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Background: Diabetic ketoacidosis (DKA) is a life-threatening emergency that can result from delayed diagnosis of type 1 diabetes mellitus (T1DM). Three-quarters of Australian children with a new diagnosis of T1DM visit their general practitioner (GP) the week prior to developing DKA, with similar trends observed internationally., Objective: To summarise interventions in general practice to reduce diagnostic delay in paediatric T1DM and to evaluate their effectiveness., Methods: Six databases (Ovid, Web of Science, CINAHL, Evidence-Based Medicine Reviews, Google Scholar and EMBASE) were searched. Any English language, less than 20 years study involving interventions targeting GPs specifically in the prevention of paediatric DKA, was included. Primary outcomes were (a) the number of children presenting to the hospital in DKA following diagnostic delay after a GP visit and (b) DKA rate. The secondary outcome was changes in GPs' behaviour regarding timeliness of referrals. Two reviewers completed title, abstract and full-text review, with conflicts resolved by a third reviewer. ROBINS-I risk of bias was used for appraisal. High heterogeneity among studies rendered meta-analysis unsuitable. Structured tabulation of results was completed for analysis. The date of last search was 2 July 2023., Results: Eight studies were included (three conference abstracts and five peer-reviewed publications.) We identified six intervention types attempting to facilitate timely diagnosis of type 1 diabetes in the general practice setting: direct communication, indirect communication, education sessions, electronic clinical decision support tools, updated referral pathways and provision of glucose and/or ketone monitors. Due to the limited number of peer-reviewed studies identified by this review, we were not able to identify the extent to which these interventions were successful., Conclusion: Paucity of information regarding study methodology and high heterogeneity among study design and outcome measures limited our conclusions regarding acceptability, effectiveness and reach. Future studies should include GPs in their design and consider the sustainability of interventions in the long term., Prospero Registration Number: CRD42023412504., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Photodynamic therapy (PDT) is a light-based anticancer therapy that can induce tumor necrosis and/or apoptosis. Two important factors contributing to the efficacy of PDT are the concentration of the photosensitizer in the tumor tissue and its preferential accumulation in the tumor tissue compared to that in normal tissues. In this study, we investigated the use of optical imaging for monitoring whole-body bio-distribution of the fluorescent (660 nm) photosensitizer Bremachlorin in vivo, in a murine pancreatic ductal adenocarcinoma (PDAC) model. Moreover, we non-invasively, examined the induction of tumor necrosis after PDT treatment using near-infrared fluorescent imaging of the necrosis avid cyanine dye IRDye®-800CW Carboxylate. Using whole-body fluorescence imaging, we observed that Bremachlorin preferentially accumulated in pancreatic tumors. Furthermore, in a longitudinal study we showed that 3 hours after Bremachlorin administration, the fluorescent tumor signal reached its maximum. In addition, the tumor-to-background ratio at all-time points was approximately 1.4. Ex vivo, at 6 hours after Bremachlorin administration, the tumor-to-muscle or -normal pancreas ratio exhibited a greater difference than it did at 24 hours, suggesting that, in terms of efficacy, 6 hours after Bremachlorin administration was an effective time point for PDT treatment of PDAC. In vivo administration of the near infrared fluorescence agent IRDye®-800CW Carboxylate showed that PDT, 6 hours after administration of Bremachlorin, selectively induced necrosis in the tumor tissues, which was subsequently confirmed histologically. In conclusion, by using in vivo fluorescence imaging, we could non-invasively and longitudinally monitor, the whole-body distribution of Bremachlorin. Furthermore, we successfully used IRDye®-800CW Carboxylate, a near-infrared fluorescent necrosis avid agent, to image PDT-induced necrotic cell death as a measure of therapeutic efficacy. This study showed how fluorescence can be applied for optimizing, and assessing the efficacy of, PDT., (© 2024. The Author(s).)

Background: The Blood Cancer Network Ireland and National Cancer Registry Ireland worked to create an Enhanced Blood Cancer Outcomes Registry (EBCOR). Enhanced data in acute myeloid leukaemia (AML) included an extensive data dictionary, bespoke software and longitudinal follow-up., Aims: To demonstrate the utility of the database, we applied the data to examine a clinically relevant question: Charlson comorbidity index (CCI) usefulness in predicting AML patients' survival., Methods: A software designer and consultant haematologists in Cork University Hospital worked together to standardise a data dictionary, train registrars and populate a database. One hundred and forty-one AML patients underwent enhanced data registration. Comorbidities identified by chart review were used to examine the capability of the CCI and age at diagnosis to predict mortality using Kaplan-Meier curves, Cox regression and receiver operating characteristic curves., Results: In regression analysis, a dose-response relationship was observed; patients in the highest CCI tertile displayed a greater risk (HR = 4.90; 95% CI 2.79-8.63) of mortality compared to subjects in tertile 2 (HR = 2.74; 95% CI 1.64-4.57) and tertile 1 (reference). This relationship was attenuated in an analysis which adjusted for age at diagnosis. The area under the curve (AUC) for the CCI was 0.76 (95% CI 0.68-0.84) while the AUC for age at diagnosis was 0.84 (95% CI 0.78-0.90)., Conclusions: Results suggest that the CCI provides no additional prognostic information beyond that obtained from age alone at AML diagnosis and that an EBCOR can provide a rich database for cancer outcomes research, including predictive models and resource allocation., (© 2024. The Author(s).)

Background: Intra-operative pain during Caesarean delivery (PDCD) is the leading cause of successful litigation against obstetric anaesthesiologists. PDCD may require conversion to general anaesthesia (GA). The aim of this analysis is to assess our incidence of PDCD and associated GA conversion., Methods: Data were collected from electronic patient records. Data included baseline demographics, incidence of PDCD and rates of GA conversion, proportion of PDCD cases attributable to failed epidural (EA) or spinal anaesthesia (SA), and level of sensory and motor blockade in cases of PDCD. Results were audited against current standards set by the Royal College of Anaesthetists 'rates of PDCD should be <5% for category 4, <15% for categories 2-3, and <20 % for category 1 CD ' and that 'rates of conversion to GA due to neuraxial complications should be <1% for category 4, <5% for categories 2-3 and <15% for category 1 patients'., Results: During the 12-month study period, 2,429 patients underwent CD, of whom 52 (2.1%) experienced PDCD. The incidence of PDCD was 3.1% (41/1,309) for category 1-3 patients, while 1% (11/1,120) of category 4 patients experienced PDS. Of the 52 patients with PDCD, 17 patients required GA (33%). SA was used in 24/52 (47%) cases and EA in 28/52 (53%) cases. The median level of sensory block in patients with PDCD was located at the T4 dermatome, the median level of motor block was Bromage level 2., Conclusions: PDCD occurred in 2.1% of CD, one-third required conversion to GA. Most patients experiencing PDCD met current motor and sensory blockade criteria., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: None declared.

Introduction: Chronic kidney disease (CKD) is increasingly recognised as a growing global public health problem. Early detection and management can significantly reduce the loss of kidney function. The proposed trial aims to evaluate the impact of a community pharmacy-led intervention combining CKD screening and medication review on CKD detection and quality use of medicines (QUM) for patients with CKD. We hypothesise that the proposed intervention will enhance detection of newly diagnosed CKD cases and reduce potentially inappropriate medications use by people at risk of or living with CKD., Methods and Analysis: This study is a multicentre, pragmatic, two-level cluster randomised controlled trial which will be conducted across different regions in Australia. Clusters of community pharmacies from geographical groups of co-located postcodes will be randomised. The project will be conducted in 122 community pharmacies distributed across metropolitan and rural areas. The trial consists of two arms: (1) Control Group: a risk assessment using the QKidney CKD risk assessment tool, and (2) Intervention Group: a risk assessment using the QKidney CKD plus Point-of-Care Testing for kidney function markers (serum creatinine and estimated glomerular filtration rate), followed by a QUM service. The primary outcomes of the study are the proportion of patients newly diagnosed with CKD at the end of the study period (12 months); and rates of changes in the number of medications considered problematic in kidney disease (number of medications prescribed at inappropriate doses based on kidney function and/or number of nephrotoxic medications) over the same period. Secondary outcomes include proportion of people on potentially inappropriate medications, types of recommendations provided by the pharmacist (and acceptance rate by general practitioners), proportion of people who were screened, referred, and took up the referral to visit their general practitioners, and economic and other patient-centred outcomes., Ethics and Dissemination: The trial protocol has been approved by the Human Research Ethics Committee at the University of Sydney (2022/044) and the findings of the study will be presented at scientific conferences and published in peer-reviewed journal(s)., Trial Registration Number: Australian New Zealand Clinical Trials Registry (ACTRN12622000329763)., Competing Interests: Competing interests: DJ has received consultancy fees, research grants, speaker’s honoraria and travel sponsorships from Baxter Healthcare and Fresenius Medical Care, consultancy fees from AstraZeneca, Bayer and AWAK, speaker’s honoraria from ONO and Boehringer Ingelheim and Lilly, and travel sponsorships from Ono and Amgen. He is a current recipient of an Australian National Health and Medical Research Council Leadership Investigator Grant. KS has received consultancy fees and speaker’s honoraria from Baxter Healthcare and speaker’s honoraria from Roche. He is on the medical advisory board of Fresenius Medical Care for Australia and New Zealand., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

This work investigates real-time monitoring of extrusion-induced degradation in different grades of PLA across a range of process conditions and machine set-ups. Data on machine settings together with in-process sensor data, including temperature, pressure, and near-infrared (NIR) spectra, are used as inputs to predict the molecular weight and mechanical properties of the product. Many soft sensor approaches based on complex spectral data are essentially 'black-box' in nature, which can limit industrial acceptability. Hence, the focus here is on identifying an optimal approach to developing interpretable models while achieving high predictive accuracy and robustness across different process settings. The performance of a Recursive Feature Elimination (RFE) approach was compared to more common dimension reduction and regression approaches including Partial Least Squares (PLS), iterative PLS (i-PLS), Principal Component Regression (PCR), ridge regression, Least Absolute Shrinkage and Selection Operator (LASSO), and Random Forest (RF). It is shown that for medical-grade PLA processed under moisture-controlled conditions, accurate prediction of molecular weight is possible over a wide range of process conditions and different machine settings (different nozzle types for downstream fibre spinning) with an RFE-RF algorithm. Similarly, for the prediction of yield stress, RFE-RF achieved excellent predictive performance, outperforming the other approaches in terms of simplicity, interpretability, and accuracy. The features selected by the RFE model provide important insights to the process. It was found that change in molecular weight was not an important factor affecting the mechanical properties of the PLA, which is primarily related to the pressure and temperature at the latter stages of the extrusion process. The temperature at the extruder exit was also the most important predictor of degradation of the polymer molecular weight, highlighting the importance of accurate melt temperature control in the process. RFE not only outperforms more established methods as a soft sensor method, but also has significant advantages in terms of computational efficiency, simplicity, and interpretability. RFE-based soft sensors are promising for better quality control in processing thermally sensitive polymers such as PLA, in particular demonstrating for the first time the ability to monitor molecular weight degradation during processing across various machine settings.

Introduction: The location of T-cells during tumor progression and treatment provides crucial information in predicting the response in vivo ., Methods: Here, we investigated, using our bioluminescent, dual color, T-cell reporter mouse, termed TbiLuc, T-cell location and function during murine PDAC tumor growth and checkpoint blockade treatment with anti-PD-1 and anti-CTLA-4. Using this model, we could visualize T-cell location and function in the tumor and the surrounding tumor microenvironment longitudinally. We used murine PDAC clones that formed in vivo tumors with either high T-cell infiltration (immunologically 'hot') or low T-cell infiltration (immunologically 'cold')., Results: Differences in total T-cell bioluminescence could be seen between the 'hot' and 'cold' tumors in the TbiLuc mice. During checkpoint blockade treatment we could see in the tumor-draining lymph nodes an increase in bioluminescence on day 7 after treatment., Conclusions: In the current work, we showed that the TbiLuc mice can be used to monitor T-cell location and function during tumor growth and treatment., Competing Interests: Author RM was employed by the company Percuros BV. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 McMorrow, Zambito, Nigg, Lila, van den Bosch, Lowik and Mezzanotte.)

Background: Diabetes distress, experienced by up to 40% of people with type 2 diabetes (T2D), is the negative emotional response to the burden of living with and managing diabetes. It is associated with suboptimal glycaemia and diabetes self-management. Research indicates that people with diabetes do not recall being asked about emotional distress by healthcare professionals., Aim: To explore the experiences, needs, and expectations of people with T2D regarding emotional support received in Australian general practice., Design & Setting: Exploratory qualitative study in Victoria, Australia., Method: Semi-structured interviews were undertaken to explore emotional health and support received in general practice in 12 adults with T2D who primarily attend general practice. Interviews were audio-recorded, transcribed verbatim, and analysed using the framework approach., Results: The following three major themes were identified: (1) Beneath the surface of diabetes care; (2) Importance of GP-patient relationship; and (3) Communication counts. Participants experienced diabetes care as focused primarily on medical management rather than the emotional aspects of living with T2D. While people's experiences of diabetes care in general practice primarily focused on physical health, the GP care beyond the presenting complaint has an essential role in identifying emotional issues and enabling support. Emotional issues were more likely to be discussed and acknowledged by the GP where there was a long-standing relationship between GP and patient., Conclusion: Pre-existing positive GP-patient relationships and supportive communication enable people with 2TD to raise emotional issues as part of diabetes care., (Copyright © 2022, The Authors.)

Background: Peripheral neuropathy, peripheral arterial disease and diabetes-related foot ulcers are the most important risk factors for future amputation. Up to 50% of people with diabetes have distal symmetrical polyneuropathy as a complication of diabetes. Distal symmetrical polyneuropathy results in loss of protective sensation in the feet, increasing the risk of diabetes-related foot ulceration., Objective: The aim of this article is to provide structured guidance for detecting diabetes-related peripheral neuropathy, appropriate referral based on risk assessment and prevention of diabetes‑related foot ulceration., Discussion: As a result of the often-asymptomatic nature of diabetes-related peripheral neuropathy, general practice is an ideal location for screening all adults with diabetes for loss of protective sensation. Loss of protective sensation in a person with diabetes indicates an at-risk foot. Increased frequency of foot examination, education in self-care, appropriate footwear and referral to podiatry for non‑ulcerative foot problems can reduce the development of diabetes-related foot ulcers.

Aim: Diabetes distress is experienced by up to 36% of adults with type 2 diabetes. Australian type 2 diabetes guidelines recommend annual assessment of diabetes distress in general practice. This study explores general practitioners' knowledge, current practice, and factors influencing implementation of guidelines, including Person Reported Outcome Measure (PROM) use., Methods: A cross-sectional online survey was disseminated via e-mail to 4776 Australian general practitioners listed on the Australasian Medical Publishing Company database., Results: 264 (5%) surveys were returned. 75% indicated that general practitioners were the most appropriate professionals to assess diabetes distress. Sixteen percent reported asking about diabetes distress during type 2 diabetes consultations more than half the time, with 13% using a PROM more than half the time: 64% use the Kessler-10, and 1.9% use the Problem Areas in Diabetes (PAID) scale. While general practitioners had positive beliefs about the consequences of assessing and addressing diabetes distress, they also reported barriers in motivation, environment, and knowledge of guidelines., Conclusion: Most respondents endorsed general practitioners' role in assessing diabetes distress, but few ask about or assess diabetes distress in routine consultations. To support uptake of guideline recommendations for diabetes-specific PROM use, environmental factors, specifically time, need to be addressed., Competing Interests: Conflicts of interest The authors have no conflicts of interests to declare., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The use of personal protective equipment (PPE) has become essential to reduce the transmission of coronavirus disease 2019 (COVID-19) as it prevents the direct contact of body fluid aerosols expelled from carriers. However, many countries have reported critical supply shortages due to the spike in demand during the outbreak in 2020. One potential solution to ease pressure on conventional supply chains is the local fabrication of PPE, particularly face shields, due to their simplistic design. The purpose of this paper is to provide a research protocol and cost implications for the rapid development and manufacturing of face shields by individuals or companies with minimal equipment and materials. This article describes a best practice case study in which the establishment of a local manufacturing hub resulted in the swift production of 12,000 face shields over a seven-week period to meet PPE shortages in the North-West region of Ireland. Protocols and processes for the design, materials sourcing, prototyping, manufacturing, and distribution of face shields are described. Three types of face shields were designed and manufactured, including Flat, Laser-cut, and 3D-printed models. Of the models tested, the Flat model proved the most cost-effective (€0.51/unit), while the Laser-cut model was the most productive (245 units/day). The insights obtained from this study demonstrate the capacity for local voluntary workforces to be quickly mobilised in response to a healthcare emergency, such as the COVID-19 pandemic., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)