Developing a deep learning natural language processing algorithm for automated reporting of adverse drug reactions.

The detection of adverse drug reactions (ADRs) is critical to our understanding of the safety and risk-benefit profile of medications. With an incidence that has not changed over the last 30 years, ADRs are a significant source of patient morbidity, responsible for 5%-10% of acute care hospital admissions worldwide. Spontaneous reporting of ADRs has long been the standard method of reporting, however this approach is known to have high rates of under-reporting, a problem that limits pharmacovigilance efforts.

Cure of Limb-Threatening XDR Infection: Combining Genome Sequencing, Therapeutic Drug Level Monitoring, and Surgical Debridement.

We describe a case of limb-threatening osteomyelitis and metalware infection with carbapenemase-producing extensively drug-resistant successfully cured with aggressive surgical debridement and combined intravenous fosfomycin and colistin. Real-time therapeutic drug monitoring was used to maximize probability of efficacy and minimize potential for toxicity.

Correction to: A Machine-Learning Algorithm to Optimise Automated Adverse Drug Reaction Detection from Clinical Coding.

CK: Principal Investigator. CM and CK were responsible for the study design and conception; all authors were responsible for acquisition and validation of the data; CM was responsible for analysis and interpretation of the data; and all authors contributed to reviewing drafts of the manuscript and approved the final version for publication.

A Machine-Learning Algorithm to Optimise Automated Adverse Drug Reaction Detection from Clinical Coding.

Introduction: Adverse drug reaction (ADR) detection in hospitals is heavily reliant on spontaneous reporting by clinical staff, with studies in the literature pointing to high rates of underreporting [1]. International Classification of Diseases, 10th Revision (ICD-10) codes have been used in epidemiological studies of ADRs and offer the potential for automated ADR detection systems.

Objective: The aim of this study was to develop an automated ADR detection system based on ICD-10 codes, using machine-learning algorithms to improve accuracy and efficiency.

Association of good oncological response to therapy with the development of rheumatic immune-related adverse events following PD-1 inhibitor therapy.

Aim: To investigate whether any patient or treatment characteristics are associated with the development of rheumatic immune-related adverse events (irAEs) following programmed cell death protein 1 (PD-1) inhibitor therapy for cancer.

Method: This was a retrospective chart review of all patients who were dispensed nivolumab or pembrolizumab at a single center before 1 January, 2017, with follow-up until 1 July, 2017. Patients with any diagnosis of a non-cutaneous irAE were identified, regardless of severity, and rheumatic irAEs were characterized.

Rheumatic immune-related adverse events secondary to anti-programmed death-1 antibodies and preliminary analysis on the impact of corticosteroids on anti-tumour response: A case series.

Importance: Rheumatic immune-related adverse events (irAEs) occur in approximately 10-20% of anti-programmed death 1 (anti-PD1)-treated cancer patients. There are limited data on the natural history, optimal treatment and long-term oncological outcomes of patients with rheumatic irAEs.

Objective: The objective of the study was to describe the spectrum and natural history of rheumatic irAEs and the potential impact of rheumatic irAEs and immunomodulators on anti-PD1 tumour efficacy.

Comparison of diurnal blood pressure and urine production between people with and without chronic spinal cord injury.

Study Design: Observational study.

Objectives: To quantify diurnal blood pressure (BP) patterns and nocturnal hypertension and to measure diurnal urine production in people with chronic spinal cord injury (SCI), compared with controls without SCI.

Setting: Chronic SCI population in the community in Victoria, Australia.

Massive splenomegaly due to concurrent primary Epstein-Barr virus and cytomegalovirus infection in a patient on adalimumab.

A 32-year-old man who was receiving adalimumab for seronegative rheumatoid arthritis presented with a 4-week history of fever, night sweats, fatigue, myalgias and diarrhoea. On examination, he had obvious splenomegaly but no lymphadenopathy or pharyngitis. Full blood count revealed mild neutropenia and significant lymphocytosis, with a blood film showing atypical lymphocytes.

Network analysis of an in vitro model of androgen-resistance in prostate cancer.

Background: The development of androgen resistance is a major limitation to androgen deprivation treatment in prostate cancer. We have developed an in vitro model of androgen-resistance to characterise molecular changes occurring as androgen resistance evolves over time. Our aim is to understand biological network profiles of transcriptomic changes occurring during the transition to androgen-resistance and to validate these changes between our in vitro model and clinical datasets (paired samples before and after androgen-deprivation therapy of patients with advanced prostate cancer).

Fosfomycin for Treatment of Prostatitis: New Tricks for Old Dogs.

Treatment options for prostatitis caused by multidrug-resistant gram-negative bacilli are limited. We report two cases cured with oral fosfomycin and provide a pharmacokinetic analysis of fosfomycin predose concentrations during treatment.

Optimal timing of oral fosfomycin administration for pre-prostate biopsy prophylaxis.

Objectives: As the optimal administration time for fosfomycin peri-procedural prophylaxis is unclear, we sought to determine optimal administration times for fosfomycin peri-procedural prophylaxis.

Methods: Plasma, peripheral zone and transition zone fosfomycin concentrations were obtained from 26 subjects undergoing transurethral resection of the prostate (TURP), following a single oral dose of 3 g of fosfomycin. Population pharmacokinetic modelling was completed with the Nonparametric Adaptive Grid (NPAG) algorithm (Pmetrics package for R), with a four-compartment model.

CD151 is associated with prostate cancer cell invasion and lymphangiogenesis in vivo.

CD151, a member of the tetraspanin family, is associated with regulation of migration of normal and tumour cells via cell surface microdomain formation. CD151 was found in our laboratory to have a prognostic value in prostate cancer and is a promoter of prostate cancer migration and invasion. These roles involve association with integrins on both cell-cell and cell-stroma levels.

Positive surgical margins: rate, contributing factors and impact on further treatment: findings from the Prostate Cancer Registry.

Objective: To describe the characteristics of patients with and without positive surgical margins (PSMs) and to analyse the impact of PSMs on secondary cancer treatment after radical prostatectomy (RP), with short-term follow-up.

Patients And Methods: We analysed data from 2385 consecutive patients treated using RP, who were notified to the Prostate Cancer Registry by 37 hospitals in Victoria, Australia between August 2008 and February 2012. Independent and multivariate models were constructed to predict the likelihood of PSMs.

Patterns of care for men diagnosed with prostate cancer in Victoria from 2008 to 2011.

Objective: To describe patterns of care for men diagnosed with prostate cancer in Victoria, Australia, between 2008 and 2011.

Design, Setting And Patients: Men who were diagnosed with prostate cancer at 11 public and six private hospitals in Victoria from August 2008 to February 2011, and for whom prostate cancer notifications were received by the Prostate Cancer Registry.

Main Outcome Measures: Characteristics of men diagnosed with prostate cancer; details of treatment provided within 12 months of diagnosis, according to National Comprehensive Cancer Network risk categories; and characteristics of men who did not receive active treatment within 12 months of diagnosis.

Function and expression of ATIP and its variants in cardiomyoblast cell line H9c2.

Hypothesis: Cardiac hypertrophy in myocytes is in part regulated by changes in expression of a novel Ang II type 2 receptor (AT2-receptor) interacting protein identified as ATIP.

Introduction: The role of the AT2-receptor in cardiac hypertrophy is controversial, with some reports indicating that AT2-receptor activation has detrimental effects on disease progression, whereas others indicate that it has a beneficial role.

Materials And Methods: In an effort to unravel this paradox, we examined the expression and function of ATIP in cell-based models of cardiac hypertrophy using QPCR, immunohistochemistry, cell proliferation, morphological and transfection techniques in H9c2 cardio-myoblast and myotubules.

The Prostate Cancer Registry: monitoring patterns and quality of care for men diagnosed with prostate cancer.

Objective: To establish a pilot population-based clinical registry with the aim of monitoring the quality of care provided to men diagnosed with prostate cancer.

Patients And Methods: All men aged >18 years from the contributing hospitals in Victoria, Australia, who have a diagnosis of prostate cancer confirmed by histopathology report notified to the Victorian Cancer Registry are eligible for inclusion in the Prostate Cancer Registry (PCR). A literature review was undertaken aiming to identify existing quality indicators and source evidence-based guidelines from both Australia and internationally.

Tropisetron versus metoclopramide for the treatment of nausea and vomiting in the emergency department: A randomized, double-blinded, clinical trial.

Aim: We aimed to compare the relative efficacy of tropisetron and metoclopramide in treating nausea/vomiting in undifferentiated ED patients.

Methods: We undertook a randomized, double-blinded, clinical trial. Adult patients requiring treatment for nausea/vomiting were randomly assigned to either tropisetron (5 mg) or metoclopramide (10 mg), by i.

Gene sequencing and tissue expression of unknown isoforms of an angiotensin II type 2 receptor interacting protein, ATIP, in the rat.

To investigate the expression of the unknown angiotensin II type 2 receptor interacting protein (ATIP) isoforms in the rat we used the known sequences of human and mouse ATIP to design sequencing primers to enable us to sequence rat ATIP3 and ATIP4. Exon 4, which is present in human but not mouse ATIP, was not identified in the coding region of rat ATIP. The expression levels of these genes in a range of rat tissues were examined, and we concluded that there is little similarity in the relative tissue distribution of the various ATIP isoforms in rat and human.

Recent developments in prostate cancer biomarker research: therapeutic implications.

This review aims to present an overview of recent clinical trials targeting biomarkers in advanced prostate cancer. We searched ClinicalTrials.gov for early phase clinical trials on treatments of prostate cancer that have been recently completed, are ongoing or are actively recruiting participants.

The Expression of MTUS1/ATIP and Its Major Isoforms, ATIP1 and ATIP3, in Human Prostate Cancer.

Angiotensin II (Ang II), the main effector of the renin angiotensin system, acts upon two distinct transmembrane receptors, the Ang II type 1 and the type 2 (AT2-) receptor, to induce promotion and inhibition of ERK2 phosphorylation. The AT2-receptor, through an interaction with its putative signaling partner MTUS1/ATIP (AT2-receptor interacting protein), inhibits the mitogenic effects of EGF in prostate cancer cell lines representing both early and late stage disease. This is the first report on the expression of ATIP in normal and malignant human prostatic biopsies.

The migration and invasion of human prostate cancer cell lines involves CD151 expression.

The molecular mechanisms underlying prostate cancer metastasis remain poorly understood. The tetraspanin family member CD151 has been reported as an 'adaptor' between integrins and signal pathways. The role of CD151 in prostate cancer metastasis in vitro was investigated in this study.

Expression and function of ATIP/MTUS1 in human prostate cancer cell lines.

Background: We have previously demonstrated Ang II type 2 (AT(2)-) receptor-mediated inhibition of EGF-induced prostate cancer cell growth in androgen-dependent (LNCaP) and independent (PC3) prostate cancer cell lines.

Methods: To explore the signaling pathways involved in this inhibitory effect, we examined the interaction of the AT(2)-receptor with its novel regulatory partner ATIP using real time PCR, over-expression, siRNA and [(3)H]thymidine incorporation assays.

Results: The results in human prostate cancer cell lines demonstrate the presence of ATIP in both cell lines examined, and suggest that (i) the AT(2)-receptor through an interaction with ATIP mediates an anti-growth factor effect in both androgen-dependent and androgen-independent cell lines; (ii) ATIP expression decreases as the rate of cell growth and androgen-independence increase; and (iii) EGF may act on cell growth in part by reducing the content of ATIP present in the cells.