Use of insertable cardiac monitors for the detection of atrial fibrillation in patients with cryptogenic stroke in the United States is cost-effective.

Objectives: Atrial fibrillation (AF) is the most common arrhythmia and a major marker of ischemic stroke risk. Early detection is crucial and, once diagnosed, anticoagulation therapy can be initiated to reduce stroke risk. The aim of this study was to assess the cost-effectiveness of employing an insertable cardiac monitor (ICM), BIOMONITOR, for the detection of AF compared to standard of care (SoC) ECG and Holter monitoring in patients with cryptogenic stroke, that is, stroke of unknown origin and where paroxysmal, silent AF is suspected. Materials and methods: A Markov model was developed which consisted of five main health states reflecting the potential lifetime evolution of the AF disease: post cryptogenic stroke (index event), subsequent mild, moderate and severe stroke, and death. Sub-states were included to track a patient's AF diagnostic status and the use of antiplatelet or anticoagulant therapy. AF detection was assumed to result in a treatment switch from aspirin to anticoagulants, except among those with a history of major bleeding. Detection yield and accuracy, clinical actions and treatment effects were derived from the literature and validated by an expert clinician. All relevant costs from a US Medicare perspective were included. Results and conclusions: An ICM-based strategy was associated with a reduction of 37 secondary ischemic strokes per 1000 patients monitored compared with SoC. Total per-patient costs with an ICM were higher (US$90,052 vs. US$85,157) although stroke-related costs were reduced. The use of an ICM was associated with a base-case incremental cost-effectiveness ratio of US$18,487 per life year gained compared with SoC and US$25,098 per quality-adjusted life year gained, below established willingness-to-pay thresholds. The conclusions were found to be robust over a range of input values. From a US Medicare perspective the use of a BIOMONITOR ICM represents a cost-effective diagnostic strategy for patients with cryptogenic stroke and suspected AF.

Cost-effectiveness analysis of pancreatin minimicrospheres in patients with pancreatic exocrine insufficiency due to chronic pancreatitis.

OBJECTIVE: Chronic pancreatitis (CP) is the most common cause of pancreatic exocrine insufficiency (PEI). Management of PEI due to CP is achieved through lifelong treatment with pancreatic enzyme replacement therapy (PERT). To the authors' knowledge, no cost-effectiveness analysis on the benefit of PERT in CP patients with PEI has been performed to date. The objective of this analysis was to examine the cost-effectiveness of Creon (pancreatin minimicrospheres [MMS]), one of the main PERTs available in Poland, in treating patients with CP-related PEI. METHODS: The cost-effectiveness of pancreatin MMS in the treatment of patients with CP-related PEI vs no PERT treatment was estimated using a decision analysis based on clinical data from relevant studies. The model horizon was 20 years. Main outcomes included the percentage of patients with controlled PEI, survival, total medical costs, number of quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). All costs were analysed from the Polish payer perspective. RESULTS: The model included clinical data from 176 patients treated in five pancreatin MMS randomized trials. Treatment with pancreatin MMS resulted in a considerably higher proportion of patients with controlled PEI compared to those not treated with any PERT. Over a horizon of 20 years, the total treatment cost and the ICER for pancreatin MMS was €8223 and €6312 per QALY, respectively. LIMITATIONS: Important limitations include the lack of long-term and comparative clinical data available. The use of 'no PERT treatment' as a comparator against pancreatin MMS treatment may not accurately reflect current practice in Poland. CONCLUSIONS: Treatment of CP-related PEI with pancreatin MMS is cost-effective from a Polish payer perspective, with an ICER below the accepted 'willingness to pay' threshold of 3-times gross domestic product (GDP) per capita. These results are likely to apply to other European countries.

Cost-effectiveness analysis of micafungin versus caspofungin for treatment of systemic Candida infections in the UK.

OBJECTIVE: To evaluate the cost-effectiveness of micafungin compared to caspofungin in the treatment of systemic Candida infections (SCIs) in the UK, including invasive candidiasis and candidaemia. RESEARCH DESIGN AND METHODS: Cost-effectiveness of both echinocandin antifungal drugs was estimated using decision analysis. Response to treatment, resource utilisation, and costs in the model were derived from a phase 3, head-to-head comparative trial. The model includes only data directly related to the treatment of the systemic Candida infection over the study duration (a maximum period of 14 weeks). Transition probabilities were calculated based on the efficacy results from the clinical trial. MAIN OUTCOME MEASURES: The model's effectiveness outcome is surviving patients who are successfully treated, based on the absence of signs and symptoms, radiographic abnormalities, and culture/histologic evidence associated with the fungal infection. In addition, subgroup analyses were performed to identify cost-effectiveness in several specific patient groups. RESULTS: The total medical treatment costs for the micafungin group were pound 29,095, which is similar to the total costs for the caspofungin group (pound 29,953). In the micafungin arm 60% of the patients and in the caspofungin arm 58% of the patients were successfully treated and alive. Cost-effectiveness ratio of micafungin was pound 48,771, and of caspofungin pound 52,066 per successfully treated patient. Because the costs are lower and the effectiveness is higher for micafungin in comparison with caspofungin, micafungin is more cost-effective than caspofungin. However, probabilistic sensitivity and subgroup analysis show that the differences cannot be considered significant due to a large variance although micafungin remained the most cost-effective option throughout all but one of the sensitivity analyses. CONCLUSIONS: Costs and effects of micafungin compare to those of caspofungin in the treatment of systemic Candida infections in the UK. The results indicate that micafungin is cost-effective compared to caspofungin, although the difference was not found to be significant.

Economic analysis of micafungin versus liposomal amphotericin B for treatment of candidaemia and invasive candidiasis in Germany.

OBJECTIVE: To investigate the economic impact of micafungin (MICA) for treatment of invasive candidiasis and candidaemia (systemic Candida infections), a health economic analysis was conducted comparing MICA with liposomal amphotericin B (L-AMB). RESEARCH DESIGN AND METHODS: The model was based on a phase III, randomised, double-blind, clinical trial which compared MICA with L-AMB. The model entailed a period of 14-20 weeks starting from initiation of treatment and was analysed from a German hospital perspective. MAIN OUTCOME MEASURES: The main outcome measures were defined as the percentage of patients achieving clinical and mycological response after initial treatment and who were alive at the end of the study (EOS), and the total treatment-associated costs over the study period. RESULTS: The health economic analysis shows that with MICA, 52.9% of patients are successfully treated and were alive at EOS compared to 49.1% for L-AMB. In addition, MICA has, on average, lower treatment-associated costs than L-AMB with euro43 243 and euro49 216 per patient, respectively. Because the costs are lower and the effectiveness is higher for MICA in comparison with L-AMB, MICA is more cost-effective than L-AMB. However, the results of the probabilistic sensitivity analysis show that the differences cannot be considered significant due to a large variance, although MICA remained the most cost-effective option throughout the one-way sensitivity analyses. CONCLUSIONS: The lower costs and higher effectiveness reported for MICA versus L-AMB in this analysis indicate that MICA may be a more cost-effective therapy in the treatment of invasive candidiasis and candidaemia when compared with L-AMB.

Double Gires-Tournois interferometer negative-dispersion mirrors for use in tunable mode-locked lasers.

We report the implementation and operation of novel superhigh-reflectivity negative-dispersion dielectric mirrors for use in tunable ultrafast laser systems. The mirror structure is divided into two distinct regions: an underlying superhigh-reflectivity dielectric quarter-wavelength stack and an overlying negative-dispersion section consisting of only a few layers and forming simple multiple Gires-Tournois interferometers. The example that we present was designed for operation from 800 to 900 nm and has a near-constant group-delay dispersion of -40 fs(2) and a peak reflectivity greater than 99.99%. We show a comparison of the predicted and the measured mirror performance and application of these mirrors in a mode-locked Ti:sapphire laser tunable from 805 to 915 nm.

Dispersion measurements of water with white-light interferometry.

We measure the second- and third-order dispersion coefficients, d(2)k/domega(2) and d(3)k/domega(3), of water for wavelengths from 0.45 to 1.3 mum using a Michelson white-light interferometer. In this interval, the second-order dispersion ranges from 0.068 to -0.1 fs(2)/mum, and the third-order dispersion ranges from 0.048 to 1.18 fs(3)/mum. We observe an oscillation in d(2)k/domega(2) near 1.1 mum that is due to water absorption features near that wavelength. From the dispersion coefficients, derivatives of the index of refraction of water are calculated and compared with available equations. These measured values of d(2)n/dlambda(2) and d(3)n/dlambda(3) should be useful in the evaluation and improvement of existing equations for n(lambda) in water.

Computer software for testing drug susceptibility of malaria parasites.

A computer program is described for the automated analysis of data obtained by flow cytometry for in vitro antimalarial drug susceptibility testing. Samples of malaria-infected red blood cells (RBC), which were cultured in the presence of different concentrations of antimalarial drugs, were stained with Hoechst. The Hoechst fluorescence intensity of infected RBC corresponds to DNA content of the parasites and to their stage of development. After measurement of the samples by a FACStar flow cytometer equipped with a UV laser and an autosampler, FCS 1.0 data files were generated. The HP PAS-CAL program developed for these files identifies five different populations--uninfected RBC, infected RBC, free parasites, leukocytes, and debris--on the basis of their light scatter and fluorescence characteristics. The program calculates the percentage of infected cells, the total number of parasite nuclei, and the average number of nuclei per parasite. The results of each culture are presented as a drug dose-response curve. During data analysis, user interaction is limited to selecting the first file of the first culture. The algorithm then processes each culture automatically. Potential problems or difficulties in analysis are flagged. To date, a total of 862 drug tests have been evaluated and fall into two classes, an extended microtest and the World Health Organization standardized microtest. These tests gave satisfactory results in more than 99% of the cases.

Flow cytometric screening of blood samples for malaria parasites.

An automated method for the detection and estimation of malaria parasites in blood samples using flow cytometry is presented. In a single-step procedure 50 microliters of blood sample was collected in 1 ml of lysis solution containing formaldehyde, causing red blood cells to lyse while parasites and white blood cells are preserved. Thus prepared, samples could be transported and remained stored in lysis solution until flow cytometric analysis was performed. The cells were stained for DNA with the fluorescent dye Hoechst 33258 and subsequently analyzed by a FACStar flow cytometer. Parasites and white blood cells were distinguished and counted based on blue Hoechst fluorescence and forward scattering. Since red blood cells were lysed, parasite numbers were given related to the number of white blood cells similar to what is done in microscopic examination of thick blood smears. In dilution experiments with animal and human material, parasite counts by flow cytometry correlated very well with the theoretically calculated numbers (regression coefficients of > 0.94). In human material parasitemias of approximately 0.005% were detected. In a pilot study, 700 samples were collected in Thailand and screened by microscopic examination of thick smears and by flow cytometry; 29 were found positive by combining both methods, 2 were missed by flow cytometry, and 20 were missed by microscopists in the field. After microscopic reexamination in the central laboratory, 15 of these 20 were found positive, 5 remained unconfirmed.