Kristen Migliaccio-Walle

The morbidity and mortality following a diagnosis of peripheral arterial disease: Long-term follow-up of a large database

BackgroundAwareness of the significance of peripheral arterial disease is increasing, but quantitative estimates of the ensuing burden and the impact of other risk factors remains limited. The objective of this study was to fill this need.MethodsMorbidity and mortality were examined in 16,440 index patients diagnosed with peripheral arterial disease in Saskatchewan, Canada between 1985 and 1995. Medical history and patient characteristics were available retrospectively to January 1980 and follow-up was complete to March 1998. Crude and adjusted event rates were calculated and Kaplan-Meier survival curves estimated. Cox proportional hazards analyses were conducted to examine the effect of risk factors on these rates. Patients suffering a myocardial infarction or ischemic stroke in Saskatchewan provided two reference populations.ResultsHalf of the index patients were male; the majority was over age 65; 73% had at least one additional risk factor at index diagnosis; 10% suffered a subsequent stroke, another 10% a myocardial infarction, and 49% died within the mean follow-up of 5.9 years. Annual mortality (8.2%) was higher among patients with PAD than after a myocardial infarction (6.3%) but slightly lower than that in patients suffering a stroke (11.3%). Index patients with comorbid disease (e.g., diabetes) were at highest risk of death and other events.ConclusionA diagnosis of peripheral arterial disease is critical evidence of more widespread atherothrombotic disease, with substantial risks of subsequent cardiovascular events and death. Given that the majority has additional comorbidities, these risks are further increased.

Economic evaluation of galantamine in the treatment of mild to moderate Alzheimer's disease in the United States.

BACKGROUND Alzheimers disease (AD) is estimated to affect up to 11% of those aged > or =65 years in the United States, and the number of patients with AD is predicted to increase over the next few decades as the population ages. The substantial social and economic burden associated with AD is well established, with the cost of management increasing as the disease progresses. OBJECTIVE The aim of this study was to evaluate the economic impact of galantamine 16 and 24 mg/d relative to no pharmacologic treatment in the management of mild to moderate AD in the United States based on the concept of need for full-time care (FTC). METHODS Calculations were made using the Assessment of Health Economics in Alzheimers Disease model, which applies predictive equations to estimate the need for FTC and the associated costs. The predictive equations were developed from longitudinal data on patients with AD. Inputs to the equations were derived by analyzing the data from 2 randomized, placebo-controlled, galantamine clinical trials. Resource use (from a payer perspective) was estimated from US clinical trial data, and costs were estimated from several US databases. Analyses were carried out over 10 years, and costs and benefits were discounted at 3%. RESULTS In the base case, 3.9 to 4.6 patients need to start treatment with galantamine to avoid 1 year of FTC, depending on dose. Treated patients spent 7% to 8% more time pre-FTC and 12% to 14% less time requiring FTC, resulting in savings of 2408 to 3601 US dollars. Time horizons below 3 years, very high discontinuation rates, or increased survival with galantamine reversed the savings. Conversely, limiting treatment to responders delayed FTC by 6 to 7 months, with savings of approximately 9097 to 11,578 US dollars. CONCLUSIONS These results suggest that use of galantamine in patients with AD in the United States could reduce the use of costly resources such as formal home care and nursing homes, leading to cost savings over time.

Long-Term Patterns of Use and Treatment Failure With Anticholinergic Agents for Overactive Bladder

BACKGROUND Overactive bladder (OAB) involves a complex set of symptoms with a lifetime prevalence of any symptom in ~30% of women and 20% of men. Anticholinergic agents are associated with poor medication persistence in OAB treatment. OBJECTIVE This study evaluated the long-term patterns of use and treatment failure in patients prescribed anticholinergic agents for OAB. METHODS This was a nonexperimental, retrospective cohort study. Medical, pharmacy, and eligibility data from the IMS LifeLink Health Plans Claims Database were used. Men and women aged ≥18 years were eligible for inclusion with an International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis of OAB in any field during the patient study period from January 2005 to June 2010. First documentation of a prescription filled between July 2005 and June 2008 for an anticholinergic agent was defined as the index prescription. Other inclusion criteria were: ≥1 pharmacy claim for an anticholinergic drug between July 2005 and June 2008; continuous enrollment 6 months before the index date, during which no anticholinergic drugs were filled; and 24 months of follow-up from the index prescription. Study outcomes were treatment failure, discontinuation, switch, reinitiation, and adherence. Treatment failure was defined as having a treatment discontinuation (ie, treatment gap of ≥45 days) or switching anticholinergic therapy. RESULTS The analytic cohort comprised 103,250 patients with a mean age of 58.7 years. A majority were female (73%) and privately insured (75%). The vast majority of patients (91.7%) failed to meet their treatment goals with their index anticholinergic agent over the 24-month follow-up period. Of these, 5.8% switched, 51.3% permanently discontinued all anticholinergic agents, and 34.6% reinitiated treatment sometime after 45 days. The mean (SD) time to treatment failure was 159 (216.0) days, with a mean of 1.3 (0.5) unique anticholinergic agents per patient. Forty-eight percent of patients demonstrated appropriate adherence as determined by a medication possession ratio ≥80%. CONCLUSIONS This study provides real-world data on treatment patterns over 2 years in a large cohort of patients diagnosed with OAB. Despite the potential for better adherence with some anticholinergic agents, these analyses suggest that such benefits have not yet been realized, and many patients end up without effective pharmacotherapy. Thus, there is a need for new therapies and strategies to increase persistence and adherence to improve outcomes in OAB.

Generalizing the results of clinical trials to actual practice: the example of clopidogrel therapy for the prevention of vascular events

PURPOSE An important element in translating the results obtained in clinical trials of a new treatment to clinical practice is the estimated event rate in patients who would be eligible to receive that treatment. We estimated the effect of clopidogrel, compared with aspirin, in actual practice using the relative risk reduction observed in the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) trial. SUBJECTS AND METHODS Ischemic event rates were estimated for 12,931 aspirin users drawn from the Saskatchewan Health population between 1990 and 1995 who had an index diagnosis of myocardial infarction, ischemic stroke, or peripheral arterial disease. To estimate the absolute risk reduction, the 8.7% relative risk reduction from clopidogrel compared with aspirin that was observed in CAPRIE was applied to these rates. RESULTS The rates of ischemic events were greater in actual practice than among the control patients in the CAPRIE trial. In the Saskatchewan population, patients experienced an outcome event (myocardial infarction, stroke including intracranial hemorrhage, or death) at a rate of 15.9 per 100 patient-years, compared with only 6.9 per 100 patient-years in CAPRIE. If the same 8.7% relative risk reduction seen in the CAPRIE trial is also true for patients seen in routine clinical practice, the greater absolute risk in actual practice would reduce the number needed to treat to prevent one event from 200 patients to 70 patients. CONCLUSION Absolute risk rates may be substantially greater in clinical practice than in the selected patients enrolled in randomized trials. As a result, similar reductions in relative risk, if true for clinical practice, may yield substantially more benefit in clinical practice than in randomized trials.

To what degree does cognitive impairment in Alzheimer's disease predict dependence of patients on caregivers?

BackgroundPatients with Alzheimers disease experience a progressive loss of cognitive function, and the ability to independently perform activities of daily life. Sometimes a dependent stage is reached quite early in the disease, when caregivers decide that the patients can no longer be left alone safely. This is an important aspect of Alzheimers for patients, their families, and also health care providers. Understanding the relationship between a patients current cognitive status and their need for care may assist clinicians when recommending an appropriate management plan. In this study, we investigated the relationship of cognitive function to dependence on caregivers before the patients reach a severe stage of the disease.MethodsData were obtained on 1,289 patients with mild-to-moderate Alzheimers disease studied in two randomised clinical trials of galantamine (Reminyl®). Cognition was assessed using the cognitive part of the Alzheimers Disease Assessment Scale (ADAS-cog) and Mini-Mental State Examination (MMSE). Patients were considered dependent if they required >12 hours of supervision each day or had high care needs. The Disability Assessment for Dementia (DAD) scale was also used as a measure of dependence. Disability was predicted directly using MMSE and ADAS-cog and compared to predictions from converted scores.ResultsThe odds ratio of dependence was significantly higher amongst the patients with worse cognitive impairment, adjusting for age, gender and antipsychotic medication use. For example, a 4-point difference in ADAS-cog score was associated with an increase of 17% (95% CI 11–23) in the adjusted odds for >12 hours of supervision, and of 35% (95% CI 28–43) for dependence. Disability predicted directly using actual ADAS-cog and scores converted from MMSE values had close agreement using the models developed.ConclusionIn patients with mild-to-moderate Alzheimers disease, even relatively small degrees of poorer cognitive function increased the risk of losing the ability to live independently.

NICE cost-effectiveness appraisal of cholinesterase inhibitors: was the right question posed? Were the best tools used?

The National Institute for Health and Clinical Excellence (NICE) recently issued updated guidance on the use of cholinesterase inhibitors in the treatment of Alzheimer’s disease. NICE initially recommended that cholinesterase inhibitors no longer be used, but final guidance restricted treatment to patients with disease of a moderately severe stage. This decision was based largely on results from a heavily criticised economic evaluation that used an adaptation of the Assessment of Health Economics in Alzheimer’s Disease (AHEAD) model. As the developers of the AHEAD model, we examined the appropriateness of NICE’s economic analyses and presentation of results. We attempted to replicate NICE’s results by modifying the original AHEAD model. Sensitivity analyses were then run using the modified AHEAD model to evaluate the extent of uncertainty in predictions.The AHEADNICE analyses resulted in an incremental cost-effectiveness ratio for galantamine of £82 000 per QALY gained (year 2003 values) from the perspective of the UK NHS and Personal Social Services. This was later revised to £46 000 per QALY, compared with <£9000 per discounted QALY gained (year 2001 values) in the original AHEAD model. Using our modified AHEAD with effectiveness estimates matching those of AHEADNICE, we show that NICE’s choice and presentation of sensitivity analyses obscured the instability of their estimates.In the final NICE evaluation, the recommendation to delay treatment with cholinesterase inhibitors until patients have moderately severe disease was based on critical assumptions in the economic analyses that had little evidence to support them. The case of NICE’s guidance on cholinesterase inhibitors highlights the importance of transparent and valid economic evaluations and the dangers of using inappropriate modelling technologies, basing analyses on a limited subset of the available data, and insufficiently reflecting the uncertainty in estimates that are intended to inform decision makers.

Costs and medical care consequences associated with the diagnosis of peripheral arterial disease

AbstractBackground: Peripheral arterial disease (PAD) is increasingly recognised as an indicator of disseminated atherothrombosis, but its impact on use of healthcare resources is not well understood. Objective: To provide a quantitative description of the resource utilisation and costs incurred following PAD. Methods: Hospitalisations, physician visits and the corresponding direct medical costs were examined in 16 440 patients with a diagnosis of PAD (1985–1995) in Saskatchewan, Canada, and compared with 15 590 reference patients with a diagnosis of myocardial infarction (MI) [1990–1995]. Medical history and patient characteristics were available retrospectively to January 1980 and follow-up to December 2000. Rates and timing of all-cause and cardiovascular hospitalisations and physician visits within discrete periods in the 10 years following PAD diagnosis, and 5 years following MI, were evaluated, as were lengths of stay and predictors of hospitalisation. Results: Average follow-up was 5.9 years among patients with PAD and 3.6 years for MI. Half (55%) of patients with PAD were male versus 64% of reference patients. The mean ages were 67.3 and 66.9 years, respectively. Patients with PAD were hospitalised most frequently soon after diagnosis, with rates subsequently decreasing to 0.14 per month. These rates were similar in the reference group except for the period immediately following MI. The average 5-year cost post-diagnosis (2002

Assessing the Health and Economic Impact of Galantamine Treatment in Patients with Alzheimer’s Disease in the Health Care Systems of Different Countries

Can) per patient was

Economic analysis of initial HIV treatment. Efavirenz- versus indinavir-containing triple therapy.

Can41 968 vs

The time course of subsequent hospitalizations and associated costs in survivors of an ischemic stroke in Canada

Can48 578 for the reference population. Conclusions: A diagnosis of PAD not only imposes a severe burden on patients and their families, but it also significantly increases the use of healthcare resources and the associated costs. By the end of year 1, this burden is comparable with a diagnosis of MI.