combined with the long residence time of topical moxifloxacin enables a dosing strategy of three times daily for 5 days. Topical moxifloxacin is also the first ophthalmic antibacterial in Europe provided as a multidose, self-preserved, topical solution, thus avoiding the risk of benzalkonium chloride preservative-related allergic reactions and swelling. In addition, topical moxifloxacin has a near neutral pH (6.8) and is well tolerated by patients. Given the characteristics of the novel topical fluoroquinolones, a change in the healthcare treatment strategy for acute infectious conjunctivitis is to be recommended. Topical application of fluoroquinolones, such as moxifloxacin multidose self-preserved solution, should be considered earlier in the treatment path for conjunctivitis. Notwithstanding the premium price attached to this novel topical antibacterial, use of topical moxifloxacin for bacterial conjunctivitis can be cost effective and even generate total healthcare budget savings by reducing both the costs of managing treatment failures and the use of clinicians' time to manage such failures.

Predicting the long-term effects of cardiac resynchronization therapy on mortality from baseline variables and the early response a report from the CARE-HF (Cardiac Resynchronization in Heart Failure) Trial.

OBJECTIVES: This study was designed to investigate whether selected baseline variables and early response markers predict the effects of cardiac resynchronization therapy (CRT) on long-term mortality. BACKGROUND: Cardiac resynchronization therapy reduces long-term morbidity and mortality in patients with moderate or severe heart failure and markers of cardiac dyssynchrony, but not all patients respond to a similar extent. METHODS: In the CARE-HF (Cardiac Resynchronization in Heart Failure) study, 813 patients with heart failure and markers of cardiac dyssynchrony were randomly assigned to receive or not receive CRT in addition to pharmacological treatment and were followed for a median of 37.6 months. A model including assigned treatment, 15 pre-specified baseline variables, and 8 markers of response at 3 months was constructed to predict all-cause mortality. RESULTS: On multivariable analysis, plasma concentration of amino terminal pro-brain natriuretic peptide (univariate and multivariable model chi-square test: 105.0 and 48.4; both p < 0.0001) and severity of mitral regurgitation (chi-square test: 44.0 and 17.9; both p < 0.0001) at 3 months, regardless of assigned treatment, were the strongest predictors of mortality. Ischemic heart disease as the cause of ventricular dysfunction (chi-square test: 34.9 and 7.4; p < 0.0001 and p = 0.0066), being in New York Heart Association functional class IV (chi-square test: 18.8 and 9.6; p < 0.0001 and p = 0.0020), or having less interventricular mechanical delay (chi-square test: 29.8 and 8.8; p < 0.0001 and p = 0.0029) at baseline all predicted a worse outcome. However, the reduction in mortality in patients assigned to CRT was similar before (hazard ratio: 0.602; 95% confidence interval: 0.468 to 0.774) and after (hazard ratio: 0.679; 95% confidence interval: 0.494 to 0.914) adjustment for variables measured at baseline and at 3 months. CONCLUSIONS: Patients who have more severe mitral regurgitation or persistently elevated amino terminal pro-brain natriuretic peptide despite treatment for heart failure, including CRT, have a higher mortality. However, patients assigned to CRT had a lower mortality even after adjusting for variables measured before and 3 months after intervention. The effect of CRT on mortality cannot be usefully predicted using such information. (CARE-HF CArdiac Resynchronization in Heart Failure; NCT00170300).