Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn’s disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource

Objective: Thiopurines are widely used as maintenance therapy in inflammatory bowel disease (IBD) but the evidence base for their use is sparse and their role increasingly questioned. Using the largest series reported to date, we assessed the long-term effectiveness of thiopurines in ulcerative colitis (UC) and Crohn’s disease (CD), including their impact on need for surgery. Design: Outcomes were assessed in 11 928 patients (4968 UC, 6960 CD) in the UK IBD BioResource initiated on thiopurine monotherapy with the intention of maintaining medically induced remission. Effectiveness was assessed retrospectively using patient-level data and a definition that required avoidance of escalation to biological therapy or surgery while on thiopurines. Analyses included overall effectiveness, time-to-event analysis for treatment escalation and comparison of surgery rates in patients tolerant or intolerant of thiopurines. Results: Using 68 132 patient-years of exposure, thiopurine monotherapy appeared effective for the duration of treatment in 2617/4968 (52.7%) patients with UC compared with 2378/6960 (34.2%) patients with CD (p<0.0001). This difference was corroborated in a multivariable analysis: after adjusting for variables including treatment era, thiopurine monotherapy was less effective in CD than UC (OR 0.47, 95% CI 0.43 to 0.51, p<0.0001). Thiopurine intolerance was associated with increased risk of surgery in UC (HR 2.44, p<0.0001); with a more modest impact on need for surgery in CD (HR=1.23, p=0.0015). Conclusion: Thiopurine monotherapy is an effective long-term treatment for UC but significantly less effective in CD

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

Measuring microbial viability. How to do it and what does it mean?

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Collaborating across sectors to provide early intervention for Aboriginal and Torres Strait Islander children with disability and their families: a qualitative study of provider perspectives

Aboriginal and Torres Strait Islander children experience a higher prevalence of disability than other Australian children. Early intervention from across the health, education, and social service sectors is vital for improving outcomes, but families face lack of coordination between services. This study aimed to inform improvements in service access for families of urban-dwelling Aboriginal children with disability through exploring providers’ perceptions of factors that influenced working together across sectors. Semi-structured interviews were conducted. Data analysis was informed by the general inductive approach and the Collaborative Practice to Enhance Patient Care Outcomes framework. Twenty-four providers participated. Interprofessional collaborative practice was influenced by interdependent interactional and organizational factors. Interactional factors fit within one of two dimensions: the ability of providers to share common goals and vision within a complex cross-sector service landscape, and influence of interpersonal relationships on their sense of belonging working in a cross-cultural space. Organizational factors also fit within one of two dimensions: the influence of governance in relation to its role in coordination and unlocking the strength of schools as service settings, and the need to formalize processes for effective interprofessional communication. Interprofessional collaborative practice was managed within the context of systemic factors relating to policy and funding. These findings demonstrate the complex interplay of factors related to the cross-sector involvement of providers in early intervention service provision. Consideration of these factors is required to facilitate collaborative cross-sector responses to improve service access for Aboriginal families. Abbreviations: WHO: world health organization; ACCHS: aboriginal community controlled health service; GP: general practitioner; NDIS: national disability insurance scheme

'It's quite a complex trail for families now' : provider understanding of access to services for Aboriginal children with a disability

Aboriginal and Torres Strait Islander children experience a higher prevalence of disability and socio-economic disadvantage than other Australian children. Early intervention from across the health, education and social service sectors is vital for improving outcomes, but families face a number of barriers to service access which impede intervention. This study aimed to inform ways to improve access to services for families of urban-dwelling Aboriginal children with a range of disabilities. A qualitative approach was taken to explore providers’ perceptions of factors that either impeded or enabled families’ access to services. In this research, the term ‘provider’ refers to individuals who are employed in a range of sectors to deliver a service involving assessment or management of an individual with a disability. Semi-structured in-depth interviews with 24 providers were conducted. Data analysis was informed by the general inductive approach and then applied deductively to the candidacy framework to generate additional insights. Candidacy focuses on how potential users access the services they need and acknowledges the joint negotiation between families and providers regarding such access. Our research identified that candidacy was influenced by the historical legacy of colonisation and its ongoing socio-cultural impact on Aboriginal people, as well as funding and current policy directives. Enacting culturally sensitive and meaningful engagement to better understand families’ needs and preferences for support, as well as support for providers to develop their understanding of family contexts, will contribute to facilitating service access for Aboriginal children with a disability

Cell Surface Proteomics Provides Insight into Stage-Specific Remodeling of the Host-Parasite Interface in Trypanosoma brucei*

African trypanosomes are devastating human and animal pathogens transmitted by tsetse flies between mammalian hosts. The trypanosome surface forms a critical host interface that is essential for sensing and adapting to diverse host environments. However, trypanosome surface protein composition and diversity remain largely unknown. Here, we use surface labeling, affinity purification, and proteomic analyses to describe cell surface proteomes from insect-stage and mammalian bloodstream-stage Trypanosoma brucei. The cell surface proteomes contain most previously characterized surface proteins. We additionally identify a substantial number of novel proteins, whose functions are unknown, indicating the parasite surface proteome is larger and more diverse than generally appreciated. We also show stage-specific expression for individual paralogs within several protein families, suggesting that fine-tuned remodeling of the parasite surface allows adaptation to diverse host environments, while still fulfilling universally essential cellular needs. Our surface proteome analyses complement existing transcriptomic, proteomic, and in silico analyses by highlighting proteins that are surface-exposed and thereby provide a major step forward in defining the host-parasite interface