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.

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.

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.

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.

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.

The association between adherence to levodopa/carbidopa/entacapone therapy and healthcare utilization and costs among patients with Parkinson's disease: a retrospective claims-based analysis.

BACKGROUND: Suboptimal adherence to long-term therapies is common and may potentially have adverse consequences on patient outcomes and healthcare costs. OBJECTIVE: To assess the association between adherence to levodopa/carbidopa/entacapone therapy and healthcare utilization and costs in patients with Parkinson's disease. METHODS: A retrospective historical cohort study, conducted in the US, using a health insurance claims database, with data spanning from 1 January 2000 to 31 December 2005. Subjects included patients with Parkinson's disease who were treated with levodopa (L), carbidopa (C) and entacapone (E) either as separate tablets (LC + E) or as a single-tablet formulation (LCE). The association between satisfactory adherence (defined as 'proportion of days covered' for LCE or LC + E during 1-year follow-up ≥80%) and healthcare utilization and costs was examined using multivariate regression to control for pretreatment adherence to LC and other patient characteristics. RESULTS: Compared with unsatisfactory adherence (n = 598), satisfactory adherence (n = 617) was associated with 39% fewer Parkinson's disease-related hospitalizations (95% CI 20, 54; p < 0.001), 47% lower all-cause inpatient costs (95% CI 18, 65; p = 0.004) and 18% lower all-cause total costs (95% CI 11, 24; p < 0.001). On an adjusted basis, all-cause total costs were $US3508 less for those with satisfactory versus unsatisfactory adherence. In both the LC + E and LCE groups, satisfactory adherence was associated with significant reductions in all-cause hospitalizations (39% and 46%, respectively), and all-cause total costs (10% and 31%, respectively). The association between adherence and total healthcare costs was stronger for patients receiving LCE. CONCLUSIONS: Better adherence to levodopa/carbidopa/entacapone therapy is associated with lower healthcare utilization and costs. Non-adherence to LCE is associated with a greater increase in costs than non-adherence to LC + E. Efforts should be made to ensure adherence to both therapies.

Adherence with levodopa/carbidopa/entacapone versus levodopa/carbidopa and entacapone as separate tablets in patients with Parkinson's disease.

BACKGROUND: Observational studies suggest that single-tablet formulations are associated with improved adherence versus the same components taken as separate tablets. The objective of this study was to compare adherence in patients with Parkinson's disease (PD) receiving levodopa therapy as levodopa/carbidopa/entacapone tablets (LCE) versus levodopa/carbidopa (LC) tablets and entacapone (E) as separate tablets (LC and E). METHODS: This was a retrospective, observational cohort study using a large health insurance claims database. Subjects included persons with a PD diagnosis who were receiving LC without E and then received either an add-on therapy with E as a separate tablet (LC and E) or LCE as one tablet (LCE). The primary study outcome was treatment adherence, estimated from pharmacy refills based on the 'percent of days covered' (PDC) with LCE or LC and E during follow-up and compared for patients receiving LCE and LC and E using multivariate regression analyses. RESULTS: In multivariate analyses controlling for differences between groups in baseline characteristics, including pre-index dosage of and adherence with LC, receipt of LCE (n = 388) was associated with 79% lower mean non-adherence during follow-up (95% CI: 73-83%; p < 0.001) versus LC and E (n = 823), 86% lower odds of unsatisfactory adherence (95% CI: 80-91%; p < 0.001), and a 26% lower risk of discontinuation (95% CI: 6-42%; p < 0.013). LIMITATIONS: This was an observational study with the inherent potential for selection bias. Pharmacy claims may not provide an accurate estimate of adherence. Requiring subjects to have a certain number of prescriptions before and after the index date may yield a sample that is not representative of all patients initiating levodopa therapy in typical clinical practice. CONCLUSIONS: Better adherence with LCE may have important implications for maintaining function in patients receiving chronic oral levodopa therapy. Further research is needed to confirm these results and examine the association between improved adherence and clinical and economic outcomes.

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.

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.

The native bacterioplankton community in the central baltic sea is influenced by freshwater bacterial species.

The Baltic Sea is one of the largest brackish environments on Earth. Despite extensive knowledge about food web interactions and pelagic ecosystem functioning, information about the bacterial community composition in the Baltic Sea is scarce. We hypothesized that due to the eutrophic low-salinity environment and the long water residence time (>5 years), the bacterioplankton community from the Baltic proper shows a native "brackish" composition influenced by both freshwater and marine phylotypes. The bacterial community composition in surface water (3-m depth) was examined at a single station throughout a full year. Denaturing gradient gel electrophoresis (DGGE) showed that the community composition changed over the year. Further, it indicated that at the four extensive samplings (16S rRNA gene clone libraries and bacterial isolates from low- and high-nutrient agar plates and seawater cultures), different bacterial assemblages associated with different environmental conditions were present. Overall, the sequencing of 26 DGGE bands, 160 clones, 209 plate isolates, and 9 dilution culture isolates showed that the bacterial assemblage in surface waters of the central Baltic Sea was dominated by Bacteroidetes but exhibited a pronounced influence of typical freshwater phylogenetic groups within Actinobacteria, Verrucomicrobia, and Betaproteobacteria and a lack of typical marine taxa. This first comprehensive analysis of bacterial community composition in the central Baltic Sea points to the existence of an autochthonous estuarine community uniquely adapted to the environmental conditions prevailing in this brackish environment.

Consequences and costs of noncompliance with iron chelation therapy in patients with transfusion-dependent thalassemia: a literature review.

BACKGROUND: Patients with thalassemia major require iron chelation therapy (ICT) to prevent complications from transfusional iron overload. Deferoxamine is effective, but requires administration as a slow continuous subcutaneous or intravenous infusion five to seven times per week. Deferiprone is a three-times-daily oral iron chelator, but has limited availability in the United States. Deferasirox is a once-daily oral iron chelator that was approved in the United States in 2005 for patients older than 2 years of age with transfusional iron overload. STUDY DESIGN AND METHODS: Published evidence on rates of compliance with ICT and the association between compliance, and the incidence and costs of complications of iron overload, in patients with thalassemia major was reviewed. RESULTS: A total of 18 studies were identified reporting data on compliance with ICT, including 7 that examined deferoxamine only, 6 that examined deferiprone only, and 5 that compared deferoxamine and deferiprone; no studies reporting compliance with deferasirox were identified. In studies of deferoxamine only, estimated mean compliance ranged from 59 to 78 percent. Studies of deferiprone generally reported better compliance, ranging from 79 to 98 percent. Results of comparative studies of deferoxamine and deferiprone suggest that compliance may be better with oral therapy. Numerous studies demonstrate that that poor compliance with ICT results in increased risk of cardiac disease and endocrinopathies, as well as lower survival. Although data on the costs of noncompliance are limited, a recent model-based study estimated the lifetime costs of inadequate compliance with deferoxamine to be $33,142. CONCLUSIONS: Inadequate compliance with ICT in thalassemia major is common and results in substantial morbidity and mortality, as well as increased costs.

Caregiver preference for rivastigmine patches versus capsules for the treatment of Alzheimer disease.

Alzheimer disease (AD) has a significant impact on caregivers. Administering and managing medications is one of their many daily tasks. More effective modes of drug administration may benefit patient and caregiver, and may improve compliance. A prospective outcome of the IDEAL (Investigation of TransDermal Exelon in ALzheimer's disease) trial was to evaluate caregiver preference for rivastigmine patches compared with capsules. The 24-week, randomized, double-blind, double-dummy, placebo- and active-controlled IDEAL trial investigated once-daily rivastigmine patches vs twice-daily capsules in moderate AD patients. Caregivers rated patch adhesion throughout. The AD Caregiver Preference Questionnaire (ADCPQ) assessed patch vs capsule from caregivers' perspective, based on expectations, preferences, and satisfaction with treatment. A total of 1,059 caregivers completed the ADCPQ while their respective patients were on study drug. More than 70% of caregivers preferred the patch to capsules overall. The patch was preferred to capsules with respect to ease of use (p < 0.0001) and ease of following the schedule (p < 0.0001). Caregivers indicated greater satisfaction overall (p < 0.0001) and less interference with daily life (p < 0.01) with the patch vs capsules. The preference substudy of the IDEAL trial demonstrated that caregivers of AD patients preferred patches to capsules for drug delivery. Preference for the patch may indicate reduced caregiver stress, substantiated by greater satisfaction and less interference with daily life. These benefits may lead to improved compliance.

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.

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.

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.

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.

Caregiver preference for rivastigmine patch relative to capsules for treatment of probable Alzheimer's disease.

BACKGROUND: Family caregivers comprise a critical component in the care of Alzheimer's disease (AD) patients. Among their many tasks, caregivers are responsible for administering and managing medications. Effective interventions incorporate the needs of both the AD patient and the caregiver, and understanding treatment preferences may maximize intervention effectiveness. Transdermal patches may offer advantages over conventional oral formulations. METHODS: A 24-week randomized controlled trial compared the rivastigmine patch to the rivastigmine capsule and placebo in patients with probable AD. At baseline and Weeks 8 and 24, the AD Caregiver Preference Questionnaire (ADCPQ) was used to evaluate caregiver expectations, preferences and satisfaction with treatment. Double-dummy treatment blinding ensured that caregiver preference for the patch or capsule was not confounded by perceptions of efficacy or tolerability. Reasons for preference were also elicited. The analytic sample included caregivers who completed the ADCPQ at Weeks 8 and/or 24. RESULTS: One thousand and fifty-nine caregivers completed the ADCPQ. More than 70% of caregivers preferred the rivastigmine patch to the capsule. The patch was significantly preferred to the capsule with respect to ease of following the schedule and ease of use. Caregivers indicated greater satisfaction overall, greater satisfaction with administration, and less interference with daily life with the patch versus the capsule (all p

Global patterns of diversity and community structure in marine bacterioplankton.

Because of their small size, great abundance and easy dispersal, it is often assumed that marine planktonic microorganisms have a ubiquitous distribution that prevents any structured assembly into local communities. To challenge this view, marine bacterioplankton communities from coastal waters at nine locations distributed world-wide were examined through the use of comprehensive clone libraries of 16S ribosomal RNA genes, used as operational taxonomic units (OTU). Our survey and analyses show that there were marked differences in the composition and richness of OTUs between locations. Remarkably, the global marine bacterioplankton community showed a high degree of endemism, and conversely included few cosmopolitan OTUs. Our data were consistent with a latitudinal gradient of OTU richness. We observed a positive relationship between the relative OTU abundances and their range of occupation, i.e. cosmopolitans had the largest population sizes. Although OTU richness differed among locations, the distributions of the major taxonomic groups represented in the communities were analogous, and all local communities were similarly structured and dominated by a few OTUs showing variable taxonomic affiliations. The observed patterns of OTU richness indicate that similar evolutionary and ecological processes structured the communities. We conclude that marine bacterioplankton share many of the biogeographical and macroecological features of macroscopic organisms. The general processes behind those patterns are likely to be comparable across taxa and major global biomes.

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.