Modeling healthcare quality: life expectancy SURS in the G7 countries and Korea

In this study I have made efforts towards investigating healthcare in two arenas. First, can a model with life expectancy as a proxy for healthcare quality be used to objectify the study of efficiency in the G7 countries and Korea? Table 1 and the results section have illuminated many factor variables which vary between countries and characterize the environments in which different healthcare systems have developed. The analysis also illuminates an inherent structural difference in the mechanism of delivering healthcare throughout the developed world. Secondly, can these aggregate data be used to show us anything new about the studies performed by Peter Zweifel and Friedrich Breyer? Did the SISYPHUS Syndrome disappear in the early 1990s as Zweifel suggested in 2002? No, in Table 2 I have demonstrated through SURS that over the time period 1990-2009 there are clear statistically significant SISYPH variables in at least Canada, Germany, Korea, and Britain. Lastly, can I confirm Breyer’s model of HCE in Germany and can it be useful in other countries? Yes to extent possible the methodologies were replicated in a SURS fashion in an effort to simultaneously test and examine different variables in different countries. I was unable to confirm the results of Breyer in his 2011 examination of the sickness fund members for Germany. However, I was able to offer primitive characterizations of the other G7 countries and Korea and how their HCE move.healthcare expenditures ; healthcare factor variables ; sisyphus syndrome

Modeling healthcare quality: life expectancy SURS in the G7 countries and Korea

In this study I have made efforts towards investigating healthcare in two arenas. First, can a model with life expectancy as a proxy for healthcare quality be used to objectify the study of efficiency in the G7 countries and Korea? Table 1 and the results section have illuminated many factor variables which vary between countries and characterize the environments in which different healthcare systems have developed. The analysis also illuminates an inherent structural difference in the mechanism of delivering healthcare throughout the developed world. Secondly, can these aggregate data be used to show us anything new about the studies performed by Peter Zweifel and Friedrich Breyer? Did the SISYPHUS Syndrome disappear in the early 1990s as Zweifel suggested in 2002? No, in Table 2 I have demonstrated through SURS that over the time period 1990-2009 there are clear statistically significant SISYPH variables in at least Canada, Germany, Korea, and Britain. Lastly, can I confirm Breyer’s model of HCE in Germany and can it be useful in other countries? Yes to extent possible the methodologies were replicated in a SURS fashion in an effort to simultaneously test and examine different variables in different countries. I was unable to confirm the results of Breyer in his 2011 examination of the sickness fund members for Germany. However, I was able to offer primitive characterizations of the other G7 countries and Korea and how their HCE move

Modeling healthcare quality: life expectancy SURS in the G7 countries and Korea

In this study I have made efforts towards investigating healthcare in two arenas. First, can a model with life expectancy as a proxy for healthcare quality be used to objectify the study of efficiency in the G7 countries and Korea? Table 1 and the results section have illuminated many factor variables which vary between countries and characterize the environments in which different healthcare systems have developed. The analysis also illuminates an inherent structural difference in the mechanism of delivering healthcare throughout the developed world. Secondly, can these aggregate data be used to show us anything new about the studies performed by Peter Zweifel and Friedrich Breyer? Did the SISYPHUS Syndrome disappear in the early 1990s as Zweifel suggested in 2002? No, in Table 2 I have demonstrated through SURS that over the time period 1990-2009 there are clear statistically significant SISYPH variables in at least Canada, Germany, Korea, and Britain. Lastly, can I confirm Breyer’s model of HCE in Germany and can it be useful in other countries? Yes to extent possible the methodologies were replicated in a SURS fashion in an effort to simultaneously test and examine different variables in different countries. I was unable to confirm the results of Breyer in his 2011 examination of the sickness fund members for Germany. However, I was able to offer primitive characterizations of the other G7 countries and Korea and how their HCE move

Complex pattern of interaction between in utero hypoxia-ischemia and intra-amniotic inflammation disrupts brain development and motor function

Background: Infants born preterm commonly suffer from a combination of hypoxia-ischemia (HI) and infectious perinatal inflammatory insults that lead to cerebral palsy, cognitive delay, behavioral issues and epilepsy. Using a novel rat model of combined late gestation HI and lipopolysaccharide (LPS)-induced inflammation, we tested our hypothesis that inflammation from HI and LPS differentially affects gliosis, white matter development and motor impairment during the first postnatal month. Methods: Pregnant rats underwent laparotomy on embryonic day 18 and transient systemic HI (TSHI) and/or intra-amniotic LPS injection. Shams received laparotomy and anesthesia only. Pups were born at term. Immunohistochemistry with stereological estimates was performed to assess regional glial loads, and western blots were performed for protein expression. Erythropoietin ligand and receptor levels were quantified using quantitative PCR. Digigait analysis detected gait deficits. Statistical analysis was performed with one-way analysis of variance and post-hoc Bonferonni correction. Results: Microglial and astroglial immunolabeling are elevated in TSHI + LPS fimbria at postnatal day 2 compared to sham (both P < 0.03). At postnatal day 15, myelin basic protein expression is reduced by 31% in TSHI + LPS pups compared to shams (P < 0.05). By postnatal day 28, white matter injury shifts from the acute injury pattern to a chronic injury pattern in TSHI pups only. Both myelin basic protein expression (P < 0.01) and the phosphoneurofilament/neurofilament ratio, a marker of axonal dysfunction, are reduced in postnatal day 28 TSHI pups (P < 0.001). Erythropoietin ligand to receptor ratios differ between brains exposed to TSHI and LPS. Gait analyses reveal that all groups (TSHI, LPS and TSHI + LPS) are ataxic with deficits in stride, paw placement, gait consistency and coordination (all P < 0.001). Conclusions: Prenatal TSHI and TSHI + LPS lead to different patterns of injury with respect to myelination, axon integrity and gait deficits. Dual injury leads to acute alterations in glial response and cellular inflammation, while TSHI alone causes more prominent chronic white matter and axonal injury. Both injuries cause significant gait deficits. Further study will contribute to stratification of injury mechanisms in preterm infants, and guide the use of promising therapeutic interventions

Prenatal Hypoxia–Ischemia Induces Abnormalities in CA3 Microstructure, Potassium Chloride Co-Transporter 2 Expression and Inhibitory Tone

Infants who suffer perinatal brain injury, including those with encephalopathy of prematurity, are prone to chronic neurological deficits, including epilepsy, cognitive impairment, and behavioral problems, such as anxiety, inattention, and poor social interaction. These deficits, especially in combination, pose the greatest hindrance to these children becoming independent adults. Cerebral function depends on adequate development of essential inhibitory neural circuits and the appropriate amount of excitation and inhibition at specific stages of maturation. Early neuronal synaptic responses to γ-amino butyric acid (GABA) are initially excitatory. During the early postnatal period, GABAAR responses switch to inhibitory with the upregulation of potassium-chloride co-transporter KCC2. With extrusion of chloride by KCC2, the Cl− reversal potential shifts and GABA and glycine responses become inhibitory. We hypothesized that prenatal hypoxic–ischemic brain injury chronically impairs the developmental upregulation of KCC2 that is essential for cerebral circuit formation. Following late gestation hypoxia–ischemia (HI), diffusion tensor imaging in juvenile rats shows poor microstructural integrity in the hippocampal CA3 subfield, with reduced fractional anisotropy and elevated radial diffusivity. The loss of microstructure correlates with early reduced KCC2 expression on NeuN-positive pyramidal neurons, and decreased monomeric and oligomeric KCC2 protein expression in the CA3 subfield. Together with decreased inhibitory post-synaptic currents during a critical window of development, we document for the first time that prenatal transient systemic HI in rats impairs hippocampal CA3 inhibitory tone. Failure of timely development of inhibitory tone likely contributes to a lower seizure threshold and impaired cognitive function in children who suffer perinatal brain injury

A Paradigm Shift on the Question of B Cells in Transplantation? Recent Insights on Regulating the Alloresponse

B lymphocytes contribute to acute and chronic allograft rejection through their production of donor-specific antibodies (DSAs). In addition, B cells present allopeptides bound to self-MHC class II molecules and provide costimulation signals to T cells, which are essential to their activation and differentiation into memory T cells. On the other hand, both in laboratory rodents and patients, the concept of effector T cell regulation by B cells is gaining traction in the field of transplantation. Specifically, clinical trials using anti-CD20 monoclonal antibodies to deplete B cells and reverse DSA had a deleterious effect on rates of acute cellular rejection; a peculiar finding that calls into question a central paradigm in transplantation. Additional work in humans has characterized IL-10-producing B cells (IgM memory and transitional B cells), which suppress the proliferation and inflammatory cytokine productions of effector T cells in vitro. Understanding the mechanisms of regulating the alloresponse is critical if we are to achieve operational tolerance across transplantation. This review will focus on recent evidence in murine and human transplantation with respect to non-traditional roles for B cells in determining clinical outcomes

Charting the Path Forward for Risk Prediction in Liver Transplant for Hepatocellular Carcinoma: International Validation of HALTHCC Among 4,089 Patients

DDD: Prognosticating outcomes in liver transplant (LT) for hepatocellular carcinoma (HCC) continues to challenge the field. While Milan Criteria (MC) generalized the practice of LT for HCC and improved outcomes, its predictive character has degraded with increasing candidate and oncological heterogeneity. We sought to validate and recalibrate a previously developed, preoperatively calculated, continuous risk score, the hazard associated with liver transplantation in HCC (HALTHCC) in an international cohort. From 2002-2014, 4,089 patients (both MC in and out [25.2%]) across 16 centers in North America, Europe, and Asia were included. A continuous risk score using pre-LT levels of alpha feto-protein, model for end stage liver disease sodium score, and tumor burden score was recalibrated amongst a randomly selected cohort (n=1,021) and validated in the remainder (n=3,068). This study demonstrated significant heterogeneity by site and year, reflecting practice trends over the last decade. On explant pathology, both vascular invasion(VI) and poorly differentiated component(PDC) increased with increasing HALTHCC score. The lowest risk patients (HALTHCC 0-5) had lower rates of VI and PDC than the highest risk patients (HALTHCC>35) (VI:7.7%[1.2-14.2] vs 70.6%[48.3-92.9] and PDC:4.6%[0.1-9.8%] vs 47.1%[22.6-71.5]; P<0.0001 for both). This trend was robust to MC status. This international study was used to adjust the coefficients in the HALTHCC score. Before recalibration, HALTHCC had the greatest discriminatory ability for overall survival (C-index=0.61) compared to all previously reported scores. Following recalibration, the prognostic utility increased for both recurrence (C-index=0.71) and overall survival (C-index=0.63). CONCLUSION: This large international trial validated and refined the role for the continuous risk metric, HALTHCC, in establishing pre-LT risk amongst candidates with HCC worldwide. Prospective trials introducing HALTHCC into clinical practice are warranted. This article is protected by copyright. All rights reserved

Charting the Path Forward for Risk Prediction in Liver Transplant for HCC: International Validation of HALTHCC amongst 4,089 patients.

DDD: Prognosticating outcomes in liver transplant (LT) for hepatocellular carcinoma (HCC) continues to challenge the field. While Milan Criteria (MC) generalized the practice of LT for HCC and improved outcomes, its predictive character has degraded with increasing candidate and oncological heterogeneity. We sought to validate and recalibrate a previously developed, preoperatively calculated, continuous risk score, the hazard associated with liver transplantation in HCC (HALTHCC) in an international cohort. From 2002-2014, 4,089 patients (both MC in and out [25.2%]) across 16 centers in North America, Europe, and Asia were included. A continuous risk score using pre-LT levels of alpha feto-protein, model for end stage liver disease sodium score, and tumor burden score was recalibrated amongst a randomly selected cohort (n=1,021) and validated in the remainder (n=3,068). This study demonstrated significant heterogeneity by site and year, reflecting practice trends over the last decade. On explant pathology, both vascular invasion(VI) and poorly differentiated component(PDC) increased with increasing HALTHCC score. The lowest risk patients (HALTHCC 0-5) had lower rates of VI and PDC than the highest risk patients (HALTHCC>35) (VI:7.7%[1.2-14.2] vs 70.6%[48.3-92.9] and PDC:4.6%[0.1-9.8%] vs 47.1%[22.6-71.5]; P<0.0001 for both). This trend was robust to MC status. This international study was used to adjust the coefficients in the HALTHCC score. Before recalibration, HALTHCC had the greatest discriminatory ability for overall survival (C-index=0.61) compared to all previously reported scores. Following recalibration, the prognostic utility increased for both recurrence (C-index=0.71) and overall survival (C-index=0.63). CONCLUSION: This large international trial validated and refined the role for the continuous risk metric, HALTHCC, in establishing pre-LT risk amongst candidates with HCC worldwide. Prospective trials introducing HALTHCC into clinical practice are warranted. This article is protected by copyright. All rights reserved