Assessing the cost-effectiveness of the rivastigmine transdermal patch for Alzheimer's disease in the UK using MMSE- and ADL-based models.

OBJECTIVE: Assess long-term cost-effectiveness of rivastigmine patch in Alzheimer's disease (AD) management in the UK, using cognitive and functional models based on clinical trial efficacy data. METHODS: Incremental costs and Quality Adjusted Life Years (QALYs) associated with rivastigmine patch and capsule treatment versus best supportive care (BSC) were calculated using two economic models, one based solely on Mini-Mental State Examination (MMSE) scores, and one also incorporating activities of daily living (ADL) scores. The clinical pathway was populated with data from a clinical trial of rivastigmine patch (9.5 mg/24 h) and capsules (12 mg/day) versus placebo. Costs were based on the UK health and social care costs and basic UK National Health Service (NHS) prices. Disease progression was modelled beyond the trial period over 5 years using published equations to predict natural decline in AD patients. Base case costing variables included drugs, clinical monitoring, and institutionalization. RESULTS: The MMSE model estimated incremental costs per QALY of £10 579 for rivastigmine patch and £15 154 for capsule versus BSC. The MMSE-ADL model estimated incremental costs per QALY of £9114 for rivastigmine patch and £13 758 for capsules. The main difference between the models was a greater number of institutionalized days avoided for rivastigmine versus BSC estimated by the MMSE-ADL model. CONCLUSIONS: Both the MMSE and MMSE-ADL models suggest that rivastigmine patch and capsules are cost-effective treatments versus BSC. Incorporating ADL evidence makes a marginal but important difference to estimates in this case. Future economic evaluations of AD treatment should include measures of both cognition and functioning.

Cost-Utility Analysis of Ravulizumab Compared with Eculizumab in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria, characterized by intravascular hemolysis and venous thrombosis, can be managed with eculizumab, an inhibitor of the complement system; however, patients may periodically experience breakthrough hemolysis. Ravulizumab is a newly approved treatment for paroxysmal nocturnal hemoglobinuria that may reduce breakthrough hemolysis risk, thus improving health-related quality of life and reducing treatment costs. OBJECTIVE: The objective of this study was to compare the costs and benefit of treatment with ravulizumab vs eculizumab in adult patients with paroxysmal nocturnal hemoglobinuria, from a US payer perspective. METHODS: A cost-utility analysis was conducted using a semi-Markov model, informed by clinical experts. Lifetime costs and benefit (quality-adjusted life-years) (both discounted at 3% per annum) and incremental cost-effectiveness ratios were estimated, over a lifetime horizon. Results are reported for an entire treated population and subgroups of eculizumab treatment history. Scenario analyses were characterized by assumptions of non-inferiority between treatments, in terms of breakthrough hemolysis incidence and blood transfusion requirements, and of variations in eculizumab dosing adjustments used in response to breakthrough hemolysis. RESULTS: In the base-case analysis for the overall population, there was a positive impact on health-related quality of life (quality-adjusted life-year gain of 1.67) and costs were lower (- $1,673,465), for ravulizumab vs eculizumab. This led to a negative incremental cost-effectiveness ratio (- $1,000,818, indicating cost savings per quality-adjusted life-year gained). Health-related quality-of-life improvement and cost savings were also observed in all cohorts and scenario analyses. CONCLUSIONS: In adults with paroxysmal nocturnal hemoglobinuria, ravulizumab is associated with improved health-related quality of life and provides a large cost saving from the perspective of a US payer, when compared with eculizumab.

Predicting time to nursing home placement based on activities of daily living scores--a modelling analysis using data on Alzheimer's disease patients receiving rivastigmine or donepezil.

OBJECTIVE: To quantify the impact of activities of daily living (ADL) scores on the risk of nursing home placement (NHP) in Alzheimer's disease (AD) patients. SETTING: Models predicting NHP for AD patients have depended on cognitive deterioration as the primary measure. However, there is increased recognition that both patient functioning and cognition are predictive of disease progression. METHODS: Using the database from a prospective, randomised, double-blind trial of rivastigmine and donepezil, two treatments indicated for AD, Cox regression models were constructed to predict the risk of NHP using age, gender, ADL and MMSE (Mini-Mental State Examination) scores as independent variables. PARTICIPANTS: Patients aged 50-85 years, with MMSE scores of 10-20, and a diagnosis of dementia of the Alzheimer type. RESULTS: Cox regression analyses indicated that being female, older age, lower ADL score at baseline, and deterioration in ADL all significantly increased the risk of NHP. Over 2 years, risk of NHP increased by 3% for each 1-point deterioration in ADL score independent of cognition. CONCLUSION: Data analyses from this long-term clinical trial established that daily functioning is an important predictor of time to NHP. Further research may be required to confirm whether this finding translates to the real world.

Cost associated with hematopoietic stem cell transplantation: a retrospective claims data analysis in Germany.

AIM: Quantify hematopoietic stem cell transplantation (HSCT) costs in German patients with acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). METHODS: The primary outcome was direct and indirect costs in patients with ALL/DLBCL/FL who received HSCT between 2010 and 2014. Costs were evaluated two to four quarters before to eight quarters after HSCT. RESULTS: Among 258 patients with HSCT, direct costs were €290,125/patient (pediatric ALL), €246,266/patient (adult ALL), €230,399/patient (DLBCL/FL allogeneic) and €107,457/patient (DLBCL/FL autologous). Indirect costs with HSCT were €52,939/patient (adult ALL), €20,285/patient (DLBCL/FL allogeneic) and €29,881/patient (DLBCL/FL autologous). CONCLUSION: Direct and indirect costs associated with HSCT are substantial for patients with ALL, DLBCL and FL. Novel therapies that reduce HSCT use could reduce medical costs.

Outcomes, utilization, and costs among thalassemia and sickle cell disease patients receiving deferoxamine therapy in the United States.

Deferoxamine mesylate (DFO) reduces morbidity and mortality associated with transfusional iron overload. Data on the utilization and costs of care among U.S. patients receiving DFO in typical clinical practice are limited however. This was a retrospective study using a large U.S. health insurance claims database spanning 1/97-12/04 and representing 40 million members in >70 health plans. Study subjects (n = 145 total, 106 sickle cell disease [SCD], 39 thalassemia) included members with a diagnosis of thalassemia or SCD, one or more transfusions (whole blood or red blood cells), and one or more claims for DFO. Mean transfusion episodes were 12 per year. Estimated mean DFO use was 307 g/year. Central venous access devices were required by 20% of patients. Cardiac disease was observed in 16% of patients. Mean total medical costs were $59,233 per year including $10,899 for DFO and $8,722 for administration of chelation therapy. In multivariate analyses, potential complications of iron overload were associated with significantly higher medical care costs. In typical clinical practice, use of DFO in patients with thalassemia and SCD receiving transfusions is low. Administration costs represent a large proportion of the cost of chelation therapy. Potential complications of iron overload are associated with increased costs.

Economic burden following allogeneic hematopoietic stem cell transplant in patients with diffuse large B-cell lymphoma.

This study describes short-term and long-term healthcare resource utilization (HRU) and costs following an allogeneic hematopoietic stem cell transplant (HSCT) in adult patients with diffuse large B-cell lymphoma (DLBCL) in a real-world setting. Among 101 patients with DLBCL receiving an allogeneic HSCT, HRU and direct healthcare costs for up to three years after the allogeneic HSCT are described. HRU and costs were substantial, with the most intensive HRU and highest healthcare costs observed during the first year after HSCT (38 inpatient days; 68 days with office visits and average healthcare costs of $455,741). Although HRU and costs decreased over time, they remained high even in the third year after HSCT (four inpatient days; 27 days with office visits and average healthcare costs of $72,957). Overall, this study showed that the economic burden following an allogeneic HSCT in DLBCL patients is significant.

Cost-effectiveness of letrozole versus tamoxifen as initial adjuvant therapy in hormone receptor-positive postmenopausal women with early-stage breast cancer.

BACKGROUND: In Breast International Group (BIG) 1-98, a randomized, double-blind trial comparing 5 years of initial adjuvant therapy with letrozole versus tamoxifen in postmenopausal women with hormone receptor-positive early breast cancer, letrozole significantly improved disease-free survival by 19% and reduced risk of breast cancer recurrence by 28% and distant recurrence by 27%. PATIENTS AND METHODS: A Markov model was used to estimate the incremental cost per quality-adjusted life year (QALY) gained with 5 years of initial adjuvant therapy with letrozole versus tamoxifen from a US health care system perspective. Probabilities and costs of breast cancer recurrence and treatment-related adverse events and health-state utilities were based on published results of BIG 1-98 and other published studies. Costs and QALYs were estimated over the lifetime of a cohort of postmenopausal women with hormone receptor-positive early breast cancer, aged 60 years at initiation of therapy. In our base case, we assumed that benefits of letrozole on risk of breast cancer recurrence are maintained for 5 years after therapy discontinuation ("carry-over effect") and examined the effects of this assumption on results in sensitivity analyses. RESULTS: Under base-case assumptions, letrozole yields an additional 0.409 QALYs versus tamoxifen at an additional cost of $9705, yielding a cost per QALY gained for letrozole versus tamoxifen of $23,743 (95% confidence interval, $14,087-$51,129). Assuming no carry-over effects, letrozole yields 0.264 QALYs at a cost of $10,341, for a cost per QALY gained of $39,098 (95% confidence interval, $23,968- $83,501). CONCLUSION: In postmenopausal women with hormone receptor-positive early breast cancer, initial adjuvant treatment with letrozole is cost-effective from the US health care system perspective.

Cost effectiveness of once-daily oral chelation therapy with deferasirox versus infusional deferoxamine in transfusion-dependent thalassaemia patients: US healthcare system perspective.

BACKGROUND: Deferasirox is a recently approved once-daily oral iron chelator that has been shown to reduce liver iron concentrations and serum ferritin levels to a similar extent as infusional deferoxamine. OBJECTIVE: To determine the cost effectiveness of deferasirox versus deferoxamine in patients with beta-thalassaemia major from a US healthcare system perspective. METHODS: A Markov model was used to estimate the total additional lifetime costs and QALYs gained with deferasirox versus deferoxamine in patients with beta-thalassaemia major and chronic iron overload from blood transfusions. Patients were assumed to be 3 years of age at initiation of chelation therapy and to receive prescribed dosages of deferasirox and deferoxamine that have been shown to be similarly effective in such patients. Compliance with chelation therapy and probabilities of iron overload-related cardiac disease and death by degree of compliance were estimated using data from published studies. Costs ($US, year 2006 values) of deferoxamine administration and iron overload-related cardiac disease were based on analyses of health insurance claims of transfusion-dependent thalassaemia patients. Utilities were based on a study of patient preferences for oral versus infusional chelation therapy, as well as published literature. Probabilistic and deterministic sensitivity analyses were employed to examine the robustness of the results to key assumptions. RESULTS: Deferasirox resulted in a gain of 4.5 QALYs per patient at an additional expected lifetime cost of $US126,018 per patient; the cost per QALY gained was $US28,255. The cost effectiveness of deferasirox versus deferoxamine was sensitive to the estimated costs of deferoxamine administration and the quality-of-life benefit associated with oral versus infusional therapy. Cost effectiveness was also relatively sensitive to the equivalent daily dose of deferasirox, and the unit costs of deferasirox and deferoxamine, and was more favourable in younger patients. CONCLUSION: Results of this analysis of the cost effectiveness of oral deferasirox versus infusional deferoxamine suggest that deferasirox is a cost effective iron chelator from a US healthcare perspective.

Treatment interruptions and non-adherence with imatinib and associated healthcare costs: a retrospective analysis among managed care patients with chronic myelogenous leukaemia.

OBJECTIVES: Identify treatment interruptions and non-adherence with imatinib; examine the clinical and patient characteristics related to treatment interruptions and non-adherence; and estimate the association between treatment interruptions and non-adherence with imatinib and healthcare costs for US managed care patients with chronic myeloid leukaemia (CML). METHODS: This retrospective analysis utilised electronic healthcare claims data from a US managed care provider. Adult patients with CML (as determined by International Classification of Diseases, ninth revision, Clinical Modification [ICD-9-CM] diagnosis code) were identified who began treatment with imatinib from 1 June 2001 through 31 March 2004. Treatment interruptions (i.e. failure to refill imatinib within 30 days from the run-out date of the prior prescription) were identified during the 12-month follow-up period. Medication possession ratio (MPR), calculated as total days' supply of imatinib divided by 365, was also examined. Healthcare costs (i.e. paid amounts for all prescription medications and medical services received, including health plan and patient liability) were examined in three ways: (i) total healthcare costs; (ii) total healthcare costs exclusive of imatinib costs; and (iii) total medical costs. All costs were converted to US dollars (2004 values) using the medical component of the Consumer Price Index. MPR was modelled using ordinary least squares regression. Presence of treatment interruptions was modelled using logistic regression. The association between MPR and healthcare costs was estimated using a generalised linear model specified with a gamma error distribution and a log link. All models included adjustment for age, gender, number of concomitant medications, starting dose of imatinib and cancer complexity. RESULTS: A total of 267 patients were identified. Average age was approximately 50 years, and 43% were women. Mean MPR was 77.7%, with 31% of patients having a treatment interruption. However, all of these patients resumed imatinib within the study period. In this population, MPR decreased as the number of concomitant medications increased (p = 0.002), and was lower among women (p = 0.003), patients with high cancer complexity (p = 0.003) and patients with a higher starting dose of imatinib (p = 0.04). Women were approximately twice as likely as men to have a treatment interruption (p = 0.009), as were patients with a high cancer complexity (p = 0.03). After adjusting for the aforementioned covariates, MPR was found to be inversely associated with healthcare costs excluding imatinib (p < 0.001) and medical costs (p < 0.001). A 10% point difference in MPR was associated with a 14% difference in healthcare costs excluding imatinib and a 15% difference in medical costs. For example, patients with an MPR of 75% incur an additional 4072 US dollars in medical costs annually compared with patients with an MPR of 85%. CONCLUSIONS: Treatment interruptions and non-adherence with imatinib, both of which could lead to undesired clinical and economic outcomes, appear to be prevalent. Physicians and pharmacists should educate patients and closely monitor adherence to therapy, as improving adherence and limiting treatment interruptions may not only optimise clinical outcomes but also reduce the economic burden of CML.

Valsartan versus lisinopril or extended-release metoprolol in preventing cardiovascular and renal events in patients with hypertension.

PURPOSE: The objective of this study was to compare cardiovascular and renal events in patients with hypertension receiving the angiotensin II-receptor blocker valsartan versus those receiving the angiotensin-converting-enzyme lisinopril or the beta-blocker metoprolol succinate in an extended-release formulation. METHODS: A retrospective study was conducted using a health insurance claims database spanning the period from January 1997 through December 2003 and representing approximately 40 million members enrolled in over 70 health plans across the United States. Study subjects included all persons in the database with two or more outpatient prescriptions for valsartan, lisinopril, or extended-release metoprolol and two or more prior claims with a diagnosis of hypertension. Those with a history of major cardiovascular or renal events (diagnosis of myocardial infarction, stroke, heart failure, ventricular arrhythmias, or cardiac arrest; coronary revascularization procedure; diagnosis of renal failure; or dialysis or kidney transplantation) or using other antihypertensive medications except diuretics during the 12 months before treatment with valsartan, lisinopril, or extended-release metoprolol were excluded. Risks of major cardiovascular or renal event during follow-up were analyzed using Cox proportional hazards regression. RESULTS: A total of 29,357 antihypertensive patients were identified who initiated therapy with valsartan (n = 6,645), lisinopril (n = 17,320), or extended-release metoprolol (n = 5,392). In multivariate analyses, therapy with valsartan was associated with a significantly lower risk of a major cardiovascular or renal event versus extended-release metoprolol (heart rate [HR], 0.70; 95% confidence interval [CI], 0.56-0.87; p = 0.0015). Patients receiving valsartan had a nominally lower risk of a major cardiovascular or renal event than those receiving lisinopril, although this difference was not statistically significant (HR, 0.89; 95% CI, 0.74-1.07; p = 0.1987). CONCLUSION: Results of this observational study suggest that the use of valsartan may reduce the risk of major cardiovascular and renal events compared with extended-release metoprolol.

Risk of cancer treatment-associated bone loss and fractures among women with breast cancer receiving aromatase inhibitors.

BACKGROUND: Aromatase inhibitors (AIs) are a novel hormonal therapy for patients with breast cancer. However, AIs can cause bone loss by blocking estrogen production. This study aims to assess the association between AIs and treatment-related bone loss in a large managed-care population of women with breast cancer. PATIENTS AND METHODS: With use of medical and pharmacy claims, data from > 5 million beneficiaries between January 1, 1998, and January 31, 2005, we identified 12,368 patients with > or = 2 breast cancer claims in a 6-month period who also had no bone metastases and no previous osteoporosis or fracture claims. Patients who had received antiestrogen (eg, tamoxifen) therapy were also excluded. One thousand three hundred fifty-four patients receiving an AI (anastrozole, exemestane, or letrozole) were compared with 11,014 controls who did not receive an AI with respect to their risk of bone loss. The observation start date for the AI and control groups was defined as the service date of the first AI claim and breast cancer claim, respectively. The endpoints include (1) bone loss, consisting of osteoporosis or osteopenia, and (2) clinical fractures. RESULTS: The univariate analysis found that the prevalence of bone loss was 8.7% in the AI group versus 7.1% in the control group, resulting in a significant relative risk of 1.3 (95% confidence interval [CI], 1.1-1.6; P = 0.01). The prevalence of bone fracture was also significantly increased in the AI group compared with the controls (13.5% vs. 10.3%) with a relative risk of 1.4 (95% CI, 1.2-1.6, P = 0.001). Multivariate Cox proportional hazards regressions showed that after adjusting for age and comorbidities, the risk of bone loss remained significantly higher in the AI group than in the non-AI group, with a 27% (95% CI, 4%-55%; P = 0.02) and 21% (95% CI, 3%-43%; P = 0.02) increase in the risk of bone loss and fractures, respectively. CONCLUSION: This retrospective longitudinal analysis of a large cohort of patients with breast cancer corroborates previous findings from smaller clinical trials and demonstrates that AI therapies carry an increased risk of bone loss. Monitoring and treatment management strategies to reduce bone loss risk are warranted in women receiving an AI for breast cancer.

Estimating costs of care for patients with newly diagnosed metastatic colorectal cancer.

BACKGROUND: This study examines the resource use patterns and costs of care for patients with incident metastatic colorectal cancer (mCRC) based on analyses of retrospective claims data from selected health plans in the United States. PATIENTS AND METHODS: A case-control analysis was performed using claims from years 1998-2004. Incident mCRC cases were identified based on evidence of a colorectal cancer diagnosis and a metastatic disease diagnosis. Incident mCRC cases could have no other evidence of cancer in the 1-year period before the date of their first mCRC diagnosis. Cases were matched to non-mCRC controls based on age, sex, geographic region, and duration of plan enrollment. Costs were evaluated by phase of disease: diagnosis, treatment, or death phases. Ordinary least squares regressions were performed to evaluate impact of covariates in each phase. RESULTS: Total costs in the follow-up period averaged $97,031 more for mCRC cases than for controls. The main cost drivers for mCRC were hospitalizations ($37,369) and specialist visits ($34,582), which included chemotherapy administration. Approximately 40% of the 672 patients with mCRC who qualified for the phase analysis were identified with a fatal event during follow-up. Monthly costs were similar in the diagnostic phase ($12,205) and death phase ($12,328), but were significantly lower in the treatment phase ($4722). Both mean/median monthly costs increased over time during the study period, regardless of disease phase. CONCLUSION: The economic burden of mCRC is substantial for patients with commercial health plans in the United States, and costs of care have increased substantially in recent years.

Functional impairment, healthcare costs and the prevalence of institutionalisation in patients with Alzheimer's disease and other dementias.

INTRODUCTION: The progressive decline in functional status for patients with Alzheimer's disease and other dementias (ADOD) is well documented. However, there is limited information on the economic benefits of interventions improving functional status in an ADOD population. This study estimated the relationship between the degree of functional impairment in patients with ADOD and their healthcare costs and prevalence of institutionalisation. METHODS: Retrospective cross-sectional analyses of the Medicare Current Beneficiary Survey (MCBS) were performed. A nationally representative sample of Medicare beneficiaries with ADOD was identified from the 1995-8 waves of the MCBS (n = 3138): 34% in the community, 57% institutionalised and 9% residing in both settings during the year. Three measures of functioning were used: the number of activities of daily living (ADLs) and independent ADLs (IADLs) impaired; an index summarising number and severity of ADL and IADL impairments; and the Katz Index of ADLs. Healthcare costs included costs for all healthcare services received in all settings, regardless of whether they were covered by insurance or paid out of pocket. The relationships between each measure of impairment and healthcare costs and prevalence of institutionalisation were estimated using linear and logistic regression. RESULTS: Healthcare costs (1995-8 values) for all ADOD patients increased by 1,958 US dollars (p < 0.001) for each additional ADL impairment and 549 US dollars (p = 0.073) for each additional IADL impairment. For community-dwelling ADOD patients, healthcare costs increased by 1,541 US dollars (p < 0.001) for each additional ADL and 714 US dollars (p = 0.022) for each additional IADL. Costs also increased by severity on the summary index and the Katz Index. Odds of institutionalisation also increased by the three measures of functional impairment. CONCLUSION: Although relationships between function and costs have been described previously, the exact nature of these relationships has not been investigated solely in patients with dementia. The data from this study suggest a strong relationship between functional impairment and healthcare costs, specifically in patients with dementia. Even IADL impairments, which are common in mild to moderate dementia, may significantly raise costs. The results suggest that therapies and care management that improve functioning may possibly reduce other healthcare costs.

Antipsychotic drug use among nursing home residents taking rivastigmine.

OBJECTIVE: To evaluate whether or not rivastigmine use is associated with a decrease in the initiation of antipsychotic drug therapy among nursing home residents in the United States. METHODS: A retrospective analysis was performed using Minimum Data Set data and physician order files for newly admitted residents of 452 US nursing facilities from 2000 through 2002. The rivastigmine group included those who were diagnosed with Alzheimers disease (AD) and began rivastigmine treatment within 30 days of diagnosis. Patients were required to be on treatment for a minimum of 30 days. The control group included those who were diagnosed with AD, but did not receive a cholinesterase inhibitor. All subjects were antipsychotic drug-naive within 30 days of baseline (initiation of rivastigmine or initial AD diagnosis). A Cox proportional hazards model was used to estimate predicted risk of antipsychotic drug use. RESULTS: This study included 845 patients in the rivastigmine group and 517 patients in the control group. The rivastigmine group had fewer female patients, was younger, and had more verbal distress, sleep issues, sadness, loss of interest, and behavioral symptoms at baseline compared with the control group (P < .01). Overall initiation of antipsychotics was lower in the rivastigmine group (8.6%) compared with the control group (17.0%). Patients in the control group were almost 2 times more likely (relative risk = 1.86; P < .001) to take antipsychotics compared with patients taking rivastigmine, after adjusting for demographic covariates and mental health conditions or behavioral symptoms at baseline. Patients with baseline mental health conditions or behavioral symptoms were more likely to start antipsychotics than those without such conditions (P < .001). CONCLUSIONS: Study results suggest that nursing home residents with Alzheimers disease treated with rivastigmine have a reduced risk of initiating therapy with an antipsychotic drug compared with residents who do not receive cholinesterase inhibitor treatment.

Five-year direct costs of acute lymphoblastic leukemia pediatric patients undergoing allogeneic stem cell transplant.

AIM: To assess the 5-year healthcare resource utilization (HRU) and direct payer costs following allogeneic hematopoietic stem cell transplants (HSCTs) in acute lymphoblastic leukemia pediatric patients using data from two large US administrative databases. PATIENTS & METHODS: Among the 209 patients with acute lymphoblastic leukemia, HRU and costs were described over the up to 5 years after the HSCT. RESULTS: HRU and costs following the HSCTs were substantial. The highest average costs and most intensive HRU were observed within the first year following the HSCTs (49 outpatient visits; 29 laboratory service visits; 68 inpatient days), with a first year cost of US$683,099 and substantial costs over the following years. CONCLUSION: HRU and direct costs associated with allogeneic HSCTs are substantial.

Drug persistency of two cholinesterase inhibitors: rivastigmine versus donepezil in elderly patients with Alzheimer's disease.

OBJECTIVES: To compare persistency rates and persistency days in patients with Alzheimer's disease (AD) who initiated therapy with either rivastigmine or donepezil, and to identify factors influencing persistency in a real-world setting. DESIGN AND METHODS: This study used data collected by MarketScan from 1 January 1999 to 31 December 2002. Patients were included if they were newly diagnosed with AD and filled at least one prescription for rivastigmine or donepezil between 1 July 2000 and 30 June 2001, were > or =65 years of age on the index prescription date, and had continuous health and prescription insurance during the entire study period. Patients were excluded if they filled a prescription for any cholinesterase inhibitor during the 18 months prior to initiation of the study drugs. Patients who refilled their initial cholinesterase inhibitor prescription within a permissible gap of 60 days after depleting the drug supply from the prior prescription were considered to be persistent. Sensitivity analysis was performed to test the robustness of the persistency definition. The Kaplan-Meier method was used to determine persistency rates across time and Cox proportional hazards models were used to estimate relative risks of discontinuation or switch with adjustment for other covariates, and to identify factors significantly influencing persistency of the study drugs. RESULTS: Of the newly treated AD patients, the proportion of rivastigmine and donepezil patients who continued their medication was the same (47%; p = 0.5). On average, rivastigmine users continuously used their medication for 234 days (median 312 days) while those taking donepezil used their medication for 235 days (median 315 days) [p = 0.91]. Patients were more likely to discontinue or switch their initial cholinesterase inhibitor if they used a central nervous system (CNS) medication before initiation of therapy (relative risk [RR] = 1.23; 95% CI 1.01, 1.51 without adjustment for study variables; RR = 1.30; 95% CI 1.05, 1.60 with adjustment for study variables). On the other hand, patients were less likely to discontinue their cholinesterase inhibitor if they visited their physician office frequently (RR = 0.24; 95% CI 0.18, 0.32 without adjustment; RR = 0.23; 95% CI 0.17, 0.30 with adjustment) or if they were hospitalised after initiation of their cholinesterase inhibitor therapy (RR = 0.60; 95% CI 0.39, 0.91 without adjustment; RR = 0.65; 95% CI 0.42, 0.99 with adjustment). CONCLUSION: Patients who were newly diagnosed with AD and initiated therapy with either rivastigmine or donepezil had similar levels of persistency with their initial AD therapy in a real-world setting.

The use of the occupational disruptiveness scale of the neuropsychiatric inventory-nursing home version to measure the impact of rivastigmine on the disruptive behavior of nursing home residents with Alzheimer's disease.

OBJECTIVES: The Neuropsychiatric Inventory-Nursing Home Version (NPI-NH) was used to study the impact of rivastigmine (Exelon; Novartis Pharmaceuticals Corporation, East Hanover, NJ), on occupational disruptiveness (OD), a proxy measure for professional caregiver burden. METHODS: The study was a prospective, multicenter, open-label, single-arm trial with NH residents prescribed rivastigmine (up to 6 mg bid) for Alzheimer's disease (AD) treatment. The NPI-NH was completed by NH staff caregivers at time of initiation of treatment with rivastigmine (T1), at treatment weeks 10 to 14 (T2), at treatment weeks 24 to 28 (T3), and at treatment weeks 50 to 54 (T4). RESULTS: Observations ranged from 173 at baseline to 73 at week 52. All but one patient had either moderate or severe dementia. Total OD score means were 4.7 +/- 6.1, 3.9 +/- 5.0, 4.19 +/- 5.6, and 2.79 +/- 2.8 at baseline, and weeks 12, 26, and 52 (T1-T4), respectively, with significant difference found between T1 and T4. Except for euphoria and disinhibition at T3 and T4, all correlations between OD scores and the domain scores of the NPI, were significant. Rivastigmine dose was an independent variable that affected OD change. CONCLUSION: Treatment with rivastigmine was associated with a reduction in the self-reported professional caregiver burden, as assessed by the NPI-NH OD scale.

The economic impact of laparoscopic living-donor nephrectomy on kidney transplantation.

BACKGROUND: End-stage renal disease accounts for $17.9 billion annually in direct medical costs in the United States. This study assessed the flow of expenditures from a Medicare perspective for laparoscopic donor nephrectomy compared with living and cadaveric transplantation and continued dialysis. METHODS: This study involved a nonrandomized, retrospective investigation of patients with end-stage renal disease and charges using institutional and physician/supplier charges from the United States Renal Data System. The subjects were classified as laparoscopic living-donor transplant, living-donor transplant, cadaveric transplant, or dialysis patients. The first treatment date was set as the index date, and monthly charges were plotted from 12 months before and up to 48 months after the index date. RESULTS: There were 230,769 dialysis patients and 44,063 transplant patients (181 laparoscopic living-donor, 11,466 living-donor, and 32,416 cadaveric). Monthly institutional charges were similar in the year preceding the index date, but they were higher for transplantation in the month after the index date and lower in subsequent periods. Two-year post-index cumulative charges were as follows: Monthly institutional charges were similar for the living-donor ($191,374) and laparoscopic living-donor ($192,053) transplant patients, followed by the cadaveric transplant ($229,449) and dialysis ($250,348) patients, whereas physician/supplier charges were highest for the laparoscopic living-donor transplant ($104,583) patients, followed by the dialysis ($73,730), cadaveric transplant ($70,369), and living-donor transplant ($65,897) patients. The break-even points for the living-donor, laparoscopic living-donor, and cadaveric transplant patients compared with the dialysis patients were 10, 14, and 18 months, respectively. CONCLUSIONS: The laparoscopic procedure may be a beneficial alternative to the conventional open donor nephrectomy procedure and cadaveric transplantation, and it provides considerable benefits compared with dialysis.

Impact of rivastigmine use on the risk of nursing home placement in a US sample.

INTRODUCTION: Although numerous studies have evaluated predictors of nursing home placement (NHP), few have focused on the effects of cholinesterase inhibitor (ChEI) use on NHP. The objective of this study was to compare the risk of NHP between rivastigmine patients versus no-ChEI patients (control group), and secondly, between rivastigmine versus donepezil patients. METHODS: A retrospective analysis of a large US medical claims database was performed. Eligible subjects were identified from those who had continuous medical coverage from 1 April 2000 to 30 June 2002. Rivastigmine and donepezil subjects were new users, defined as having received no ChEI treatment during the initial 6 months of the study. Control subjects were diagnosed with Alzheimer's disease (AD) at some point after the initial 6-month period. All subjects were followed from baseline (initiation of ChEI therapy or initial AD diagnosis) to the date of NHP or 30 June 2002, whichever occurred first. RESULTS: In the rivastigmine (n=1181), donepezil (n=3864), and control (n=517) groups, 3.7%, 4.4% and 11.0% of subjects, respectively, had an NHP (p <0.001 for rivastigmine versus control). A Cox proportional hazard model, controlling for age, gender, comorbidities and behavioural disorders, showed that the control subjects were almost 3-fold more likely to have NHP than rivastigmine subjects (hazard ratio [HR]=2.71; 95% CI 1.82, 4.03). The difference in the risk of NHP was not significant between the rivastigmine and donepezil groups (HR=1.23; 95% CI 0.89, 1.71). DISCUSSION: This study demonstrated that rivastigmine decreased the risk of NHP in a large insured population.

Risk of antipsychotic drug use in patients with Alzheimer's disease treated with rivastigmine.

BACKGROUND AND OBJECTIVE: Cholinesterase inhibitors may offer some improvement in the behavioural symptoms of Alzheimer's disease. The dual inhibitory mechanism of action of rivastigmine (inhibition of acetylcholinesterase and butyrylcholinesterase) may improve behavioural symptoms and may delay the need for antipsychotics. This study was conducted to investigate the effect of rivastigmine on the time to first antipsychotic drug use among patients with Alzheimer's disease, compared with patients with Alzheimer's disease not treated with a cholinesterase inhibitor. DESIGN AND METHODS: This study used MarketScan research databases from 1 January 1999 to 31 March 2002. Patients were included if they: (a). were diagnosed with Alzheimer's disease on two occasions or filled a prescription for rivastigmine for the first time during the index period from 1 July 2000 to 31 December 2001; (b). were 65 years of age and older; (c). had continuous health and prescription insurance coverage during the entire study period; and (d). had not used an antipsychotic medication within 18 months prior to their index Alzheimer's disease prescription or diagnosis. The 'no cholinesterase inhibitor' group included patients who were newly diagnosed with Alzheimer's disease, but did not use any cholinesterase inhibitors. Chi-square, Student's t-, and log-rank tests were used to test differences in study variables between groups. Cox proportional hazards models were used to estimate predicted risk of first antipsychotic drug use. RESULTS: The study included 497 patients in the rivastigmine group and 749 patients in the 'no cholinesterase inhibitor' group. The rivastigmine group patients were younger compared with the 'no cholinesterase inhibitor' group patients (p < 0.01). The overall usage of antipsychotics was considerably lower for patients taking rivastigmine (9.8%) compared with those not taking cholinesterase inhibitors (25.6%). Patients taking rivastigmine were 64% less likely (relative risk = 0.36; p < 0.0001) to take antipsychotics compared with patients not taking cholinesterase inhibitors, after adjusting for demographic covariates, comorbid conditions, and use of other CNS drugs and anticonvulsants. Age was the only other factor that influenced antipsychotic use; older patients were significantly more likely to start antipsychotics than younger patients. CONCLUSION: This study provides initial evidence that patients with Alzheimer's disease treated with rivastigmine have a reduced risk of initiating therapy with an antipsychotic drug compared with patients who receive no cholinesterase inhibitor treatment. These findings may imply that rivastigmine use could delay the onset of behavioural symptoms that require treatment with antipsychotic medications.