University College Cork

About: University College Cork is a education organization based out in Cork, Ireland. It is known for research contribution in the topics: Population & Irish. The organization has 12056 authors who have published 28452 publications receiving 958414 citations. The organization is also known as: Coláiste na hOllscoile Corcaigh & National University of Ireland, Cork.

AR101 Oral Immunotherapy for Peanut Allergy

Abstract: BACKGROUND Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions. METHODS In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms. RESULTS Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; P<0.001). During the exit food challenge, the maximum severity of symptoms was moderate in 25% of the participants in the active-drug group and 59% of those in the placebo group and severe in 5% and 11%, respectively. Adverse events during the intervention period affected more than 95% of the participants 4 to 17 years of age. A total of 34.7% of the participants in the active-drug group had mild events, as compared with 50.0% of those in the placebo group; 59.7% and 44.4% of the participants, respectively, had events that were graded as moderate, and 4.3% and 0.8%, respectively, had events that were graded as severe. Efficacy was not shown in the participants 18 years of age or older. CONCLUSIONS In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. (Funded by Aimmune Therapeutics; PALISADE ClinicalTrials.gov number, NCT02635776 .).

Advanced Maternal Age and Adverse Pregnancy Outcome: Evidence from a Large Contemporary Cohort

Abstract: Background Recent decades have witnessed an increase in mean maternal age at childbirth in most high-resourced countries. Advanced maternal age has been associated with several adverse maternal and perinatal outcomes. Although there are many studies on this topic, data from large contemporary population-based cohorts that controls for demographic variables known to influence perinatal outcomes is limited. Methods We performed a population-based cohort study using data on all singleton births in 2004-2008 from the North Western Perinatal Survey based at The University of Manchester, UK. We compared pregnancy outcomes in women aged 30-34, 35-39 and ≥40 years with women aged 20-29 years using log-linear binomial regression. Models were adjusted for parity, ethnicity, social deprivation score and body mass index. Results The final study cohort consisted of 215,344 births; 122,307 mothers (54.19%) were aged 20-29 years, 62,371(27.63%) were aged 30-34 years, 33,966(15.05%) were aged 35-39 years and 7,066(3.13%) were aged ≥40 years. Women aged 40+ at delivery were at increased risk of stillbirth (RR = 1.83, [95% CI 1.37-2.43]), pre-term (RR = 1.25, [95% CI: 1.14-1.36]) and very pre-term birth (RR = 1.29, [95% CI:1.08-1.55]), Macrosomia (RR = 1.31, [95% CI: 1.12-1.54]), extremely large for gestational age (RR = 1.40, [95% CI: 1.25-1.58]) and Caesarean delivery (RR = 1.83, [95% CI: 1.77-1.90]). Conclusions Advanced maternal age is associated with a range of adverse pregnancy outcomes. These risks are independent of parity and remain after adjusting for the ameliorating effects of higher socioeconomic status. The data from this large contemporary cohort will be of interest to healthcare providers and women and will facilitate evidence based counselling of older expectant mothers.

Prevention of potentially inappropriate prescribing for elderly patients: a randomized controlled trial using STOPP/START criteria.

Abstract: Inappropriate prescribing is particularly common in older patients and is associated with adverse drug events (ADEs), hospitalization, and wasteful utilization of resources. We randomized 400 hospitalized patients aged ≥ 65 years to receive either the usual pharmaceutical care (control) or screening with STOPP/START criteria followed up with recommendations to their attending physicians (intervention). The Medication Appropriateness Index (MAI) and Assessment of Underutilization (AOU) index were used to assess prescribing appropriateness, both at the time of discharge and for 6 months after discharge. Unnecessary polypharmacy, the use of drugs at incorrect doses, and potential drug-drug and drug-disease interactions were significantly lower in the intervention group at discharge (absolute risk reduction 35.7%, number needed to screen to yield improvement in MAI = 2.8 (95% confidence interval 2.2-3.8)). Underutilization of clinically indicated medications was also reduced (absolute risk reduction 21.2%, number needed to screen to yield reduction in AOU = 4.7 (95% confidence interval 3.4-7.5)). Significant improvements in prescribing appropriateness were sustained for 6 months after discharge.

Evaluation of a Cocktail of Three Bacteriophages for Biocontrol of Escherichia coli O157:H7

Abstract: Escherichia coli O157:H7 is an endemic pathogen causing a variety of human diseases including mild diarrhea, hemorrhagic colitis, hemolytic-uremic syndrome, and thrombotic thrombocytopenic purpura. This study concerns the exploitation of bacteriophages as biocontrol agents to eliminate the pathogen E. coli O157:H7. Two distinct lytic phages (e11/2 and e4/1c) isolated against a human strain of E. coli O157:H7, a previously isolated lytic phage (pp01), and a cocktail of all three phages were evaluated for their ability to lyse the bacterium in vivo and in vitro. Phage e11/2, pp01, and the cocktail of all three virulent phages resulted in a 5-log-unit reduction of pathogen numbers in 1 h at 37°C. However, bacteriophage-insensitive mutants (BIMs) emerged following the challenge. All tested BIMs had a growth rate which approximated that of the parental O157 strain, although many of these BIMs had a smaller, more coccoid cellular morphology. The frequency of BIM formation (10−6 CFU) was similar for e11/2, pp01, and the phage cocktail, while BIMs insensitive to e4/1c occurred at the higher frequency (10−4 CFU). In addition, BIMs commonly reverted to phage sensitivity within 50 generations. In an initial meat trial experiment, the phage cocktail completely eliminated E. coli O157:H7 from the beef meat surface in seven of nine cases. Given that the frequency of BIM formation is low (10−6 CFU) for two of the phages, allied to the propensity of these mutants to revert to phage sensitivity, we expect that BIM formation should not hinder the use of these phages as biocontrol agents, particularly since low levels of the pathogen are typically encountered in the environment.