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Our objective was to explore protective and risk factors for a forensic admission among the mentally ill. The most influential risk factors included violent crime prior to the crime that leads to the index hospitalization, conviction of the biological father, and no use of psychotropic medications before the age of 18. The main contributions of this study in comparison to previous studies in this domain included the use of multinational setting, greedy Bayesian algorithm, generalized country-independent factors, a merger model with high predictive performance, various measures of predictive performance including relative predictive value, and independent learning and test sets.

The main objective of the study was to assess the cost and quality of life (QoL) effects of elective dialysis patients during the first year of end-stage renal disease (ESRD) treatment in one Finnish treatment centre.A prospective case-series study was performed involving all elective dialysis patients (n=29) in a Finnish dialysis unit during 2003-2004. Direct costs of ESRD treatment were obtained from the hospital database and the Social Insurance Institution. The QoL effects were measured at the initiation of treatment, at 6 and at 12 months using 15D, a generic QoL instrument.The average cost of ESRD treatment was 69,085 euro. The improvement in the patients' QoL score was statistically and clinically significant during the first treatment year. The most significant changes were seen in the dimensions of breathing and vitality. The condition of patients commencing haemodialysis (HD) was more severe than that of patients commencing peritoneal dialysis (PD) as indicated by worse residual kidney function and poorer quality of life at the initiation.In this small patient population, treatment of ESRD during the first year seemed to improve or maintain the QoL of the patients.

Budesonide/formoterol maintenance and reliever therapy has shown its effectiveness as a treatment for moderate-to-severe asthma.To explore the cost-effectiveness of budesonide/formoterol maintenance and reliever therapy as compared to fixed combination therapies (budesonide/formoterol and salmeterol/fluticasone) with terbutaline as needed in the treatment of asthma in Finland.Patients without asthma exacerbations during a 6-month period were used as the effectiveness variable in the within-trial economic analysis. Finnish unit costs were applied to pooled resource use data, and multinomial cost-effectiveness plane and acceptability curves were formed based on bootstrapping.Use of budesonide/formoterol maintenance and reliever therapy significantly reduced the rate of severe asthma exacerbations as compared with a fixed dose of budesonide/formoterol or salmeterol/fluticasone and terbutaline as needed. Total costs over 6 months were 496 euros per patient for those who used the budesonide/formoterol maintenance and reliever therapy treatment model, which was 78-101 euros lower than the cost of fixed combinations of salmeterol/fluticasone or budesonide/formoterol with terbutaline as needed. The results indicate that the budesonide/formoterol maintenance and reliever therapy achieves a high probability (93%) of cost effectiveness irrespective of willingness to pay level.Budesonide/formoterol maintenance and reliever therapy may be considered in the treatment of moderate-to-severe asthma instead of conventional treatment with combination products in view of its good clinical efficacy and a high probability of cost-effectiveness in the Finnish setting. However, a cost-effectiveness analysis with a longer time horizon, more Finnish-specific data, and ICS + short/long-acting inhaled beta(2)-agonist as an additional comparator is still warranted.

This study evaluated the long-term cost-effectiveness of atorvastatin 20 mg, rosuvastatin 10 mg and simvastatin 40 mg in primary and secondary prevention of CHD in Finland.The effect of statin therapy on the incidence of CHD and the expected total costs of the disease were described using a Markov state transition model. Due to the limited amount of evidence concerning mortality and morbidity for rosuvastatin, the model was used to transmute the efficiency data of all statins (decrease in total cholesterol) into long-term endpoints (myocardial infarction, death) using risk functions of the FINRISK and 4S studies. The study followed a characterized cohort of 55-year-old Finnish men with an average 3.3-6.6% baseline risk of dying from cardiovascular disease within a 10-year period.Incremental cost-effectiveness ratios (ICERs) for atorvastatin and rosuvastatin, compared with simvastatin, measured as cost of life years gained (euro/LYG) and cost of quality adjusted life years gained (euro/QALY).The use of rosuvastatin increased the life expectancy by 0.27 years on average (LYG) compared with simvastatin, producing additional 0.08 quality-adjusted life-years (QALYs). Compared with simvastatin, the cost of one LYG with rosuvastatin was euro10 834 and the cost of one QALY gained was euro36 548 (discount rate 5% per annum). Corresponding figures for atorvastatin were euro31 286/LYG and euro105 599/QALY.If the decision makers' willingness to pay for a QALY gained is around euro40 000 there is a high probability (50%) that rosuvastatin represents a cost-effective form of therapy in the prevention of CHD in middle-aged men with an average 3.3-6.6% risk of dying within 10 years from cardiovascular disease. However, the true clinical impact of these results needs confirmation from on-going clinical trials, as the role of rosuvastatin in reducing clinical events is pending, but for simvastatin and atorvastatin established.

Background: Cytokine therapy is currently used as first-line treatment of metastatic renal cell carcinoma (mRCC). Until recently, treatments with proven efficacy after the failure of first-line cytokine therapy were not available. In recent clinical trials, sunitinib has been associated with good response rates in patients with mRCC. Objective: The aim of this study was to analyze the cost-effectiveness of sunitinib as second-line therapy for cytokine-refractory mRCC compared with current routine clinical practice in Finland (ie, best supportive care [BSC], including palliative biochemotherapy). Methods: A probabilistic decision-analytic model was developed to estimate the cost-effectiveness of sunitinib. Data were gathered from clinical trials, literature sources, and expert opinions, as well as from a local sample (n = 39) from 2 university hospitals in Finland. Clinical experts treating patients with mRCC in Finland provided the information on care practices of prescribing sunitinib. The analysis was conducted from the perspective of the health care payer in Finland. Results: According to estimated incremental cost-effectiveness ratios (ICERs), 1 progression-free month gained cost €4802 (2005 Euros); 1 life-year gained cost €30,831; and 1 quality-adjusted life-year (QALY) gained cost €43,698, compared with BSC, in the treatment of mRCC. The expected mean cost in BSC was €5543. When parameter uncertainty was considered, the probability of sunitinib being the more cost-effective choice of treatment was ~70% at the willingness-to-pay level of €45,000/QALY gained. Conclusions: Based on the results of this cost-effectiveness analysis, sunitinib is potentially cost-effective as a second-line treatment of mRCC compared with the treatment currently practiced in Finnish hospitals. The ICER (€/QALY gained) obtained in the present study was less than the value considered suitable for novel oncology treatments.

Purpose: The cost-effectiveness of first-line chronic lymphocytic leukemia treatments was assessed among patients unsuitable for full doses of fludarabine. Methods: The study's key outcome was the life-time incremental cost-effectiveness ratio (ICER) (euro/quality-adjusted life-year [QALY] gained) with an annual 3% discounting. A probabilistic Markov model with 3 health states (progression-free, progression, and death) was developed. Survival time was modeled based on age-matched clinical data by using appropriate survival distributions. Each health state was assigned an EuroQoL-5D-3L quality-of-life estimate and Finnish payer costs according to treatment received, and Binet stage of disease; severe adverse events and treatment inconvenience were also included. Six approaches considered the risk and value of key outcomes: cost-effectiveness efficiency frontiers; Bayesian treatment ranking (BTR) rated the lowest ICERs and best QALY gains; the cost-effectiveness acceptability frontier demonstrated optimal treatment; expected value of perfect information; and the cost-benefit assessment (CBA), a type of clinical value analysis, increased the clinical interpretation and appeal of modeled outcomes by including both relative and absolute (impact investment [benefit obtained with a fixed limited budget]) benefit assessments. Findings: The ICERs compared with chlorambucil varied from (sic)29,334 with obinutuzumab + chlorambucil to (sic)82,159 with ofatumumab + chlorambucil. Based on the BTR of ICERs versus chlorambucil, obinutuzumab + chlorambucil was the most cost-effective with 93% probability; rituximab + chlorambucil was the second most cost-effective (73%); and rituximab + bendamustine was the third most cost-effective (65%). The ICERs of obinutuzumab + chlorambucil were (sic)20,038, (sic)11,556, and (sic)15,586 compared with rituximab + chlorambucil, rituximab + bendamustine, and ofatumumab + chlorambucil. Obinutuzumab + chlorambucil was the most cost-effective treatment, with 54% and 99% probability at (sic)30,000 and (sic)50,000/ QALY gained, respectively. The corresponding expected values of perfect information were (sic)1438 and (sic)44 per patient. Based on the BTR of QALYs gained, obinutuzumab + chlorambucil was the most effective, with 100% probability; rituximab + chlorambucil was the second most effective (56%); and rituximab + bendamustine was the third most effective treatment (81%). Results were robust in sensitivity analyses. For obinutuzumab + chlorambucil, the CBA demonstrated the best clinical value to cost-effectiveness relation and the longest time progression-free with a limited budget. Implications: The mean results were sensitive to large changes in time horizon, indirect comparison hazard ratios, survival distributions, and discounting; however, obinutuzumab + chlorambucil provided considerable effectiveness and best value for money among chronic lymphocytic leukemia patients unsuitable to receive full doses of fludarabine. In this case, CBA concurred with the key outcome of the study. However, the CBA cannot fully substitute the key outcome, and further cost-effectiveness studies with different cancer types are needed to assess the validity of a limited CBA. (C) 2016 The Authors. Published by Elsevier HS Journals, Inc.

Recent developments in infrared laser technology have enabled the design of a compact instrumentation for two-photon excitation microparticle fluorometry (TPX). The microparticles can be used in immunoassays as the antibody-coated solid phase to capture an antigen and then detect it with a fluorescently labeled tracer antibody. Unlike most other methods, TPX technology allows low-volume, homogeneous immunoassays with real-time measurements of assay particles in the presence of a moderate excess of fluorescent tracer. In this study, the TPX assay system was used for the reagent characterization and the measurement of C-reactive protein (CRP) in diluted plasma samples, targeting the assay range useful in infectious disease diagnosis. The pentameric structure of the CRP permitted the optimization of an assay with the lowest detectable concentration of 1 μg/L (7.5 pM) by using a single monoclonal antibody both for capture and as the tracer. With a 1:200 predilution of samples, the measurement range of the assay was 1–150 mg/L, but an additional 1:10 dilution was required for higher concentrations. The TPX method showed a good correlation with the reference result obtained in a routine hospital laboratory, demonstrating the feasibility of the technology for immunodiagnostic applications.

A new type of instrumentation for single-step bioaffinity assays and microvolume fluorometry is presented. The concept is based on the use of two-photon excitation by a low-cost near-infrared laser and individual observation of bioactive fluorescent microparticles. The applicability of the instrument is demonstrated by a microparticle based multiplexed bioaffinity assay where several fluorescent markers are simultaneously excited. This instrument can be applied in the growing fields of drug discovery, in life science research, and in routine laboratory diagnostics.

We studied the use of a dramatically reduced testingzone in combination with two-photon excitation andphoton-burst analysis in high-throughput rare-event detec-tion simulation using a modified flow cytometer. Two-photon excitation measurements were performed with amode-locked titanium:sapphire laser. Fluorescence emis-sion was measured with a photon-counting avalanchephotodiode. Measured signal was analysed offline byautocorrelation and burst detection methods. Test sampleswere composed of full blood and orange fluorescentpolystyrene nanospheres mixed in full blood. Resultsshow that two-photon fluorescence excitation and time-correlation analysis provide a good signal-to-noise ratio forrare-event particle detection in a turbid sample environ-ment. Cytometry36:183–188,1999.

Kinetic analysis of high-conversion free-radical polymerization is discussed in terms of the complete solution of the classical kinetic scheme, which involves initiation, propagation, termination, and chain-transfer reactions. Expressions for kinetics of formation of each species existing in the polymerization mixture are presented. To demonstrate the applicability of the mathematical model, monomer conversion and the formation of the insoluble polymer component in the dispersion polymerization of styrene and methyl methacrylate (MMA) in 2-propanol have been measured at 70 °C. The values obtained for kd and kp/kt1/2, where kd, kp, and kt are dissociation, propagation, and termination rate constants, respectively, are in agreement with those reported in the literature.

We introduce a new design for the optical cuvette and a new optical lay-out for the Scanning Flow Cytometer (SFC) that permits measurement of the angular dependency of the scattered light from individual moving particles. The improved optical scheme of the SFC allows measurement of the angular scattering pattern of individual particles at polar angles from 10° to 120° with integration at azimuthal angles from 0° to 360° and with angular resolution of better than 0.5°. The performance of the SFC is demonstrated using certified polystyrene particles as reference material. The aim of this work is to develop a flow cytometer, which, by recording the entire light scattering pattern of individual biological particles, would provide more information about the particle structure than the ordinary wide angle, forward and side scattering concepts. Cytometry 31:78–84, 1998. © 1998 Wiley-Liss, Inc.

Objective To assess the frequency of warfarin use, the achieved international normalised ratio (INR) balance among warfarin users and the primary healthcare outpatient costs of patients with atrial fibrillation (AF). Design Retrospective, non-interventional registry study. Setting Primary healthcare. Participants All patients with AF (n=2746) treated in one Finnish health centre between October 2010 and March 2012. Methods Data on healthcare resource use, warfarin use, individually defined target INR range and INR test results were collected from the primary healthcare database for patients with AF diagnosis. The analysed dataset consisted of a 1-year follow-up. Warfarin treatment balance was estimated with the proportion of time spent in the therapeutic INR range (TTR). The cost of used healthcare resources was valued separately with national and service provider unit costs to estimate the total outpatient treatment costs. The factors potentially impacting the treatment costs were assessed with a generalised linear regression model. Results Approximately 50% of the patients with AF with CHADS-VASc ≥1 used warfarin. The average TTR was 65.2% but increased to 74.5% among patients using warfarin continuously (ie, without gaps exceeding 56 days between successive INR tests) during follow-up. One-third of the patients had a TTR of below 60%. The average outpatient costs in the patient cohort were €314.44 with the national unit costs and €560.26 with the service provider unit costs. The costs among warfarin users were, on average, €524.11 or €939.54 higher compared with the costs among non-users, depending on the used unit costs. A higher TTR was associated with lower outpatient costs. Conclusions The patients in the study centre using warfarin were, on average, well controlled on warfarin, yet one-third of patients had a TTR of below 60%.

The flying light scattering indicatrix (FLSI) method has been improved by employing a set of empirical equations combined with a decision tree which has been used for simultaneous real-time measurements and calculation of the size and refractive index of individual spherical particles. Empirical equations have been developed for determination of particle parameters over the range m to m and 1.37 to 1.60 for size and refractive index respectively. The FLSI method has been used for determination of the precision of a scanning flow cytometer for analysis of individual particles. A two-dimensional map (size X refractive index) was created for polystyrene latex and milk fat particles.

Background Cost-effectiveness studies explicitly reporting infusion times, drug-specific administration costs for infusions or real-payer intravenous drug cost are few in number. Yet, administration costs for infusions are needed in the health economic evaluations assessing intravenously-administered drugs. Objectives To estimate the drug-specific administration and total cost of biologic intravenous rheumatoid arthritis (RA) drugs in the adult population and to compare the obtained costs with published cost estimates. Methods Cost price data for the infusions and drugs were systematically collected from the 2011 Finnish price lists. All Finnish hospitals with available price lists were included. Drug administration and total costs (administration cost + drug price) per infusion were analysed separately from the public health care payer’s perspective. Further adjustments for drug brand, dose, and hospital type were done using regression methods in order to improve the comparability between drugs. Annual expected drug administration and total costs were estimated. A literature search not limited to RA was performed to obtain the per infusion administration cost estimates used in publications. The published costs were converted to Finnish values using base-year purchasing power parities and indexing to the year 2011. Results Information from 19 (95%) health districts was obtained (107 analysable prices out of 176 observations). The average drug administration cost for infliximab, rituximab, abatacept, and tocilizumab infusion in RA were €355.91; €561.21; €334.00; and €293.96, respectively. The regression-adjusted (dose, hospital type; using semi-log ordinary least squares) mean administration costs for infliximab and rituximab infusions in RA were €289.12 (95% CI €222.61–375.48) and €542.28 (95% CI €307.23–957.09). The respective expected annual drug administration costs were €2312.96 for infliximab during the first year, €1879.28 for infliximab during the forthcoming years, and €1843.75 for rituximab. The obtained average administration costs per infusion were higher (1.8–3.3 times depending on the drug) than the previously published purchasing power adjusted and indexed average administration costs for infusions in RA. Conclusions The administration costs of RA infusions vary between drugs, and more effort should be made to find realistic drug-specific estimates for cost-effectiveness evaluations. The frequent assumption of intravenous drug administration costs equalling outpatient visit cost can underestimate the costs.

The goal of the present work was to measure the efficacy of a multicomponent programme designed to provide tailored support for the caregivers of disabled persons. A total of 135 caregivers–care receiver dyads were randomly divided into an intervention group (n = 66) and a control group (n = 69). One-third of the care receivers were demented, and two-thirds had other diseases. Health centres (publicly funded primary health care systems) in 8 rural and urban communities in southeast Finland. The multicomponent support programme for the caregivers consisted of a 2-week rehabilitation period. The control group received standard care. Continuation of the caregiver and care receiver relationship, care receiver mortality at the 2-year follow-up as well as the health-related quality of life (15D scale) and Zung’s depression scale of the caregiver at the 1-year follow-up were evaluated. At the 2-year follow-up, the caregiver–care receiver relationship was terminated for any reason in 11 cases (17%) in the intervention group, and in 25 cases (36%) in the control group. After adjusting, the primary outcome (i.e., termination of care giving for any reason) indicated statistical significance (p = 0.04) with a hazard rate of 1.83 (95% confidence interval 1.03–3.29). With a similar adjustment, the difference in mortality and placement to institutional care between the two groups demonstrated a trend towards statistical significance. The caregivers’ health, as related to quality of life and depressive symptoms, remained unchanged in both groups at the 1-year follow-up. These results indicate that a tailored support programme for caregivers may help the caregiver to continue the caregiver–care receiver relationship and delay institutionalization.

Background: Chronic obstructive pulmonary disease (COPD) is associated with increased mortality and poor health-related quality of life (HRQoL) compared with the general population. The objective of this study was to identify clinical characteristics which predict mortality and very poor HRQoL among the COPD population and to develop a Bayesian prediction model. Methods: The data consisted of 738 patients with COPD who had visited the Pulmonary Clinic of the Helsinki and Turku University Hospitals during 1995-2006. The data set contained 49 potential predictor variables and two outcome variables: survival (dead/alive) and HRQoL measured with a 15D instrument (very poor HRQoL = 0.70). In the first phase of model validation we randomly divided the material into a training set (n = 538), and a test set (n = 200). This procedure was repeated ten times in random fashion to obtain independently created training sets and corresponding test sets. Modeling was performed by using the training set, and each model was tested by using the corresponding test set, repeated in each training set. In the second phase the final model was created by using the total material and eighteen most predictive variables. The performance of six logistic regressions approaches were shown for comparison purposes. Results: In the final model, the following variables were associated with mortality or very poor HRQoL: age at onset, cerebrovascular disease, diabetes, alcohol abuse, cancer, psychiatric disease, body mass index, Forced Expiratory Volume (FEV1) % of predicted, atrial fibrillation, and prolonged QT time in ECG. The prediction accuracy of the model was 77%, sensitivity 0.30, specificity 0.95, positive predictive value 0.68, negative predictive value 0.78, and area under the ROC curve 0.69. While the sensitivity of the model reminded limited, good specificity, moderate accuracy, comparable or better performance in classification and better performance in variable selection and data usage in comparison to the logistic regression approaches, and positive and negative predictive values indicate that the model has potential in predicting mortality and very poor HRQoL in COPD patients. Conclusion: We developed a Bayesian prediction model which is potentially useful in predicting mortality and very poor HRQoL in patients with COPD.

A two-pulse experiment is described, using stimulated emission to reduce the fluorescence of 1-ethyl-4-(4-(p-dimethylaminophenyl)-1,3-butadienyl)-pyridinium perchlorate (Pyridine 2) in a microscope of high numerical aperture. The experiment employed a 130 fs pulse at 375 nm for excitation and a 20 ± 5 ps pulse at 750 nm for stimulated emission. The pulses were provided by a mode-locked Ti:sapphire laser. The 375 nm excitation pulse was obtained by frequency-doubling and the 20 ± 5 ps infrared pulse by optical grating dispersion. The population of the excited state was monitored by varying the temporal delay between the excitation and stimulating pulse. This method enabled the measurement of the lifetime of the dye. For Pyridine 2 in glycerol, we determined a lifetime of 0.86 ± 0.2 ns. The decrease of fluorescence was due to stimulated emission, as was established by measurements of the temporal behaviour of the fluorescence signal upon amplitude modulation of the stimulating beam. We present a theoretical analysis of the temporal behaviour of depletion by stimulated emission in a two-pulse experiment.

We show the possibility of resolving point objects having an axial distance of 100–200 nm with a precision of ± 15 nm with a two-photon excitation 4Pi-microscope. The resolution is demonstrated by axial imaging of clustered fluorescence beads. A comparison of the axial resolution of the two-photon excitation 4Pi-microscope with a regular two-photon excitation microscope shows a four-fold improvement in axial resolution.

We investigate the effect of annular apertures in two-photon excitation confocal and non-confocal microscopy. In a theoretical study, we show that the use of annular apertures in two-photon excitation microscopy leads to resolution increase without diffraction fringes. We determine experimentally the axial resolution of annular aperture confocal and non-confocal two-photon excitation microscopes and compare it with that of the standard two-photon excitation contrasts. Images of fluorescence beads obtained with a transmission annular aperture two-photon excitation microscope demonstrate the applicability of annular apertures for enlarging the focal depth in high resolution two-photon excitation imaging.

Objective Extended release (XR) and immediate release (IR) quetiapine have differing dosing, titration and plasma concentration profiles. The authors assessed whether the use of quetiapine XR and IR in schizophrenia spectrum disorders (SCZ) and bipolar disorder (BD) differ. Design Retrospective non-interventional registry study. Setting Secondary healthcare. Participants All SCZ and BD (ICD-10 codes F20–F29, F30–F31) patients discharged between June 2008 and June 2010 from a Finnish psychiatric hospital with any use of quetiapine during their inpatient stay. Primary and secondary outcome measures Differences in patient characteristics between quetiapine XR and IR users were tested. To assess the profile of XR versus IR patients, logistic regressions were performed. Results 43 patients used quetiapine XR, 58 used quetiapine IR and 55 used both formulations (n=156). 102 patients were diagnosed with SCZ and 54 with BD, with no significant differences between the quetiapine formulations. The mean daily dose of quetiapine XR was significantly higher than that of quetiapine IR (542 mg vs 328 mg; p, Article summary Article focus Quetiapine exists in an extended (XR) and an immediate release (IR) formulation with different dosing, titration and plasma concentration profiles. This study assesses whether these differences lead to differential use of the two quetiapine formulations when treating schizophrenia spectrum disorders and bipolar disorder in a routine inpatient care setting. Key messages Use of quetiapine XR and IR differs in a routine inpatient care setting: quetiapine XR was used in higher doses and more often as monotherapy when compared with quetiapine IR. Certain patient characteristics differ between quetiapine XR and IR users: the odds for being treated with quetiapine XR in hospital were lower for older patients, patients with a substance abuse diagnosis, and prior IR use. Strengths and limitations of this study The study depicts real-life use patterns of quetiapine XR and IR in an unrestricted patient population: all patients with schizophrenia spectrum disorder or bipolar disorder and any use of quetiapine during their inpatient stay were included. The results may not be generalisable to other settings as the use of quetiapine may differ in other countries and in the outpatient clinical setting in Finland.

Background The cost-effectiveness analyses of follicular lymphoma (FL) treatments have focused on the second-line rituximab maintenance in patients with relapsed FL. The assessment of full FL treatment chain has been lacking. Objective The aim of this study was to assess the cost-effectiveness of FL treatment sequences. Methods Transitions between progression-free first-line treatment (PF1), progression-free second-line treatment (PF2), progression, and death health states were simulated with a probabilistic Markov model with half-cycle correction. At first, patients were assumed to be receiving rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) induction. The first-line RCHOP induction responders continued without (RCHOP) or with (RCHOPR) the first-line rituximab-maintenance treatment. In the case of PF1 failure, patients received RCOPR/bendamustine or RCOPR/COP according to the European Society for Medical Oncology guidance. In the case of PF2 failure, patients were expected to receive the best supportive care (BSC). The survivals and adverse events were estimated with direct and indirect comparisons. Health outcomes and Finnish payer (drug, drug administration, monitoring, test, progression, serious adverse event) costs valued in 2010 euros were discounted with 3% per annum. Results The mean discounted lifetime overall survival with FL was 9.6 to 11.5 years, quality-adjusted survival was 7.2 to 8.8 quality-adjusted life-years (QALYs), progression-free time was 7.7 to 10.2 years, and costs were €153,425 to €168,549, depending on the treatment sequence. The incremental cost-effectiveness ratios for RCHOPR→RCOPR/bendamustine→BSC, RCHOPR→RCOPR/COP→BSC, and RCHOP→RCOPR/bendamustine→BSC were €9575/€8014/€5900, €9881/€8310/€6013, and €8812/€7194/€5808, respectively, per QALY/life-year/progression-free year gained in comparison with RCHOP→RCOPR/COP→BSC. According to the cost-effectiveness acceptability frontier, the treatment of 61.8% to 72.7% patients with RCHOPR→RCOPR/bendamustine→BSC was cost effective at €20,000 to €30,000/QALY gained (expected value of perfect information [EVPI], €1287 to €1976/patient). The relative results were found to be robust in sensitivity analyses, and, in the direct comparison that included only head-to-head data, the first-line rituximab maintenance had 93.1% cost-effectiveness probability at €20,000/QALY gained (EVPI, €282/patient). Conclusion Sequences that included first-line rituximab maintenance is and second-line bendamustine are potentially cost effective in the treatment of FL. Limitations Because of data available, health outcomes of the first-line rituximab induction were excluded, the second-line patients on COP were assumed to incur the cost of COP, and the efficacy and adverse events of CHOP and the efficacy and adverse events of bendamustine were estimated indirectly according to a comparison of rituximab+bendamustine and RCHOP, and treatment benefits were truncated.

Scanning confocal microscopy using pulsed illumination is investigated theoretically and experimentally. The point-spread-function of a confocal microscope operating with pulsed illumination is derived and compared to its continuous wave counterpart. High aperture confocal images of scattering point-like objects are recorded with pulses of 220 fs, and with a continuous beam. The images are compared paying particular attention to differences in resolution and contrast. Whereas no significant change in resolution has been observed for pulsed mode, the contrast of scanning reflection microscopy is enhanced when pulsed operation is employed. For ultrashort transform-limited pulses (

Two-photon excitation fluorescence imaging is feasible with continuous wave lasers. Images of biological specimens are obtained by employing photon counting in conjunction with an increased recording time. The approach allows two-photon three-dimensional imaging of fluorescently labelled specimens with inexpensive lasers.

The effect of refractive index mismatch on the image quality in two-photon confocal fluorescence microscopy is investigated by experiment and numerical calculations. The results show a strong decrease in the image brightness using high-aperture objectives when the image plane is moved deeper into the sample. When exciting at 740 nm and recording the fluorescence around 460 nm in a glycerol-mounted sample using a lens of a numerical aperture of 1·4 (oil immersion), a 25% decrease in the intensity is observed at a depth of 9 μm. In an aqueous sample, the same decrease is observed at a depth of 3 μm. By reducing the numerical aperture to 1·0, the intensity decrease can be avoided at the expense of the overall resolution and signal intensity. The experiments are compared with the predictions of a theory that takes into account the vectorial character of light and the refraction of the wavefronts according to Fermat's principle. Advice is given concerning how the effects can be taken into account in practice.

In the present study europium chelates were introduced as alternative fluorescent labels for microscopy and their effect on enhanced autofluorescence caused by the glutaraldehyde fixative was investigated. Glutaraldehyde fixation was used to stabilize the cells for a permanent mount after the immunocytochemical reaction. The europium signal in time-resolved fluorescence microscopy was shown to be free of autofluorescence when strong cross-linking fixation with glutaraldehyde was used and the signal-to-background ratio obtained was 2,400 or better. It was also shown that the europium signal was stable in daylight and at room temperature. Fluorescent europium chelate used in this experiment provides excellent contrast and long-term stability for the samples with glutaraldehyde fixation and permanent mounting. © 1994 Wiley-Liss, Inc.

The aim of this study was to assess the cost-utility and value of reducing the uncertainty associated with the decision to use first-line biologic treatment (bDMARD) after the failure of one or more traditional drugs (tDMARD) in moderate-to-severe rheumatoid arthritis (msRA) in Finland.The treatment sequences were compared among 3000 hypothetical Finnish msRA patients using a probabilistic microsimulation model in a lifetime scenario. Adalimumab + methotrexate, etanercept + methotrexate, or tocilizumab + methotrexate were used as first biologics followed by rituximab + methotrexate and infliximab + methotrexate. Best supportive care (BSC), including tDMARDs, was assumed to be used after the exhaustion of the biologics. Methotrexate alone was added as a further comparator. Efficacy was based on ACR responses that were obtained from a mixed treatment comparison. The resources were valued with Finnish unit costs (year 2010) from the healthcare payer perspective. Additional analyses were carried out, including productivity losses. The Health Assessment Questionnaire (HAQ) values were mapped to the EQ-5D values using the tocilizumab trials; 3% annual discounting for costs and quality-adjusted life years (QALY) and extensive sensitivity analyses were completed.Incremental cost per QALY gained and multinomial expected value of perfect information (mEVPI).bDMARDs significantly increase the QALYs gained when compared to methotrexate alone. Tocilizumab + methotrexate was more cost-effective than adalimumab + methotrexate or etanercept + methotrexate in comparison with methotrexate alone, and adalimumab + methotrexate was dominated by etanercept + methotraxate. A QALY gained with retail-priced (wholesale-priced) tocilizumab + methotrexate costs €18,957 (€17,057) compared to methotrexate alone. According to the cost-effectiveness efficiency frontier and cost-effectiveness acceptability frontier (CEAF), tocilizumab + methotrexate should be considered before rituximab + methotrexate, infliximab + methotrexate, and BSC. Based on the CEAF, tocilizumab + methotrexate had a 60-93% probability of being cost-effective with €20,000 per QALY gained (mEVPI €230-2182).Tocilizumab + methotrexate is a potentially cost-effective bDMARD treatment for msRA, indicating a low value of additional research information with the international threshold values.Efficacy based on an indirect comparison (certolizumab pegol, golimumab excluded), fixed treatment sequence after the exhaustion of first bDMARD, Swedish resource use data according to HAQ scores, and inpatient costs assumed to include surgery.

The flying light-scattering indicatrix (FLSI, angular dependency of the intensity of light scattered by a moving individual particle) method, based on a scanning flow cytometer (SFC) that permits measurement of individual particle characteristics from light-scattering data, has been used for the determination of size distribution of the following particles: polystyrene latex, milk fat, and spores (Penicillium levitum, Aspergillus pseudoglaucus). The optical system of the SPC and empirical equations provided absolute sizing at the rate of 50 particles/s. Size distributions obtained with the FLSI method and a best-fit procedure using Mie scattering theory have been compared.

The aim of this study was to examine risk factors that predict persistent healthcare frequent attendance among a frequent attender (FA) population.Prospective cohort study without intervention.Primary healthcare centre in Tampere, Finland.A total of 85 primary healthcare working-age patients participated in the study. All participants were FAs in the first study year.We identified two groups of patients: temporary FAs and persistent FAs. A patient was considered as a persistent FA if he or she visited the health centre at least eight times a year for at least three out of four follow-up years. Some 59 different variables were examined as potential risk factors for persistent FA. P-course, a web-based Naïve Bayesian classification tool, was used for the modelling of the data.In our model, the most influential predictive risk factors for persistent frequent attendance in an FA population were female gender, body mass index above 30, former frequent attendance, fear of death, alcohol abstinence, low patient satisfaction, and irritable bowel syndrome. New observations were high body mass index, alcohol abstinence, irritable bowel syndrome, low patient satisfaction, and fear of death.In FA analyses, distinction between temporary and persistent frequent attendance should be made. Our Bayesian model could be used for identifying persistent FAs in uncertain situations. The model can quite easily be further developed as a practical decision support tool for general practitioners. However, before its use in practice, the external validity of the model will need to be defined.

Fluorescent lanthanide chelates with long decay times allow the suppression of the fast decaying autofluorescence in biological specimens. This property makes lanthanide chelates attractive as labels for fluorescence microscopy. As a consequence of the suppression of the background fluorescence the sensitivity can be increased. We modified a standard epifluorescence microscope for time-resolved fluorescence imaging by adding a pulsed light source and a chopper in the narrow aperture plane. A cooled CCD-camera was used for detection and the images were digitally processed. A fluorescent europium chelate was conjugated to antisera and to streptavidin. These conjugates were used for the localization of tumor associated antigen C242 in the malignant mucosa of human colon, for the localization of type II collagen mRNA in developing human cartilaginary growth plates, and for the detection of HPV type specific gene sequences in the squamous epithelium of human cervix. The specific slowly decaying fluorescence of the europium label could be effectively separated from the fast decaying background fluorescence. It was possible to use the europium label at the cell and tissue level and the autofluorescence was effectively suppressed in in situ hybridization and immunohistochemical reactions in both frozen and formaldehydefixed, wax-embedded specimens.

To evaluate the cost-effectiveness of generic atorvastatin 20 mg (A20), branded rosuvastatin 10 mg (R10), generic simvastatin 40 mg (S40) and the combination of generic S40 + branded ezetimibe 10 mg (S40 + EZ10) for the secondary prevention of coronary heart disease (CHD) in Finnish patients not meeting the target goal of low-density lipoprotein cholesterol (LDL-C) with S40.A probabilistic Markov model was employed to evaluate the costs and health outcomes of the different therapies based on the cardiovascular events avoided. The model included Framingham risk equations, Finnish population characteristics, event rates, quality of life estimates, resource use and unit costs. The LDL-C lowering efficacies were gathered from a systematic literature review, based on a search of Medline carried out in June 2008 (no time limit).Incremental cost per quality-adjusted life year (QALY) gained and incremental cost per life year gained (LYG).The efficacy (LDL-C decrease) gained from switching S40 to S40 + EZ10 was consistent in the literature review, whereas the LDL-C decrease gained from switching S40 to A20/R10 was uncertain. The incremental cost per QALY gained from switching generic S40 was lowest for S40 + EZ10 (22,841 euros [24,017 euros] and 26,595 euros [46,686 euros] for diabetic and non-diabetic men [women], respectively). The respective incremental cost per QALY gained for S40 + EZ10 vs. A20 were 19,738 euros (21,405 euros) and 23,596 euros (40,087 euros). A20 dominated R10. Based on the cost-effectiveness acceptability frontier with a willingness-to-pay value of 30,000 euros per QALY gained, the probability of cost-effectiveness for switching generic S40 to S40 + EZ10 was 100% for men and diabetic women. Sensitivity analyses showed that results were robust.In the Finnish secondary prevention population that is not at goal on S40, switching generic S40 to S40 + EZ10 is more cost-effective than switching S40 to generic A20 or R10.

Obesity is the most important risk factor for obstructive sleep apnea (OSA). However, although included in clinical guidelines, no randomized controlled studies have been performed on the effects of weight reduction on mild OSA.The aim of this prospective, randomized controlled parallel-group 1-year follow-up study was to determine whether a very low calorie diet (VLCD) with supervised lifestyle counseling could be an effective treatment for adults with mild OSA.Seventy-two consecutive overweight patients (body mass index, 28-40) with mild OSA were recruited. The intervention group (n = 35) completed the VLCD program with supervised lifestyle modification, and the control group (n = 37) received routine lifestyle counseling. The apnea-hypopnea index (AHI) was the main objectively measured outcome variable. Change in symptoms and the 15D-Quality of Life tool were used as subjective measurements.The lifestyle intervention was found to effectively reduce body weight (-10.7 +/- 6.5 kg; body mass index, -3.5 +/- 2.1 [mean +/- SD]). There was a statistically significant difference in the mean change in AHI between the study groups (P = 0.017). The adjusted odds ratio for having mild OSA was markedly lowered (odds ratio, 0.24 [95% confidence interval, 0.08-0.72]; P = 0.011) in the intervention group. All common symptoms related to OSA, and some features of 15D-Quality of Life improved after the lifestyle intervention. Changes in AHI were strongly associated with changes in weight and waist circumference.VLCD combined with active lifestyle counseling resulting in marked weight reduction is a feasible and effective treatment for the majority of patients with mild OSA, and the achieved beneficial outcomes are maintained at 1-year follow-up.