13 research outputs found
Effect of Lanadelumab Compared with Placebo on Prevention of Hereditary Angioedema Attacks : a Randomized Clinical Trial
Importance: Current treatments for long-term prophylaxis in hereditary angioedema have limitations. Objective: To assess the efficacy of lanadelumab, a fully human monoclonal antibody that selectively inhibits active plasma kallikrein, in preventing hereditary angioedema attacks. Design, Setting, and Participants: Phase 3, randomized, double-blind, parallel-group, placebo-controlled trial conducted at 41 sites in Canada, Europe, Jordan, and the United States. Patients were randomized between March 3, 2016, and September 9, 2016; last day of follow-up was April 13, 2017. Randomization was 2:1 lanadelumab to placebo; patients assigned to lanadelumab were further randomized 1:1:1 to 1 of the 3 dose regimens. Patients 12 years or older with hereditary angioedema type I or II underwent a 4-week run-in period and those with 1 or more hereditary angioedema attacks during run-in were randomized. Interventions: Twenty-six-week treatment with subcutaneous lanadelumab 150 mg every 4 weeks (n = 28), 300 mg every 4 weeks (n = 29), 300 mg every 2 weeks (n = 27), or placebo (n = 41). All patients received injections every 2 weeks, with those in the every-4-week group receiving placebo in between active treatments. Main Outcome and Measures: Primary efficacy end point was the number of investigator-confirmed attacks of hereditary angioedema over the treatment period. Results: Among 125 patients randomized (mean age, 40.7 years [SD, 14.7 years]; 88 females [70.4%]; 113 white [90.4%]), 113 (90.4%) completed the study. During the run-in period, the mean number of hereditary angioedema attacks per month in the placebo group was 4.0; for the lanadelumab groups, 3.2 for the every-4-week 150-mg group; 3.7 for the every-4-week 300-mg group; and 3.5 for the every-2-week 300-mg group. During the treatment period, the mean number of attacks per month for the placebo group was 1.97; for the lanadelumab groups, 0.48 for the every-4-week 150-mg group; 0.53 for the every-4-week 300-mg group; and 0.26 for the every-2-week 300-mg group. Compared with placebo, the mean differences in the attack rate per month were -1.49 (95% CI, -1.90 to -1.08; P <.001); -1.44 (95% CI, -1.84 to -1.04; P <.001); and -1.71 (95% CI, -2.09 to -1.33; P <.001). The most commonly occurring adverse events with greater frequency in the lanadelumab treatment groups were injection site reactions (34.1% placebo, 52.4% lanadelumab) and dizziness (0% placebo, 6.0% lanadelumab). Conclusions and Relevance: Among patients with hereditary angioedema type I or II, treatment with subcutaneous lanadelumab for 26 weeks significantly reduced the attack rate compared with placebo. These findings support the use of lanadelumab as a prophylactic therapy for hereditary angioedema. Further research is needed to determine long-term safety and efficacy. Trial Registration: EudraCT Identifier: 2015-003943-20; ClinicalTrials.gov Identifier: NCT02586805
48 Inhaled 7% hypertonic saline in infants with cystic fibrosis: is it safe and tolerable?
184 Is chronic infection with methicillin resistant Staphylococcus aureus (MRSA) worse than methicillin sensitive Staphylococcus aureus (MSSA) in CF patients?
348 Epidemiological and clinical features of patients attending a reference cystic fibrosis center in Argentina
Opioids inhibit visceral afferent activation of catecholamine neurons in the solitary tract nucleus
A medium-density genetic linkage map of the bovine genome
A cattle genetic linkage map was constructed which covers more than 95 percent of the bovine genome at medium density. Seven hundred and forty six DNA polymorphisms were genotyped in cattle families which comprise 347 individuals in full sibling pedigrees. Seven hundred and three of the loci are linked to at least one other locus. All linkage groups are assigned to chromosomes, and all are orientated with regards to the centromere. Them is little overall difference in the lengths of the bull and cow linkage maps although there are individual differences between maps of chromosomes. One hundred and sixty polymorphisms are in or near genes, and the resultant genome-wide comparative analyses indicate that while there is greater conservation of synteny between cattle and humans compared with mice, the conservation of gene order between cattle and humans is much less than would be expected from the conservation of synteny. This map provides a basis for high-resolution mapping of the bovine genome with physical resources such as Yeast and Bacterial Artificial Chromosomes as well as providing the underpinning for the interpolation of information from the Human Genome Project
Vasorelaxant Effect of Novel Nitric Oxide-Hydrogen Sulfide Donor Chalcone in Isolated Rat Aorta: Involvement of cGMP Mediated sGC and Potassium Channel Activation
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Coronary Artery Calcification (CAC) and PostâTrial Cardiovascular Events and Mortality Within the Women's Health Initiative (WHI) EstrogenâAlone Trial
Background: Among women aged 50 to 59 years at baseline in the Women's Health Initiative (WHI) EstrogenâAlone (EâAlone) trial, randomization to conjugated equine estrogenâalone versus placebo was associated with lower risk of myocardial infarction and mortality, and, in an ancillary study, the WHIâCACS (WHI Coronary Artery Calcification Study) with lower CAC, measured by cardiac computed tomography â8.7 years after baseline randomization. We hypothesized that higher CAC would be related to postâtrial coronary heart disease (CHD), cardiovascular disease (CVD), and total mortality, independent of baseline randomization or risk factors. Methods and Results: WHIâCACS participants (n=1020) were followed â8 years from computed tomography scan in 2005 (mean age=64.4) through 2013 for incident CHD (myocardial infarction and fatal CHD, n=17), CVD (n=69), and total mortality (n=55). Incident CHD and CVD analyses excluded women with CVD before scan (n=89). Women with CAC=0 (n=54%) had very low ageâadjusted rates/1000 personâyears of CHD (0.91), CVD (5.56), and mortality (3.45). In comparison, rates were â2âfold higher for women with any CAC (>0). Associations were not modified by baseline randomization to conjugated equine estrogenâalone versus placebo. Adjusted for baseline randomization and risk factors, the hazard ratio (95% confidence interval) for CAC >100 (19%) was 4.06 (2.11, 7.80) for CVD and 2.70 (1.26, 5.79) for mortality. Conclusions: Among a subset of postmenopausal women aged 50 to 59 years at baseline in the WHI EâAlone Trial, CAC at mean age of 64 years was strongly related to incident CHD, CVD, and to total mortality over â8 years, independent of baseline randomization to conjugated equine estrogenâalone versus placebo or CVD risk factors. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00000611