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

Magnetic resonance findings and outcome in ten cats with traumatic spondylomyelopathy

In this retrospective study, the MR findings of ten cats with acute post-traumatic spondylomyelopathy were described and the most useful MR sequences were determined. Spinal cord injury (SCI), bone and muscle trauma were compared with the clinical outcome (recovery or euthanasia). The extension of spinal cord injury (SCI) was measured in vertebral body length (VBL). Of the ten cats, only five fully recovered. In the recovery group, no SCI (n=1) or SCI <1 VBL (n=4) were found. In the group of euthanized dogs, SCI > 2 VBLs (n=4) or spinal cord transection (n=1) were found. Lesions were best seen on T2WSE (spinal cord injury), STIR (soft tissue trauma) and T1WSE (bone injury). Low-field MR was therefore helpful to assess feline spinal trauma and may prove helpful to predict the clinical outcome, although a larger case series is needed. The authors suggest that protocols with low-field MR should include T1WSE, T2WSE and STIR sequences

The effects of detergent, sodium tripoly-phosphate and ethoxyled oleyl-cetyl alcohol on metabolic parameters of the fungus trichothecium roseum link

The degradation of detergents that are dispersed in water and soil partially depends on the metabolic activities of fungi. Among the fungi that have this ability, Deuteromycetes are particularly noted for their biochemical characteristics. Taking this into account, it was of interest to analyze the influence of detergent and its main compounds, ethoxyled oleylcetyl alcohol (AOC) and sodium tripoly-phosphate (TTP), on the metabolism of the fungus Trichothecium roseum. Our results revealed that both detergent and AOC had an inhibitory effect on the bioproduction of free organic acids, while TTP stimulated their production. Also, detergent inhibited the bioproduction of basic amino acids, with the exception of alanine. In addition, detergent applied at 1% concentration inhibited the bioproduction of proteins and the total biomass of the fungus, while AOC and TTP inhibited the production of proteins, but stimulatedl the production of Trichothecium

Heart rate variability before and after cycle exercise in relation to different body positions

The purpose of this study was to assess the effect of three different body positions on HRV measures following short-term submaximal exercise. Thirty young healthy males performed submaximal cycling for five minutes on three different occasions. Measures of HRV were obtained from 5-min R to R wave intervals before the exercise (baseline) and during the last five minutes of a 15 min recovery (post-exercise) in three different body positions (seated, supine, supine with elevated legs). Measures of the mean RR normal-to-normal intervals (RRNN), the standard deviation of normal-to-normal intervals (SDNN), the root mean square of successive differences (RMSSD) and the low-frequency (LF) and the high-frequency (HF) spectral power were analyzed. Post-exercise RRNN, RMSSD were significantly higher in the two supine positions (p 0.05). Post-exercise time domain measures of HRV (RRNN, SDNN, RMSSD) were significantly lower compared with baseline values (p < 0.01) regardless body position. Post-exercise ln LF and ln HF in all three positions remained significantly reduced during recovery compared to baseline values (p < 0.01). The present study suggests that 15 minutes following short-term submaximal exercise most of the time and frequency domain HRV measures have not returned to pre-exercise values. Modifications in autonomic cardiac regulation induced by body posture present at rest remained after exercise, but the post-exercise differences among the three positions did not resemble the ones established at res

BRICs Nations Growing Impact on the Global Health Sector

The most notable feature of the past five centuries of global economic history dating back from Colonial Age until the present accelerated globalization is the persistence of «North–South» division between the global rich and poor. This ground pattern has been falling apart over the last three decades with the rise of BRICs emerging economies (Brazil, Russia, India, China). The Chinese Belt and Road Initiative fosters further rapid growth and synergy among these large nations. This ambitious and historically unprecedented infrastructural project if successful can lead to a formation by 2049 of a huge common economic zone bringing opportunities for multilateral development to the BRICs. These profound changes have deep implications for the global health care sector. Previous research on health and pharmaceutical spending has clearly documented that low- and middle-income economies (LMICs), led by these emerging markets, have doubled their share in global health spending from roughly 20% up to approximately 40% in purchasing power parity terms. Alongside with these global developments, a decade ago, some of the leading Western academic centers, confirm new era of rising world’s geo-economic and geopolitical multipolarity. The world witnesses this process being accelerated today and seek deeper understanding how it will reflect on long term health and pharmaceutical expenditure trends, particularly in the leading BRICs emerging markets being a front runner of such evolution.The authors declare absence of conflict of interests

A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus

Generally, the second messenger bis-(3’-5’)-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiates a developmental program that culminates in formation of spore-filled fruiting bodies. We show that c-di-GMP accumulates at elevated levels during development and that this increase is essential for completion of development whereas excess c-di-GMP does not interfere with development. MXAN3735 (renamed DmxB) is identified as a diguanylate cyclase that only functions during development and is responsible for this increased c-di-GMP accumulation. DmxB synthesis is induced in response to starvation, thereby restricting DmxB activity to development. DmxB is essential for development and functions downstream of the Dif chemosensory system to stimulate exopolysaccharide accumulation by inducing transcription of a subset of the genes encoding proteins involved in exopolysaccharide synthesis. The developmental defects in the dmxB mutant are non-cell autonomous and rescued by co-development with a strain proficient in exopolysaccharide synthesis, suggesting reduced exopolysaccharide accumulation as the causative defect in this mutant. The NtrC-like transcriptional regulator EpsI/Nla24, which is required for exopolysaccharide accumulation, is identified as a c-diGMP receptor, and thus a putative target for DmxB generated c-di-GMP. Because DmxB can be—at least partially—functionally replaced by a heterologous diguanylate cyclase, these results altogether suggest a model in which a minimum threshold level of c-di-GMP is essential for the successful completion of multicellular development in M. xanthus

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations