A systematic review of the indirect costs of schizophrenia in Europe.

Background: Schizophrenia is a chronic disease associated with significant and long-lasting effects on health, and it is also a social and financial burden, not only for patients but also for families, other caregivers, and the wider society. It is essential to conduct the assessment of indirect costs, to understand all the effects of the disease on society. Our aim is to gain a better understanding of the indirect costs of schizophrenia in Europe. Methods: We conducted a comprehensive systematic literature review covering EMBASE, Medline, and PsycINFO as well as reviewing Health Technology Assessment databases from different countries. We used a qualitative research synthesis for presenting information, as most of the studies were methodologically diverse, a quantitative analysis would have been impractical. Results: Indirect cost adjusted to inflation ranged vastly between studies included in the review from 119 Euros to 62, 034 Euros annually. The average proportion of indirect costs of total costs was 44%. Studies highlighted important cost drivers as age, gender, and disease severity, explaining the variation in costs between treatment and patient groups. Conclusions: Regardless of the methodological heterogeneity of the reviewed studies, there was an agreement about the significance of indirect costs of schizophrenia on the society. Considering the relatively high prevalence of schizophrenia in Europe, a need for more cost of illness studies especially from Central Eastern and Southern Europe is suggested.

Direct healthcare cost of schizophrenia - European overview.

PURPOSE: To provide an overview on the magnitude of the impact of schizophrenia on the healthcare system in Europe and to gain a better understanding on the most important factors influencing the variation of costs. METHODS: Studies reporting costs and healthcare utilization among patients with schizophrenia were searched in MEDLINE (via Scopus), EMBASE (via Scopus) and Cochrane Database of Systematic Reviews on 19th January 2017. RESULTS: Twenty-three studies, from the 1075 references initially identified, were included in this review. The annual cost per patient ranged from €533 in Ukraine to €13,704 in the Netherlands. Notably drug costs contributed to less than 25% of the direct healthcare cost per patient in every country, which might be explained by similar pharmaceutical prices among countries due to the reference pricing system applied in Europe. Inpatient costs were the largest component of health service costs in the majority of the countries. Despite methodological heterogeneity across studies, four major themes could be identified (age, severity of symptoms, continuation of treatment/persistence, hospitalization) that have substantial impact on the costs of schizophrenia. CONCLUSIONS: Schizophrenia represents a substantial cost for the healthcare system in Europe driven by the high cost per patient. Substantial savings could potentially be achieved by increasing investment in the following areas: (1) reducing the number of hospitalizations e.g. by increasing the efficiency of outpatient care; (2) working out interventions targeted at specific symptoms; (3) improving patient persistence and adherence in antipsychotic therapy.

Healthcare resource use in schizophrenia, EuroSC findings.

Background: It is unclear if the burden associated with schizophrenia is affected by the type and severity of patient's symptoms. Objective: This study aims to quantify healthcare resource use associated with different profiles of schizophrenia symptoms. Study design: Post-hoc analysis of data from a naturalistic follow-up study. Setting: Secondary psychiatric services in France, Germany and the UK. Patients: EuroSC cohort:, representative sample of 1,208 schizophrenia patients Main outcome measure: We classified patients into eight health states, according to the Lenert classification (HS1-HS8), and estimated 6-month healthcare resource use (outpatient and day clinic visits, and hospitalisations) across the health states. Results: Approximately half of the patients were classed as having mild symptoms (HS1), with around 20% experiencing moderate, predominantly negative symptoms (HS2). The remaining health states were represented by <10% of patients each. Very few patients experienced extremely severe symptoms (HS8). No health state was associated with excess utilisation across all resource types. In terms of outpatient visits, patients were estimated to see a psychiatrist most often (3.01-4.15 visits over 6 months). Hospital admission was needed in 11%(HS1) - 35%(HS8) of patients and inpatient stays were generally prolonged for all health states (39-57 days). The average number of inpatient days was highest for patients in HS8 (18.17 days), followed by patients with severe negative symptoms (HS4; 13.37 days). In other health states characterised by severe symptoms (HS5-HS7), the average number of inpatient days was approximately half of those seen for HS4 (6.09-7.66). Conclusion: While none of the symptom profiles was associated with excess resource usage, hospitalization days were highest for HS with severe, predominantly negative or extremely severe symptoms. Patients with predominantly negative, moderate or severe symptoms appeared to have a high number of psychologist visits - an interesting finding that may reflect a specific therapeutic approach to the treatment of these patients.

Variability of mammary blood flow in lactating Holstein-Friesian cows during the first twelve weeks of lactation.

The goals of the present study were to measure mammary blood flow volume (BFV) during the first 12 wk of lactation in dairy cows by using color Doppler sonography and to determine what affects the mammary blood flow. Forty cows were examined via color Doppler sonography on d 1, 7, 14, 28, 56, and 84 after parturition (d 0). The total BFV (BFV(total)) to the 4 mammary glands was calculated by measuring time-averaged maximum velocities (TAMV) and cross-sectional areas (A) of the left and right pudendoepigastric trunks via transrectal color Doppler sonography. Because there were no significant differences in A, TAMV, and BFV between the right and left pudendoepigastric trunks, the means of A and TAMV, and the BFV(total) of both trunks were used for calculations. The intraindividual and interindividual variability of repeated BFV measures quantified by intraclass correlation coefficients were 96 and 98%, respectively. The BFV(total) ranged from 19.9 to 27.9 L/min, with a mean of 22.3+/-4.9 L/min. Interindividual differences in BFV values were attributable to variations in A and TAMV. The interindividual variability of the BFV(total), which was determined using the coefficients of variation of the BFV(total) on individual days, ranged from 16 to 28%. All the cows had similar changes in the BFV(total) during the study. Changes in BFV(total) were not correlated with changes in the mean of A, but there was a good correlation between changes in BFV(total) and in the mean of TAMV (r=0.94). The BFV(total) was highest on d 1 of lactation, decreased 28% by d 7, and remained at this level until d 28. By d 56, the BFV(total) had increased by 15% compared with d 14 and by 10% compared with d 28. The BFV(total) on d 84 was significantly different from all other days except d 56. There were moderate correlations between daily milk yield and BFV on individual days (0.24

[Improving SNR (signal to noise ratio) in multichannel EEG recording]. / Verbesserung des SNR bei mehrkanaligen EEG-Ableitungen.

The main problem in measurements of the focal VEP (Visual Evoked Potential) is its weak SNR (Signal-to-Noise Ratio). The most common method for enhancement of the SNR is the stimulus synchronized averaging. For study of single responses other ways in SNR improvement are needed. In this contribution a new method based on space-time selective measurement is introduced, which can be interpreted as beaming a signal source. Since the anatomical structures of sources generating the focal VEP are known in general and if the electrode positions are of sufficient density over the visual cortex, a source beamer can be realized by controlling the channels' delays.

Human dendritic cells transfected with either RNA or DNA encoding influenza matrix protein M1 differ in their ability to stimulate cytotoxic T lymphocytes.

The use of tumor antigen loaded dendritic cells (DC) is one of the most promising approaches to induce a tumor specific immune response in vivo. Several strategies have been designed to load DC with tumor antigens. In this study, we investigated the delivery of in vitro transcribed RNA and plasmid DNA into monocyte-derived, ie non-proliferating human DC, using several nonviral transfection methods including electroporation and lipofection. Green fluorescent protein (GFP) was used as a reporter gene and influenza matrix protein 1 (M1) as a model antigen for HLA class I restricted antigen presentation. Using electroporation in combination with DNA or with RNA, up to 11% of DC were GFP-positive. Using liposomes as a vehicle for DNA transport up to 10% of the DC were GFP-positive. A significant increase in transfection efficacy, of up to 20%, was observed when GFP RNA was used in combination with liposomes. Importantly, the RNA transfected DC retained their typical morphological and immunophenotypical characteristics. In addition, DC transfected with M1 RNA were able to stimulate autologous peripheral M1-specific memory cytotoxic T lymphocytes (CTL), as well as M1-specific CTL clones. Furthermore, comparison of DNA-transfected DC with RNA-transfected DC revealed the latter to be far better stimulators of antigen-specific T cells. This RNA transfection technique consequently represents a very promising tool for future immunotherapy strategies.

Chromosomal aberrations in humans as genetic endpoints to assess the impact of pollution.

The chromosomal aberration assay with peripheral blood lymphocytes has been used routinely during the last three decades to survey exposure of humans to various genotoxic agents. A large number of biomonitoring studies are based on this genetic endpoint. A great deal of data exists on occupational, life-style or medical exposure situations but less evidence of the validity of the assay is available with regards to environmental exposure. In the present paper we report our investigations on the impact of pollution in two different populations using chromosomal aberrations in human peripheral blood lymphocytes as a biomarker of chronic exposure to heavy metals and dioxins/furans for a long period and as a biomarker of acute exposure to accidentally released vinyl chloride in the air. In order to study genotoxic effects (chromosomal aberrations) of heavy metals and dioxins/furans, 52 exposed individuals from a polluted area were compared to 51 matched controls from a distant non-industrialized area. A statistically significant increase was observed in the frequency of chromosomal aberrations in peripheral blood lymphocytes from the exposed population (1.90% aberrant cells vs. 1.11% for the controls). In the case of the vinyl chloride accident, chromosomal aberrations were analyzed in peripheral blood lymphocytes from 29 potentially exposed and 29 non-exposed individuals (matched controls). The exposed group showed a statistically significant increase in the frequency of aberrant cells (1.47% vs. 1.07% for the controls).

Mosaic tetrasomy 9p in a girl with multiple congenital anomalies: cytogenetic and molecular-cytogenetic studies.

We report on a 16-year-old girl with tetrasomy 9p mosaicism. Clinical investigations disclosed a malformation syndrome with craniofacial abnormalities, dysplasia of the right clavicle, short neck with cervical ribs, patella dislocation, Dandy-Walker malformation, mental retardation and blindness. Karyotype analysis of blood lymphocytes indicated an additional marker in the size of a C-group chromosome with a large heterochromatic block in 88% of the investigated metaphases. The origin and structure of this additional marker could not be determined by chromosome banding. Application of fluorescence in situ hybridisation and comparative genomic hybridisation identified the origin of the marker chromosome, demonstrating the effectiveness of molecular-cytogenetic investigations in the diagnosis of structural and numerical chromosome abnormalities.

Magnetic resonance perfusion imaging with gadolinium-DTPA. A quantitative approach for the kinetic analysis of first-pass residue curves.

RATIONALE AND OBJECTIVES: To present a mathematic approach for the analysis of first-pass gadolinium (Gd)-DTPA kinetics and to validate the numerical tools using simulated and measured kinetics. METHODS: In a capillary plasma filter, pulsatile flow was varied between 7.4 and 12.6 mL/second. After contrast bolus injection, the arterial input curve and the residue curve were recorded simultaneously. Signal intensity versus time curves were converted to concentration versus time curves. By deconvolution of these curves and tracer kinetic analysis, the mean transit time of the contrast medium through the organ model was calculated. RESULTS: A satisfactory correlation (r = 0.98) between the inverse of mean transit time and flow measured volumetrically was demonstrated. CONCLUSIONS: The kinetic analysis of first-pass curves in an organ model indicates that this approach might be useful for in vivo assessment of organ blood flow.

Isomeric N-methyl-7-deazaguanines: synthesis, structural assignment, and inhibitory activity on xanthine oxidase.

The N-methyl isomers of 2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (2a) have been synthesized regiospecifically and their structures assigned. The 3-methyl compound 3 was obtained by alkylation of the parent chromophore 2a with dimethyl sulfate, and the 1-methyl isomer 5b was obtained by condensation of ethyl 2-cyano-4,4-diethoxybutyrate with N-methylguanidine and subsequent cyclization. Methylation of 2-amino-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (7b), however, with methyl iodide in the presence of 50% NaOH, by phase-transfer techniques, followed by the replacement of halide by hydroxyl, yielded the 7-methyl compound 2b. The N-methyl isomers of 2a were all found to be inhibitors of xanthine oxidase from cow's milk. While the 3-methyl isomer 3 exhibits a Ki of 40 microM, the 7- and 1-isomers show Ki values of 4.5 and 3 microM, respectively.

[Staphylococcus epidermidis as a rare cause of sepsis]. / Staphylococcus epidermidis als seltene Ursache einer Sepsis.

Implanted synthetic materials have to be included into the differential diagnosis of sepsis. This paper reports on a case of sepsis caused by Staphylococcus epidermidis in connection with a Spitz-Holter shunt. The interval between the implantation and the recognition of the endoplastitis took 4 years. The attempt of an antibiotic sanitation had no results. The fitness for work could be restored by removal of the shunt and reimplantation.