JobsPlus evaluation

The aim of this evaluation is to provide evidence on the effectiveness of JobsPlus, a financial incentive launched in 2013 and consisting of employment subsidies for long-term unemployed. The JobsPlus scheme provides two treatment types: a subsidy of euro 7,500 for employees who had been unemployed for between one and two years, and a subsidy of euro 10,000 for employees who had been unemployed for more than two years. This analysis covers entrants from the scheme inception in July 2013 to April 2016. The effect of JobsPlus is estimated separately for the two types of subsidy exploiting the detailed information on unemployed past working histories, available in the Jobseekers Longitudinal Dataset (JLD) administrative database, applying a matching approach. The results point to a positive impact of the subsidy on JobsPlus participants who, after the programme, are less likely to be in receipt of unemployment-related benefits and show a higher probability to earn more and to work for more weeks in a year. For those we can observe over the longest duration subsequent to their JobsPlus start (four years), the difference between the two groups in their probability of receiving unemployment benefits is between 11.1 percentage points (unemployed for at least one year) and 16.4 percentage points (unemployed for at least two years).JRC.I.1-Monitoring, Indicators & Impact Evaluatio

Effect of the α4β7 integrin blocking antibody vedolizumab on the clinical and host immune response in patients with inflammatory bowel disease

Background: Inflammatory bowel disease (IBD) is a chronic, relapsing and remitting condition affecting the gastrointestinal tract. Development of IBD is thought to arise from a complex interplay of genetic susceptibility, environmental contributors, and disordered immune responses to host microbial components. Improvements in our understanding of these interactions have identified novel therapeutic targets and therapeutic interventions which will address unmet clinical need and the therapeutic gap in IBD. However, currently, response and remission rates remain static, reflecting the need and potential for future developments. Vedolizumab (VDZ) is a humanised monoclonal anti-integrin targeting the α4β7 molecule. It is designed to have gut-specific anti-inflammatory effects by blocking the interaction between α4β7+ lymphocytes and mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) on gut endothelial cells. It is thought that this may reduce lymphocyte trafficking specifically into inflamed gut tissue in IBD. Despite advances in our understanding of its clinical efficacy and its proposed mechanism of action the exact mechanism of action of this drug remains uncertain. Aim: The aim of this MD thesis is to characterise the effect of treatment with VDZ on patients with IBD at the clinical and immune system level over three studies, to determine if there are clinical or immune features that may predict or enhance response to therapy, or that may create new opportunities for treating this challenging group of conditions. Methods: Study One was a cohort study evaluating the clinical outcomes of patients with IBD treated with VDZ from 9 Irish hospitals. Study Two was designed as a prospective cohort study to assess the impact of VDZ monotherapy on the gut mucosal immune response. Mucosal biopsies were obtained from patients about to start VDZ therapy for active IBD and isolated cells from tissue were analyzed by flow cytometry to assess both mucosal α4β7+ macrophages (CD45, CD11c, CD14, CD163, CD64, CD66b, HLA DR, SIRPa, CD103, α4β7) and α4β7+ lymphocytes (CD3, CD4, CD8, CCR7, CD45 RA, αEβ7, α4β7). Study Three took a similar approach to investigate potential differences in the gut mucosal immune response of patients already established on a combination therapy (CBT) of VDZ with another anti-TNF biological therapy (e.g. VDZ + infliximab, or VDZ + adalimumab) for treatment-refractory IBD, versus those established on VDZ-monotherapy, or patients who were VDZ-naïve. Results: Analysis of 129 patients in Study One supported the clinical efficacy and safety of VDZ in IBD, with 6-month corticosteroid-free clinical remission rates of 31% and 48% in patients with ulcerative colitis (UC) and Crohn’s disease (CD), respectively; and adverse event rates of 1% and 11%, respectively. Study Two, although limited by effects of Covid-19 pandemic in Ireland, revealed that there were more α4β7+ monocytes and lymphocytes in inflamed vs non-inflamed GI mucosa, and more α4β7+ lymphocytes in mucosal samples from patients with CD vs UC. Small numbers of CD64+α4β7+ monocytes were also identified in the inflamed tissue. Study Three revealed a significant ongoing trend towards a higher percentage of α4β7+ T cells in those treated with VDZ-CBT in comparison to both other groups, in addition to an overall increase in the number of αEβ7+ cells in both CD4+ and CD8+ compartments in those treated with VDZ-CBT. Conclusion: Study One demonstrated the clinical utility of VDZ in the treatment of IBD in an Irish cohort of patients, providing valuable real-world data in line with international studies. Study Two supports reports that α4β7+ lymphocytes are more prevalent in inflamed tissue in IBD, and suggests that α4β7+ monocytes may play a role in mucosal inflammation. Study Three demonstrates ongoing presence of α4β7+ cells despite combination biologic therapy, perhaps due to a more refractory inflammatory phenotype, or the ‘re-wiring’ of inflammatory pathways. This project provides valuable information on the clinical utility of VDZ in the treatment of IBD, in addition to novel insight into the cellular and immunological effects of this important medication

A Systematic Review of the Causes and Management of Ischaemic Stroke Caused by Nontissue Emboli

Introduction. The inadvertent or purposeful introduction of foreign bodies or substances can lead to cerebral infarction if they embolize to the brain. Individual reports of these events are uncommon but may increase with the increased occurrences of their risk factors, for example, intra-arterial procedures. Method. We searched EMBASE and MEDLINE for articles on embolic stroke of nontissue origin. 1889 articles were identified and screened and 216 articles were ultimately reviewed in full text and included in qualitative analysis. Articles deemed relevant were assessed by a second reviewer to confirm compatibility with the inclusion criteria. References of included articles were reviewed for relevant publications. We categorized the pathology of the emboli into the following groups: air embolism (141 reports), other arterial gas embolisms (49 reports), missiles and foreign bodies (16 reports), and others, including drug embolism, cotton wool, and vascular sclerosant agents. Conclusion. Air and gaseous embolism are becoming more common with increased use of interventional medical procedures and increased popularity of sports such as diving. There is increasing evidence for the use of hyperbaric oxygen for such events. Causes of solid emboli are diverse. More commonly reported causes include bullets, missiles, and substances used in medical procedures

A Systematic Review of the Causes and Management of Nonthrombotic Embolic Stroke of Tissue Origin

Introduction. Various bodily tissues have been reported to enter the arterial circulation and embolize to the brain resulting in ischemic stroke. Most frequently nonthrombotic embolic stroke (NTES) of tissue origin is iatrogenic or related to an underlying disease process. With the increase in elective surgery and intravascular procedures, NTES may increase in prevalence. Aim. To compile a summary of the background, incidence, presentation, and treatment of NTES of tissue origin, by conducting a systematic review of the current literature. Summary of Review. We searched EMBASE and MEDLINE for articles on NTES of tissue origin published in English with no restriction on publication date (search date June 2017). 800 articles were identified and screened and 159 articles were ultimately reviewed in full text and included in qualitative analysis. Articles deemed relevant were assessed by a second reviewer to confirm compatibility with the inclusion criteria. References of included articles were reviewed for relevant publications. We categorized the pathology of the emboli into the following groups: amniotic fluid (4 publications), tumour (60 publications), fat (43 publications), cholesterol (19 publications), and intravascular debris (12 publications). We then summarized the available literature on each cause of NTES. Conclusions. NTES of tissue origin is an uncommon but important diagnosis to consider particularly in younger stroke patients and in certain clinical settings. Treatment for NTES is currently anecdotal and based on small case series. Embolectomy may emerge as the therapy of choice due to the longer treatment timeframe and heterogeneity of the emboli

CE22010

The WESPAS survey program is the consolidation of two existing survey programs carried out by FEAS, the Malin Shelf herring acoustic survey, and the boarfish acoustic survey. The Malin Shelf herring acoustic survey has been carried out annually since 2008 and reports on the annual abundance of summer feeding aggregations of herring to the west of Scotland and to the north and west of Ireland from 53°30’N to 58°30’N. The boarfish survey was conducted from 2011 using a chartered fishing vessel and reported the abundance of spawning aggregations of boarfish from 47°N to 57°N. In 2016 both surveys were combined into the WESPAS survey and have been carried out onboard the RV Celtic Explorer over a 42-day period, providing synoptic coverage of shelf waters from 47°30’N northwards to 58°30’N. Age stratified relative stock abundance estimates of boarfish, herring and horse mackerel within the survey area were calculated using acoustic data and biological data from trawl sampling. Stock estimates of boarfish and horse mackerel were submitted to the ICES assessment Working Group for Widely Distributed Stocks (WGWIDE) meeting in August 2022. Herring estimates are submitted to the Herring Assessment Working Group (HAWG) meeting in March every year. Survey performance will be reviewed at the ICES Planning Group meeting for International Pelagic Surveys (WGIPS) meeting in January 2023

CE21009

The WESPAS survey program is the consolidation of two existing survey programs carried out by FEAS, the Malin Shelf herring acoustic survey, and the boarfish acoustic survey. The Malin Shelf herring acoustic survey has been carried out annually since 2008 and reports on the annual abundance of summer feeding aggregations of herring to the west of Scotland and to the north and west of Ireland from 53°30’N to 58°30’N. The boarfish survey was conducted from 2011 using a chartered fishing vessel and reported the abundance of spawning aggregations of boarfish from 47°N to 57°N. In 2016 both surveys were combined into the WESPAS survey and have been carried out onboard the RV Celtic Explorer over a 42-day period, providing synoptic coverage of shelf waters from 47°30’N northwards to 58°30’N. Age stratified relative stock abundance estimates of boarfish, herring and horse mackerel within the survey area were calculated using acoustic data and biological data from trawl sampling. Stock estimates of boarfish and horse mackerel were submitted to the ICES assessment Working Group for Widely Distributed Stocks (WGWIDE) meeting in August 2021. Herring estimates are submitted to the Herring Assessment Working Group (HAWG) meeting in March every year. Survey performance will be reviewed at the ICES Planning Group meeting for International Pelagic Surveys (WGIPS) meeting in January 2022

JobsPlus evaluation

The aim of this evaluation is to provide evidence on the effectiveness of JobsPlus, a nancial incentive launched in 2013 and consisting of employment subsidies for long-term unemployed. The JobsPlus scheme provides two treatment types: a subsidy of e7,500 for employees who had been unemployed for between one and two years, and a subsidy of e10,000 for employees who had been unemployed for more than two years. This analysis covers entrants from the scheme inception in July 2013 to April 2016. The effect of JobsPlus is estimated separately for the two types of subsidy exploiting the detailed information on unemployed past working histories, available in the Jobseekers Longitudinal Dataset (JLD) administrative database, applying a matching approach. The results point to a positive impact of the subsidy on JobsPlus participants who, after the programme, are less likely to be in receipt of unemployment-related benefits and show a higher probability to earn more and to work for more weeks in a year. For those we can observe over the longest duration subsequent to their JobsPlus start (four years), the difference between the two groups in their probability of receiving unemployment benefits is between 11.1 percentage points (unemployed for at least one year) and 16.4 percentage points (unemployed for at least two years)

Gender Dysphoria – Prevalence and Co-Morbidities in an Irish Adult Population

Introduction: Gender dysphoria (GD) is a condition in which there is a marked incongruence between an individual’s psychological perception of his/her sex and their biological phenotype. Gender identity disorder was officially renamed “gender dysphoria” in the DSM-V in 2013. The prevalence and demographics of GD vary according to geographical location and has not been well-documented in Ireland. Methods: We retrospectively reviewed medical records of 218 patients with suspected or confirmed GD referred to our endocrine service for consideration of hormonal therapy (HT) between 2005 and early 2014. We documented their demographics, clinical characteristics, and treatment during the study period. Results: The prevalence of GD in the Irish population was 1:10,154 male-to-female (MTF) and 1:27,668 female-to-male (FTM), similar to reported figures in Western Europe. 159 of the patients were MTF and 59 were FTM, accounting for 72.9% and 27.1% of the cohort, respectively. The rate of referral has increased year-on-year, with 55 patients referred in 2013 versus 6 in 2005. Mean ages were 32.6 years (MTF) and 32.2 years (FTM). 22 of the patients were married and 41 had children, with 2 others having pregnant partners. 37.6% were referred by a psychologist, with the remainder evenly divided between GPs and psychiatric services. There were low rates of coexistent medical illness although psychiatric conditions were more prevalent, depression being a factor in 34.4% of patients. 5.9% of patients did not attend a mental health professional. 74.3% are currently on HT, and 9.17% have had gender reassignment surgery (GRS). Regret following hormonal or surgical treatment was in line with other Western European countries (1.83%). Conclusion: The incidence of diagnosis and referral of GD in Ireland is increasing. This brings with it multiple social, health, and financial implications. Clear and accessible treatment pathways supported by mental health professionals is essential

Severe Symptomatic Primary CMV Infection in Inflammatory Bowel Disease Patients with Low Population Seroprevalence

Background. Cytomegalovirus disease in patients with inflammatory bowel disease is frequently the result of viral reactivation. Conversely, primary CMV infection is believed to be uncommon in immunocompetent adults due to high population seroprevalence. Objectives. The aim of this study was to examine the frequency and severity of primary cytomegalovirus infection in an adult cohort of IBD patients. Study Design. A retrospective review of a prospectively maintained database of 3200 IBD patients attending a single academic centre was performed. Patients with primary CMV infection 2010–13 were identified; clinical, serologic, and virologic parameters were studied in detail. The seroprevalence of CMV in the patient population was also evaluated. Results. Eight patients with IBD (UC = 3, IBD-U = 1, CD = 4) presented with primary CMV infection. Patients presented with both gastrointestinal and extraintestinal symptoms. Mean age was 33 years, and median duration of disease was 72 months. All eight patients were receiving a thiopurine immunomodulator. Median duration of IM use was 144 weeks (range 7–720 weeks). All 8 patients required hospitalisation, with 1 ICU admission; the median length of hospital stay was 11 days (range 6–27). Infection resolved in all cases with withdrawal of immunomodulator and/or antiviral therapy. Seroprevalence of IgG to CMV, indicating prior exposure, in a subgroup of IBD patients (n=80) was 30.5% and increased with age. Conclusion. Primary cytomegalovirus infection can cause a severe illness in IBD patients, particularly those receiving immunosuppression. In areas where adult CMV seroprevalence is low, evidence of CMV should be sought in IBD patients presenting with any febrile systemic illness

Safety and efficacy of combining biologics or small molecules for inflammatory bowel disease or immune-mediated inflammatory diseases: A European retrospective observational study

Few data are available regarding the combination of biologics or small molecules in inflammatory bowel disease (IBD) patients. We report safety and efficacy of such combinations through a retrospective multicentre series.Combination therapy was defined as the concomitant use of two biologics or one biologic with a small molecule. Patient demographics, disease characteristics and types of combinations were recorded. Safety was evaluated according to the occurrence of serious infection, opportunistic infection, hospitalisation, life-threatening event, worsening of IBD or immune-mediated inflammatory diseases (IMID), cancer and death. Efficacy was evaluated as the physician global assessment of the combination and comparison of clinical/endoscopic scores of IBD/IMID activity prior and during combination.A total of 104 combinations were collected in 98 patients. Concomitant IMID were present in 41 patients. Reasons for starting combination therapy were active IBD (67%), active IMID or extra-intestinal manifestations (EIM) (22%), both (10%) and unclassified in 1. Median duration of combination was 8 months (interquartile range 5-16). During 122 patient-years of follow-up, 42 significant adverse events were observed, mostly related to uncontrolled IBD. There were 10 significant infections, 1 skin cancer and no death. IBD disease activity was clinically improved in 70% and IMID/EIM activity in 81% of the patients. Overall, combination was continued in 55% of the patients.Combination of biologics and small molecules in patients with IBD and IMID/EIM seems to be a promising therapeutic strategy but is also associated with a risk of opportunistic infections or infections leading to hospitalisation in 10%