SYNOPSISObjectives. The purpose of this study was to review instruments that assess the level of preparedness of state and local public health departments to respond to health threats such as bioterrorism.Methods. The authors examined 27 published population-based instruments for planning or evaluating preparedness that were mostly unavailable in the peerreviewed literature. Using the Essential Public Health Services framework, the instruments were evaluated for (1) clarity of measurement parameters, (2) balance between structural and process measures, (3) evidence of effectiveness, and (4) specification of an accountable entity.Results. There was a great deal of overlap but little consistency in what constitutes "preparedness" or how it should be measured. Most instruments relied excessively on subjective or structural measures, lacked scientific evidence for measures assessed, and failed to clearly define what entity was accountable for accomplishing the task or function.Conclusion. Strategies for improvement include measure standardization, better interagency communication, and investment in public health practice research to develop the underlying evidence base required for developing quality measures and assessments.
Alumina and aluminosilicate aerogels offer potential for use at temperatures above 700°C, where silica aerogels begin to sinter. Stability of alumina and aluminosilicate pore structures at high temperatures is governed by the starting aerogel structure, which, in turn is controlled by the synthesis route. Structure, morphology, and crystallization behavior are compared for aerogels synthesized from AlCl 3 and propylene oxide with those synthesized from a variety of boehmite precursors. The aerogels possessing a crystalline boehmite structure in the as-synthesized condition retained mesoporous structures to temperatures of 1200°C, while the AlCl 3 -derived aerogels, although exhibiting higher as-synthesized surface areas, crystallized and densified at 980-1005°C.
Background Sickle cell disease (SCD) is caused by abnormal sickle hemoglobin (HbS) and results in chronic hemolytic anemia, painful vaso-occlusive events (VOEs), and progressive vasculopathy that lead to significant morbidity. While acute vaso-occlusive pain is a defining clinical feature, chronic daily pain also contributes significantly to poor quality of life in many adult patients. The ongoing Phase 1/2 HGB-206 Study (NCT02140554) evaluating safety and efficacy of LentiGlobin for SCD (bb1111) gene therapy (GT) uses a modified human β-globin gene that produces GT-derived anti-sickling hemoglobin (HbAT87Q). Data from Group C patients including red blood cell (RBC) physiology, clinical outcomes, and patient-reported pain intensity are presented here. Methods Patients (≥12 and ≤50 years) with SCD and stroke or severe VOEs, including acute episodes of pain and acute chest syndrome (ACS), were enrolled. CD34+ cells collected by plerixafor mobilization/apheresis were transduced with BB305 lentiviral vector. LentiGlobin was infused following myeloablative busulfan conditioning. Patients were monitored for laboratory evaluations including Hb levels and hemolysis markers, SCD-related outcomes, pain intensity using the Patient Reported Outcomes Measurement Information System (PROMIS)-57, and adverse events (AEs). Data are median (min-max) unless otherwise stated. Results As of 3 March 2020, 40 Group C patients (23.5 [12-38] years) initiated cell collection; 25/40 were treated with LentiGlobin and followed for 12.1 (2.8-24.8) months. Neutrophil and platelet engraftment were achieved at 19 (12-27) days and 28 (19-136) days, respectively. All patients stopped RBC transfusions by 90 days post-treatment. In 16 evaluable patients with ≥6 months of follow-up, total Hb at last visit was 11.5 (9.6-16.2) g/dL, with HbAT87Q contribution of 5.2 (2.7-9.4) g/dL, HbS of 6.1 (4.9-7.8) g/dL, and median HbS ≤ 60% of total Hb. Exploratory assays showed near pancellular expression of HbAT87Q ≥6 months post-treatment (N=9 patients), with ~90% of RBCs containing βA-T87Q by 18 months, and reduction in sickling propensity comparable to sickle cell trait. At last visit post-treatment, key hemolysis markers were trending towards normalization with median (quartile [Q]1-Q3) lactate dehydrogenase of 212 (201-287) U/L, reticulocyte count of 178 (146.5-236.3) ×109/L, and total bilirubin of 19 (15.4-27.4) µmol/L (all for n=25). In 14 patients with ≥6 months of follow-up and history of vaso-occlusive crisis (VOC) or ACS, the annualized VOC+ACS rate was 4.0 (2.0-14.0) in the 2 years prior to treatment. Post-treatment, no ACS or serious VOCs were observed in these patients. One non-serious Grade 2 VOC occurred ~3.5 months after LentiGlobin infusion, resulting in a 99.5% (95% confidence interval, 92.4%-100%) mean reduction in the annualized VOC+ACS rate post-treatment (Figure 1). Patients with PROMIS-57 pain intensity scores "worse" than the population norm at baseline reported clinically meaningful improvements in pain reduction at 12 months post-treatment (n=5). Patients with scores near or "better" than the population norm at baseline (n=5) remained stable over time (Figure 2). The most common non-hematologic Grade ≥3 AEs post-treatment were stomatitis (n=15) and febrile neutropenia (n=11). Serious AEs reported in ≥2 patients post-treatment were nausea, opioid withdrawal syndrome, and vomiting (all for n=2); 3 patients had LentiGlobin-related nonserious Grade ≤2 AEs. There has been one death, unlikely related to LentiGlobin, >18 months post-treatment in a patient with significant baseline SCD-related cardiopulmonary disease. There have been no events of graft failure, vector-mediated replication-competent lentivirus, or clonal dominance. Summary LentiGlobin for SCD GT results in near pancellular βA-T87Q expression and reduced HbS expression, which impacts the pathophysiology of SCD as demonstrated by reduced RBC sickling and hemolysis and increased total Hb. Complete resolution of VOC/ACS was observed in almost all patients, with 99.5% mean reduction in the annualized VOC+ACS rate post-treatment. In addition, patients overall reported an improved pain intensity score. The safety profile post-LentiGlobin remains generally consistent with myeloablative single-agent busulfan conditioning and underlying SCD. Longer follow-up and additional patients will be presented. Disclosures Thompson: CRISPR/Vertex: Research Funding; bluebird bio, Inc.: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Biomarin: Research Funding; Baxalta: Research Funding; BMS: Consultancy, Research Funding. Walters:AllCells, Inc: Consultancy; Veevo Biomedicine: Consultancy; Editas: Consultancy. Kwiatkowski:Agios: Consultancy; bluebird bio, Inc.: Consultancy, Research Funding; Apopharma: Research Funding; Novartis: Research Funding; Terumo Corp: Research Funding; Sangamo: Research Funding; Celgene: Consultancy; Imara: Consultancy; Bristol Myers Squibb: Consultancy. Aygun:Patient-Centered Outsomes Research Institute: Research Funding; National Heart, Lung, and Blood Institute: Research Funding; National Institute of Nursing Research: Research Funding; bluebird bio: Membership on an entity's Board of Directors or advisory committees, Research Funding. Schmidt:German Cancer Research Center, Heidelberg, Germany: Current Employment; GeneWerk GmbH, Heidelberg, Germany: Other: Equity ownership. DelCarpini:bluebird bio, Inc.: Current Employment, Other: Ownership Interest and Salary. Pierciey:bluebird bio, Inc.: Current Employment, Other: Ownership Interest and Salary. Miller:bluebird bio, Inc.: Current Employment, Other: Ownership Interest and Salary. Gallagher:bluebird bio, Inc.: Current Employment, Other: Ownership Interest and Salary. Chen:bluebird bio, Inc.: Consultancy. Goyal:bluebird bio, Inc.: Current Employment, Other: Ownership Interest and Salary. Kanter:Wells Fargo: Honoraria; Cowen: Honoraria; Jeffries: Honoraria; AGIOS: Membership on an entity's Board of Directors or advisory committees; Medscape: Honoraria; GLG: Honoraria; NHLBI Sickle Cell Advisory Board: Membership on an entity's Board of Directors or advisory committees; SCDAA Medical and Research Advisory Board: Membership on an entity's Board of Directors or advisory committees; BEAM: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy; bluebird bio, inc: Consultancy, Honoraria; Novartis: Consultancy; Guidepoint Global: Honoraria.
Overall, there is a growing body of evidence for post-docetaxel treatment options available in patients with mCRPC. Further head-to-head trials or indirect treatment comparisons may be a valuable method to assess the comparative efficacy of these therapies.
Subjects had acceptable parameters of dialysis adequacy; however, 35% had evidence of malnutrition. Further research should focus on establishing a knowledge base for the nutritional management for Aboriginal dialysis subjects, and the development of a validated individual dietary assessment method for use in this population group.
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