Interaction of Crohn's Disease Susceptibility Genes in an Australian Paediatric Cohort

Genetic susceptibility is an important contributor to the pathogenesis of Crohn's disease (CD). We investigated multiple CD susceptibility genes in an Australian paediatric onset CD cohort. Newly diagnosed paediatric onset CD patients (n = 72) and controls (n = 98) were genotyped for 34 single nucleotide polymorphisms (SNPs) in 18 genetic loci. Gene-gene interaction analysis, gene-disease phenotype analysis and genetic risk profiling were performed for all SNPs and all genes. Of the 34 SNPs analysed, four polymorphisms on three genes (NOD2, IL23R, and region 3p21) were significantly associated with CD status (p<0.05). All three CD specific paediatric polymorphisms on PSMG1 and TNFRSF6B showed a trend of association with p<0.1. An additive gene-gene interaction involving TLR4, PSMG1, TNFRSF6B and IRGM was identified with CD. Genes involved in microbial processing (TLR4, PSMG1, NOD2) were significantly associated either at the individual level or in gene-gene interactive roles. Colonic disease was significantly associated with disease SNP rs7517847 (IL23R) (p<0.05) and colonic and ileal/colonic disease was significantly associated with disease SNP rs125221868 (IBD5) and SLC22A4 & SLC22A4/5 variants (p<0.05). We were able to demonstrate genetic association of several genes to CD in a paediatric onset cohort. Several of the observed associations have not been reported previously in association with paediatric CD patients. Our findings demonstrate that CD genetic susceptibility in paediatric patients presents as a complex interaction between numerous genes

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Is Social Work Still a Distinctive Profession? Students, Supervisors and Educators Reflect

Many social workers are finding themselves in practice settings where they are competing with an increasing number of allied professionals for recognition, service provision and funding. The rise in multifunctional approaches to the delivery of social and health care provisions as well as the gradual privatisation of welfare services is creating further challenges for social workers. This article reports on a research project undertaken with social work students, supervisors and educators in an Australian university which aimed to explore whether social work still had a distinctiveness in this climate and whether it was up to the challenges it was facing. While the sample is small and generalisations are limited, results from this study feed into concerns already identified in the literature which suggest that social workers need to become more proactive in responding to the current challenges in order to keep their practice distinctive, as well as reflective, responsive and relevant

'I thought they would just let me do my job': Work-based practica in social work and welfare

Social work and welfare education courses are underpinned by concepts such as equity, disadvantage and access as the guiding principles of practice with client groups. However, the ‘clients’ of the university, the students, are often disadvantaged in the current economic climate as they struggle to find the work/life balance with studying. In addition, many students who also currently work in the welfare field feel further disadvantaged as the knowledge and skills they bring to the course often go unrecognised. At the same time, university educators often struggle to locate sufficient numbers of stimulating learning opportunities for practica. We wondered if the time was right to explore work based practica (WBP) as a way of addressing these issues. And we wondered what common practica was across our networks with regard to WBP. This article presents the findings of a three-stage project on the current practices, concerns, benefits and disadvantages of WBP (that is practica in a student’s place of employment) in social work and welfare education in Australia, New Zealand and Canada. Recommendations are presented so that WBP can be a more educationally sound optio

'I thought they would just let me do my job': Work-based practica in social work and welfare

The article presents the findings of a three-stage project on the current practices, concerns, benefits and disadvantages of practica in social work and welfare education in Australia, New Zealand and Canada

'It is more complicated than you first think!' The challenges of work-based practica

Work-based practica (that is practica in the student’s usual place of employment) can be viewed as an ‘easy option’ for locating placements in the context of high competition for a limited range of practica opportunities. Students who are currently working in the human services sector as well as mature age students with family/life responsibilities also see that work-based practica (WBP) is a pragmatic and equitable way of reducing the pressure of study/work/family demands. It can also increase access to a professionally based award with a huge practica load. However we would argue that a WBP is a complex option with significant advantages and disadvantages and, before undertaken, university educators need to explore the complexities. This article presents findings on the third and final stage of a project that explored current practices, concerns, advantages and disadvantages of WBP in social work from the experiences of field-based supervisors and students who undertook WBP during their course. This stage builds on the previous two stages of this project that explored the practices, concerns and advantages and disadvantages of WBPs from the perspective of university-based educators in Australia, New Zealand, Canada, and at an international meeting of social work educators. Several recommendations are proposed if WBP is to become a viable option for students

Flow chart of available data on postnatal depression, birth outcomes, and breast feeding behaviours of mothers of infants from South Western Sydney and Sydney Local Health Districts in 2014 (n = 17,564).

<p>Flow chart of available data on postnatal depression, birth outcomes, and breast feeding behaviours of mothers of infants from South Western Sydney and Sydney Local Health Districts in 2014 (n = 17,564).</p