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Objective: The prediction and subsequent prevention of errors, which are an integral element of human behaviour, require an understanding of their cause. The incident monitoring technique was developed in the study of aviation errors in the Second World War and has been applied more recently in the field of anaesthetics. This pilot study represents one of the first attempts to apply the incident monitoring technique in the general practice environment.Method: A total of 297 GPs across Australia anonymously reported details of unintended events which harmed or could have harmed the patient. Reports were contemporaneously recorded on prepared forms which allowed a free text description of the incident, and structured responses for contributing and mitigating factors, immediate and long-term out-comes, additional costs etc.Results and Discussion: The first 500 reports were analysed using both of qualitative and quantitative methods and a brief overview of results is presented. The methodological issues arising in the application of this technique to such a large, widely spread profession, in which episodes of care are not necessarily confined to a single consultation, are discussed. This study demonstrated that the incident monitoring technique can be successfully applied in general practice and that the resulting information can facilitate the identification of common factors contributing to such events and allow the development of preventive interventions. [ABSTRACT FROM AUTHOR]

The colon is the most common site for endometriosis outside the genital tract. It has a varied presentation and can mimic numerous other conditions, both clinically and pathologically. We investigated the clinicopathological features of a series of colorectal endometriosis with a particular emphasis on the features seen in cases with colonic mucosal involvement. A total of 114 consecutive cases of colorectal endometriosis were reviewed. Forty-eight percent did not have a prior diagnosis of endometriosis and in 34 patients (30%) the endometriosis was determined as the cause for the presentation. Mucosal involvement was present in 31 specimens. Features of chronic colitis were seen in the adjacent mucosa in 90% of cases whilst there were glandular changes mimicking adenocarcinoma in two cases (1.8%). Fifty percent of cases with mucosal involvement also showed glands with a hybrid intestinal-endometrial phenotype by morphology and/or by immunohistochemistry. Endometriosis is an important mimic of other conditions., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Stage of pancreatic carcinoma at diagnosis is a strong prognostic indicator of morbidity and mortality, yet is poorly notified to population-based cancer registries ("cancer registries"). Registry-derived stage (RD-Stage) provides a method for cancer registries to use available data sources to compile and record stage in a consistent way. This project describes the development and validation of rules to capture RD-Stage (pancreatic carcinoma) and applies the rules to data currently captured in each Australian cancer registry., Materials and Methods: Rules for deriving RD-stage (pancreatic carcinoma) were developed using the American Joint Commission on Cancer (AJCC) Staging Manual 8th edition and endorsed by an Expert Working Group comprising specialists responsible for delivering care to patients diagnosed with pancreatic carcinoma, cancer registry epidemiologists and medical coders. Completeness of data fields required to calculate RD-Stage (pancreatic carcinoma) and an overall proportion of cases for whom RD stage could be assigned was assessed using data collected by each Australian cancer registry, for period 2018-2019. A validation study compared RD-Stage (pancreatic carcinoma) calculated by the Victorian Cancer Registry with clinical stage captured by the Upper Gastro-intestinal Cancer Registry (UGICR)., Results: RD-Stage (pancreatic carcinoma) could not be calculated in 4/8 (50%) of cancer registries; one did not collect the required data elements while three used a staging system not compatible with RD-Stage requirements. Of the four cancer registries able to calculate RD-Stage, baseline completeness ranged from 9% to 76%. Validation of RD-Stage (pancreatic carcinoma) with UGICR data indicated that there was insufficient data available in VCR to stage 174/457 (38%) cases and that stage was unknown in 189/457 (41%) cases in the UGICR. Yet, where it could be derived, there was very good concordance at stage level (I, II, III, IV) between the two datasets. (95.2% concordance], Kendall's coefficient = 0.92)., Conclusion: There is a lack of standardisation of data elements and data sources available to cancer registries at a national level, resulting in poor capacity to currently capture RD-Stage (pancreatic carcinoma). RD-Stage provides an excellent tool to cancer registries to capture stage when data elements required to calculate it are available to cancer registries., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Evans et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

It is indeed a privilege to be an immunologist in what is arguably the golden age of immunology. From astounding advances in fundamental knowledge to groundbreaking immunotherapeutic offerings, immunology has carved out an enviable niche for itself in basic science and clinical medicine. The need and the vital importance of appropriate education, training, and certification in clinical immunology was recognized by the World Health Organization as far back as 1972. In the United States, Ph.D. scientists with board certification in medical laboratory immunology have served as directors of high-complexity Clinical Laboratory Improvement Amendments- and College of American Pathologists-certified clinical immunology laboratories since 1977. From 1977 to 2017, board certification for medical laboratory immunology was administered by the American Society for Microbiology through the American Board of Medical Laboratory Immunology examination. The American Board of Medical Laboratory Immunology examination was phased out in 2017, and in the fall of 2019, the American Society for Clinical Pathology (ASCP) Board of Certification (BOC) examination committee took on the responsibility of developing a new doctoral-level certification examination for medical laboratory immunology. This transition to the ASCP BOC represents a well-deserved and much-needed recognition of the rapid advances in and the highly specialized nature of medical laboratory immunology and its ever-increasing relevance to patient care. This new ASCP BOC certification is called the Diplomate in Medical Laboratory Immunology, and, as of April 1, 2023, it is now available to potential examinees. In this report, we describe the examination, eligibility routes, and potential career pathways for successful diplomates., (Copyright © 2023 The Authors.)

γ-Nonalactone is a linear aliphatic lactone ubiquitous in wine, associated with coconut, sweet, and stone fruit aroma descriptors. Little research has been conducted looking at the importance of this compound to New Zealand (NZ) wine aroma. 2 H 2 13 C 2 -γ-Nonalactone, a novel isotopologue of γ-nonalactone, was synthesised in this work for use in a stable isotope dilution assay (SIDA) for quantification of γ-nonalactone in NZ Pinot noir wines for the first time. Synthesis was carried out using heptaldehyde as the starting material, and 13 C atoms and 2 H atoms were introduced via Wittig olefination and deuterogenation steps, respectively. The suitability of this compound as an internal standard was demonstrated by spiking model wine at normal and elevated conditions during sample preparation, with subsequent analysis via mass spectrometry showing stability of 2 H 2 13 C 2  > 0.99), reproducibility (0.72%), and repeatability (0.38%). Twelve NZ Pinot noir wines, representative of a range of NZ Pinot noir-producing regions, prices, and vintages, were analysed by solid-phase extraction-gas chromatography-mass spectrometry (SPE-GC-MS). The concentrations of γ-nonalactone ranged from 8.3 to 22.5 µg L -1 , was shown to have excellent linearity (R 2  > 0.99), reproducibility (0.72%), and repeatability (0.38%). Twelve NZ Pinot noir wines, representative of a range of NZ Pinot noir-producing regions, prices, and vintages, were analysed by solid-phase extraction-gas chromatography-mass spectrometry (SPE-GC-MS). The concentrations of γ-nonalactone ranged from 8.3 to 22.5 µg L -1 , the latter of which was close to the odour detection threshold of this compound. These findings provide a basis for further research into γ-nonalactone and its impact on NZ Pinot noir aroma and provide a robust method for the quantification of this compound in Pinot noir., (© 2023. The Author(s).)

While most studies on floral hemp (Cannabis sativa L.) concur that additions of nitrogen (N) increase plant growth, the performance of floral hemp is heavily influenced by environmental conditions, management and cultivar selection. In regions with a short growing season, the availability of soil N may determine plant developmental rates, final inflorescence biomass and cannabinoid concentrations, but no studies have addressed this for field-grown hemp under high-desert conditions. This field study evaluated the effect of no supplemental N and N fertilization at 90 kg ha-1 on three hemp cultivars (Berry Blossom, Red Bordeaux, and Tahoe Cinco) in Northern Nevada. N increased plant height, canopy cover, stem diameter and shoot biomass, but other physiological parameters were dependent on cultivar. For instance, inflorescence biomass and inflorescence-to-shoot ratio in Red Bordeaux was not affected by N fertilization. Similarly, cannabinoid concentrations were affected by timing of harvest and cultivar but not by N treatment. We evaluated the use of a SPAD meter for ease of determining leaf N deficiency, and correlations with leaf chlorophyll content showed that the SPAD meter was a reliable tool in two cultivars but not in Tahoe Cinco. N treatment increased overall CBD yield, which was driven by increases in inflorescence biomass. Tahoe Cinco was the best CBD yielding cultivar, as it maintained a high inflorescence-to-shoot ratio regardless of N treatment. Our study suggests that even though hemp may have a positive response to soil N management, adjustments based on genotype by environment interaction should be aimed at maximizing cannabinoid yield either by increasing biomass and/or CBD concentrations as long as THC levels are within the permissible <0.3% for U.S. industrial hemp cultivation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Farnisa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objectives: In 2022, media reports alleged that doctors, particularly general practitioners (GPs), are defrauding Medicare, claiming $8 billion lost through fraud/non-compliance. This study examined Medicare Benefits Schedule billing patterns by consultation length to estimate overcharging or undercharging by GPs, and the cost/savings to Medicare., Method: A subset of data from the Bettering the Evaluation And Care of Health (BEACH) program from 2013 to 2016, which included length of consultation information, was analysed., Results: Of 89,765 consultations, GPs undercharged 11.8% of consultations and overcharged 1.6%. Of the 2760 GPs sampled, 816 (29.6%) overcharged at least once and 2334 (84.6%) undercharged at least once. Of the GPs who overcharged at least once, 85.4% also undercharged. The total effect of GP undercharging and overcharging was a net saving of $351.7 million to Medicare., Discussion: This study shows that GPs undercharging and overcharging saved Medicare over one-third of a billion dollars in 2021-22. The findings of this study do not support the media claims of widespread fraud by GPs.

Saturated linear aliphatic lactones are widespread aroma compounds in wine, linked to stone fruit, dried red fruit, and coconut descriptors. Despite their ubiquity, bioproduction pathways associated with these compounds in wine are unclear, but higher concentrations have been linked to many common vitivinicultural practices, including grape variety, microbiological influence, oak- and bottle-aging, and wine styles such as late harvest, noble rot, and icewine. Development of analytical techniques has enabled increasingly accurate quantification of lactones in wine, shedding more light on their potential origins. This review provides an in-depth summary of the research into linear aliphatic lactones over the past 50 years and provides direction for possible future research to elucidate the biogenesis of these compounds and better estimate their impact on wine aroma.

In Australia, general practice forms a core part of the health system, with general practitioners (GPs) having a gatekeeper role for patients to receive care from other health services. GPs manage the care of patients across their lifespan and have roles in preventive health care, chronic condition management, multimorbidity and population health. Most people in Australia see a GP once in any given year. Draft reforms have been released by the Australian Government that may change the model of general practice currently implemented in Australia. In order to quantify the impact and effectiveness of any implemented reforms in the future, reliable and valid data about general practice clinical activity over time, will be needed. In this context, this commentary outlines the historical and current approaches used to obtain general practice statistics in Australia and highlights the benefits and limitations of these approaches. The role of data generated from GP electronic health record extractions is discussed. A methodology to generate high quality statistics from Australian general practice in the future is presented.

Pathologists have an important and expanding role in the diagnosis and management of inflammatory bowel disease. This role includes the initial diagnosis of the disease, assessment of the response to treatment and the identification of short-term complications such as cytomegalovirus infection and long-term complications such as dysplasia. Furthermore, the assessment of resection specimens for complication of disease is important to determining the risk of subsequent disease or inflammation within an ileal pouch. Adequate sampling of the disease at endoscopy and from the surgical resection specimen is vital to determining the ultimate information that can be provided by the pathologist. This sampling is determined by the clinical scenario. Similarly, a standardized approach to reporting and synthesizing the histologic findings will improve patient management. This is best exemplified by the increasing interest in histologic activity indices, such as the Nancy index in ulcerative colitis, and in the standardized reporting for inflammatory bowel disease dysplasia recommended by the SCENIC international consensus., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background & Aims: Fibrosis, the primary cause of morbidity in chronic liver disease, is induced by pro-inflammatory cytokines, immune cell infiltrates, and tissue resident cells that drive excessive myofibroblast activation, collagen production, and tissue scarring. Rho-associated kinase 2 (ROCK2) regulates key pro-fibrotic pathways involved in both inflammatory reactions and altered extracellular matrix remodelling, implicating this pathway as a potential therapeutic target., Methods: We used the thioacetamide-induced liver fibrosis model to examine the efficacy of administration of the selective ROCK2 inhibitor KD025 to prevent or treat liver fibrosis and its impact on immune composition and function., Results: Prophylactic and therapeutic administration of KD025 effectively attenuated thioacetamide-induced liver fibrosis and promoted fibrotic regression. KD025 treatment inhibited liver macrophage tumour necrosis factor production and disrupted the macrophage niche within fibrotic septae. ROCK2 targeting in vitro directly regulated macrophage function through disruption of signal transducer and activator of transcription 3 (STAT3)/cofilin signalling pathways leading to the inhibition of pro-inflammatory cytokine production and macrophage migration. In vivo , KDO25 administration significantly reduced STAT3 phosphorylation and cofilin levels in the liver. Additionally, livers exhibited robust downregulation of immune cell infiltrates and diminished levels of retinoic acid receptor-related orphan receptor gamma (RORγt) and B-cell lymphoma 6 (Bcl6) transcription factors that correlated with a significant reduction in liver IL-17, splenic germinal centre numbers and serum IgG., Conclusions: As IL-17 and IgG-Fc binding promote pathogenic macrophage differentiation, together our data demonstrate that ROCK2 inhibition prevents and reverses liver fibrosis through direct and indirect effects on macrophage function and highlight the therapeutic potential of ROCK2 inhibition in liver fibrosis., Lay Summary: By using a clinic-ready small-molecule inhibitor, we demonstrate that selective ROCK2 inhibition prevents and reverses hepatic fibrosis through its pleiotropic effects on pro-inflammatory immune cell function. We show that ROCK2 mediates increased IL-17 production, antibody production, and macrophage dysregulation, which together drive fibrogenesis in a model of chemical-induced liver fibrosis. Therefore, in this study, we not only highlight the therapeutic potential of ROCK2 targeting in chronic liver disease but also provide previously undocumented insights into our understanding of cellular and molecular pathways driving the liver fibrosis pathology., Competing Interests: The authors declare no competing financial interests. BRB receives remuneration as an advisor to Magenta Therapeutics and BlueRock Therapeutics; received research funding from BlueRock Therapeutics, Rheos Medicines, Childrens' Cancer Research Fund, and KidsFirst Fund; and is a co-founder of Tmunity. MN, WC, and AZZ are full-time employees of Kadmon Pharmaceuticals, LLC. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2021 The Authors.)

The increasing use of gastrointestinal endoscopic procedures has led to the recognition by histopathologists of non-conventional (or special-type) dysplasias of the gastrointestinal tract. These lesions can be recognised in association with prevalent underlying gastrointestinal conditions, such as Barrett oesophagus, chronic atrophic gastritis, and inflammatory bowel disease. The diagnosis of these special types can be challenging, and their biological behaviours are not fully characterised. The aim of this review is to provide a global view of non-conventional dysplastic lesions observed in the various segments of the tubular gastrointestinal tract and describe their salient features. Furthermore, as the clinical implications of these various subtypes have not been broadly tested in practice and are not represented in most management guidelines, we offer guidance on the best management practices for these lesions., (© 2020 John Wiley & Sons Ltd.)

Introduction: Celiac disease is an autoimmune disorder where intestinal immunopathology arises after gluten consumption. Previous studies suggested that hookworm infection restores gluten tolerance; however, these studies were small (n = 12) and not placebo controlled., Methods: We undertook a randomized, placebo-controlled trial of hookworm infection in 54 people with celiac disease. The 94-week study involved treatment with either 20 or 40 Necator americanus third-stage larvae (L3-20 or L3-40) or placebo, followed by escalating gluten consumption (50 mg/d for 12 weeks, 1 g intermittent twice weekly for 12 weeks, 2 g/d sustained for 6 weeks, liberal diet for 1 year)., Results: Successful study completion rates at week 42 (primary outcome) were similar in each group (placebo: 57%, L3-20: 37%, and L3-40: 44%; P = 0.61), however gluten-related adverse events were significantly reduced in hookworm-treated participants: Median (range) adverse events/participant were as follows: placebo, 4 (1-9); L3-20, 1 (0-9); and L3-40, 0 (0-3) (P = 0.019). Duodenal villous height:crypt depth deteriorated similarly compared with their enrolment values in each group (mean change [95% confidence interval]: placebo, -0.6 [-1.3 to 0.2]; L3-20, -0.5 [-0.8 to 0.2]; and L3-40, -1.1 [-1.8 to 0.4]; P = 0.12). A retrospective analysis revealed that 9 of the 40 L3-treated participants failed to establish hookworm infections. Although week 42 completion rates were similar in hookworm-positive vs hookworm-negative participants (48% vs 44%, P = 0.43), quality of life symptom scores were lower in hookworm-positive participants after intermittent gluten challenge (mean [95% confidence interval]: 38.9 [33.9-44] vs 45.9 [39.2-52.6])., Discussion: Hookworm infection does not restore tolerance to sustained moderate consumption of gluten (2 g/d) but was associated with improved symptom scores after intermittent consumption of lower, intermittent gluten doses.

Several types of nonconventional dysplasia have been recently described in inflammatory bowel disease (IBD). However, strict morphologic criteria are lacking, and their clinicopathologic features (including potential association with conventional dysplasia and/or colorectal cancer [CRC]) are poorly understood. A total of 106 dysplastic or serrated lesions in 58 IBD patients with CRC were retrospectively identified from five institutions. Thirty-six cases of nonconventional dysplasia were identified in 26 (45%) of the 58 patients and occurred with similar frequency in men and women (58% and 42%, respectively), with a mean age of 54 years (range: 24-73) and a long history of IBD (mean: 17 years, range: 2-43). Six morphologic patterns were recognized. Hypermucinous dysplasia (n = 15; 42%) presented as either a 'pure type' (n = 5; 14%) or a 'mixed type' with either conventional or another nonconventional subtype (n = 10; 28%). Serrated lesions, as a group, were equally common (n = 15; 42%) and included three variants: traditional serrated adenoma-like (n = 10; 28%), sessile serrated lesion-like (n = 1; 3%), and serrated lesion, not otherwise specified (n = 4; 11%). Dysplastic lesions with increased Paneth cell differentiation (n = 4; 11%) and goblet cell deficient dysplasia (n = 2; 6%) were rare. Twelve (46%) of the 26 patients had only nonconventional dysplasia, whereas the remaining 14 patients (54%) had both nonconventional and conventional dysplasias. Nonconventional dysplasia was most often graded as low-grade dysplasia (81%), which was less common in conventional dysplasia (37%) (p = 0.003). When present alone, nonconventional dysplasia was predominantly found in the left colon (81%, p = 0.006) as a polypoid or raised lesion (75%, p < 0.001) compared with when it occurred simultaneously with conventional dysplasia (35% and 50%, respectively). When both nonconventional and conventional dysplasias occurred simultaneously, they were found in the same colonic segment in all but 3 patients (79%). Nonconventional dysplasia was also commonly detected in the same colonic segment as CRC or immediately adjacent to the CRC at a rate (85%) similar to conventional dysplasia (96%). CRC occurring in patients with only nonconventional dysplasia was more likely to be high-grade (poorly differentiated; 36%) than CRC that occurred in association with conventional dysplasia (10%) (p = 0.026). In conclusion, nonconventional dysplasia is common in IBD patients with CRC. It appears to develop in the same field of carcinomatous development, and it is not uncommonly associated with conventional dysplasia.

Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal carcinoma. The significance of serrated lesions resembling traditional serrated adenoma (TSA) in IBD patients is unclear. In this retrospective study, we analyzed 52 TSA-like lesions arising in 30 IBD patients and diagnosed in colectomy or endoscopic specimens. The 27 colectomy lesions presented predominantly as ill-defined areas with granular appearance, with a median size of 15 mm, located throughout the large bowel and associated with synchronous advanced colorectal lesions in 58%. Low-grade serrated dysplasia was present in 56%, high-grade serrated dysplasia in 37%, and TSA-type cytology in 7%. Increased Ki-67 immunostaining and abnormal p53 expression were identified in 96% and 48%, respectively; 74% had a KRAS mutation, and 4% had a BRAF mutation. Endoscopically resectable TSA-like lesions were all discrete polypoid lesions, smaller in size (median 9 mm), predominantly in the distal large bowel, with an adjacent precursor polyp in 24%, and associated with synchronous and metachronous advanced colorectal lesions in 6%. Most (92%) show TSA-type cytology. p53 overexpression was present in 4%, KRAS mutation in 41%, and BRAF mutation in 32%. None of the 52 TSA-like lesions demonstrated loss of MLH1 or SATB2 expression by immunohistochemistry. On follow-up, 4 patients were diagnosed with colorectal carcinoma or high-grade adenomatous IBD-associated dysplasia. None of the patients with lesions showing TSA-type cytology only developed an advanced lesion. Our findings suggest that some TSA-like lesions, essentially from colectomy, may represent a form of IBD-associated dysplasia associated with an increased risk of advanced neoplasia., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although severe deficiencies of canalicular transporter enzymes due to biallelic mutations are well known as causes of progressive cholestatic liver disease in children, it is increasingly recognized that milder disease may occur if a single, heterozygous gene mutation is present. This mild disease, generally presenting initially in adulthood, may have a variety of clinical and histological appearances. Bland canalicular cholestasis is the prototypic change, but it is now clear that some gene mutations, particularly in ABCB4 (encoding MDR3), can cause other patterns that include early cholesterol calculus formation, bile duct injury and disappearance, ductular reactions mimicking large duct obstruction, and, in rare cases, progressive fibrosis. Because the features can be subtle and not diagnostic in isolation, it is generally the combination of a biliary pattern of injury with a suggestive clinical and family history that allows the diagnosis to be suspected. Increased awareness and improved access to genetic testing are likely to result in more frequent diagnosis of these disorders., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: To determine the clinicopathological features of pyloric gland adenomas (PGA) that arise in the duodenum., Methods and Results: Fifty-seven cases of duodenal PGA were identified and analysed from 56 patients. Clinicopathological and immunohistochemical analyses were performed. PGA tend to occur in older individuals (median age = 73.5), with a slight female predominance (25 males, 31 females). PGA arise more commonly in the proximal duodenum (68.75% in D1, 25% in D2 and 6.25% in D3) and usually present as mucosal nodules (98.2%) or plaques (1.8%), with a mean size of 14.8 mm. There is associated gastric heterotopia in 22.8% of cases. PGA showing features of high-grade dysplasia were significantly larger in size than PGA, showing only low-grade dysplasia (23.1 versus 8.7 mm; P = 0.0001) and more likely to show a tubulovillous rather than a pure tubular architecture (P = 0.025). In our series, 10 of 56 patients had intramucosal or invasive carcinoma associated with the duodenal PGA (17.9%). Three of these carcinomas showed lymph node metastasis. Following definitive treatment, local recurrence occurred in only three patients., Conclusions: Duodenal PGA tend to occur in the proximal duodenum of older individuals. Larger size and tubulovillous architecture correlates with high-grade dysplasia and associated adenocarcinoma. The low recurrence rate of these lesions would suggest that endoscopic management is appropriate, provided that the lesion can be completely resected., (© 2019 John Wiley & Sons Ltd.)

Aims: Appendicitis with a Crohn's-like histological appearance generally raises concern for Crohn's disease, Yersinia infection, and interval appendectomy. Actinomyces infection is a recognised cause of chronic appendicitis that can histologically mimic Crohn's disease., Methods and Results: We report on 20 cases of appendicitis with Crohn's-like histological features that were due to Actinomyces. Most patients presented with acute or chronic abdominal pain. Imaging studies suggested a mass in five cases. Two patients had interval appendectomy. Histological features showed Crohn's-like appendicitis in 16 cases, with moderate to marked fibrosis and granulomas in seven cases. The other four cases had less consistent histological findings. None of the patients developed Crohn's disease during the follow-up interval (median, 37 months)., Conclusions: Actinomyces can be associated with Crohn's-like appendicitis with marked fibrosis, transmural inflammation, lymphoid hyperplasia, and granulomas., (© 2019 John Wiley & Sons Ltd.)

Background:: Electronic medical records are increasingly used for research with limited external validation of their data., Objective:: This study investigates the validity of electronic medical data (EMD) for estimating diabetes prevalence in general practitioner (GP) patients by comparing EMD with national Bettering the Evaluation and Care of Health (BEACH) data., Method:: A "decision tree" was created using inclusion/exclusion of pre-agreed variables to determine the probability of diabetes in absence of diagnostic label, including diagnoses (coded/free-text diabetes, polycystic ovarian syndrome, impaired glucose tolerance, impaired fasting glucose), diabetic annual cycle of care (DACC), glycated haemoglobin (HbA1c) > 6.5%, and prescription (metformin, other diabetes medications). Via SQL query, cases were identified in EMD of five Illawarra and Southern Practice Network practices (30,007 active patients; from 2 years to January 2015). Patient-based Supplementary Analysis of Nominated Data (SAND) sub-studies from BEACH investigating diabetes prevalence (1172 GPs; 35,162 patients; November 2012 to February 2015) were comparison data. SAND results were adjusted for number of GP encounters per year, per patient, and then age-sex standardised to match age-sex distribution of EMD patients. Cluster-adjusted 95% confidence intervals (CIs) were calculated for both datasets., Results:: EMD diabetes prevalence (T1 and/or T2) was 6.5% (95% CI: 4.1-8.9). Following age-sex standardisation, SAND prevalence, not significantly different, was 6.7% (95% CI: 6.3-7.1). Extracting only coded diagnosis missed 13.0% of probable cases, subsequently identified through the presence of metformin/other diabetes medications (*without other indicator variables) (6.1%), free-text diabetes label (3.8%), HbA1c result* (1.6%), DACC* (1.3%), and diabetes medications* (0.2%)., Discussion:: While complex, proxy variables can improve usefulness of EMD for research. Without their consideration, EMD results should be interpreted with caution., Conclusion:: Enforceable, transparent data linkages in EMRs would resolve many problems with identification of diagnoses. Ongoing data quality improvement remains essential.

Hepatocellular adenomas are benign liver lesions with a risk of rupture and malignant transformation. Various molecular subgroups have been identified which appear to have characteristic morphological and immunohistochemical features. We examined the morphology and immunohistochemical profile of a series of 121 HCA from 97 patients to identify the HCA subtypes present and determine the number at risk for malignant transformation according to the World Health Organization (WHO) criteria for hepatocellular adenomas. There were 34 HNF1α inactivated HCA (28%), 61 inflammatory HCA (50%), 15 β-catenin activated HCA (12%) and 11 unclassified adenomas (9%). This proportion of cases was similar to that seen in other series utilising molecular classification. The morphological features of the adenomas were suggestive but not definite indicators of the subtypes present. Morphological features that showed overlap between the subtypes included steatosis within the lesion, a ductular reaction and focal atypia, so that immunohistochemical typing was required for accurate classification. In conclusion, immunohistochemistry is a clinically useful surrogate for identifying underlying molecular changes in the HCA subtypes., (Copyright © 2018 Royal College of Pathologists of Australasia. All rights reserved.)

Background: There is currently no accepted standard definition for chronic conditions., Objective: The objective of this article is to provide an overview of the characteristics that define health conditions as chronic., Discussion: A list of health conditions classified as chronic should be made available to all general practitioners and policymakers in Australia. This will assist in the claims process for chronic disease management and aid the selection of patients for healthcare home enrolment. Based on assessment of the usual duration, prognosis, sequelae and pattern of recurrence or deterioration, a defined list of chronic conditions classified according to the International Classification of Primary Care, version 2 (ICPC-2) is available for consideration.

Background: The objective of this study was to examine prevalence rates of lifestyle risk factors in the Western Victorian Primary Health Network (WV PHN) general practice patient population and the corresponding levels of clinical advice and counselling., Methods: Analysed data from the Bettering the Evaluation and Care of Health (BEACH) program from April 2011 to March 2015 were examined, providing a comparison of three geographical areas of general practice patients: WV PHN, Victoria and Australia., Results: Rates of clinical advice and counselling for diet and exercise provided by general practitioners (GPs) in the WV PHN network were significantly lower than Victorian and Australian rates, despite the region's higher obesity rates. Smoking rates were higher in the WV PHN compared with Australia, but there was no difference in the levels of smoking cessation advice disseminated. Across all regions, one in four patients drank alcohol at hazardous levels., Discussion: GPs in rural practice require further support, encouragement and resources to provide diet and exercise advice to their patients more frequently.

Brunner's gland cysts are rare, benign lesions of the duodenum usually seen as incidental, polypoid or cystic lesions of the duodenum. We present a series of 25 cases of Brunner's gland cyst, the largest case series to date. All the cases were identified during endoscopic assessment for unrelated causes. The mean age of the patients was 66.2 years and the sex ratio was approximately equal. Most were detected as a small (3-10 mm) polypoid lesion in the second part of the duodenum, away from the ampulla. Most of the cysts were unilocular and all were lined by undulating, cytologically bland cuboidal to columnar cells with clear cytoplasm and small, basal nuclei. No mitotic activity or proliferative activity was seen. No recurrence was noted, despite incomplete removal in many cases. We agree with the hypothesis that Brunner's gland cysts are likely to be caused by local obstruction to the draining duct of Brunner's glands., (Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Two series of high molecular weight disulfonated poly(arylene ether sulfone) random copolymers were synthesized as proton exchange membranes for high-temperature water electrolyzers. These copolymers differ based on the position of the ether bonds on the aromatic rings. One series is comprised of fully para-substituted hydroquinone comonomer, and the other series incorporated 25 mol % of a meta-substituted comonomer resorcinol and 75 mol % hydroquinone. The influence of the substitution position on water uptake and electrochemical properties of the membranes were investigated and compared to that of the state-of-the-art membrane Nafion. The mechanical properties of the membranes were measured for the first time in fully hydrated conditions at ambient and elevated temperatures. Submerged in water, these hydrocarbon-based copolymers had moduli an order of magnitude higher than Nafion. Selected copolymers of each series showed dramatically increased proton conductivities at elevated temperature in fully hydrated conditions, while their H 2 gas permeabilities were well controlled over a wide range of temperatures. These improved properties were attributed to the high glass transition temperatures of the disulfonated poly(arylene ether sulfone)s.

Background: Dispensing data suggest potential issues with the quality use of medicines for airways disease., Objective: The objective of this article was to describe the management of asthma and chronic obstructive pulmonary disease (COPD) in general practice, and investigate the appropriateness of prescribing., Methods: The method used for this study consisted of a national cross‑sectional survey of 91 Australian general practitioners (GPs) participating in the Bettering the Evaluation and Care of Health (BEACH) program., Results: Data were available for 2589 patients (288 asthma; 135 COPD). For the patients with asthma, GPs classified asthma as well controlled in 76.4%; 54.3% were prescribed inhaled corticosteroids (ICS), mostly (84.9%) as combination therapy, and mostly at moderate-high dose; only 26.3% had a written action plan. GPs classified COPD as mild for 42.9%. Most patients with COPD (60.9%) were prescribed combination ICS therapy and 36.7% were prescribed triple therapy., Discussion: There were substantial differences between guideline-based and GP- recorded assessment and prescription for asthma and COPD. Further research is needed to improve care and optimise patient outcomes with scarce health resources.

Disruption of the retinoblastoma (RB) tumor suppressor pathway, either through genetic mutation of upstream regulatory components or mutation of RB1 itself, is believed to be a required event in cancer. However, genetic alterations in the RB-regulated E2F family of transcription factors are infrequent, casting doubt on a direct role for E2Fs in driving cancer. In this work, a mutation analysis of human cancer revealed subtle but impactful copy number gains in E2F1 and E2F3 in hepatocellular carcinoma (HCC). Using a series of loss- and gain-of-function alleles to dial E2F transcriptional output, we have shown that copy number gains in E2f1 or E2f3b resulted in dosage-dependent spontaneous HCC in mice without the involvement of additional organs. Conversely, germ-line loss of E2f1 or E2f3b, but not E2f3a, protected mice against HCC. Combinatorial mapping of chromatin occupancy and transcriptome profiling identified an E2F1- and E2F3B-driven transcriptional program that was associated with development and progression of HCC. These findings demonstrate a direct and cell-autonomous role for E2F activators in human cancer.

Temperature is a major environmental factor influencing land surface volatilization at the time of agricultural field fumigation. Cooler fumigation soil temperatures relevant to Pacific Northwest (PNW) application practices with metam sodium/potassium should result in appreciably reduced methyl isothiocyanate (MITC) emission rates, thus minimizing off target movement and bystander inhalation exposure. Herein, a series of laboratory controlled flow-through soil column assessments were performed evaluating MITC emissions over the range of cooler temperatures (2-13°C). Assessments were also conducted at the maximum allowed label application temperature of 32°C. All assessments were conducted at registration label-specified field moisture capacity, and no more than 50% cumulative MITC loss was observed over the 2-day post-fumigation timeframe. Three-fold reductions in MITC peak fluxes at cooler PNW application temperatures were observed compared to the label maximum temperature. This study supports current EPA metam sodium/potassium label language that indicates surface fumigations during warmer soil conditions should be discouraged.

Crohn's disease is a chronic inflammatory disorder that can affect any part of the gastrointestinal tract. Our objective was to review the histological findings in index biopsies from the terminal ileum and other gastro-intestinal tract sites of Crohn's disease patients prior any treatment and to compare them with the findings from patients with non-specific ileitis. A total of 111 consecutive Crohn's disease cases (55 females, median age 27 years) with extra-ileal biopsies were retrospectively selected. Upper gastrointestinal inflammatory changes were found in 68 % of gastric biopsies, 60 % of oesophageal biopsies and 43 % of duodenal biopsies with no significant difference in frequency between paediatric and adult cases. Crohn's colitis was more common in paediatric cases than adult cases (85 % versus 57 %). Granuloma in at least one extra-ileal site was observed in 40 %, more frequently in paediatric cases than in adults (78 vs 27 %). Compared with Crohn's disease cases, the group of 151 non-specific ileitis cases (75 females, median age 52 years) were more likely to have normal upper and lower gastrointestinal biopsies and to show less frequent crypt architectural changes in the terminal ileum. In summary, Crohn's disease ileitis is often associated with inflammation elsewhere in the gastrointestinal tract while non-specific ileitis was infrequently associated with inflammation elsewhere for both paediatric and adult patients. These findings support the role of systematic biopsies in multiple gastrointestinal sites to help distinguishing Crohn's ileitis from non-specific ileitis in paediatric and adult population.

Background: Chronic heart failure is a common clinical syndrome associated with high healthcare system use., Objective: The aim of this study was to explore the management of chronic heart failure in Australian general practice., Methods: Data from the Bettering the Evaluation and Care of Health program were used to determine the prevalence of chronic heart failure, use of natriuretic peptide testing, prescribing patterns, hospitalisation rates and referrals to community-based heart failure management programs in three study periods between 2010 and 2015., Results: Data on 8989 patients from 308 general practitioners were analysed. Of these patients, 324 had chronic heart failure (prevalence 3.6%; 95% confidence interval [CI]: 3.1-4.2), 44% (95% CI: 34.5-53.6) of whom had been hospitalised for the condition. The mean number of prescribed heart failure medication agents was 2.26 (95% CI: 2.13-2.39) per patient. Discharge under community heart failure programs was not routine., Discussion: Chronic heart failure is a significant burden in general practice. Strategies to optimise management and avoid hospitalisation, where possible, are needed.

Objectives: To quantify the time that general practitioners spend on patient care that is not claimable from Medicare (non-billable) and the monetary value of this work were it claimable, and to identify variables independently associated with non-billable time., Design: Prospective, cross-sectional survey, April 2012 - March 2014., Setting: Australian general practice; a substudy of the national Bettering the Evaluation and Care of Health (BEACH) program., Participants: 1935 randomly sampled GPs (77.4% participation rate) from across Australia provided filled questionnaires on 66 458 patient encounters., Main Outcome Measures: Non-billable time spent on patient care since patient's previous consultation; duration of and reasons for non-billable time; estimate of its monetary value were it claimable from Medicare; variables associated with non-billable time., Results: 69.5% of GPs reported non-billable care outside patient visits; 8019 patient encounters (12.1%) were associated with an occasion of non-billable time. Mean time spent per occasion was 10.1 min (range, 1-240 min). Reasons for non-billable time included arranging tests and referrals, consulting specialists or allied health professionals, medication renewals, and advice and education, and encompassed all International Classification of Primary Care Version 2 chapters. The notional average annual value per GP of this work was $10 525.95 (level A rebate) to $23 008.05 (level B). Non-billable time was independently associated with female GPs, younger GPs (under 55 years), female patients, patients aged 65 years or more, and one or more chronic problems being managed at the recorded encounter., Conclusion: Most GPs spend a significant amount of unpaid time on patient care between consultations, an inherent problem of the fee-for-service system. This work should inform discussions of future funding models.

Otitis media (OM) is one of the most common infections in children. The cause can be viral, but is most often bacterial. It remains one of the most common reasons for antibiotic prescribing for children. Many episodes of acute OM are self-limiting and resolve without treatment, but antibiotics are often prescribed because these infections can develop into serious, sometimes life-threatening complications.