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Aims Treatment of iron deficiency (ID) in patients with heart failure (HF) with intravenous iron substitution [ferric carboxymaltose (FCM)] has previously shown significant improvements in exercise capacity, New York Heart Association (NYHA) functional class, quality of life, and reduction of hospitalization. The aim of this study was to estimate the budget impact of FCM treatment for patients with HF and ID. Methods and results Individual patient data from four double-blind randomized controlled trials were pooled for this analysis. Expected outcomes were modelled for a treatment period of 1 year, using multivariate statistical methods. Associated unit costs were derived from claims data. Budget impact was calculated from the perspective of the Statutory Health Insurance. Multiple deterministic sensitivity analyses were performed. The annual budget impact for therapy with FCM vs. no-iron therapy was €2 735 505 and €2 695 474 for 1000 patients, respectively, resulting in additional annual costs of €40.03 for each treated patient. Main costs drivers are the FCM treatment cost and cost of hospitalizations due to HF worsening. FCM therapy compared with no-iron therapy resulted in reduced cost per 1000 patients: for reduced hospitalization due to HF worsening (52 vs. 129 hospitalizations amounting to €230 591 vs. €597 078), for reduced other medication (€1 611 007 vs. €1 679 908), fewer outpatient visits (€332 523 vs. €378 019), and home visits (€29 627 vs. €40 469). Sensitivity analyses showed robustness of the results. Conclusions Therapy with FCM has a minimal budget impact of €40 031 per 1000 patients per year. This budget impact translates into reduced and shorter hospitalizations and improved symptomatic status of the patients.

Rationale, aims and objectives Invasive pneumococcal diseases (IPD) are associated with substantial burden in adults (≥50 years). Moreover, adults with vascular, metabolic or respiratory diseases have been shown to have a 3–6 times higher risk of IPD when compared with their healthy controls. These persons at higher risk are likely to benefit most from pneumococcal vaccinations. The 13-valent pneumococcal conjugate vaccine (PCV13) was recently introduced to prevent the 13 most prevalent serotypes causing invasive pneumococcal disease in adults. The objective of this study was to estimate the expected 5-year economic impact of targeted PCV13 vaccination compared with no vaccination in Finnish adults (≥50 years) at moderate or high risk for IPD. Methods A budget impact model was developed to predict the impact of PCV13 vaccination in terms of the costs and IPD events avoided for years 2012–2016. Results Approximately 35% of the 2.2 million Finns over 50 years of age can be considered to be at moderate or high risk for IPD because of underlying chronic medical conditions. Vaccination of these people with PCV13 could provide an estimated net budget savings of about €218 million compared with the current no-vaccination situation over the next 5 years. Among the risk groups considered, the largest absolute net savings (€66.2 million) could be expected to be obtained by vaccinating people with heart disease, due to its high prevalence in the target population. Conclusion In Finland, the immunization with PCV13 vaccine, of adults (≥50 years) at moderate and high risk of IPD, is estimated to lead to substantial cost savings in the 5 years after vaccination.

Introduction Obstructive sleep apnoea (OSA) has been reported to associate with anxiety, but earlier observations are scarce and the role of the persistence of anxiety in this connection is unclear. Objectives To examine the associations between OSA and anxiety, and in particular clarify the observations regarding the role of the persistence of anxiety in this connection. Methods A total of 61 overweight patients with mild OSA participated in a 12-month lifestyle modification study and reported the presence of anxiety both at baseline and on 12-month follow up. They were divided into three groups (no anxiety, n = 25; past anxiety, n = 13; persistent anxiety, n = 23), and the degree of illness was assessed with the apnoea-hypopnea index (AHI). Results The persistence of anxiety was linearly associated with the AHI (P = 0.025), which was highest in individuals with persistent anxiety. The likelihood of belonging to the group with persistent anxiety increased 18% for each one-unit increase in the AHI in a model adjusted for age, gender and bodyfat % (odds ratio 1.18, 95% confidence interval 1.03–1.34, P = 0.014). Further adjustments for daytime sleepiness and the effect of participating in the lifestyle modification intervention did not alter this finding. Conclusion Our observations suggest that the persistence of anxiety is independently associated with elevated levels of sleep-disordered breathing and that lifestyle modification interventions with a focus on diet and exercise alone may not be sufficient to treat OSA in individuals with simultaneous persistent anxiety. Please cite this paper as: Lehto SM, Sahlman J, Soini EJ, Gylling H, Vanninen E, Seppa J, Viinamaki H and Tuomilehto H. The association between anxiety and the degree of illness in mild obstructive sleep apnoea. Clin Respir J 2012; 7: 197–203.

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.

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.

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.

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.

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.