Use of Surrogate end points in HTA

The different actors involved in health system decision-making and regulation have to deal with the question which are valid parameters to assess the health value of health technologies

Deconvolution of the relaxations associated with local and segmental motions in poly(methacrylate)s containing dichlorinated benzyl moieties in the ester residue

9 pages, 15 figures, 1 scheme.The relaxation behavior of poly(2,3-dichlorobenzyl methacrylate) is studied by broadband dielectric spectroscopy in the frequency range of 10–1–109 Hz and temperature interval of 303–423 K. The isotherms representing the dielectric loss of the glassy polymer in the frequency domain present a single absorption, called B process. At temperatures close to Tg, the dynamical (alfa) relaxation already overlaps with the (beta) process, the degree of overlapping increasing with temperature. The deconvolution of the (alfa) and (beta) relaxations is facilitated using the retardation spectra calculated from the isotherms utilizing linear programming regularization parameter techniques. The temperature dependence of the (beta) relaxation presents a crossover associated with a change in activation energy of the local processes. The distance between the (alfa) and (beta) peaks, expressed as log(fmax;/fmax;) where fmax is the frequency at the peak maximum, follows Arrhenius behavior in the temperature range of 310–384 K. Above 384 K, the distance between the peaks remains nearly constant and, as a result, the (alfa) onset temperature exhibited for many polymers is not reached in this system. The fraction of relaxation carried out through the (alfa) process, without (beta) assistance, is larger than 60% in the temperature range of 310–384 K where the so-called Williams ansatz holds.This work was financially suported by the DGCYT and CAM through Grant Nos. MAT2002-04042-C02 and GR/ MAT/0723/2004. Two of the authors (L.G. and D.R.) thank the FONDECYT for partial financial support through Grant Nos. 21050956 and 1050962, respectively.Peer reviewe

Viraneler

Ercüment Ekrem'in Dersaadet ve Diken'de tefrika edilen Viraneler adlı romanıDersaadet'te tefrika edilirken süreli yayın kapandığından tefrika yarım kalmıştır. Devamı Diken gazetesinde yayımlanmıştır.Diken'de tefrika edilirken roman yarım kalmıştır. Kopuk adıyla İleri gazetesinde tefrika edilmiştir.Telif hakları nedeniyle romanın tam metni verilememiştir

Dose-escalation using intensity-modulated radiotherapy for prostate cancer - evaluation of quality of life with and without 18F-choline PET-CT detected simultaneous integrated boost

<p>Abstract</p> <p>Background</p> <p>In comparison to the conventional whole-prostate dose escalation, an integrated boost to the macroscopic malignant lesion might potentially improve tumor control rates without increasing toxicity. Quality of life after radiotherapy (RT) with vs. without ¹⁸F-choline PET-CT detected simultaneous integrated boost (SIB) was prospectively evaluated in this study.</p> <p>Methods</p> <p>Whole body image acquisition in supine patient position followed 1 h after injection of 178-355MBq ¹⁸F-choline. SIB was defined by a tumor-to-background uptake value ratio > 2 (GTV_PET). A dose of 76Gy was prescribed to the prostate (PTV_prostate) in 2Gy fractions, with or without SIB up to 80Gy. Patients treated with (n = 46) vs. without (n = 21) SIB were surveyed prospectively before (A), at the last day of RT (B) and a median time of two (C) and 19 month (D) after RT to compare QoL changes applying a validated questionnaire (EPIC - expanded prostate cancer index composite).</p> <p>Results</p> <p>With a median cut-off standard uptake value (SUV) of 3, a median GTV_PETof 4.0 cm³and PTV_boost(GTV_PETwith margins) of 17.3 cm³was defined. No significant differences were found for patients treated with vs. without SIB regarding urinary and bowel QoL changes at times B, C and D (mean differences ≤3 points for all comparisons). Significantly decreasing acute urinary and bowel score changes (mean changes > 5 points in comparison to baseline level at time A) were found for patients with and without SIB. However, long-term urinary and bowel QoL (time D) did not differ relative to baseline levels - with mean urinary and bowel function score changes < 3 points in both groups (median changes = 0 points). Only sexual function scores decreased significantly (> 5 points) at time D.</p> <p>Conclusions</p> <p>Treatment planning with ¹⁸F-choline PET-CT allows a dose escalation to a macroscopic intraprostatic lesion without significantly increasing toxicity.</p

Quantitative analysis of residual protein contamination of podiatry instruments reprocessed through local and central decontamination units

&lt;p&gt;Background: The cleaning stage of the instrument decontamination process has come under increased scrutiny due to the increasing complexity of surgical instruments and the adverse affects of residual protein contamination on surgical instruments. Instruments used in the podiatry field have a complex surface topography and are exposed to a wide range of biological contamination. Currently, podiatry instruments are reprocessed locally within surgeries while national strategies are favouring a move toward reprocessing in central facilities. The aim of this study was to determine the efficacy of local and central reprocessing on podiatry instruments by measuring residual protein contamination of instruments reprocessed by both methods. Methods&lt;/p&gt; &lt;p&gt;The residual protein of 189 instruments reprocessed centrally and 189 instruments reprocessed locally was determined using a fluorescent assay based on the reaction of proteins with o-phthaldialdehyde/sodium 2-mercaptoethanesulfonate.&lt;/p&gt; &lt;p&gt;Results: Residual protein was detected on 72% (n = 136) of instruments reprocessed centrally and 90% (n = 170) of instruments reprocessed locally. Significantly less protein (p &#60; 0.001) was recovered from instruments reprocessed centrally (median 20.62 μg, range 0 - 5705 μg) than local reprocessing (median 111.9 μg, range 0 - 6344 μg).&lt;/p&gt; &lt;p&gt;Conclusions: Overall, the results show the superiority of central reprocessing for complex podiatry instruments when protein contamination is considered, though no significant difference was found in residual protein between local decontamination unit and central decontamination unit processes for Blacks files. Further research is needed to undertake qualitative identification of protein contamination to identify any cross contamination risks and a standard for acceptable residual protein contamination applicable to different instruments and specialities should be considered as a matter of urgency.&lt;/p&gt

Gaining Greater Insight into HCV Emergence in HIV-Infected Men Who Have Sex with Men: The HEPAIG Study

OBJECTIVES: The HEPAIG study was conducted to better understand Hepatitis C virus (HCV) transmission among human immuno-deficiency (HIV)-infected men who have sex with men (MSM) and assess incidence of HCV infection among this population in France. METHODS AND RESULTS: Acute HCV infection defined by anti-HCV or HCV ribonucleic acid (RNA) positivity within one year of documented anti-HCV negativity was notified among HIV-infected MSM followed up in HIV/AIDS clinics from a nationwide sampling frame. HIV and HCV infection characteristics, HCV potential exposures and sexual behaviour were collected by the physicians and via self-administered questionnaires. Phylogenetic analysis of the HCV-NS5B region was conducted. HCV incidence was 48/10 000 [95% Confidence Interval (CI):43-54] and 36/10 000 [95% CI: 30-42] in 2006 and 2007, respectively. Among the 80 men enrolled (median age: 40 years), 55% were HIV-diagnosed before 2000, 56% had at least one sexually transmitted infection in the year before HCV diagnosis; 55% were HCV-infected with genotype 4 (15 men in one 4d-cluster), 32.5% with genotype 1 (three 1a-clusters); five men were HCV re-infected; in the six-month preceding HCV diagnosis, 92% reported having casual sexual partners sought online (75.5%) and at sex venues (79%), unprotected anal sex (90%) and fisting (65%); using recreational drugs (62%) and bleeding during sex (55%). CONCLUSIONS: This study emphasizes the role of multiple unprotected sexual practices and recreational drugs use during sex in the HCV emergence in HIV-infected MSM. It becomes essential to adapt prevention strategies and inform HIV-infected MSM with recent acute HCV infection on risk of re-infection and on risk-reduction strategies

Occurrence of genes of putative fibrinogen binding proteins and hemolysins, as well as of their phenotypic correlates in isolates of S. lugdunensis of different origins

<p>Abstract</p> <p>Background</p> <p><it>Staphylococcus lugdunensis </it>is an important human pathogen that causes potentially fatal endocarditis, osteomyelitis and skin and soft tissue infections similar to diseases caused by <it>Staphylococcus aureus</it>. Nevertheless, in contrast to <it>S. aureus</it>, data on pathogenicity factors of <it>S. lugdunensis </it>is scarce. Two adhesins, a fibrinogen and a von Willebrand factor binding protein, and a <it>S. lugdunensis </it>synergistic hemolysin (SLUSH) have been previously described. Moreover, the newly sequenced genome of <it>S. lugdunensis </it>revealed genes of other putative fibrinogen binding adhesins and hemolysins. The aim of this study was to gain more insight into the occurrence of genes likely coding for fibrinogen binding adhesins and hemolysins using clinical strains of <it>S. lugdunensis</it>.</p> <p>Findings</p> <p>Most of the putative adhesin genes and hemolysin genes investigated in this study were highly prevalent, except for the SLUSH gene cluster. In contrast to previous reports, binding to fibrinogen was detected in 29.3% of the <it>S. lugdunensis </it>strains. In most strains, hemolysis on blood agar plates was weak after 24 h and distinct after 48 h of incubation. The fibrinogen binding and hemolysis phenotypes were also independent of the type of clinical specimen, from which the isolates were obtained.</p> <p>Conclusion</p> <p>In this study we described a pyrrolidonyl arylamidase negative <it>S. lugdunensis </it>isolate. Our data indicate that a matrix-assisted laser desorption ionisation time-of-flight MS-based identification of <it>S. lugdunensis </it>or species-specific PCR's should be performed in favour of pyrrolidonyl arylamidase testing. In contrast to the high occurrence of putative fibrinogen binding protein genes, 29.3% of the <it>S. lugdunensis </it>strains bound to fibrinogen. Putative hemolysin genes were also prevalent in most of the <it>S. lugdunensis </it>strains, irrespective of their hemolysis activity on Columbia blood agar plates. Similar to a previous report, hemolysis after 48 h of incubation is also indicative for <it>S. lugdunensis</it>. The SLUSH gene cluster was detected in an estimated 50% of the strains, indicating that this locus is different or non-prevalent in many strains.</p