Low Risk Index Research Articles

Predictores e impacto pronóstico de la insuficiencia cardiaca tras el implante percutáneo de válvula aórtica con una prótesis autoexpandible

Introduction and objectivesThe purpose of this analysis was to assess the incidence, predictors and prognostic impact of acute heart failure (AHF) after transcatheter aortic valve implantation (TAVI) using a self-expanding prosthesis. MethodsFrom November 2008 to June 2017, all consecutive patients undergoing TAVI in our center were prospectively included in our TAVI registry. The predictive effect of AHF on all-cause mortality following the TAVI procedure was analyzed using Cox regression models. ResultsA total of 399 patients underwent TAVI with a mean age of 82.4 ± 5.8 years, of which 213 (53.4%) were women. During follow-up (27.0 ± 24.1 months), 29.8% (n = 119) were admitted due to AHF, which represents a cumulative incidence function of 13.2% (95%CI, 11.1%-15.8%). At the end of follow-up, 150 patients (37.59%) had died. Those who developed AHF showed a significantly higher mortality rate (52.1% vs 31.4%; HR, 1.84; 95%CI, 1.14-2.97; P = .012). Independent predictors of AHF after TAVI were a past history of heart failure (P = .019) and high Society of Thoracic Surgeons score (P = .004). We found that nutritional risk index and chronic obstructive pulmonary disease were strongly correlated with outcomes in the AHF group. ConclusionsTAVI was associated with a high incidence of clinical AHF. Those who developed AHF had higher mortality. Pre-TAVI AHF and high Society of Thoracic Surgeons score were the only independent predictors of AHF in our cohort. A low nutritional risk index and chronic obstructive pulmonary disease were independent markers of mortality in the AHF group.

Myeloablative Fractionated Busulfan Conditioning Regimen in Older Patients: Results of a Phase II Study

Background: Traditionally, pre-transplant conditioning regimen is given over 4-6 days before hematopoietic cell transplant (HCT). Delivering higher dose chemotherapy preparative regimen over a longer time period has not been tested previously. We hypothesized that the delivery of myeloablative dose of busulfan over a 3-week period may reduce toxicity and non-relapse mortality (NRM), without affecting relapse, and tested this in a prospective phase II study. Methods: Patients between 18 and 70 years of age with hematological malignancies and adequate organ function, with 8/8-HLA matched related or unrelated donor were eligible. They received a fixed dose of busulfan 80mg/m2 as outpatient on days -20 and -13. Then, fludarabine 40mg/m2 was given on days -6 to -2 followed by busulfan dosed to achieve target area under the curve (AUC) of 20,000 mol/min for the whole course based on pharmacokinetic studies. GVHD prophylaxis was cyclophosphamide (PTCy) 50mg/kg on days 3 and 4 and tacrolimus. Mycophenolate mofetil (MMF) was added to later unrelated donor recipients. All patients received standard supportive care. The primary endpoint was day 100 NRM. Results: We enrolled 52 patients with a median age of 62 (range, 39-69) years. Almost half (n=25, 48%) had AML or MDS and the other half (n=26, 50%) had had CML or MPD; 1 (2%) had multiple myeloma. Low, intermediate, high and very-high disease risk index (DRI) was present in 3 (6%), 34 (65%), 14 (27%) and 1 (2%). HCT-comorbidity index was >3 in 23 (44%) and 1-2 (n=23, 44%). A majority (n=32, 62%) had an unrelated donor. With a median follow up of 14 months (range, 3-23), NRM at day 100 was 1.9% (n=1) and 8% (95% CI, 0-15) at 1 year. Overall survival, progression-free survival and relapse at 1-year were 83% (95% CI, 73-95%), 78% (95% CI, 67-91%), and 14% (95% CI, 4-24%), respectively [Table]. There were no graft failures. The median time to neutrophil engraftment was 17 days (range, 13-33) and that of platelets (> 20K/µL, n=45) was 24 days (range, 9-266). Day 100 grade II-IV and III-IV acute GVHD rates were 37% (95% CI, 23-50%) and 6% (95% CI, 0-12%), respectively; 1-year chronic GVHD and extensive chronic GVHD rates were 9% (95% CI, 0-17%) and 7% (95% CI, 0-14%), respectively. Overall survival at 1-year differed significantly among patients with low/intermediate DRI (94%; 87-100%) and those with high/very high DRI (53%; 31-91%), P=0.001. Conclusion: Myeloablative fractionated busulfan regimen with PTCy GVHD prophylaxis is feasible in older patients, has low incidence of severe acute GVHD, chronic GVHD, and NRM and results in promising overall survival. Table Disclosures Popat: Bayer: Research Funding; Incyte: Research Funding; Jazz: Consultancy. Bashir:Imbrium: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; StemLine: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acrotech: Research Funding; Celgene: Research Funding. Ciurea:Miltenyi: Research Funding; Spectrum: Membership on an entity's Board of Directors or advisory committees; MolMed: Membership on an entity's Board of Directors or advisory committees; Kiadis Pharma: Membership on an entity's Board of Directors or advisory committees, Other: stock holder. Kebriaei:Amgen: Research Funding; Pfizer: Honoraria; Jazz: Consultancy; Kite: Honoraria. Nieto:Astra-Zeneca: Research Funding; Affimed: Research Funding; Affimed: Consultancy; Novartis: Research Funding. Oran:AROG pharmaceuticals: Research Funding; Astex pharmaceuticals: Research Funding. Qazilbash:Autolous: Consultancy; Bioclinica: Consultancy; Speaker: Other: Speaker; Amgen: Other: Advisory Board. Molldrem:M. D. Anderson & Astellas Pharma: Other: Royalties. OffLabel Disclosure: Fludarabine & Busulfan as conditioning agent prior to transplant

Predictors and outcomes of heart failure after transcatheter aortic valve implantation using a self-expanding prosthesis.

The purpose of this analysis was to assess the incidence, predictors and prognostic impact of acute heart failure (AHF) after transcatheter aortic valve implantation (TAVI) using a self-expanding prosthesis. From November 2008 to June 2017, all consecutive patients undergoing TAVI in our center were prospectively included in our TAVI registry. The predictive effect of AHF on all-cause mortality following the TAVI procedure was analyzed using Cox regression models. A total of 399 patients underwent TAVI with a mean age of 82.4 ± 5.8 years, of which 213 (53.4%) were women. During follow-up (27.0 ± 24.1 months), 29.8% (n=119) were admitted due to AHF, which represents a cumulative incidence function of 13.2% (95%CI, 11.1%-15.8%). At the end of follow-up, 150 patients (37.59%) had died. Those who developed AHF showed a significantly higher mortality rate (52.1% vs 31.4%; HR, 1.84; 95%; CI, 1.14-2.97; P=.012). Independent predictors of AHF after TAVI were a past history of heart failure (P=.019) and high Society of Thoracic Surgeons score (P=.004). We found that nutritional risk index and chronic obstructive pulmonary disease were strongly correlated with outcomes in the AHF group. TAVI was associated with a high incidence of clinical AHF. Those who developed AHF had higher mortality. Pre-TAVI AHF and high Society of Thoracic Surgeons score were the only independent predictors of AHF in our cohort. A low nutritional risk index and chronic obstructive pulmonary disease were independent markers of mortality in the AHF group.

Neighborhood Risk and Hospital Use for Pediatric Asthma, Rhode Island, 2005-2014.

IntroductionStudies consistently show that children living in poor neighborhoods have worse asthma outcomes. The objective of our study was to assess the association between negative neighborhood factors (ie, neighborhood risk) and pediatric asthma hospital use. MethodsThis retrospective study used data from children aged 2 to 17 years in a statewide (Rhode Island) hospital network administrative database linked to US Census Bureau data. We defined an asthma visit as an International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code of 493 in any diagnosis field. We used 8 highly correlated measures for each census-block group to construct an index of neighborhood risk. We used maps and linear regression to assess the association of neighborhood risk with average annual census-block–group rates of asthma emergency department visits and hospitalizations. We used multivariable analyses to identify child characteristics and neighborhood risk associated with an asthma revisit, accounting for the child’s sociodemographic information, season, and multiple measurements per child.ResultsFrom 2005 through 2014, we counted 359,195 visits for 146,889 children. Of these, 12,699 children (8.6%) had one or more asthma visits. Linear regression results showed 1.18 (95% confidence interval, 1.06–1.30) more average annual emergency departments visits per 100 children and 0.41 (95% confidence interval, 0.34–0.47) more average annual hospitalizations per 100 children in neighborhoods in the highest-risk index quintile than in neighborhoods in the lowest-risk index quintile. ConclusionInterventions to improve asthma outcomes among children should move beyond primary care or clinic settings and involve a careful evaluation of social context and environmental triggers.

Potential length of stay reduction with outpatient management of low risk febrile neutropenia in a regional cancer centre.

e18000 Background: Febrile neutropenia is a serious complication of chemotherapy. The Multinational Association for Supportive Care in Cancer (MASCC) risk index score can reliably identify patients with febrile neutropenia at low risk of serious complications. Outpatient management programs utilising protocol based risk stratification, daily ambulatory nursing visits, telephone follow up and early outpatient review have been successfully piloted in other Australian cancer treatment centres. Methods: We performed a retrospective review of medical records for all patients admitted at our institution with febrile neutropenia between January 1 2016 and December 31 2018. We collected information regarding patient characteristics, cancer diagnosis and treatment, determined the MASCC risk index score, and if low risk, we determined the potential eligibility for outpatient care and potential reduction in length of stay. Results: A total of 98 hospital admissions with febrile neutropenia were analysed. Of these, 66 were determined to have a MASCC low risk index score. 58 patients met the eligibility criteria for outpatient management. The median age was 67 years. 71% were female. The most common tumour type was breast cancer. 52% were treated with palliative intent. The median length of stay was 3 days. The median potential reduction in length of stay for each admission was 2 days. The total potential reduction in length of stay was 198 days. No admission resulted in serious complications indicating the safety of outpatient care. Conclusions: Febrile neutropenia is a common complication of chemotherapy and a leading cause of hospital admission. This review demonstrates a significant number of hospital admission days can be avoided with outpatient care. We intend to conduct a prospective pilot study at our centre to institute an outpatient febrile neutropenia program for such low risk groups with potential reduction in hospital bed length of stay. This has significant implications on health resource usage, service provision planning and patient quality of life.

Assessment of Concentrations and Ecological Risk of Heavy Metals at Resident and Remediated Soils of Uncontrolled Mining Site at Dareta Village, Zamfara, Nigeria

This study determined the levels of some heavy metals at resident and remediated soils of uncontrolled gold mining activities with a view to providing information on the extent of contamination and ecological risk to the resident area. The soil samples were collected from two site at the resident and one remediated soil, and analyzed for metals (Cr, Ni, Pb, Fe, Cu, Cd and Mn) using Atomic Absorption spectrophotometer (AAS). The concentrations of heavy metals (mg/kg) in residents samples ranged from 1.500-13.30 (Cr), 0.0001-0.05 (Ni), 0.18-3.754 (Pb), 0.0003-0.10 (Fe), 0.0005-0.88 (Cu), 0.0009-0.27 (Cd) and 0.0003-0.0035 (Mn) and for the remediated sample are 12.3000, 0.0001, 1.1989, 0.0002, 0.0006, 0.0003, and 0.0003 for Cr, Ni, Pb, Fe, Cu, Cd and Mn respectively. The calculated geo-accumulation index (Igeo) shows that the soil samples fall under unpolluted to moderately pollute for all the studied metals with respect to all studied sites. Pollution Load Index values (PLI>1) were all less than 1 for each metals in all studied sites, thus indicating perfection. The contamination factor (Cf) and degrees of contamination (Cd) of the soil samples were very slightly contaminated to slightly contaminated with Cr and Cd; The ecological risk results revealed that site A, B and Remediated samples were fall under low ecological risk index with values of 0.28, 10.28 and 0.33 respectively. The contaminations of these studied metals may not add ecological risk to the local environment. Keywords : Assessment, Ecological risk Heavy Metals, Uncontrolled Mining

Clinical Outcomes of Matched Unrelated Allogeneic Stem Cell Transplant Patients: Low Dose ATG Vs. No ATG

Introduction Anti-thymocyte globulin (ATG) is an immunoglobulin directed to human T lymphocytes, and may decrease the risk of chronic graft versus host disease (cGVHD) in allogenic hematopoietic cell transplantation (HCT). ATG, especially at higher doses (≥ 7.5 mg/kg), has been associated with higher incidence of disease relapse and infection. Our institution utilizes low dose rabbit ATG 2.5 mg/kg. In this retrospective study, we evaluated outcomes of HCT patients (pts) receiving low dose ATG vs. not undergoing in-vivo T-cell depletion Patients and Methods Pts with 8/8 HLA Matched Unrelated Donors (MUD) undergoing HCT between 2007-2016 were included. Pts were divided into two cohorts: those receiving low dose ATG vs. those that did not. Both cohorts received standard GVHD prophylaxis. Primary outcome was overall survival (OS). Secondary outcomes included relapse free survival (RFS), EBV or CMV reactivation, CMV disease, invasive fungal infection, acute GVHD (aGVHD) grades III-IV, and moderate to severe cGVHD. A series of univariate and multivariant Cox proportional hazard regression models were conducted for outcomes of interest. A Kaplan-Meier survival curve was used to depict probability of survival by ATG cohort. Results We identified 209 patients,129 in ATG group and 80 in non-ATG group. There were no differences in the age, sex, ABO incompatibility, or performance status. The ATG cohort had fewer low disease risk index (DRI) and more pts with intermediate or high DRI (2.4%, 64.6%, 28.3% vs 18.4%, 51.3%, 23.7% respectively); these differences were statistically significant between the two groups (p = There was no significant difference in OS between the two groups at up to 5 years post-transplant (p=0.35; Fig. 1). The primary predictor of OS was DRI very high vs low [HR 6.0 (2-18) p Conclusions Our study shows no significant difference in survival or death from relapse for patients who receive ATG. Importantly, patients receiving ATG had a lower rate of cGVHD with no increased rates of infectious complications. Low dose ATG did not appear to increase the risk of relapse, even when considering only myeloid malignancies. These findings suggest that low dose ATG can improve cGVHD with no impact on survival, relapse, or infectious complications. Additional prospective trials using low dose ATG compared to no ATG are warranted.

Clinical Outcomes of Matched Unrelated Allogeneic Stem Cell Transplant Patients: Low Dose ATG Vs. No ATG

Introduction - Allogenic hematopoietic cell transplantation (HCT) remains potential curative treatment for hematologic malignancies. Anti-thymocyte globulin (ATG) is an immunoglobulin directed to human T lymphocytes, and may decrease the risk of chronic graft versus host disease (cGVHD). Use of ATG has been associated with higher incidence of disease relapse and infection.While the optimal dosing of ATG has not been well established, higher doses (≥ 7.5 mg/kg) have a stronger association with infection and disease relapse. Our institution utilizes low dose rabbit ATG at 2.5 mg/kg for in-vivo T-cell depletion. In this retrospective study we evaluated outcomes in patients receiving low dose ATG to those not undergoing in-vivo T-cell depletion with the hypothesis that low dose ATG protects against cGVHD without impacting infectious complications or relapse.Patients and Methods - We evaluated all patients with 8/8 HLA Matched unrelated Donors (MUD) undergoing HCT between 2007 and 2016. Patients were divided in to two cohorts, those receiving low dose ATG to those that did not. Both cohorts received standard GVHD prophylaxis with calcineurin inhibition plus methotrexate or mycophenolate. The primary outcome was overall survival (OS). Secondary outcomes included relapse free survival (RFS), EBV reactivation, CMV reactivation, CMV disease, invasive fungal infection, incidence of acute GVHD (aGVHD) grades III-IV, and moderate to severe cGVHD. A subset analysis was performed to assess relapse free survival (RFS) in patients with myeloid malignancies.Descriptive statistics were utilized for baseline characteristics; and a series of univariate and multivariant Cox proportional hazard regression models were conducted for outcomes of interest. A Kaplan-Meier (K-M) survival curve was used to depict probability of survival by ATG cohort.Results - We identified 209 patients, with 129 (62%) in ATG group and 80 (38%) in non-ATG group. At baseline, there were no differences in the age at transplant, sex, ABO incompatibility, or performance status. The ATG cohort had fewer low disease risk index (DRI) patients and more patients with intermediate or high DRI (2.4%, 64.6%, 28.3% vs 18.4%, 51.3%, 23.7% respectively), and Fisher's Exact test showed that this difference between ATG groups was statistically significant, p = <0.001. The ATG cohort also had significantly different rates of myeloablative (MA) conditioning regimens from the non-ATG cohort with fewer receiving MA (31% vs 53% p < 0.01).No statistically significant differences in OS were observed between the two ATG cohorts at up to 5 years post-transplant (p=0.35; Fig. 1). The primary predictor of OS was DRI very high vs low [HR 6.0 (2-18) p < 0.01]. The ATG exposed cohort had significantly lower risk of cGVHD [HR 0.17 (0.08-0.37) p = <0.001]. There was no difference in risk of death from relapse, incidence of EBV or CMV reactivation, CMV disease, invasive fungal infection, or grade III-IV acute GVHD. Low dose ATG was not associated with inferior RFS, including in subset analysis of patients with myeloid malignancies [HR 0.85 (0.5-1.4) p = 0.549].Conclusions - Our study shows no significant difference in survival or death from relapse for patients who receive ATG. Importantly, patients receiving ATG had a lower rate of cGVHD with no increased rates of infectious complications. Low dose ATG did not appear to increase the risk of relapse, even when considering only myeloid malignancies. These findings suggest that low dose ATG can improve cGVHD with no impact on survival, relapse, or infectious complications. Additional prospective trials using low dose ATG compared to no ATG are warranted. DisclosuresPalmer:Novartis: Research Funding.

Evaluation of adverse drug reactions associated with direct oral anticoagulants recorded in the Italian Pharmacovigilance Network database using a specifically developed risk index

The introduction into clinical practice of direct oral anticoagulants (DOAC) has widened the scenario in the prevention and treatment of thromboembolism. However, the evaluation of the balance between the thrombotic and hemorrhagic risks is a critical issue in the choice of an oral anticoagulant agent. The availability of safety and efficacy data for each drug represents the basis to operate treatment choices. As there are no head-to-head studies comparing the different DOACs in terms of safety and efficacy, and considering the differences in registrative trial designs and characteristics of enrolled populations, several meta-analyses and real-life studies have tried to trace the safety and efficacy profiles on DOACs, but at present no definitive conclusions can be drawn due to numerous existing biases. One possible aid to help clinicians in their treatment choice is the evaluation of self-reported adverse drug reactions (ADRs) available in drug regulatory agency databases such as the Italian Medicines Agency (AIFA) pharmacovigilance database. We conducted a search in the National Pharmacovigilance Network database, available on AIFA website, in order to retrieve all the ADRs related to oral anticoagulants occurred in the period 2016-2017. We then calculated an ADR risk index (RI) for each drug, where an RI =1 indicates a balance between the percentage of ADR share and the percentage of market share for each DOAC; and an RI <1 indicates a rate of ADR lower than the rate of market share (more safe DOAC). The results showed that rivaroxaban is the DOAC with the lowest RI among the four molecules available today in Italy. Despite the limitations of this study, we believe that ADR RI can be a valuable adjunctive tool to help clinicians in their everyday clinical practice.

Combined Haploidentical and Umbilical Cord Blood Allogeneic Stem Cell Transplantation for High-Risk Lymphoma and Chronic Lymphoblastic Leukemia

Limited studies have reported on outcomes for lymphoid malignancy patients receiving alternative donor allogeneic stem cell transplants. We have previously described combining CD34-selected haploidentical grafts with umbilical cord blood (haplo-cord) to accelerate neutrophil and platelet engraftment. Here, we examine the outcome of patients with lymphoid malignancies undergoing haplo-cord transplantation at the University of Chicago and Weill Cornell Medical College. We analyzed 42 lymphoma and chronic lymphoblastic leukemia (CLL) patients who underwent haplo-cord allogeneic stem cell transplantation. Patients underwent transplant for Hodgkin lymphoma (n = 9, 21%), CLL (n = 5, 12%) and non-Hodgkin lymphomas (n = 28, 67%), including 13 T cell lymphomas. Twenty-four patients (52%) had 3 or more lines of therapies. Six (14%) and 1 (2%) patients had prior autologous and allogeneic stem cell transplant, respectively. At the time of transplant 12 patients (29%) were in complete remission, 18 had chemotherapy-sensitive disease, and 12 patients had chemotherapy-resistant disease. Seven (17%), 11 (26%), and 24 (57%) patients had low, intermediate, and high disease risk index before transplant. Comorbidity index was evenly distributed among 3 groups, with 13 (31%), 14 (33%), and 15 (36%) patients scoring 0, 1 to 2, and ≥3. Median age for the cohort was 49 years (range, 23 to 71). All patients received fludarabine/melphalan/antithymocyte globulin conditioning regimen and post-transplant graft-versus-host disease (GVHD) prophylaxis with tacrolimus and mycophenolate mofetil. The median time to neutrophil engraftment was 11 days (range, 9 to 60) and to platelet engraftment 19.5 days (range, 11 to 88). Cumulative incidence of nonrelapse mortality was 11.6% at 100 days and 19 % at one year. Cumulative incidence of relapse was 9.3% at 100 days and 19% at one year. With a median follow-up of survivors of 42 months, the 3-year rates of GVHD relapse free survival, progression-free survival, and overall survival were 53%, 62%, and 65%, respectively, for these patients. Only 8% of the survivors had chronic GVHD. In conclusion, haplo-cord transplantation offers a transplant alternative for patients with recurrent or refractory lymphoid malignancies who lack matching donors. Both neutrophil and platelet count recovery is rapid, nonrelapse mortality is limited, excellent disease control can be achieved, and the incidence of chronic GVHD is limited. Thus, haplo-cord achieves high rates of engraftment and encouraging results.

A Phase II Study of Tacrolimus and Thymoglobulin, As Graft-Versus-Host-Disease Prophylaxis in Patients Undergoing Related Donor Allogeneic Hematopoietic Cell Transplantation

A Phase II study of Tacrolimus and Thymoglobulin, as Graft-Versus-Host-Disease Prophylaxis in Patients Undergoing Related Donor Allogeneic Hematopoietic Cell TransplantationIntroduction: Regimens used for the prevention of acute GVHD in allogeneic transplantation usually consist of combinations of a calcineurin inhibitor with an additional agent such as methotrexate, mycophenolate or sirolimus. Previously, we and others have demonstrated efficacy of the addition of thymoglobulin to these standard GVHD regimens in preventing both acute and chronic GVHD without increasing relapse rates. Given the proven activity of thymoglobulin, we now report the outcomes of a prospective phase II trial testing the combination of tacrolimus and thymoglobulin in the prevention of GVHD in patients undergoing matched related allogeneic transplants.Patients and Methods: Patients were eligible if they were between ages 18 to 75 years with hematologic malignancies in complete or partial remission at the time of transplant. Patients received thymoglobulin (4.5 mg/kg total dose) in divided doses from day -3 to -1 days prior to transplant. All patients were also given tacrolimus to maintain a therapeutic level from day -3 to day +60. After 60-days post-transplant, tacrolimus was tapered in the absence of GVHD and discontinued by day + 181. Primary objective was to determine incidence and severity of acute GVHD (aGVHD). Secondary objectives were to determine neutrophil and platelet engraftment time, estimate incidence of chronic GVHD (cGVHD), overall survival (OS), relapse free survival (RFS) and GVHD-free relapse-free survival (GRFS) at 1-year post-transplant. The cumulative incidence of GVHD was calculated using relapse and NRM as competing risks. The OS, RFS and GRFS were reported using KM method. The proportions of incidence of infections were reported with the Wilson's 95% Confidence Interval.Results: A total 20 patients were enrolled in our study. The median age was 59 years (range, 38-69) and the median follow-up duration was 54.3 months (95% CI, 43.6-NA). Seven patients had MDS, 5 had AML, 4 had NHL, one with CLL, 2 had CML, and one had ALL. Low, intermediate and high disease risk index was noted in 5%, 70%, and 25% of these patients respectively. Conditioning regimens included busulfan (BU)/fludarabine (FLU) (n=7), BEAM (BCNU, etoposide, ara-c and melphalan) ± rituximab (n=4), BU/FLU/total-body irradiation (TBI) (n=7), FLU/melphalan/TBI (n=2). All patients received peripheral blood stem cell transplants (PBSCT). The median day to neutrophil and platelet engraftment was 11 days (range, 7-12) and 17 days (range, 0-25) respectively. The 1-year incidence of grade II-IV aGVHD was 45% (95% CI, 22.3-65.4) and of grade III-IV aGVHD was 10% (95% CI, 1.6%-27.8%). The median time to development of grade II-IV aGVHD was 21 days (range, 14-105). The incidence of cGVHD at 1-year post-transplant was 70% (95% CI, 42.9-86.0) and the median time to development of cGVHD was 114 days (range, 46-616). Fourteen patients (60% with 95% CI, 34.3-78.4) developed extensive cGVHD at 1-year post-transplant. The incidence of relapse and non-relapse mortality at 2-year post-transplant were 35% (95% CI, 15.1-55.9) and 10.0% (95% CI, 1.6-27.8) respectively. Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) reactivation were noted among 35% and 40% of patients respectively. Eight patients relapsed and the median time of relapse was 317 days (range, 31-994). OS, RFS and GRFS at 1-year post-transplant were 85% (95% CI, 70.7-100), 65% (95% CI, 47.1-89.7) and 25% (95% CI, 11.7-53.4) respectively. Causes of death for 8 patients were: 5 relapse, 2 cGVHD, and 1 multiorgan failure.Conclusion: We reported a novel GVHD prevention regimen using tacrolimus and thymoglobulin. Our data suggest that combination can be used safely and thymoglobulin may replace either mycophenolate, methotrexate or sirolimus while avoiding some of the toxicities commonly associated with these agents. More importantly, rates of acute and chronic GVHD as well as GRFS appear to be comparable to other GVHD regimens. No significantly increased rates of opportunistic infections were noticed. Further studies in larger patient groups are warranted to better define the role of this regimen in GVHD prevention. [Display omitted] [Display omitted] [Display omitted] DisclosuresDeol:Jazz Pharmaceuticals: Consultancy.

Uncertainty and Risk Factors Assessment for Cross-Country Pipelines Projects Using AHP

Infrastructure cross-country pipelines projects carry out higher risk than traditional because they entail high capital outlays and intricate site conditions. The high-risk exposure associated with infrastructure cross-country pipelines projects needs special attention from contractors to analyze and manage their risks. They cannot be eliminated but can be minimized or transferred from one project stakeholder to another. Therefore, current research aims for identifying the risk factors that affect infrastructure cross-country pipelines projects based on experts experience and company’s point of view which participated in similar projects. The risk factors classified under two categories to company level risks and project level risks. The risk factors were assessed using risk assessment models that facilitate this assessment procedure, prioritize these projects based upon its risk indexes and evaluate risk contingency value. Analytical hierarchy process (AHP) used to evaluate risk factors weights (likelihood) and FUZZY LOGIC approach to evaluate risk factors impact (Risk consequences) using software aids such as EXCEL and MATLAB software, accordingly risk indexes for both company level and project level evaluated and overall project risk index determined. Five case studies in different countries were selected to determine the highest risk factors and to implement the designed models and test its results. Results show that project no 3 in Iraq conquer the highest risk index (39.75%); however, project 5 in Egypt has the lowest risk index (5.24%). Results of risk factors in other countries are (32.81%) in Emirates, (17.27%) in Saudi Arabia and (11.67%) in Libya. Therefore, the developed model can be used to sort projects based upon risk, which facilitate company’s decision of which project can be pursued.

Risk-based Security Assessment in Distribution Network with the Integration of Photovoltaic

With the development of distribution network, distributed generation such as wind and photovoltaic (PV) power will become increasingly prominent in the near future. PV is widely constructed because of advantages it has. However, the volatility and randomness of PV makes it more complex than traditional energy in the security assessment of distribution network. Based on risk theory, considering the randomness of PV, node low voltage risk index and line overload risk index are established in this paper. Also, K (N - 1 + 1) principle for distribution network which is developed from traditional (N-1) deterministic principle is applied to reflect the flexible structure of distribution network. IEEE three-feeder example system is utilized to investigate the influence of PV power on the security assessment of distribution network.

Impact of obstetric factors on outcome of extremely preterm births in Sweden: prospective population-based observational study (EXPRESS).

A population-based observational study investigated the contribution of obstetric factors to the survival and postnatal development of extremely preterm infants. Mortality up to 1 year and neurodevelopment at 2.5 years (Bayley-III test, cerebral palsy, vision, hearing) were evaluated in infants born before 27 weeks of gestation in Sweden 2004-2007 (n = 1011), using logistic regression analyses of risk factors. Of 844 fetuses alive at admission, 8.4% died in utero before labor, 7.8% died intrapartum. Of 707 live-born infants, 15% died within 24 h, 70% survived ≥365 days, 64% were assessed at 2.5 years. The risk of death within 24 h after birth decreased with gestational age [odds ratio (OR) 0.3; 95% CI 0.2-0.4], antenatal corticosteroids (OR 0.3; 95% CI 0.1-0.6), and cesarean section (OR 0.4; 95% CI 0.2-0.9); it increased with multiple birth (OR 3.0; 95% CI 1.5-6.0), vaginal breech delivery (OR 2.3; 95% CI 1.0-5.1), 5-min Apgar score <4 (OR 50.4; 95% CI 28.2-90.2), and birth at a level II hospital (OR 2.6; 95% CI 1.2-5.3). The risk of death between 1 and 365 days remained significantly decreased for gestational age and corticosteroids. The risk of mental developmental delay at 2.5 years decreased with gestational age, birthweight and fetal growth; it increased with vaginal breech delivery (OR 2.0; 95% CI 1.2-7.4), male gender, low Apgar score and high Clinical Risk Index for Babies score. Several obstetric factors, including abdominal delivery, influenced the risk of death within the first day of life, but not later. Antenatal corticosteroids and gestational age decreased the mortality up to 1 year. Mental developmental delay was related to vaginal breech delivery.

A compilation of safety impact information for extractables associated with materials used in pharmaceutical packaging, delivery, administration, and manufacturing systems.

Leachables from packaging systems, manufacturing systems, or delivery devices can accumulate in drug products and potentially affect the drug product. Although drug products can be analyzed for leachables (and material extracts can be analyzed for extractables), not all leachables or extractables can be fully identified. Safety thresholds can be used to establish whether the unidentified substances can be deemed to be safe or whether additional analytical efforts need to be made to secure the identities. These thresholds are typically based on the statistical analysis of datasets containing toxicological information for more or less relevant compounds. This article contains safety data for over 500 extractables that were identified in laboratory characterizations of polymers used in pharmaceutical applications. The safety data consists of structural toxicity classifications of the extractables as well as calculated risk indices, where the risk indices were obtained by subjecting toxicological safety data, such as NOELs (no observed effects), NOAELs (no adverse effects), TDLOs (lowest published toxic dose), and others to a systematic evaluation process using appropriate uncertainty factors. Thus the risk index values represent daily exposures for the lifetime intravenous administration of drugs. The frequency distributions of the risk indices and Cramer classifications were examined. The risk index values were normally distributed around a range of 5 to 20 mg/day, and the risk index associated with the 95% level of the cumulative frequency plot was 0.1 mg/day. Approximately 50% of the extractables were in Cramer Class 1 (low risk of toxicity) and approximately 35% were in Cramer Class 3 (high risk of toxicity). Approximately 20% of the extractables produced an in vitro or in silico mutagenicity alert. In general, the distribution of risk index values was not strongly correlated with the either extractables' Cramer classification or by mutagenicity alerts. However, extractables with either in vitro or in silico alerts were somewhat more likely to have low risk index values.

Antihyperlipidemic effect of &lt;i&gt;Berberis orthobotrys&lt;/i&gt; in hyperlipidemic animal models

The present study was undertaken to evaluate antihyperlipidemic effect of aqueous methanolic extract of Berberis orthobotrys in experimentally induced hyperlipidemic animal models. Atorvastatin was used as standard drug. The crude extract (50 and 100 mg/kg) significantly prevented the increase in low density lipoprotein (LDL), very low density lipoprotein (VLDL), total cholesterol (TC), triglyceride (TG), atherogenic index and coronary risk index in high fat diet, cholesterol, fructose and olive oil-induced hyperlipidemic rat models whereas in ethanol treated mice, the extract reduced VLDL, TG and TC levels. The high density lipoprotein (HDL) level was significantly increased in high fat diet, olive oil and cholesterol induced hyperlipidemic rats. The reduction in serum level of above parameters with 100 mg/kg dose of extract was comparable with atorvastatin. It is concluded, that B. orthobotrys has atheroprotective and lipid lowering potential. DOI: http://dx.doi.org/10.3329/bjp.v9i3.19922

Social-Ecological Patterns of Soil Heavy Metals Based on a Self-Organizing Map (SOM): A Case Study in Beijing, China

The regional management of trace elements in soils requires understanding the interaction between the natural system and human socio-economic activities. In this study, a social-ecological patterns of heavy metals (SEPHM) approach was proposed to identify the heavy metal concentration patterns and processes in different ecoregions of Beijing (China) based on a self-organizing map (SOM). Potential ecological risk index (RI) values of Cr, Ni, Zn, Hg, Cu, As, Cd and Pb were calculated for 1,018 surface soil samples. These data were averaged in accordance with 253 communities and/or towns, and compared with demographic, agriculture structure, geomorphology, climate, land use/cover, and soil-forming parent material to discover the SEPHM. Multivariate statistical techniques were further applied to interpret the control factors of each SEPHM. SOM application clustered the 253 towns into nine groups on the map size of 12 × 7 plane (quantization error 1.809; topographic error, 0.0079). The distribution characteristics and Spearman rank correlation coefficients of RIs were strongly associated with the population density, vegetation index, industrial and mining land percent and road density. The RIs were relatively high in which towns in a highly urbanized area with large human population density exist, while low RIs occurred in mountainous and high vegetation cover areas. The resulting dataset identifies the SEPHM of Beijing and links the apparent results of RIs to driving factors, thus serving as an excellent data source to inform policy makers for legislative and land management actions.

Measuring Pension Liabilities under GASB Statement No. 68

SYNOPSIS While retired government employees clearly depend on public sector defined benefit pension funds, these plans also contribute significantly to U.S. state and national economies. Growing public concern about the funding adequacy of these plans, hard hit by the great recession, raises questions about their future viability. After several years of study, the Governmental Accounting Standards Board (GASB) approved two new standards, GASB 67 and 68, with the goal of substantially improving the accounting for and transparency of financial reporting of state/municipal public employee defined benefit pension plans. GASB 68, the focus of this paper, requires state/municipal governments to calculate and report a net pension liability based on a single discount rate that combines the rate of return on funded plan assets with a low-risk index rate on the unfunded portion of the liability. This paper illustrates the calculation of estimates for GASB 68 reportable net pension liabilities, funded ratios, and single discount rates for 48 fiscal year state employee defined benefit plans by using an innovative valuation model and readily available data. The results show statistically significant increases in reportable net pension liabilities and decreases in the estimated hypothetical GASB 68 funded ratios and single discount rates. Our sensitivity analyses examine the effect of changes in the low-risk rate and time period on these results. We find that reported discount rates of weaker plans approach the low-risk rate, resulting in higher pension liabilities and creating policy incentives to increase risky assets in pension portfolios.

Yield of the second surveillance colonoscopy based on the results of the index and first surveillance colonoscopies

The risk of advanced colorectal neoplasia (ACN) after the first surveillance colonoscopy is not well quantified. The aim of the current study was to quantify the risk of ACN on the second surveillance colonoscopy based on previous colonoscopic findings. This was a single-site study of patients with index adenomas who underwent two surveillance colonoscopies. ACN was defined as advanced adenoma (≥ 1 cm, villous histology, or high-grade dysplasia) or as "high-risk" findings (advanced adenoma or ≥ 3 non-advanced adenoma [NAA]). Among 509 patients with low-risk index findings, 61 (12.0 %; 95 % confidence interval [CI], 9.3 % - 15.1 %) had high-risk findings on the first surveillance colonoscopy, 11 of whom (18.0 %; 95 %CI 9.4 % - 30.0 %) had high-risk findings on second surveillance colonoscopy compared with 39 (8.7 %; 95 %CI 6.3 % - 11.7 %) of the remaining 448 patients who had normal or low-risk findings on the first surveillance colonoscopy (relative risk [RR] = 2.07; 95 %CI 1.12 - 3.83). Among 456 patients with high-risk index findings, 91 (20.0 %; 95 %CI 16.3 % - 23.9 %) had high-risk findings on the first surveillance colonoscopy, 20 of whom (22.0 %; 95 %CI 14.0 % - 31.9 %) had high-risk findings on second surveillance colonoscopy compared with 40 (11.0 %; 95 %CI 8.0 % - 146 %) of the remaining 365 patients who had normal or low-risk findings on first surveillance colonoscopy (RR = 2.01; 95 %CI 1.04 - 3.32). Results were similar when only advanced adenomas were considered. Patients with high-risk findings on index and first surveillance colonoscopies require close surveillance. Those with low-risk findings on index colonoscopy and normal/non-advanced findings on the first surveillance colonoscopy have low subsequent risk of ACN. These and previous data may be useful for generating recommendations for the timing of the second surveillance colonoscopy.

Dynamic Risk-Based Asset Allocation

In asset allocation, the equal risk contribution (ERC) approach has rapidly gained popularity: portfolio weights are dynamically set such that the asset classes contribute equally to the portfolio risk. As such, the portfolio loads automatically less on the more risky asset and, by diversifying across asset classes, portfolio drawdowns are reduced. When the equity subportfolio is allocated based on market capitalization weights, the ERC portfolio allocation tends to be dominated by the bond allocation. While the resulting portfolio has a low risk, it is - in today's market regime of low interest rates - also characterized by only moderate expected returns. For this reason, American fund managers have advocated to overlay the ERC portfolio with leverage. Such a leveraged risk-diversified portfolio is commonly referred to as a risk-parity strategy. This paper explores two leverage-free alternatives to increase tactically the equity allocation and preserve a completely risk-based asset allocation approach, which dynamically adjusts to the changing risk regimes. The first one consists of replacing the market capitalization-weighted equity index with a low-risk equity index. The second suggestion to increase the equity allocation is to deviate from an equal risk contribution objective to a 60/40 risk allocation strategy. We show that these two modifications increase significantly the weight of the equity portion in the portfolio, while still keeping the total risk of the dynamically rebalanced portfolios at a low level.