Oncology monoclonal antibodies expenditure trends and reimbursement projections in the emerging Balkan market

Monoclonal antibodies applied in clinical oncology present a therapeutic promise for many patients with cancer. Nevertheless these expensive protocols are associated with extremely high acquisition and administration costs. The issue of societal affordability of such treatment options is particularly at stake among middle income European economies. Medicines Agency of Serbia issues regular annual reports on public expenditure on pharmaceuticals since 2004. According to these official data total public expenditure on drugs doubled from 2004-2012 (from € 339,279,304 to € 742,013,976). During the same nine years public expenditure on antineoplastic pharmaceuticals was rising at much faster pace, approximately five times from € 10,297,616 in 2004 to € 51,223,474 in 2012. Absolutely record growth belongs to the value of turnover of monoclonal antibodies indicated in diverse malignancies. These costs became almost twenty times higher in 2012 compared to 2004 (€ 19,687,454 towards € 1,033,313 in the past). National pharmaceutical expenditure trend projections in this country show strong recovery in 2012 after severe blow to the overall health care market imposed by the worldwide crisis. Universal health insurance coverage and sustainable health care financing provision will remain difficult issues for Balkan economies in years to come. Although monoclonal antibodies exhibit undisputed therapeutic efficiency in certain malignant disorders, cost-effectiveness estimates must be taken into consideration by policy makers deciding on reimbursement

Pharmaceutical expenditure changes in Serbia and Greece during the global economic recession

Aim: Clarity on health expenditures is essential for the timely identification of risks that jeopardize the democratic provision of health services and the credibility of health insurance systems. Furthermore, observing health outcomes with geographical scope is essential for making multilateral associations. This study aimed at conveying information on the variability of important economic parameters of the health sector of Serbia and Greece from 2007 to 2012, when the most serious financial crisis in the post-war economic history hit the global economy. Methods: Exchange rates, purchase-power-parities (PPP) and price indices were used for the bilateral review of health and pharmaceutical expenditure dynamics during 2007-2012. Prescription and dispensing changes were also studied taking into account the anatomical therapeutic chemical (ATC) structure of drugs consumed. Results: Greece was forced to cut down its total health care and pharmaceutical expenditure and mainly its out-of-pocket payments were more seriously affected by the recession. Surprisingly, emerging market of Serbia, although severely damaged by global recession, succeeded to maintain 19% growth of its per capita health expenditure and even 25% increase of its per capita spending on pharmaceuticals. Innovative pharmaceuticals showed an upward trend in both countries. Conclusions: These two countries might serve as an example of two distinct pathways of mature and emerging health care markets during financial constraints caused by global recession. Our findings show that producing disease-based feedback, in the long run, may empower the assessment of the return on investment on medical technology and healthcare systems’ cost-effectiveness

New Electronic Interface Circuits for Humidity Measurement Based on the Current Processing Technique

The paper describes a new electronic conditioning circuit based on the current-processing technique for accurate and reliable humidity measurement, without post-processing requirements. Pseudobrookite nanocrystalline (Fe2TiO5) thick film was used as capacitive humidity transducer in the proposed design. The interface integrated circuit was realized in TSMC 0.18 mu m CMOS technology, but commercial devices were used for practical realization. The sensing principle of the sensor was obtained by converting the information on environment humidity into a frequency variable square-wave electric current signal. The proposed solution features high linearity, insensitivity to temperature, as well as low power consumption. The sensor has a linear function with relative humidity in the range of Relative Humidity (RH) 30-90 %, error below 1.5 %, and sensitivity 8.3 x 10(14) Hz/F evaluated over the full range of changes. A fast recovery without the need of any refreshing methods was observed with a change in RH. The total power dissipation of readout circuitry was 1 mW

Crystal growth of K2TiGe3O9 in the glass

The kinetics and mechanism of isothermal crystal growth of K2TiGe3O9 from a glass of the same stoichiometric composition were studied. The crystal growth rate U = 1 x 10-11-1.27 x 10-10 m s-1 was experimentally determined in the temperature interval of t = 540-600°C. In the range of high undercooling, Δt=435-375°C, spherical crystals growing at (374 ± 19) kJ mol-1 was observed

Elevated serum uric acid reduce heart damage in patients undergoing open-heart surgery

Objectives: Peroxynitrite is species claimed to propagate ischemia/reperfusion damage. In this report levels of serum uric acid (UA), a peroxynitrite scavenger, are compared with creatine phosphokinase (CPK) in male patients before and after open-heart surgery in order to asses if increased levels of UA may protect heart from biochemical damage induced by peroxynitrite during the coronary by-pass grafting (CABG) intervention. Methods: 45 male patients (16 carvedilol pretreated (6.25 mg/ daily, during 6 weeks before surgery, mean age 55.3±1.7 years, range 50-71) and 29 patients without carvedilol pretreatment (mean age 58.3±1.4 years, range 47-73) underwent elective CABG were examined. Study inclusion criteria were CABG performed on two and more coronary-vessels with aortic crossclamp during 30-40 minutes. For assessment of patients objective health status before operations Euro- SCORE were used. Serum uric acid (UA) levels and creatine phosphokinase (CPK) were measured spectrophotometricaly by using a quantitative enzymatic assay. Results: Carvedilol pretreated patients had higher amount of serum UA (p<0.05) comparing to non-treated patients. During the surgical procedure patients are subjected to temporary ischemia due to transfer from corporeal to extracorporeal circulation. In this period of time the amount of UA decreased in carvedilol pretreated group (406±46 (t1) vs. 300±22 mmol/L (t2)) to the level of non-treated patients (328±14 (t1) vs. 322±18 mmol/L. Carvedilol pretreated patients and non-treated patients had the same level of CPK at the beginning of the surgical procedure (t1) (78±6 vs. 83+13 U/L) but lower increase (p<0.05) in CPK activity in carvedilol pretreated patients in respect to nontreated patients (338±46 vs. 644±103 U/L) at the end of procedure (t2). Such results suggest that open heart surgery led to elevated CPK levels, but this effect was less pronounced in patients with higher level of UA. Conclusions: Our results suggest possible role of UA in the protection from reperfusion injury. Increase of UA before surgery may be beneficial factor during CABG procedure in patients treated with carvedilol by decreasing level of peroxynitrite as one of molecular causes of reperfusion injury. Our results showed influence of UA on CPK levels at the end of surgical procedure, indicating that increased levels of UA may protect heart from biochemical damage induced by peroxynitrite during the CABG intervention.Ciljevi: Postoji mišljenje da Peroxynitrite širi - pojačava oštećenja koja potiču od ishemije /reperfuzije. U ovom radu poređen je nivo mokraćne kiseline (UA) u serumu, sakupljača peroksinitrita, sa nivoom kreatin fosfokinaze (CPK) kod muškaraca pre i nakon operacije na otvorenom srcu, a u cilju procene da li povećani nivoi UA mogu služiti kao zaštita od biohemijskih oštećenja izazvanih upotrebom peroksinitrita tokom hirurške CABG intervencije. Metode: Ispitivano je 45 bolesnika (16 je prethodno primalo karvedilol - 6.25 mg dnevno, tokom 6 nedelja pre operacije, prosečne starosti 55.3±1.7 godina, 55-71, i 29 bolesnika koji nisu primali karvedilol, prosečne starosti 58.3±1.4 godina, 47-73) koji su bili podvrgnuti CABG hirurškoj intervenciji. Kriterijumi za uključenje u studiju su bili izvođenje CABG na dva ili više sudova sa klemovanjem aorte u trajanju od 30 - 40 minuta. Za procenu zdravstvenog stanja bolesnika pre operacije korišćen je EuroSCORE. Nivoi UA i kreatin fosfokinaze (CPK) u serumu su mereni uz pomoć spektrofotometrije korišćenjem kvantitativnog enzimskog eseja. Rezultati: U bolesnika koji su prethodno primali karvedilol uočeni su uvećani nivoi UA u serumu (p< 0.05) u poređenju sa bolesnicima koji nisu primali pomenuti lek. Tokom hirurške procedure bolesnici su podvrgnuti privremenoj ishemiji zbog prebacivanja sa telesnog na vantelesni krvotok. U tom periodu vrednosti UA su snižene u bolesnika koji su prethodno primali karvedilol (406+46 (t1) naspram 300±22 mol/L (t2)) bolesnika koji ga nisu primali (328±14 (t1) naspram 322±18 mol/L). Bolesnici koji su primali karvedilol i oni koji nisu imali su isti nivo CPK na početku hirurške procedure (t1) (78±6 naspram 83±13 U/L) ali je na kraju procedure uočen niži porast aktivnosti CPK (p<0.05) u bolesnika koji su primali karvedilol u poređenju sa bolesnicima koji nisu (338±46 prema 644±103 U/L) (t2). Ovakvi rezultati sugerišu da intervencija na otvorenom srcu dovodi do povećanja nivoa CPK, ali je taj efekat bio manje izražen u bolesnika koji su imali viši nivo UA. Zaključak: Naši rezultati ukazuju na moguću pozitivnu ulogu mokraćne kiseline u zaštiti od oštećenja koja može prouzrokovati reperfuzija. Povećanje nivoa UA pre operacije može predstavljati koristan faktor tokom CABG procedure u bolesnika koji su primali karvedilol, jer snižava nivo peroksinitrita kao jedan od uzroka oštećenja od reperfuzije. Naši rezultati pokazuju uticaj UA na nivoe CPK pri kraju hirurške intervencije, što pak ukazuje na to da uvećani nivoi UA mogu štititi srce od biohemijskih oštećenja izazvana peroksinitritom tokom CABG intervencije

Shungite - a Russian mineral: possible application as a microwave absorber

The paper presents results of investigation of the influence of mechanical activation of shungite, a Russian natural mineral rich in silica and carbon, on its sintering behavior. The mechanical activation of the starting powder was performed in a high-energy ball mill in time intervals from 0 to 480 minutes. The phase composition of the starting mixtures and sintered samples was analyzed by the X-ray diffraction method. The scanning electron microscopy was performed in order to determine changes in the microstructure. Sintering was performed at various temperatures for 2 h, in an Ar and vacuum atmosphere. Dielectric properties of the sintered samples were measured in the frequency range from 1 to 500 MHz. The obtained results indicate that sintered shungite powder is a good candidate for applications as an absorber of electromagnetic waves in microwave engineering

Activity of antioxidative defense enzymes in the blood of patients with liver echinococcosis

Background/Aim. Chronic echinococcocal disease is the parasite human disease caused by the penetration of larval (asexual) stages of the canine tapeworm (Echinococcus granulosus) in the liver of humans. After the penetration of the parasite, the host organism react by activating complement- depending immune response. The aim of this study was to elucidate the influence of larval form of Echinococcus granulosus in the liver on the activity of antioxidative defense enzymes in the blood of patients before and after the surgical intervention. Methods. We investigated the activity of antioxidative defense enzymes: copper/zinc containing superoxide dismutase (CuZn SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and glutathione-S-transferase (GST) in the blood of patients before and after the surgical intervention in respect to the controls, clinically healthy persons. Results. Our results showed that the activity of the GSH-Px was significantly decreased in the plasma of the patients with echinocococal disease before the surgery in respect to the controls. The activity of GST was significantly higher in the blood of the patients after the surgery in comparison to the controls. Conclusion. Chronic liver echinoccocal disease caused significant changes of some antioxidative defense enzymes, first of all Se-dependent enzyme GSH-Px, which could be a suitabile biomarker in the biochemical evaluation of the disease. This work represents a first comprehensive study of the activity of antioxidative defense enzymes in cronic liver echinococcocosis in the patients before and after the surgical intervention in respect to the clinically healthy persons

Da li holesterol vezan za hemoglobin utiče na anti-oksidativni enzimski sistem u humanim eritrocitima?

In a previous study, it was shown that the lipid fraction, which is occasionally observed in red blood cell hemolysates, represents cholesterol (Ch) associated with phospholipid firmly bound to haemoglobin (termed Hb-Ch). The current study was conducted to investigate whether Hb-Ch could affect the primary anti-oxidant enzyme defence system in human erythrocytes. Sixty healthy volunteers were used for the current study. Group 1 consisted of 28 subjects without or with a low level of Hb-Ch. Group 2 comprised 32 subjects with a considerably higher level of Hb-Ch. The activities of erythrocyte superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, as well as the content of methaemoglobin (metHb) were measured in both groups. The results indicated that the amount of Hb-Ch neither influenced the activities of the erythrocyte anti-oxidant enzymes nor altered the level of metHb. However, a higher amount of Hb-Ch changed the correlations in the part of the anti-oxidant defence system relating to glutathione, suggesting increased peroxidative pressure from plasma lipids. Group 2 also had significantly increased concentrations of total plasma Ch and triglycerides. Together, these facts are strong indications that the anti-oxidant defence system in human erythrocytes finely retunes its composition according to plasma oxidative demands.U prethodnom radu pokazano je da lipidna frakcija koja se javlja u hemolizatu zdravih ljudi predstavlja holesterol (asosovan sa fosfolipidima) čvrsto vezan za hemoglobin (Hb-Ch). U ovom radu ispitivan je uticaj Hb-Ch na anti-oksidativni enzimski sistem u humanim eritrocitima. Određena je aktivnost superoksid-dizmutaze, katalaze, glutation-peroksidaze i glutation-reduktaze, kao i sadržaj met-hemoglobina (metHb) u eritrocitima 60 ljudi, podeljenih u dve grupe na osnovu količine Hb-Ch. Rezultati pokazuju da količina prisutnog Hb-Ch ne menja aktivnost merenih enzima, niti nivo metHb. Međutim, u grupi ispitanika sa povećanim sadržajem Hb-Ch zapažene su korelativne promene u delu anti-oksidativnog enzimskog sistema povezanog sa glutationom. U istoj grupi detektovane su i veće koncentracije ukupnog holesterola i triglicerida u plazmi, što zajedno ukazuje na povećani peroksidativni pritisak iz plazme. Ovi rezultati ukazuju da odbrambeni anti-oksidativni enzimski sistem u humanim eritrocitima prilagođava svoju organizaciju prema zahtevima iz svog okruženja.

Ventilation inhibits sympathetic action potential recruitment even during severe chemoreflex stress

© 2017 the American Physiological Society. This study investigated the influence of ventilation on sympathetic action potential (AP) discharge patterns during varying levels of high chemoreflex stress. In seven trained breath-hold divers (age 33 ± 12 yr), we measured muscle sympathetic nerve activity (MSNA) at baseline, during preparatory rebreathing (RBR), and during 1) functional residual capacity apnea (FRCApnea) and 2) continued RBR. Data from RBR were analyzed at matched (i.e., to FRCApnea) hemoglobin saturation (HbSat) levels (RBRMatched) or more severe levels (RBREnd). A third protocol compared alternating periods (30 s) of FRC and RBR (FRC-RBRALT). Subjects continued each protocol until 85% volitional tolerance. AP patterns in MSNA (i.e., providing the true neural content of each sympathetic burst) were studied using wavelet-based methodology. First, for similar levels of chemoreflex stress (both HbSat: 71 ± 6%; P = NS), RBRMatched was associated with reduced AP frequency and APs per burst compared with FRCApnea (both P _ 0.001). When APs were binned according to peak-to-peak amplitude (i.e., into clusters), total AP clusters increased during FRCApnea (+10 ± 2; P \u3c 0.001) but not during RBRMatched (+1 ± 2; P = NS). Second, despite more severe chemoreflex stress during RBREnd (Hb-Sat: 56 ± 13 vs. 71 ± 6%; P = 0.001), RBREnd was associated with a restrained increase in the APs per burst (FRCApnea: +18 ± 7; RBREnd: +11 ± 5) and total AP clusters (FRCApnea: +10 ± 2; RBREnd: +6 ± 4) (both P \u3c 0.01). During FRC-RBRALT, all periods of FRC elicited sympathetic AP recruitment (all P \u3c 0.001), whereas all periods of RBR were associated with complete withdrawal of AP recruitment (all P = NS). Presently, we demonstrate that ventilation per se restrains and/or inhibits sympathetic axonal recruitment during high, and even extreme, chemoreflex stress. NEW & NOTEWORTHY The current study demonstrates that the sympathetic neural recruitment patterns observed during chemoreflex activation induced by rebreathing or apnea are restrained and/or inhibited by the act of ventilation per se, despite similar, or even greater, levels of severe chemoreflex stress. Therefore, ventilation modulates not only the timing of sympathetic bursts but also the within-burst axonal recruitment normally observed during progressive chemoreflex stress