The depletion of susceptibles effect in the assessment of burden-of-illness: the example of age-related macular degeneration in the community-dwelling elderly population of Quebec.

BACKGROUND: With the aging of the population, age-related macular degeneration (AMD) is becoming a public health concern. Few studies have assessed its consequences on morbidity and mortality, and the findings are conflicting. OBJECTIVES: To assess the risk of depression, fracture, institutionalization, and death among elderly patients with suspected exudative AMD and the impact of the depletion of susceptibles effect in a burden-of-illness study. METHODS: A population-based retrospective cohort study was conducted in the community-dwelling elderly population of Quebec. The cohort was assembled through the Quebec medical claims database (RAMQ). Among patients age 65 and older with a claim involving a diagnosis of AMD over the years 2000 to 2004, those with suspected exudative AMD (n=2,071) were retained, using fluorescein angiography as a marker. The reference cohort consisted of a sample of 16,932 elderly without a claim involving AMD or visual impairment. RESULTS: Suspected exudative AMD was associated with an increased risk of depression (hazard ratio HR=1.3, 95%CI 1.18-1.43) and fracture (HR=1.19, 95%CI 1.03-1.37), but a decreased risk of institutionalization (HR=0.55, 95%CI 0.42-0.71) and death (HR=0.68, 95%CI 0.59-0.78). After adjustment for the incident/prevalent status of the AMD, the association between suspected exudative AMD and institutionalization was no longer statistically significant (HR=0.75, 95%CI 0.5-1.12). CONCLUSIONS: These findings enhance the need to detect visual loss and to consider patients' ability to adapt to AMD, to maintain their quality of life. Failure to account for duration of illness and the depletion of susceptibles effect may bias results of burden-of-illness studies.

Depression and mortality in the visually-impaired, community-dwelling, elderly population of Quebec.

PURPOSE: To assess the effect of visual impairment (VI) on the risk of depression or death in the community-dwelling elderly population. METHODS: A population-based, retrospective fixed cohort study was conducted in the community-dwelling elderly (age > or = 65 years) outpatient population of Quebec. The cohort was assembled through the Quebec medical services database and consisted of the 5063 patients aged > or = 65 years who received a diagnosis of VI during the years 2000-2004. The reference cohort consisted of 16 932 elderly subjects who were randomly selected among members of the public drug programme. The outcome variables were depression and death. The main independent variable was VI and covariates included age, gender, chronic disease score, fracture and diabetes. RESULTS: Controlling for covariates, VI was associated with an increased risk of depression although the effect was not modified by severity (hazard ratio [HR] = 1.35, 95% confidence interval [CI] 1.10-1.66 for severe VI; HR = 1.35, 95% CI 1.09-1.69 for moderate VI). Visual impairment was associated with an increased risk of mortality; patients with moderate vision loss had a higher risk of death (HR = 1.70, 95% CI 1.55-1.87) than those with severe vision loss (HR = 1.34, 95% CI 1.21-1.48). CONCLUSIONS: Given the ageing of the population, VI in elderly subjects is becoming a public health concern. These findings enhance the need to detect and treat VI in order to improve the quality of life and to prevent premature mortality in the elderly population.

Cost-effectiveness of pegaptanib compared to photodynamic therapy with verteporfin and to standard care in the treatment of subfoveal wet age-related macular degeneration in Canada.

BACKGROUND: Age-related macular degeneration (AMD) is characterized by loss of central vision and is the leading cause of blindness among persons over the age of 50 years in Canada. The wet form of AMD has 3 subtypes-occult, minimally classic, and predominantly classic. Photodynamic therapy (PDT) with verteporfin is indicated only for the category of predominantly classic wet AMD. Currently, there are no treatments available for the other AMD subtypes. Pegaptanib sodium was the first pharmacologic therapy approved in Canada for the treatment of subfoveal wet AMD regardless of subtype. OBJECTIVE: The aim of this study was to examine the cost-effectiveness of pegaptanib versus PDT with verteporfin and versus standard care for the treatment of subfoveal wet AMD in patients aged 65 years in Canada. METHODS: A Markov model based on visual acuity in the better-seeing eye was developed. Clinical efficacy was taken from the clinical trials. Costs of treatment, comorbidities (eg, depression, fractures, need for assisted living), vision rehabilitation, visual aids, and adverse events were considered. Costs, utilities, and mortality were estimated from data from the available published literature. Costs were reported in 2004 Canadian dollars, and costs and outcomes were discounted at 3% per annum. Lifetime costs, quality-adjusted life-years (QALYs), and vision years gained (VYGs) were estimated. Sensitivity analyses were performed to determine model robustness. RESULTS: Patients who received pegaptanib experienced more QALYs gained (4.17) and VYGs (3.83) compared with patients who received PDT (3.87 and 3.01, respectively) or standard care (3.96 and 3.26). Mean total costs per patient were greater in patients who received pegaptanib compared to those who received PDT or standard care ($20,016 vs $15,345 or $7669, respectively). The incremental cost per QALY in patients receiving pegaptanib compared to those receiving PDT was $49,052 and $59,039 for patients receiving pegaptanib versus standard care. The incremental cost per VYG was $20,401 and $21,559 with pegaptanib versus PDT and standard care, respectively. Sensitivity analyses found that the model was relatively robust to changes in various model parameters. CONCLUSION: The results of this analysis suggest that in Canada, pegaptanib is a cost-effective treatment for subfoveal wet AMD in elderly patients, regardless of lesion subtype, compared to PDT with verteporfin and to standard care.

Burden of illness of neovascular age-related macular degeneration in Canada.

BACKGROUND: Age-related macular degeneration (AMD) is a retinal disease affecting more than 2 million Canadians over the age of 50. The neovascular form of AMD is responsible for 90% of severe vision loss associated with the disease. This study was conducted to assess the burden of neovascular AMD in the Canadian population. METHODS: A cross-sectional, observational study was conducted of self-reported functional health, well-being, and disease burden among elderly subjects in Canada with (n = 67) and without (n = 99) neovascular AMD. Subjects completed telephone surveys of the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), the EuroQol questionnaire (EQ-5D), and the Hospital Anxiety and Depression Scale (HADS). Subjects also reported their history of falls and fractures and annual health care resource utilization. RESULTS: Subjects with neovascular AMD reported significantly worse vision-related functioning and overall well-being than controls (adjusted mean scores on the NEI-VFQ-25: 48.0 vs. 87.5; p < 0.0001) and significantly more depression symptoms than controls (HADS depression: 5.8 vs. 4.3; p = 0.037). Subjects with neovascular AMD also reported more than twice the need for assistance with daily activities compared with controls (19.4% vs. 9.1%; p = 0.013) and a nearly 3 times higher fall rate than the control group (22.4% vs. 8.1%; p = 0.014). The annual neovascular AMD cost per patient was Can dollars 11,334, which is over 8 times that of elderly subjects without neovascular AMD (Can dollars 1,412). Over half of the neovascular AMD costs were direct medical costs. INTERPRETATION: Neovascular AMD is associated with significant limitation in functional abilities and quality of life, resulting in increased health care resource utilization and high patient support costs. These findings emphasize the need for new treatments for neovascular AMD that will prevent vision loss and progression to blindness in order to lessen the ensuing economic burden.

Do proton-pump inhibitors confer additional gastrointestinal protection in patients given celecoxib?

OBJECTIVE: Celecoxib has a superior upper-gastrointestinal (GI) safety profile compared with nonselective nonsteroidal antiinflammatory drugs (NS-NSAIDs). It is unclear whether the utilization of a proton-pump inhibitor (PPI) with celecoxib confers additional protection in elderly patients. We assessed the association between GI hospitalizations and use of celecoxib with a PPI versus celecoxib alone, and NS-NSAIDs with a PPI or NS-NSAIDs alone in elderly patients. METHODS: We conducted a population-based retrospective cohort study using the government of Quebec health services administrative databases. Elderly patients were included at their first dispensing date for celecoxib or an NS-NSAID between April 1999 and December 2002. Prescriptions were separated into 4 groups: celecoxib, celecoxib plus PPI, NS-NSAIDs, and NS-NSAIDs plus PPI. Cox regression models with time-dependent exposure were used to compare the hazard rates of GI hospitalization between the 4 groups adjusting for patient characteristics at baseline. RESULTS: There were 1,161,508 prescriptions for celecoxib, 360,799 for celecoxib plus PPI, 715,176 for NS-NSAIDs, and 148,470 for NS-NSAIDs plus PPI. The adjusted hazard ratios (HRs; 95% confidence intervals [95% CIs]) were 0.69 (0.52-0.93) for celecoxib plus PPI versus celecoxib, 0.98 (0.67-1.45) for NS-NSAIDs plus PPI versus celecoxib, and 2.18 (1.82-2.61) for NS-NSAIDs versus celecoxib. Subgroup analyses showed that use of a PPI with celecoxib may be beneficial in patients ages >/=75 years but was not better than celecoxib alone among those ages 66-74 years (HR 0.98, 95% CI 0.63-1.52). CONCLUSION: Addition of a PPI to celecoxib conferred extra protection for patients ages >/=75 years. PPI did not seem necessary with celecoxib for patients ages 66-74 years.

Utilization of non-steroidal anti-inflammatory drugs in Quebec: adherence to the Canadian consensus on prescription guidelines.

BACKGROUND: Adverse events associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) have led to the publication of Canadian prescription guidelines. Prescription practices following the publication of these guidelines and the introduction of COX-2 inhibitors in the Quebec formulary of reimbursed medications remain largely unexplored. OBJECTIVES: To compare the prevalence of contra-indications and selected risk factors for NSAID-toxicity among COX-2 inhibitor users and non-selective NSAID users. METHODS: A case-control analysis was conducted in a random sample of Quebec adult drug plan members who were treated with celecoxib (n=42,422 cases), rofecoxib (n=25,674 cases), full-dose (anti-inflammatory doses) of non-selective NSAIDs (n=9,673 cases), or low-dose NSAIDs (n=2,745 controls) in the year 2000. Data were obtained from the Quebec prescription and medical services databases (RAMQ). RESULTS: Patients with a history of gastropathy were more likely to be prescribed COX-2 inhibitors than low-dose NSAIDs; the odds ratios were 1.73 (95%CI: 1.56-1.91) and 1.49 (1.33-1.66), respectively for celecoxib and rofecoxib. Corresponding results for concomitant use of anticoagulants were 1.95 (1.34-2.83) for celecoxib and 1.87 (1.26-2.77) for rofecoxib, and for use of corticosteroids they were 1.29 (1.08-1.54) and 1.23 (1.01-1.49). Conversely, patients with the following characteristics were less likely to receive COX-2 inhibitors than low-dose non-selective NSAIDs: age 75+ (OR=0.64; 0.56-0.72 for celecoxib, OR=0.48; 0.76-0.99 for rofecoxib), hypertension (OR=0.83; 0.75-0.92 for celecoxib, OR=0.87; 0.77-0.97 for rofecoxib), and concomitant use of diuretics (OR=0.72; 0.63-0.82 for celecoxib; OR=0.77; 0.66-0.89 for rofecoxib). CONCLUSION: Patients with risk factors for NSAID gastropathy were more likely prescribed COX-2 inhibitors, while the presence of other contra-indications led to the prescription of low-dose non-selective NSAIDs. However, 12.7% of users of full-dose non-selective NSAIDs were age 75+ and 12.0% had a history of gastropathy, which are considered important risk factors for adverse events.