Publications by authors named "CONNELL W"

Background & Aims: Crohn's perianal fistula healing rates remain low. We evaluated the efficacy of a protocolised multidisciplinary treatment strategy optimising care in adults with Crohn's perianal fistulas.

Methods: A new treatment strategy was established at a single tertiary centre.

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Chemical probes interrogate disease mechanisms at the molecular level by linking genetic changes to observable traits. However, comprehensive chemical screens in diverse biological models are impractical. To address this challenge, we develop ChemProbe, a model that predicts cellular sensitivity to hundreds of molecular probes and drugs by learning to combine transcriptomes and chemical structures.

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Background: The optimal dosing strategy for infliximab in steroid-refractory acute severe ulcerative colitis (ASUC) is unknown. We compared intensified and standard dose infliximab rescue strategies and explored maintenance therapies following infliximab induction in ASUC.

Methods: In this open-label, multicentre, randomised controlled trial, patients aged 18 years or older from 13 Australian tertiary hospitals with intravenous steroid-refractory ASUC were randomly assigned (1:2) to receive a first dose of 10 mg/kg infliximab or 5 mg/kg infliximab (randomisation 1).

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Article Synopsis
  • Thiopurine co-therapy with anti-TNFα agents improves drug levels and reduces the chance of developing antibodies in patients with inflammatory bowel disease (IBD).* -
  • A study analyzed the relationship between 6-thioguanine nucleotide (6-TGN) levels and anti-TNFα levels among IBD patients from 2015 to 2021, showing a significant link with infliximab but not adalimumab.* -
  • The research identified optimal 6-TGN cut-off levels for effective therapeutic anti-TNFα levels, suggesting lower levels may suffice for treatment, particularly for infliximab.*
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Background And Aims: The risk of intrahepatic cholestasis of pregnancy [ICP] is increased in thiopurine-exposed pregnancies. Thiopurine 'shunting', with a 6-methylmercaptopurine [MMP] to 6-thioguanine [TGN] ratio of >11, progresses over pregnancy, and may promote ICP development. We aimed to explore the association between thiopurine exposure and ICP, including the hypothesised impact of thiopurine shunting, and identify risk minimisation strategies.

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The challenge of systematically modifying and optimizing regulatory elements for precise gene expression control is central to modern genomics and synthetic biology. Advancements in generative AI have paved the way for designing synthetic sequences with the aim of safely and accurately modulating gene expression. We leverage diffusion models to design context-specific DNA regulatory sequences, which hold significant potential toward enabling novel therapeutic applications requiring precise modulation of gene expression.

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Background: Despite reassuring clinical safety data, thrombocytosis, anemia, lymphopenia, and liver function derangements have been observed in infants born to women with inflammatory bowel disease (IBD) treated with thiopurines and biologics. We aimed to define the prevalence, course, associations, and clinical impact of hematological and biochemical abnormalities in such infants.

Methods: This multicenter prospective cohort study assessed clinical, hematologic, and biochemical outcomes of infants exposed to thiopurines or biologics in utero for management of maternal IBD.

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Article Synopsis
  • - Foreign body ingestion is a frequent reason for Emergency Department visits, particularly in vulnerable groups such as the elderly, individuals with psychiatric issues, and prisoners, with a study in Melbourne analyzing data from 2017 to 2021 involving 63 patients.
  • - The study found that a significant portion (65%) of cases involved prisoners, with common ingested items being batteries (23%), drug-containing balloons (17%), and razor blades (16%); most ingestions were categorized as high-risk.
  • - Conservative management was successfully applied in 55% of cases without complications, although 31% of patients returned within 30 days, highlighting the ongoing challenges in managing those with high-risk, intentional ingestions and mental health concerns.
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Chemical probes interrogate disease mechanisms at the molecular level by linking genetic changes to observable traits. However, comprehensive chemical screens in diverse biological models are impractical. To address this challenge, we developed ChemProbe, a model that predicts cellular sensitivity to hundreds of molecular probes and drugs by learning to combine transcriptomes and chemical structures.

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Background: Inflammatory bowel disease (IBD) is best managed by a multidisciplinary team within a dedicated IBD service. IBD nurses play an important role within this team. We aimed to evaluate the contribution of our comprehensive outpatient IBD nursing service on patient outcomes, quality of care, and healthcare costs.

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Background: Patients with inflammatory bowel disease (IBD) are at increased risk of malignancy and infection compared to the general population.

Aims: We aim to identify risk factors for malignancy or serious infection in our IBD cohort.

Methods: Patients with IBD from a single tertiary referral centre were included.

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Background: In medically refractory Ulcerative Colitis (UC), proctocolectomy with ileoanal pouch procedure (IAPP) is the preferred continence-preserving surgical option. Functional outcomes post-surgery and long-term complication rates in the biologic era remain ambiguous. This review primarily aims to provide an update on these outcomes.

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Background And Objectives: The role of therapeutic drug monitoring for ustekinumab in the treatment of Crohn's disease has not been defined. This study aimed to explore the relationship of serum ustekinumab trough concentration (UTC) with clinical and biochemical disease outcomes in a real-world setting.

Methods: We performed a retrospective analysis of Crohn's disease patients treated at a single tertiary centre.

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Background: In 2014, infliximab (IFX) was listed on the Australian Pharmaceutical Benefits Scheme for acute severe ulcerative colitis (ASUC) and is now the preferred option for medical salvage, superseding cyclosporin A (CsA). Optimal dosing schedules for IFX remain unknown.

Aim: The authors aim to evaluate the effect of changing from predominantly CsA to almost exclusively IFX for the treatment of steroid-refractory ASUC on colectomy rates.

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Article Synopsis
  • Elderly patients with inflammatory bowel disease (IBD) were found to have lower rates of steroid-free clinical remission compared to younger adults, suggesting poorer management outcomes for the older cohort.
  • The study showed that elderly patients used biologic treatments like infliximab and adalimumab less frequently and had less contact with specialized IBD nursing, which is crucial for preventative care.
  • Overall, the findings indicate a need to improve care models for elderly IBD patients by enhancing their access to multidisciplinary care and education on preventative health measures.
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Artificial intelligence (AI) technology is being evaluated for its potential to improve colonoscopic assessment of inflammatory bowel disease (IBD), particularly with computer-aided image classifiers. This review evaluates the clinical application and diagnostic test accuracy (DTA) of AI algorithms in colonoscopy for IBD. A systematic review was performed on studies evaluating AI in colonoscopy of adult patients with IBD.

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Background And Aims: Alterations in body composition are common in inflammatory bowel disease [IBD] and have been associated with differences in patient outcomes. We sought to consolidate knowledge on the impact and importance of body composition in IBD.

Methods: We performed a systematic search of MEDLINE, EMBASE and conference proceedings by combining two key research themes: inflammatory bowel disease and body composition.

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Heterogeneous genetic and environmental factors contribute to the psoriasis phenotype, resulting in a wide range of patient response to targeted therapies. Here, we investigate genetic factors associated with response to the IL-12/23 inhibitor ustekinumab in psoriasis. To date, only HLA-C*06:02 has been consistently reported to associate with ustekinumab response in psoriasis.

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Artificial Intelligence (AI) has the power to improve our lives through a wide variety of applications, many of which fall into the healthcare space; however, a lack of diversity is contributing to limitations in how broadly AI can help people. The UCSF AI4ALL program was established in 2019 to address this issue by targeting high school students from underrepresented backgrounds in AI, giving them a chance to learn about AI with a focus on biomedicine, and promoting diversity and inclusion. In 2020, the UCSF AI4ALL three-week program was held entirely online due to the COVID-19 pandemic.

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Article Synopsis
  • Strictures commonly occur in Crohn's disease, and while surgery and endoscopic dilation are standard treatments, this study investigates if intensive drug therapy can effectively treat strictures with inflammatory components, challenging the idea that drug therapy is contraindicated.
  • An open-label, single-centre randomised controlled trial in Australia involved patients aged 18 or older with de novo or postoperative intestinal strictures, assessing the effectiveness of intensive high-dose adalimumab combined with thiopurine versus standard adalimumab therapy.
  • The trial aimed to measure the primary endpoint of improvement in obstructive symptoms after 12 months; 123 patients were screened, with 77 participating in the study, which was registered and completed
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Background: Preventive health measures reduce treatment and disease-related complications including infections, osteoporosis, and malignancies in patients with inflammatory bowel disease (IBD). Although guidelines and quality measures for IBD care highlight the importance of preventive care, their uptake remains variable. This systematic review evaluates interventions aimed at improving the rates of provision and uptake of preventive health measures, including vaccinations, bone density assessment, skin cancer screening, cervical cancer screening, and smoking cessation counseling.

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