Improving long-term disaster recovery research in Australia through boosting dataset comparability

Emergencies and disasters are increasing in frequency and complexity in Australia and around the world.1 It is well established that the effects of these events take a long time to recover from. There is strong and growing evidence to show that different segments of society are exposed to disasters in different ways, with people and communities affected in interconnected and compounding ways

A prospective evaluation of treatment with Selective Internal Radiation Therapy (SIR-spheres) in patients with unresectable liver metastases from colorectal cancer previously treated with 5-FU based chemotherapy

BACKGROUND: To prospectively evaluate the efficacy and safety of selective internal radiation (SIR) spheres in patients with inoperable liver metastases from colorectal cancer who have failed 5FU based chemotherapy. METHODS: Patients were prospectively enrolled at three Australian centres. All patients had previously received 5-FU based chemotherapy for metastatic colorectal cancer. Patients were ECOG 0–2 and had liver dominant or liver only disease. Concurrent 5-FU was given at investigator discretion. RESULTS: Thirty patients were treated between January 2002 and March 2004. As of July 2004 the median follow-up is 18.3 months. Median patient age was 61.7 years (range 36 – 77). Twenty-nine patients are evaluable for toxicity and response. There were 10 partial responses (33%), with the median duration of response being 8.3 months (range 2–18) and median time to progression of 5.3 mths. Response rates were lower (21%) and progression free survival shorter (3.9 mths) in patients that had received all standard chemotherapy options (n = 14). No responses were seen in patients with a poor performance status (n = 3) or extrahepatic disease (n = 6). Overall treatment related toxicity was acceptable, however significant late toxicity included 4 cases of gastric ulceration. CONCLUSION: In patients with metastatic colorectal cancer that have previously received treatment with 5-FU based chemotherapy, treatment with SIR-spheres has demonstrated encouraging activity. Further studies are required to better define the subsets of patients most likely to respond

Distress and satisfaction with research participation: Impact on retention in longitudinal disaster research

© 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).Previous studies of the impact of post-trauma research participation indicate that while the research experience may be emotional, it can still be valued by participants. This paper describes participant experiences of the Australian post-bushfire research study–Beyond Bushfires. It examines the relationships between distress during research participation, probable mental health conditions, and satisfaction with the research experience over time. A range of strategies was incorporated into the study, including a distress and risk assessment and referral protocol, to minimise any risk of harm for people who had experienced the 2009 bushfires and their aftermath. Participants included 1056 respondents (Wave 1) interviewed via telephone and web-based survey between December 2011 through January 2013, and 736 (76.1%) of the participants were re-surveyed between July and November 2014 (Wave 2). Research impact was monitored through two questions about survey experience on each occasion. Reported distress at completing the survey was generally low, while overall satisfaction was relatively high. Participants’ reported satisfaction was not associated with their reported level of distress as a result of the survey; and reported participation distress at Wave 1 did not predict whether a respondent would return to complete the survey at Wave 2. Fire-related Posttraumatic stress symptoms were associated with increased satisfaction and likelihood to return at Wave 2. These findings suggest that for Beyond Bushfires survey respondents the perceived benefits outweighed the costs of participation over time

Trends in seasonal influenza vaccine uptake during pregnancy in Western Australia: Implications for midwives

Background: Antenatal influenza vaccination is an important public health intervention for preventing serious illness in mothers and newborns, yet uptake remains low. Aim: To evaluate trends in seasonal influenza vaccine coverage and identify determinants for vaccination among pregnant women in Western Australia. Methods: We conducted an annual telephone survey in a random sample of post-partum women who delivered a baby in Western Australia between 2012 and 2014. Women were asked whether influenza vaccination was recommended and/or received during their most recent pregnancy; women were also asked why or why they were not immunised. Findings: Between 2012 and 2014, influenza vaccine coverage increased from 22.9% to 41.4%. Women who reported receiving the majority of their antenatal care from a private obstetrician were significantly more likely to have influenza vaccination recommended to them than those receiving the majority of their care from a public antenatal hospital or general practitioner (p \u3c 0.001). In 2014, the most common reason women reported for accepting influenza vaccination was to protect the baby (92.8%) and the most common reason for being unimmunised was lack of a healthcare provider recommendation (48.5%). Discussion: Antenatal influenza vaccination uptake is increasing, but coverage remains below 50%. A recommendation from the principal care provider is an important predictor of maternal influenza vaccination. Conclusion: Antenatal care providers, including midwives, have a key role in providing appropriate information and evidence-based recommendations to pregnant women to ensure they are making informed decisions. Consistent recommendations from antenatal care providers are critical to improving influenza vaccine coverage in pregnant women

Lateral flow test engineering and lessons learned from COVID-19

The acceptability and feasibility of large-scale testing with lateral flow tests (LFTs) for clinical and public health purposes has been demonstrated during the COVID-19 pandemic. LFTs can detect analytes in a variety of samples, providing a rapid read-out, which allows self-testing and decentralized diagnosis. In this Review, we examine the changing LFT landscape with a focus on lessons learned from COVID-19. We discuss the implications of LFTs for decentralized testing of infectious diseases, including diseases of epidemic potential, the ‘silent pandemic’ of antimicrobial resistance, and other acute and chronic infections. Bioengineering approaches will play a key part in increasing the sensitivity and specificity of LFTs, improving sample preparation, incorporating nucleic acid amplification and detection, and enabling multiplexing, digital connection and green manufacturing, with the aim of creating the next generation of high-accuracy, easy-to-use, affordable and digitally connected LFTs. We conclude with recommendations, including the building of a global network of LFT research and development hubs to facilitate and strengthen future diagnostic resilience

Risk factors for death in 632 patients with sickle cell disease in the United States and United Kingdom

Background: The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD) is controversial. Methods and Results: We evaluated the relationship between an elevated estimated pulmonary artery systolic pressure and mortality in patients with SCD. We followed patients from the walk-PHaSST screening cohort for a median of 29 months. A tricuspid regurgitation velocity (TRV)≥3.0 m/s cuttof, which has a 67-75% positive predictive value for mean pulmonary artery pressure ≥25 mm Hg was used. Among 572 subjects, 11.2% had TRV≥3.0 m/sec. Among 582 with a measured NT-proBNP, 24.1% had values ≥160 pg/mL. Of 22 deaths during follow-up, 50% had a TRV≥3.0 m/sec. At 24 months the cumulative survival was 83% with TRV≥3.0 m/sec and 98% with TRV47 years, male gender, chronic transfusions, WHO class III-IV, increased hemolytic markers, ferritin and creatinine were also associated with increased risk of death. Conclusions: A TRV≥ 3.0 m/sec occurs in approximately 10% of individuals and has the highest risk for death of any measured variable. The study is registered in ClinicalTrials.gov with identifier: NCT00492531

Effect of aspirin on cancer incidence and mortality in older adults.

BACKGROUND: ASPirin in Reducing Events in the Elderly (ASPREE), a randomized double-blind placebo-controlled trial (RCT) of daily low-dose aspirin (100 mg) in older adults, showed an increase in all-cause mortality, primarily due to cancer. In contrast prior RCTs, mainly involving younger individuals, demonstrated a delayed cancer benefit with aspirin. We now report a detailed analysis of cancer incidence and mortality. METHODS: 19,114 Australian and U.S. community-dwelling participants aged 70+ years (U.S. minorities 65+ years) without cardiovascular disease, dementia or physical disability were randomized and followed for a median of 4.7 years. Fatal and non-fatal cancer events, a prespecified secondary endpoint, were adjudicated based on clinical records. RESULTS: 981 cancer events occurred in the aspirin and 952 in the placebo groups. There was no statistically significant difference between groups for all incident cancers (HR = 1.04, 95% CI = 0.95 to 1.14), hematological cancer (HR = 0.98, 95% CI = 0.73 to 1.30), or all solid cancers (HR = 1.05, 95% CI = 0.95 to 1.15), including by specific tumor type. However, aspirin was associated with an increased risk of incident cancer that had metastasized (HR = 1.19, 95% CI = 1.00 to 1.43) or was stage 4 at diagnosis (HR = 1.22, 95% CI = 1.02 to 1.45), and with higher risk of death for cancers that presented at stages 3 (HR = 2.11, 95% CI = 1.03 to 4.33) or 4 (HR = 1.31, 95% CI = 1.04 to 1.64). CONCLUSIONS: In older adults, aspirin treatment had an adverse effect on later stages of cancer evolution. These findings suggest that in older persons, aspirin may accelerate the progression of cancer and thus, suggest caution with its use in this age group

Ethical Use and Impact of Participatory Approaches to Research in Post-Disaster Environments: An Australian Bushfire Case Study

Copyright © 2018 L. Gibbs et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This paper presents a case study of Beyond Bushfires, a large, multisite, mixed method study of the psychosocial impacts of major bushfires in Victoria, Australia. A participatory approach was employed throughout the study which was led by a team of academic investigators in partnership with service providers and government representatives and used on-site visits and multiple methods of communication with communities across the state to inform decision-making throughout the study. The ethics and impacts of conducting and adapting the approach within a post-disaster context will be discussed in reference to theories and models of participatory health research. The challenges of balancing local interests with state-wide implications will also be explored in the description of the methods of engagement and the study processes and outcomes. Beyond Bushfires demonstrates the feasibility of incorporating participatory methods in large, post-disaster research studies and achieving rigorous findings and multilevel impacts, while recognising the potential for some of the empowering aspects of the participatory experience to be reduced by the scaled-up approach

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN