Seasonal patterns of oral antihistamine and intranasal corticosteroid purchases from Australian community pharmacies : a retrospective observational study

Acknowledgments The abstract of this paper was presented at the Respiratory Effectiveness Group 2016 Annual Summit as a poster presentation with interim findings. The poster’s abstract was published in “Poster Abstracts” in The Journal of Thoracic Disease (Vol. 8, Supplement 5, 5 July 2016). http://jtd.amegroups.com/article/view/8504.Peer reviewedPublisher PD

Expression of KOC, S100P, mesothelin and MUC1 in pancreatico-biliary adenocarcinomas: development and utility of a potential diagnostic immunohistochemistry panel

<b>Background</b> Pancreatico-biliary adenocarcinomas (PBA) have a poor prognosis. Diagnosis is usually achieved by imaging and/or endoscopy with confirmatory cytology. Cytological interpretation can be difficult especially in the setting of chronic pancreatitis/cholangitis. Immunohistochemistry (IHC) biomarkers could act as an adjunct to cytology to improve the diagnosis. Thus, we performed a meta-analysis and selected KOC, S100P, mesothelin and MUC1 for further validation in PBA resection specimens.<p></p> <b>Methods</b> Tissue microarrays containing tumour and normal cores in a ratio of 3:2, from 99 surgically resected PBA patients, were used for IHC. IHC was performed on an automated platform using antibodies against KOC, S100P, mesothelin and MUC1. Tissue cores were scored for staining intensity and proportion of tissue stained using a Histoscore method (range, 0–300). Sensitivity and specificity for individual biomarkers, as well as biomarker panels, were determined with different cut-offs for positivity and compared by summary receiver operating characteristic (ROC) curve.<p></p> <b>Results</b> The expression of all four biomarkers was high in PBA versus normal ducts, with a mean Histoscore of 150 vs. 0.4 for KOC, 165 vs. 0.3 for S100P, 115 vs. 0.5 for mesothelin and 200 vs. 14 for MUC1 (p < .0001 for all comparisons). Five cut-offs were carefully chosen for sensitivity/specificity analysis. Four of these cut-offs, namely 5%, 10% or 20% positive cells and Histoscore 20 were identified using ROC curve analysis and the fifth cut-off was moderate-strong staining intensity. Using 20% positive cells as a cut-off achieved higher sensitivity/specificity values: KOC 84%/100%; S100P 83%/100%; mesothelin 88%/92%; and MUC1 89%/63%. Analysis of a panel of KOC, S100P and mesothelin achieved 100% sensitivity and 99% specificity if at least 2 biomarkers were positive for 10% cut-off; and 100% sensitivity and specificity for 20% cut-off.<p></p> <b>Conclusion</b> A biomarker panel of KOC, S100P and mesothelin with at least 2 biomarkers positive was found to be an optimum panel with both 10% and 20% cut-offs in resection specimens from patients with PBA.<p></p&gt

Gender Diferences in Heart Failure Self-Care: A Multinational Cross-Sectional Study

Background Despite a common view that women are better at self-care, there is very little evidence to support or challenge this perspective in the heart failure (HF) population. Objective The purpose of this study was to determine if there are cross-cultural gender differences in self-reported HF self-care and to describe gender differences in the determinants of HF self-care. Design, setting, and participants A secondary analysis was completed of cross-sectional study data collected on 2082 adults with chronic HF from the United States, Australia and Thailand. Methods Comparisons were made between men and women regarding self-care maintenance, management and confidence as assessed by the Self-Care of Heart Failure Index, as well as the proportion of subjects engaged in adequate self-care. Multivariate comparisons were made to determine if gender explained sufficient variance in HF self-care and the likelihood of reporting adequate self-care, controlling for nine model covariates. Results The sample was comprised of 1306 men and 776 women. Most (73.5%) had systolic or mixed systolic and diastolic HF and 45% had New York Heart Association class III or IV HF. Although small and clinically insignificant gender differences were found in self-care maintenance, gender was not a determinant of any aspect of HF self-care in multivariate models. Married women were 37% less likely to report adequate self-care maintenance than unmarried women. Comorbidities only influenced the HF self-care of men. Being newly diagnosed with HF also primarily affected men. Patients with diastolic HF (predominantly women) had poorer self-care maintenance and less confidence in self-care. Conclusion Differences in HF self-care are attributable to factors other than gender; however, there are several gender-specific determinants of HF self-care that help identify patients at risk for practicing poor self-care

Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus

A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was able to replicate as efficiently as SARS-CoV in Calu-3 cells and similarly induced minimal transcriptomic changes before 12 h postinfection. Later in infection, HCoV-EMC induced a massive dysregulation of the host transcriptome, to a much greater extent than SARS-CoV. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. This could have an important impact on the ability of the host to mount an adaptive host response. A unique set of 207 genes was dysregulated early and permanently throughout infection with HCoV-EMC, and was used in a computational screen to predict potential antiviral compounds, including kinase inhibitors and glucocorticoids. Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact in vivo pathogenesis and could orient therapeutic strategies against that emergent virus

Longitudinal Systemic Corticosteroid Utilisation for Asthma and Other Diseases in the United Kingdom from 1990 to 2018 : A Population-based Cohort Analysis

Funding: This work was supported by AstraZeneca.Peer reviewedPostprin

Trends in systemic glucocorticoid utilization in the United Kingdom from 1990 to 2019 : a population-based, serial cross-sectional analysis

Acknowledgments The authors thank the members of the Forum for reducing Oral Corticosteroid Use in Severe asthma (FOCUS) for their involvement in the conception of the study (Table S5). Medical writing support, including preparation of the draft manuscript under the direction and guidance of the authors, incorporating author feedback, and manuscript submission, was provided by Lea Anne Gardner, PhD, RN (CiTRUS Health Group), in accordance with Good Publication Practice 2022 (GPP 2022) guidelines. This support was funded by AstraZeneca (Cambridge, UK). Data from OPCRD were obtained under license from Optimum Patient Care Limited. The interpretation and conclusions contained in this report are those of the authors alone. Funding This work was funded by AstraZeneca. In collaboration with the steering committee, AstraZeneca was involved in the study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the article for publication. All authors had full access to the data, agreed to be accountable for the accuracy and integrity of the work, and shared responsibility for the decision to submit the article for publication. Steering committee members were not compensated for their participation.Peer reviewe

An exploratory cluster randomised controlled trial of knowledge translation strategies to support evidence-informed decision-making in local governments (The KT4LG study)

Background: Childhood overweight and obesity is the most prevalent and, arguably, politically complex child health problem internationally. Governments, communities and industry have important roles to play, and are increasingly expected to deliver an evidence-informed system-wide prevention program. However, efforts are impeded by a lack of organisational access to and use of research evidence. This study aims to identify feasible, acceptable and ideally, effective knowledge translation (KT) strategies to increase evidence-informed decision making in local governments, within the context of childhood obesity prevention as a national policy priority.Methods/Design: This paper describes the methods for KT4LG, a cluster randomised controlled trial which is exploratory in nature, given the limited evidence base and methodological advances. KT4LG aims to examine a program of KT strategies to increase the use of research evidence in informing public health decisions in local governments. KT4LG will also assess the feasibility and acceptability of the intervention. The intervention program comprises a facilitated program of evidence awareness, access to tailored research evidence, critical appraisal skills development, networking and evidence summaries and will be compared to provision of evidence summaries alone in the control program. 28 local governments were randomised to intervention or control, using computer generated numbers, stratified by budget tertile (high, medium or low). Questionnaires will be used to measure impact, costs, and outcomes, and key informant interviews will be used to examine processes, feasibility, and experiences. Policy tracer studies will be included to examine impact of intervention on policies within relevant government policy documents.Discussion: Knowledge translation intervention studies with a focus on public health and prevention are very few in number. Thus, this study will provide essential data on the experience of program implementation and evaluation of a system-integrated intervention program employed within the local government public health context. Standardised programs of system, organisational and individual KT strategies have not been described or rigorously evaluated. As such, the findings will make a significant contribution to understanding whether a facilitated program of KT strategies hold promise for facilitating evidence-informed public health decision making within complex multisectoral government organisations.<br /

FULL COMMUNICATION Consumption of Dried Apple Peel Powder Increases Joint Function and Range of Motion

ABSTRACT The goal for this study was to evaluate the effects of consumption of dried apple peel powder (DAPP) on joint function and range of motion (ROM). Additional in vitro and clinical testing was performed to suggest specific mechanisms of action. An open-label clinical pilot study involved 12 healthy people with moderate loss of joint ROM and associated chronic pain. The subjects consumed 4.25 g DAPP daily for 12 weeks, with evaluations at baseline, 2, 4, 8, and 12 weeks. ROM was evaluated at each visit using dual digital inclinometry. Pain scores were collected using Visual Analogue Scales. Blood draws enabled testing of serum antioxidant protective capacity using the cellular antioxidant protection (CAP-e) bioassay. Additional in vitro testing involved testing of cyclooxygenase-2 (COX-2) and lipoxygenase inhibition, cellular antioxidant protection by the CAP-e bioassay, and formation of reactive oxygen species (ROS) by polymorphonuclear (PMN) cells by flow cytometry. Twelve weeks of consumption of DAPP was associated with improved ROM. DAPP provided antioxidants that were available to enter into and protect cells from oxidative damage in vitro, and consumption of DAPP for 12 weeks was associated with a statistically significant improvement in serum antioxidant protective status. DAPP inhibited both COX-2 and lipoxygenase enzymes, and pretreatment of inflammatory PMN cells with DAPP before inflammatory stimulus resulted in reduced ROS formation. This suggests multifaceted anti-inflammatory properties of DAPP. Consumption of DAPP was associated with improved joint function and improved serum antioxidant protection status. The observed pain reduction may be associated with the improved antioxidant status and linked to the apple polyphenols&apos; anti-inflammatory effects

Computational approaches identify a transcriptomic fingerprint of drug-induced structural cardiotoxicity

Structural cardiotoxicity (SCT) presents a high-impact risk that is poorly tolerated in drug discovery unless significant benefit is anticipated. Therefore, we aimed to improve the mechanistic understanding of SCT. First, we combined machine learning methods with a modified calcium transient assay in human-induced pluripotent stem cell-derived cardiomyocytes to identify nine parameters that could predict SCT. Next, we applied transcriptomic profiling to human cardiac microtissues exposed to structural and non-structural cardiotoxins. Fifty-two genes expressed across the three main cell types in the heart (cardiomyocytes, endothelial cells, and fibroblasts) were prioritised in differential expression and network clustering analyses and could be linked to known mechanisms of SCT. This transcriptomic fingerprint may prove useful for generating strategies to mitigate SCT risk in early drug discovery

Computational approaches identify a transcriptomic fingerprint of drug-induced structural cardiotoxicity

Structural cardiotoxicity (SCT) presents a high-impact risk that is poorly tolerated in drug discovery unless significant benefit is anticipated. Therefore, we aimed to improve the mechanistic understanding of SCT. First, we combined machine learning methods with a modified calcium transient assay in human-induced pluripotent stem cell-derived cardiomyocytes to identify nine parameters that could predict SCT. Next, we applied transcriptomic profiling to human cardiac microtissues exposed to structural and non-structural cardiotoxins. Fifty-two genes expressed across the three main cell types in the heart (cardiomyocytes, endothelial cells, and fibroblasts) were prioritised in differential expression and network clustering analyses and could be linked to known mechanisms of SCT. This transcriptomic fingerprint may prove useful for generating strategies to mitigate SCT risk in early drug discovery