47 research outputs found
Protocol to determine antibody affinity and concentration in complex solutions using microfluidic antibody affinity profiling
Hematopoietic cell transplantation in severe combined immunodeficiency : The SCETIDE 2006-2014 European cohort
Publisher Copyright: © 2021 The AuthorsBackground: Hematopoietic stem cell transplantation (HSCT) represents a curative treatment for patients with severe combined immunodeficiency (SCID), a group of monogenic immune disorders with an otherwise fatal outcome. Objective: We performed a comprehensive multicenter analysis of genotype-specific HSCT outcome, including detailed analysis of immune reconstitution (IR) and the predictive value for clinical outcome. Methods: HSCT outcome was studied in 338 patients with genetically confirmed SCID who underwent transplantation in 2006-2014 and who were registered in the SCETIDE registry. In a representative subgroup of 152 patients, data on IR and long-term clinical outcome were analyzed. Results: Two-year OS was similar with matched family and unrelated donors and better than mismatched donor HSCT (P 0.5 × 10e3/μL at +1 year were identified as independent predictors of favorable clinical and immunologic outcome. Conclusion: Recent advances in HSCT in SCID patients have resulted in improved OS and EFS in all genotypes and donor types. To achieve a favorable long-term outcome, treatment strategies should aim for optimal naive CD4 T lymphocyte regeneration.Peer reviewe
Project 1702A reports
Report 1 dated March November 1, 1953. Chemistry of elm cambium I. Collection of materials, 1953 / R. E. Kremers, Barbara Reeder -- Project report form no. 2. dated January 21, 1954. Chemistry of elm cambium II. Collection of materials, 1953, (supplementary) / Barbara Reeder, R. E. Kremers -- Project report form no. 3 dated January 27, 1954. Chemistry of black locust cambium: general considerations and outline of project / R. E. Kremers -- Project report form no. 4 dated February 2, 1954. Elm cambium III. Proximate analyses of 1953 materials / Barbara Reeder, R. E. Kremers -- Project report form no. 5 dated July 20, 1954. Microbiological assay of the free amino acid content of the cambium / Garner E. Wessman -- Project report form no. 6 dated February 17, 1955. Cambial chemistry: routine preparation of extracts for analysis / Roland E. Kremers -- Project report form no. 7 dated February 21, 1955. Cambial chemistry: aspen collections and assays, 1954 / R. E. Kremers, Barbara Reeder -- Project report form dated February 21, 1955. Cambial chemistry: American elm collections and assays, 1954 / R. E. Kremers, Barbara Reeder -- Project report form no. 9 dated February 21, 1955. Color reactions: a survey of "cambial zone" tissues of aspen, American elm and European larch with the Isenberg-Buchanan, phloroglucinol and Maule test / R. E. Kremers, Barbara Reeder, Donald Worth -- Project report form no. 10 dated March 12, 1956. Cambium chemistry: further investigation of microbiological assay method for free amino acid determinations / E. O. Dillingham.Title from folder label.Reports 1-2 have handwritten letter "A" in the project number i.e. 1702A
GOLD 2017 treatment pathways in "real life" : an analysis of the DACCORD observational study
Introduction: The 2017 update to the Global Initiative for Obstructive Lung Disease (GOLD) strategy document includes recommendations for treatment intensification or step-down in chronic obstructive pulmonary disease (COPD), although recognises that limited supporting information is available.
DACCORD is an ongoing observational, non-interventional study, recruiting patients following COPD maintenance treatment change or initiation, a subset of whom were receiving a long-acting β2-agonist (LABA) plus a long-acting muscarinic antagonist (LAMA) fixed-dose combination (FDC) on entry. Since there were no requirements in terms of prior medication (and no washout before commencing LABA/LAMA FDC), this provides an opportunity to generate "real world" data to test the GOLD 2017 recommendations.
Methods: To reduce heterogeneity, the current analyses include patients receiving indacaterol/glycopyrronium at baseline, and who, prior to the study, were receiving no COPD maintenance medication ("none"), LABA or LAMA monotherapy ("mono"), LABA plus inhaled corticosteroid (ICS; "LABA/ICS"), or triple therapy ("triple"). At the baseline visit, data collected included: demographic and disease characteristics; COPD Assessment Test (CAT); and exacerbations in the 6 months prior to entry. At 3, 6, 9 and 12 months data on exacerbations were collected, with CAT recorded at 3 and 12 months.
Results: A total of 2724 patients were included in the baseline analyses: 795, 954, 598 and 377 in the "none", "mono", "LABA/ICS" and "triple" subgroups, respectively. There were no clinically relevant differences in baseline demographics between the four groups. In terms of disease characteristics, the "triple" group had the highest proportion of patients with a disease duration of more than 1 year since diagnosis and with severe/very severe airflow limitation, but a similar percentage of non-exacerbators compared to the "none" group.
Over the 1-year follow-up, the majority of patients in all four subgroups did not exacerbate (exacerbation rates 0.16, 0.19, 0.21, and 0.26 in the "none", "mono", "LABA/ICS" and "triple" groups, respectively). At 12 months, 61.4%, 65.0%, 71.0% and 52.4% of patients had a clinically relevant improvement in CAT score.
Conclusions: Overall, the results support the GOLD recommendations in suggesting that a switch from a mono-bronchodilator or LABA plus ICS to LABA/LAMA FDC is a valid treatment option for patients with COPD. The results also validate the use of a LABA/LAMA FDC as initial maintenance treatment for COPD, and provide first "real world" evidence to support the newly added "step down" recommendation (from triple to LABA/LAMA FDC)
Utility of Interleukin-12 and Interleukin-10 in Comparison with Other Cytokines and Acute-Phase Reactants in the Diagnosis of Neonatal Sepsis
We compared the test characteristics of interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12(p-70), tumor necrosis factor-α (TNF-α), procalcitonin (PCT), C-reactive protein (CRP), and full blood count (FBC) in the diagnosis of neonatal sepsis. This prospective cohort study in the Neonatal Intensive Care Unit of Dunedin hospital of patients between July 1, 2002 and February 28, 2007 included 117 neonates commenced on antibiotics for 164 episodes of suspected sepsis. Blood cultures, FBC, CRP, IL-1β, IL-6, IL-8, IL-10, IL-12(p-70), TNF-α, and PCT were obtained at the time sepsis was first suspected and for the following 3 days. Receiver operator characteristics (ROC) plots and test characteristics were determined using culture-positive sepsis as the gold standard. At the time sepsis was first suspected, the most promising individual test was IL-12(p70) with an area under the curve (95% confidence interval [CI]) for the ROC of 0.74 (0.63 to 0.86), which (with a cutoff at 75 pg/mL) had a sensitivity (95% CI) of 28% (20 to 36%) and a specificity of 98% (96 to 100%). IL-10 had a sensitivity of 17% (10 to 23%) and a specificity of 99% (97 to 100%). IL-10 and IL-12(p70) are promising diagnostic tests that can be used to confirm sepsis in neonates
Utility of Interleukin-12 and Interleukin-10 in Comparison with Other Cytokines and Acute-Phase Reactants in the Diagnosis of Neonatal Sepsis
We compared the test characteristics of interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12(p-70), tumor necrosis factor-α (TNF-α), procalcitonin (PCT), C-reactive protein (CRP), and full blood count (FBC) in the diagnosis of neonatal sepsis. This prospective cohort study in the Neonatal Intensive Care Unit of Dunedin hospital of patients between July 1, 2002 and February 28, 2007 included 117 neonates commenced on antibiotics for 164 episodes of suspected sepsis. Blood cultures, FBC, CRP, IL-1β, IL-6, IL-8, IL-10, IL-12(p-70), TNF-α, and PCT were obtained at the time sepsis was first suspected and for the following 3 days. Receiver operator characteristics (ROC) plots and test characteristics were determined using culture-positive sepsis as the gold standard. At the time sepsis was first suspected, the most promising individual test was IL-12(p70) with an area under the curve (95% confidence interval [CI]) for the ROC of 0.74 (0.63 to 0.86), which (with a cutoff at 75 pg/mL) had a sensitivity (95% CI) of 28% (20 to 36%) and a specificity of 98% (96 to 100%). IL-10 had a sensitivity of 17% (10 to 23%) and a specificity of 99% (97 to 100%). IL-10 and IL-12(p70) are promising diagnostic tests that can be used to confirm sepsis in neonates
Dual bronchodilation vs triple therapy in the "real-life" COPD DACCORD study
Background: No observational studies have evaluated the "real-world" effectiveness of dual bronchodilation comprising a long-acting β2-agonist plus a long-acting muscarinic antagonist vs that of triple therapy (long-acting β2-agonist plus long-acting muscarinic antagonist plus inhaled corticosteroid) in COPD.
Materials and methods: DACCORD is a non-interventional, observational clinical study that recruited patients following COPD maintenance therapy initiation or change in maintenance therapy between or within therapeutic class. Given the non-interventional nature of the study, the decision to initiate or change medication had to be made by the patients’ physicians prior to inclusion in DACCORD. We used a matched-pairs analysis to compare disease progression in two patient groups: those receiving dual bronchodilation vs those receiving triple therapy (each group n=1,046).
Results: In two subgroups of patients matched according to a broad range of demographic and disease characteristics, over 1 year, fewer patients receiving dual bronchodilation exacerbated than those receiving triple therapy (15.5% vs 26.6%; P<0.001), with a greater improvement from baseline in COPD Assessment Test total score at 1 year (mean±SD -2.9±5.8 vs -1.4±5.5; P<0.001). When analyzed according to prior therapy, the highest rate of exacerbations was in patients on triple therapy prior to the study who remained on triple therapy. Those changing from mono-bronchodilator to dual bronchodilation had the greatest COPD Assessment Test total score improvement.
Conclusion: In this "real-life" cohort of patients with COPD, most of whom had not exacerbated in the 6 months prior to entry, triple therapy did not seem to improve outcomes compared with dual bronchodilation in terms of either exacerbations or health status. Our analyses clearly demonstrate the potential impact of prior medication on study results, something that should be taken into account when interpreting the results even of controlled clinical trials
A two-year evaluation of the "real life" impact of COPD on patients in Germany : the DACCORD observational study
Introduction: DACCORD is an observational, non-interventional study being conducted in German primary and secondary care centres. The study aims to describe the impact of disease (including exacerbations) and treatments over 2 years on ‘real-life’ patients with chronic obstructive pulmonary disease (COPD).
Materials and methods: Patients had a clinical and spirometry diagnosis of COPD, were aged ≥40 years and, on recruitment, were initiating or changing COPD maintenance medication. The only exclusion criteria were asthma and randomised clinical trial participation. Exacerbations data were collected every 3 months. COPD medication, COPD Assessment Test (CAT) and forced expiratory volume in 1 s (FEV1) were recorded at baseline and after 1 and 2 years.
Results: A total of 6122 patients were recruited, 3137 (51.2%) of whom completed the 2-year visit. The mean age of these patients was 65.6 years, 59% were male, 69% had mild or moderate airflow limitation, and their mean COPD Assessment Test (CAT) total score was 20.3. Overall, there was a trend towards decreasing COPD exacerbation rates over the 2-year follow-up period, with rates of 0.390 during Year 1 and 0.347 during Year 2. Rates were lower in patients with no exacerbation during the 6 months prior to entry (0.263 and 0.251 during Years 1 and 2, respectively), with 51.6% of patients having no exacerbation during the 6 months prior to entry and over the 2-year follow-up. Approximately 50% of the overall population experienced a clinically relevant improvement from baseline in CAT total score at Year 1 and 2. When assessed by treatment class (or classes), persistence to medication was high (77.8% in Year 1 and 71.4% in Year 2).
Conclusions: Overall, the 2-year follow-up data from DACCORD suggest that for most patients with COPD exacerbations are a rare event. For the majority of patients, the focus should be on managing symptoms, and the impact that these symptoms have on their daily lives. Even for those patients who do exacerbate, although prevention of exacerbations is an important factor, management of symptoms should be a key consideration. DACCORD also suggests that COPD disease progression is not inevitable – providing patients are receiving pharmacological treatment