Alcohol in Ireland: consumption, harm, cost and policy response.

Key points among the findings Alcohol –how much and what we drink • In 2014 Irish drinkers consumed 11 litres of pure alcohol each. This is equal to 29 litres of vodka, 116 bottles of wine or 445 pints of beer. • Current per capita consumption is 21% higher than the Department of Health steering group’s target which sets out to reduce per capita consumption, from 11.0 litres of pure alcohol per person to 9.1 litres. • In 2012 Ireland had the fourth highest alcohol consumption level among 36 OECD countries after Estonia, France and Lithuania. • It is not just what Irish people drink, but the way they drink that causes harm. In 2013 the HRB Alcohol Diary survey showed that more than 50% of Irish drinkers consume alcohol in a harmful manner – too much alcohol in one sitting and more than the recommended number of standard drinks in a week. Alcohol – the impact on our health • The number of people discharged from hospital whose condition was totally attributable to alcohol rose by 82% between 1995 and 2013, from 9,420 to 17,120. Males accounted for 72% of these discharges and females 28%. • There has also been a steady increase in the mean length of stay (LOS) for hospital discharges, from 6.0 days in 1995 to 10.1 days in 2013, which suggests that patients with alcohol-related diagnoses are becoming more complex in terms of their illness. • The rate of alcoholic liver disease discharges grew threefold between 1995 and 2013. The highest rate of increase was observed among 15–34 year-olds, albeit from a low rate. • The number of people discharged whose condition was partially attributed to alcohol increased from 52,491 in 2007 to 57,110 in 2011. This is approximately three times the number of discharges totally attributable to alcohol. • Between 2001 and 2010, one in ten breast cancer cases were attributable to alcohol. • Three people died each day in 2013 as a result of drinking alcohol. • In 2014, one- in-three self-harm presentations were alcohol-related. • An estimated 167,170 people suffered an alcohol-related assault. • A total of 7,549 cases entered treatment in 2013 with alcohol as their main problem drug. These cases were predominantly male and median age was 39-40 years. This is a decrease of just over 12% since 2011. This decrease could reflect a true decrease in the number of cases, reduced levels of participation or under-reporting or a combination of these factors. Alcohol – impact on the economy and tax payer • In 2013, alcohol-related discharges accounted for 160,211 bed days in public hospitals, that is 3.6% of all bed days that year; compared to 56,264 bed days or 1.7% of the total number of bed days in 1995. • €1.5 billion is the cost to the tax-payer for alcohol-related discharges from hospital. That is equal to €1 for every €10 spent on public health in 2012. This excludes the cost of emergency cases, GP visits, psychiatric admissions and alcohol treatment services. • An estimated 5,315 people on the Live Register in November 2013 had lost their job due to alcohol use. • The estimated cost of alcohol-related absenteeism was €41,290,805 in 2013

Environmental contamination with clostridioides (Clostridium) difficile in Vietnam

AIMS: To investigate the prevalence, molecular type, and antimicrobial susceptibility of Clostridioides difficile in the environment in Vietnam, where little is known about C. difficile. METHODS AND RESULTS: Samples of pig faeces, soils from pig farms, potatoes, and the hospital environment were cultured for C. difficile. Isolates were identified and typed by polymerase chain reaction (PCR) ribotyping. The overall prevalence of C. difficile contamination was 24.5% (68/278). Clostridioides difficile was detected mainly in soils from pig farms and hospital soils, with 70%-100% prevalence. Clostridioides difficile was isolated from 3.4% of pig faecal samples and 5% of potato surfaces. The four most prevalent ribotypes (RTs) were RTs 001, 009, 038, and QX574. All isolates were susceptible to metronidazole, fidaxomicin, vancomycin, and amoxicillin/clavulanate, while resistance to erythromycin, tetracycline, and moxifloxacin was common in toxigenic strains. Clostridioides difficile RTs 001A+B+CDT- and 038A-B-CDT- were predominantly multidrug resistant. CONCLUSIONS: Environmental sources of C. difficile are important to consider in the epidemiology of C. difficile infection in Vietnam, however, contaminated soils are likely to be the most important source of C. difficile. This poses additional challenges to controlling infections in healthcare settings

GATA-3 Dose-Dependent Checkpoints in Early T Cell Commitment

GATA-3 expression is crucial for T cell development and peaks during commitment to the T cell lineage, midway through the CD4CD8 (double-negative [DN]) stages 1–3. We used RNA interference and conditional deletion to reduce GATA-3 protein acutely at specific points during T cell differentiation in vitro. Even moderate GATA-3 reduction killed DN1 cells, delayed progression to the DN2 stage, skewed DN2 gene regulation, and blocked appearance of the DN3 phenotype. Although a Bcl-2 transgene rescued DN1 survival and improved DN2 cell generation, it did not restore DN3 differentiation. Gene expression analyses (quantitative PCR, RNA sequencing) showed that GATA-3–deficient DN2 cells quickly upregulated genes, including Spi1 (PU.1) and Bcl11a, and downregulated genes, including Cpa3, Ets1, Zfpm1, Bcl11b, Il9r, and Il17rb with gene-specific kinetics and dose dependencies. These targets could mediate two distinct roles played by GATA-3 in lineage commitment, as revealed by removing wild-type or GATA-3–deficient early T lineage cells from environmental Notch signals. GATA-3 worked as a potent repressor of B cell potential even at low expression levels, so that only full deletion of GATA-3 enabled pro–T cells to reveal B cell potential. The ability of GATA-3 to block B cell development did not require T lineage commitment factor Bcl11b. In prethymic multipotent precursors, however, titration of GATA-3 activity using tamoxifen-inducible GATA-3 showed that GATA-3 inhibits B and myeloid developmental alternatives at different threshold doses. Furthermore, differential impacts of a GATA-3 obligate repressor construct imply that B and myeloid development are inhibited through distinct transcriptional mechanisms. Thus, the pattern of GATA-3 expression sequentially produces B lineage exclusion, T lineage progression, and myeloid-lineage exclusion for commitment

Adapting developing country epidemiological assessment techniques to improve the quality of health needs assessments in developed countries

BACKGROUND: We were commissioned to carry out three health assessments in urban areas of Dublin in Ireland. We required an epidemiologically robust method that could collect data rapidly and inexpensively. We were dealing with inadequate health information systems, weak planning data and a history of inadequate recipient involvement in health service planning. These problems had also been identified by researchers carrying out health assessments in developing countries. This paper reports our experience of adapting a cluster survey model originally developed by international organisations to assess community health needs and service coverage in developing countries and applying our adapted model to three urban areas in Dublin, Ireland METHODS: We adapted the model to control for socio-economic heterogeneity, to take account of the inadequate population list, to ensure a representative sample and to account for a higher prevalence of degenerative and chronic diseases. We employed formal as well as informal communication methods and adjusted data collection times to maximise participation. RESULTS: The model we adapted had the capacity to ascertain both health needs and health care delivery needs. The community participated throughout the process and members were trained and employed as data collectors. The assessments have been used by local health boards and non-governmental agencies to plan and deliver better or additional services. CONCLUSION: We were able to carry out high quality health needs assessments in urban areas by adapting and applying a developing country health assessment method. Issues arose relating to health needs assessment as part of the planning cycle and the role of participants in the process

Persons ‘never treated’ in mass drug administration for lymphatic filariasis: identifying programmatic and research needs from a series of research review meetings 2020–2021

As neglected tropical disease programs rely on participation in rounds of mass drug administration (MDA), there is concern that individuals who have never been treated could contribute to ongoing transmission, posing a barrier to elimination. Previous research has suggested that the size and characteristics of the never-treated population may be important but have not been sufficiently explored. To address this critical knowledge gap, four meetings were held from December 2020 to May 2021 to compile expert knowledge on never treatment in lymphatic filariasis (LF) MDA programs. The meetings explored four questions: the number and proportion of people never treated, their sociodemographic characteristics, their infection status and the reasons why they were not treated. Meeting discussions noted key issues requiring further exploration, including how to standardize measurement of the never treated, adapt and use existing tools to capture never-treated data and ensure representation of never-treated people in data collection. Recognizing that patterns of never treatment are situation specific, participants noted measurement should be quick, inexpensive and focused on local solutions. Furthermore, programs should use existing data to generate mathematical models to understand what levels of never treatment may compromise LF elimination goals or trigger programmatic action

Association between T2-related co-morbidities and effectiveness of biologics in severe asthma

Acknowledgments The authors thank Mr. Joash Tan (BSc, Hons), of the Observational and Pragmatic Research Institute (OPRI), and Ms Andrea Lim (BSc, Hons) of the Observational Pragmatic Research Institute (OPRI) for their editorial and formatting assistance that supported the development of this publication. Funding statement: This study was conducted by the Observational and Pragmatic Research Institute (OPRI) Pte Ltd and was partially funded by Optimum Patient Care Global and AstraZeneca Ltd. AstraZeneca UK LimitedPeer reviewe