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

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

Static and Dynamic Lung Volumes in Swimmers and Their Ventilatory Response to Maximal Exercise

Purpose While the static and dynamic lung volumes of active swimmers is often greater than the predicted volume of similarly active non-swimmers, little is known if their ventilatory response to exercise is also different. Methods Three groups of anthropometrically matched male adults were recruited, daily active swimmers (n = 15), daily active in fields sport (Rugby and Football) (n = 15), and recreationally active (n = 15). Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and maximal voluntary ventilation (MVV) was measured before and after exercise to volitional exhaustion. Results Swimmers had significantly larger FVC (6.2 ± 0.6 l, 109 ± 9% pred) than the other groups (5.6 ± 0.5 l, 106 ± 13% pred, 5.5 ± 0.8, 99% pred, the sportsmen and recreational groups, respectively). FEV1 and MVV were not different. While at peak exercise, all groups reached their ventilatory reserve (around 20%), the swimmers had a greater minute ventilation rate than the recreational group (146 ± 19 vs 120 ± 87 l/min), delivering this volume by breathing deeper and slower. Conclusions The swimmers utilised their larger static volumes (FVC) differently during exercise by meeting their ventilation volume through long and deep breaths

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

Addressing the double-burden of diabetes and tuberculosis : Lessons from Kyrgyzstan

Background: The incidence of diabetes and tuberculosis co-morbidity is rising, yet little work has been done to understand potential implications for health systems, healthcare providers and individuals. Kyrgyzstan is a priority country for tuberculosis control and has a 5% prevalence of diabetes in adults, with many health system challenges for both conditions. Methods: Patient exit interviews collected data on demographic and socio-economic characteristics, health spending and care seeking for people with diabetes, tuberculosis and both diabetes and tuberculosis. Qualitative data were collected through semi-structured interviews with healthcare workers involved in diabetes and tuberculosis care, to understand delivery of care and how providers view effectiveness of care. Results: The experience of co-affected individuals within the health system is different than those just with tuberculosis or diabetes. Co-affected patients do not receive more care and also have different care for their tuberculosis than people with only tuberculosis. Very high levels of catastrophic spending are found among all groups despite these two conditions being included in the Kyrgyz state benefit package especially for medicines. Conclusions: This study highlights that different patterns of service provision by disease group are found. Although Kyrgyzstan has often been cited as an example in terms of health reforms and developing Primary Health Care, this study highlights the challenge of managing conditions that are viewed as "too complicated" for non-specialists and the impact this has on costs and management of individuals

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

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

Meaningful life is possible with locked - In syndrome the personal account of a survivor

Locked-in syndrome (LIS) is a rare condition characterised by quadriplegia and anarthria and is usually caused by a bilateral ventral ischemic pontine lesion. Patients are normally fully conscious, but their only mode of communication is with vertical eye movements and/or blinking. Although the mortality rate is high, it has been shown that patients can survive for a significant period of time. Once an LIS patient becomes medically stable, given appropriate medical care, his or her life expectancy may be several decades. LIS patients may suffer appreciably if they are treated by hospital staff as nonresponsive. Medical professionals and lay people often assume that the quality of life of an LIS patient is so poor that it is not worth living. However, the reported overall quality of life of LIS patients is not significantly different from that of healthy subjects. In this case report, we describe a 60-year-old retired man living in a locked-in state due to a brainstem infarct. His personal account vividly reveals his inner thoughts, a great deal of suffering, and his ability to cope with his condition throughout seven years of illness. LIS patients' early referral to specialist rehabilitation services and strong social support from family greatly improves LIS patients'their quality of life. Even limited physical recovery can improve quality of life and enable LIS patients to become active members of society and return to living with family