Publications by authors named "Rachel Wong"

255 Publications

The association between quality care and outcomes for a real-world population of Australian patients diagnosed with pancreatic cancer.

HPB (Oxford) 2021 Nov 16. Epub 2021 Nov 16.

School of Public Health and Preventative Medicine, Monash University, Victoria, Australia; Alfred Health, Victoria, Australia. Electronic address:

Background: This study: (i) assessed compliance with a consensus set of quality indicators (QIs) in pancreatic cancer (PC); and (ii) evaluated the association between compliance with these QIs and survival.

Methods: Four years of data were collected for patients diagnosed with PC. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A multivariable analysis tested the relationship between significant patient and hospital characteristics, patient cluster effects within hospitals and survival.

Results: 1061 patients were eligible for this study. Significant association with improved survival were: (i) in the potentially resectable group having adjuvant chemotherapy administered following surgery or a reason documented (HR, 0.29; 95 CI, 0.19-0.46); (ii) in the locally advanced group included having chemotherapy ± chemoradiation, or a reason documented for not undergoing treatment (HR, 0.38; 95 CI, 0.25-0.58); and (iii) in the metastatic disease group included having documented performance status at presentation (HR, 0.65; 95 CI, 0.47-0.89), being seen by an oncologist in the absence of treatment (HR, 0.48; 95 CI, 0.31-0.77), and disease management discussed at a multidisciplinary team meeting (HR, 0.79; 95 CI, 0.64-0.96).

Conclusion: Capture of a concise data set has enabled quality of care to be assessed.
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http://dx.doi.org/10.1016/j.hpb.2021.11.005DOI Listing
November 2021

Treatment and outcomes of unresectable and metastatic pancreatic cancer treated in public and private Australian hospitals.

Asia Pac J Clin Oncol 2021 Nov 23. Epub 2021 Nov 23.

Division of Oncology, Walter and Eliza Hall Institute, Melbourne, Victoria, Australia.

Background: Prior studies have reported for several cancer types that treatment in the private sector is associated with improved survival outcomes. Data for patients with locally advanced unresectable and metastatic pancreatic ductal adenocarcinoma (PDAC) have not previously been reported.

Methods: Analysis of patients from January 2016 to June 2020 registered to a multicentre prospective cancer database. Baseline demographic and clinicopathologic characteristics were compared. The Kaplan-Meier method was used to compare overall survival (OS). Multivariate Cox and logistic regression analyses were used to determine predictors of mortality and first-line chemotherapy treatment, respectively.

Results: Of 822 patients, 22.5% received private care. Private patients were older (median 71.5 vs. 68.9 years, p ≤ .05), had better performance status (ECOG 0 to 1: 82.2 vs. 73.5%, p = .05) and more likely to reside in an area with high socioeconomic advantage (67.0 vs. 19.6%, p ≤ .01). Private patients were more likely to receive first-line chemotherapy (69.7 vs. 54.2%, p ≤ .01) with logistic regression demonstrating private care (OR: 1.87, 95% CI: 1.20 to 2.97) as an independent predictor of receiving chemotherapy. Private patients had prolonged survival (median OS: 9.2 vs. 6.9 months, HR 1.2, p = .05). Receiving first-line chemotherapy was an independent predictor of mortality, but private care was not.

Conclusions: Care in the private system is associated with improved OS, with higher uptake of first-line chemotherapy appearing to be the main contributor. Given the discrepancy, further studies are needed to determine what factors are driving this difference.
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http://dx.doi.org/10.1111/ajco.13721DOI Listing
November 2021

Integrated Genomic Profiling and Drug Screening of Patient-Derived Cultures Identifies Individualized Copy Number-Dependent Susceptibilities Involving PI3K Pathway and 17q Genes in Neuroblastoma.

Front Oncol 2021 14;11:709525. Epub 2021 Oct 14.

Duke NUS Medical School, Singapore, Singapore.

Neuroblastoma is the commonest extracranial pediatric malignancy. With few recurrent single nucleotide variations (SNVs), mutation-based precision oncology approaches have limited utility, but its frequent and heterogenous copy number variations (CNVs) could represent genomic dependencies that may be exploited for personalized therapy. Patient-derived cell culture (PDC) models can facilitate rapid testing of multiple agents to determine such individualized drug-responses. Thus, to study the relationship between individual genomic aberrations and therapeutic susceptibilities, we integrated comprehensive genomic profiling of neuroblastoma tumors with drug screening of corresponding PDCs against 418 targeted inhibitors. We quantified the strength of association between copy number and cytotoxicity, and validated significantly correlated gene-drug pairs in public data and using machine learning models. Somatic mutations were infrequent (3.1 per case), but copy number losses in 1p (31%) and 11q (38%), and gains in 17q (69%) were prevalent. Critically, cytotoxicity significantly correlated only with CNVs, but not SNVs. Among 1278 significantly correlated gene-drug pairs, copy number of GNA13 and DNA damage response genes CBL, DNMT3A, and PPM1D were most significantly correlated with cytotoxicity; the drugs most commonly associated with these genes were PI3K/mTOR inhibitor PIK-75, and CDK inhibitors P276-00, SNS-032, AT7519, flavopiridol and dinaciclib. Predictive Markov random field models constructed from CNVs alone recapitulated the true z-score-weighted associations, with the strongest gene-drug functional interactions in subnetworks involving PI3K and JAK-STAT pathways. Together, our data defined individualized dose-dependent relationships between copy number gains of PI3K and STAT family genes particularly on 17q and susceptibility to PI3K and cell cycle agents in neuroblastoma. Integration of genomic profiling and drug screening of patient-derived models of neuroblastoma can quantitatively define copy number-dependent sensitivities to targeted inhibitors, which can guide personalized therapy for such mutationally quiet cancers.
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http://dx.doi.org/10.3389/fonc.2021.709525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551924PMC
October 2021

Improved resolution of phenotypic subsets in human T-ALL by incorporation of RNA-seq based developmental profiling.

Leuk Res 2021 11 22;110:106712. Epub 2021 Sep 22.

Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, V5Z 1L3, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.leukres.2021.106712DOI Listing
November 2021

The Effect of Pets on Human Mental Health and Wellbeing during COVID-19 Lockdown in Malaysia.

Animals (Basel) 2021 Sep 14;11(9). Epub 2021 Sep 14.

Department of Psychology, School of Social Sciences, Heriot-Watt University, Putrajaya 62200, Malaysia.

The adverse impact of SARS-CoV-2 (COVID-19) on mental and physical health has been witnessed across the globe. Associated mental health and wellbeing issues include stress, social isolation, boredom, and anxiety. Research suggests human-animal interactions may improve the overall wellbeing of an individual. However, this has been less explored in Southeast Asian countries like Malaysia and the present study examined the effect of pets on the mental health and wellbeing of Malaysians during the lockdown, or movement control order (MCO), due to COVID-19 pandemic. A cross-sectional survey was carried out, with 448 Malaysian participants, who completed online assessments for psychological outcomes, psychological wellbeing, positive-negative emotions, resilience, and coping self-efficacy. Results indicate that pet owners reported significantly better coping self-efficacy, significantly more positive emotions, and better psychological wellbeing, but contrary to expectations, there was no differences on other measures. Among pet owners, cat owners reported more positive emotions and greater wellbeing than dog owners. The results show that that pets have some impact on improved psychological health of their owners and could be integrated into recovery frameworks for promoting mental health and wellbeing.
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http://dx.doi.org/10.3390/ani11092689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470955PMC
September 2021

Money Talks: Pilot Financial Wellness Programs to Promote Positive Financial Planning Behaviors Among Residents.

Acad Med 2021 Sep 21. Epub 2021 Sep 21.

P. Ng is assistant professor of clinical medicine, Department of Medicine, Stony Brook University Hospital, Stony Brook, New York; ORCID: https://orcid.org/0000-0003-1900-6931. S. Raghavan was assistant professor of medicine, Department of Medicine, North Shore University Hospital, Northwell Health, Manhasset, New York, and Long Island Jewish Medical Center, Northwell Health, New Hyde Park, New York at the time of writing. She is now program director, Internal Medicine Residency Program, Mount Sinai Beth Israel, Icahn School of Medicine at Mount Sinai, New York, New York; ORCID: https://orcid.org/0000-0001-9645- 2463. C. Zhang is assistant professor of medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; ORCID: https://orcid.org/0000-0002-3190-9503. J.-Y. Pan is assistant professor, Department of Medicine, Montefiore Medical Center, New York, New York; ORCID: https://orcid.org/0000-0002-0522-2679. P. O'Rourke is assistant professor of medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; ORCID: https://orcid.org/0000-0002-4790-6921. R. Wong is assistant professor of clinical medicine, Department of Medicine, Stony Brook University Hospital, Stony Brook, New York; ORCID: https://orcid.org/0000-0003-3108-7324.

Problem: Graduate medical education programs and national organizations are becoming more involved in promoting trainee financial wellness. Current literature reports residents have poor financial knowledge, high debt levels, low concern about their finances, and deficits in financial preparedness, but there has been little published on best practices for implementing financial wellness programs for residents or measuring meaningful outcomes of such programs.

Approach: From June 2017-2019, the authors invited 277 internal medicine residents from the Stony Brook University Hospital, Montefiore Medical Center, and Johns Hopkins Bayview Medical Center residency programs to participate in financial wellness programs. Each institution held at least one 90-minute financial planning session; Stony Brook also had biannual financial wellness check-ins. Participants were invited to complete a pre-session, an immediate post-session, and a year-end survey to assess changes in financial planning behaviors.

Outcomes: Survey response rates were 49% (135/277) for the pre-session survey, 47% (130/277) for the immediate post-session survey, and 22% (61/277) for the year-end survey. Ninety-six percent (125/130) found the sessions helpful and 98% (120/123) recommended continuing the program in the future. At year-end, the most frequent completed financial planning actions prompted by the session included saving emergency funds, creating a monthly budget, consolidating loans via the Public Service Loan Forgiveness program, contributing to retirement savings, and participating in an employer's retirement plan. Resident liked that some sessions were during intern orientation prior to the selection of retirement plans. Postgraduate year (PGY) 1 residents were more likely to complete positive financial planning actions and to agree or strongly agree that the session prompted them to take financial planning actions than PGY2 and PGY3 residents.

Next Steps: While financial wellness programs are well received by internal medicine residents, more robust evidence is needed on curricular delivery methods and program features that promote positive financial planning behaviors.
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http://dx.doi.org/10.1097/ACM.0000000000004429DOI Listing
September 2021

Cognitive Deficits in Type-1 Diabetes: Aspects of Glucose, Cerebrovascular and Amyloid Involvement.

Pharm Res 2021 Sep 3;38(9):1477-1484. Epub 2021 Sep 3.

School of Population Health, Faculty of Health Sciences, Curtin University, Perth, WA, 6845, Australia.

The evidence shows that individuals with type-1 diabetes mellitus (T1DM) are at greater risk of accelerated cognitive impairment and dementia. Although, to date the mechanisms are largely unknown. An emerging body of literature indicates that dysfunction of cerebral neurovascular network and plasma dyshomeostasis of soluble amyloid-β in association with impaired lipid metabolism are central to the onset and progression of cognitive deficits and dementia. However, the latter has not been extensively considered in T1DM. Therefore, in this review, we summarised the literature concerning altered lipid metabolism and cerebrovascular function in T1DM as an implication for potential pathways leading to cognitive decline and dementia.
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http://dx.doi.org/10.1007/s11095-021-03100-1DOI Listing
September 2021

Transient expression of a GABA receptor subunit during early development is critical for inhibitory synapse maturation and function.

Curr Biol 2021 Oct 24;31(19):4314-4326.e5. Epub 2021 Aug 24.

Department of Neuroscience, University of Wisconsin-Madison, Madison, WI, USA; Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, USA; McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI, USA. Electronic address:

Developing neural circuits, including GABAergic circuits, switch receptor types. But the role of early GABA receptor expression for establishment of functional inhibitory circuits remains unclear. Tracking the development of GABAergic synapses across axon terminals of retinal bipolar cells (BCs), we uncovered a crucial role of early GABA receptor expression for the formation and function of presynaptic inhibitory synapses. Specifically, early α3-subunit-containing GABA (GABAα3) receptors are a key developmental organizer. Before eye opening, GABAα3 gives way to GABAα1 at individual BC presynaptic inhibitory synapses. The developmental downregulation of GABAα3 is independent of GABAα1 expression. Importantly, lack of early GABAα3 impairs clustering of GABAα1 and formation of functional GABA synapses across mature BC terminals. This impacts the sensitivity of visual responses transmitted through the circuit. Lack of early GABAα3 also perturbs aggregation of LRRTM4, the organizing protein at GABAergic synapses of rod BC terminals, and their arrangement of output ribbon synapses.
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http://dx.doi.org/10.1016/j.cub.2021.07.059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511107PMC
October 2021

Cerebrovascular Function in Hormonal Migraine: An Exploratory Study.

Front Neurol 2021 7;12:694980. Epub 2021 Jul 7.

School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia.

Migraineurs, particularly young premenopausal women, are at increased risk of cerebrovascular disease; however, there is currently limited evidence as to whether hormonal migraine is associated with poor cerebrovascular function. The objectives of this study were to: (1) investigate the potential association of cerebrovascular function with hormonal migraine and (2) determine whether abnormalities of cerebrovascular function in hormonal migraineurs are associated with migraine-related disability and/or quality of life. A cross-sectional study was undertaken in 50 hormonal migraineurs (mean age: 38.7 ± 1.2 years) and 29 controls (mean age: 35.6 ± 1.8 years). Data were collected at a single point in time from all participants during the inter-ictal period when they were free from migraine and not menstruating. Transcranial Doppler ultrasound was used to measure resting blood flow velocity and cerebrovascular responsiveness (CVR) to hypercapnia and cognitive stimulation (neurovascular coupling) in the left and right middle cerebral artery (MCA). Additionally, hormonal migraineurs completed three questionnaires to assess migraine-related disability and quality of life as well as migraine frequency and intensity: Headache Impact Test-6™, Migraine-Specific Quality of Life and Migraine Disability Assessment. Hormonal migraineurs had lower resting mean blood flow velocity (MBFV) ( = 0.009) and neurovascular coupling during cognitive stimulation ( = 0.010) in the left MCA than controls. No such differences were found in the right MCA. Additionally, heart rate ( = 0.004) was higher in hormonal migraineurs than controls. However, no differences in CVR to hypercapnia were found between hormonal migraineurs and controls. Multi-variate analysis revealed age to be a significant ( = 0.012) predictor of MBFV in the left MCA. Negative correlations between headache frequency and CVR to hypercapnia in the left ( = 0.026) and right MCA ( = 0.044) were found. Additionally, negative correlations between neurovascular coupling during the 2-Back 1.5 s task in the right MCA and the MSQoL emotional ( = 0.013) and role-function restrictive ( = 0.039) domains were found. This is the first study to show that hormonal migraineurs have poorer cerebrovascular function, as represented by lower resting MBFV and impaired neurovascular coupling in the left MCA. Future studies should investigate whether improving cerebrovascular function can prevent hormonal migraine and improve quality of life. ACTRN12618001230246.
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http://dx.doi.org/10.3389/fneur.2021.694980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292610PMC
July 2021

Treatment and Outcomes of Oligometastatic Colorectal Cancer Limited to Lymph Node Metastases.

Clin Colorectal Cancer 2021 Jun 25. Epub 2021 Jun 25.

Department of Medical Oncology, Royal Hobart Hospital, Tasmania, Australia; Menzies Research Institute, Tasmania, Australia.

Introduction: The optimal management of isolated distant lymph node metastases (IDLNM) from a colorectal primary, is not clearly established. We aimed to analyze the outcomes of patients with IDLNM treated with systemic therapies plus locoregional therapy with curative intent versus systemic therapies with palliative intent.

Materials & Methods: Clinical data were collected and reviewed from the Treatment of Recurrent and Advanced Colorectal Cancer registry, a prospective, comprehensive registry for metastatic colorectal cancer (mCRC) treated at multiple tertiary hospitals across Australia. Clinicopathological characteristics, treatment modalities and survival outcomes were analyzed in patients with IDLNM and compared to patients with disease at other sites.

Results: Of 3408 mCRC patients diagnosed 2009 to 2020, with median follow-up of 38.0 months, 93 (2.7%) were found to have IDLNM. Compared to mCRC at other sites, patients with IDLNM were younger (mean age: 62.1 vs. 65.6 years, P = .02), more likely to have metachronous disease (57.0% vs. 38.9%, P < .01), be KRAS wild-type (74.6% vs. 53.9%, P< .01) and BRAF mutant (12.9% vs. 6.2%, P = .01). Amongst mCRC patients with IDLNM, 24 (25.8%) received treatment with curative intent and had a significantly better overall median survival than those treated with palliative intent (73.5 months vs. 23.2 months, P = .01). These 24 patients had an overall median survival similar (62.7 months, P = .82) to patients with isolated liver or lung metastases also treated with curative intent.

Conclusion: Curative treatment strategies (radiotherapy or surgery), with or without systemic therapy, should be considered for mCRC patients with IDLNM where appropriate as assessed by the multidisciplinary team.
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http://dx.doi.org/10.1016/j.clcc.2021.06.003DOI Listing
June 2021

Indexing cerebrovascular health using near-infrared spectroscopy.

Sci Rep 2021 07 20;11(1):14812. Epub 2021 Jul 20.

School of Engineering, University of Newcastle, Callaghan, Australia.

Near-infrared spectroscopy (NiRS) is a relatively new technology of brain imaging with its potential in the assessment of cerebrovascular health only recently discovered. Encouraging early results suggest that NiRS can be used as an inexpensive and portable cerebrovascular health tracking device using a recently proposed pulse relaxation function (PReFx). In this paper, we propose a new NiRS timing index, [Formula: see text], of cerebrovascular health. [Formula: see text] is a novel use of the NiRS technology. [Formula: see text] is motivated by the previously proved relationship of the timing of the reflected wave with vascular resistance and compliance in the context of pressure waveforms. We correlated both [Formula: see text] and PReFx against age, a non-exercise cardiorespiratory fitness (CRF) index, and two existing indices of cerebrovascular health, namely transcranial Doppler (TCD) augmentation index, [Formula: see text], and magnetic resonance imaging (MRI) blood flow pulsatility index, [Formula: see text]. The [Formula: see text] correlations with Age, CRF, [Formula: see text] and [Formula: see text] all are significant, i.e., [Formula: see text] ([Formula: see text]), [Formula: see text] ([Formula: see text]), [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]), respectively. PReFx, however, did not have significant correlations with any of the vascular health factors. The proposed timing index is a reliable indicator of cerebrovascular aging factors in the NiRS waveform.
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http://dx.doi.org/10.1038/s41598-021-94348-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292377PMC
July 2021

Reuse of face masks among adults in Hong Kong during the COVID-19 pandemic.

BMC Public Health 2021 06 29;21(1):1267. Epub 2021 Jun 29.

School of Nursing and Health Studies, The Open University of Hong Kong, Ho Man Tin, Kowloon, Hong Kong.

Background: During the COVID-19 pandemic, over 99% of adults in Hong Kong use face masks in public. With the limited supply of face masks in the market and the uncertainty about the future development of COVID-19, reusing face masks is a legitimate way to reduce usage. Although this practice is not recommended, reusing face masks is common in Hong Kong. This study aimed to examine the practice of reusing face masks among adults in Hong Kong during the COVID-19 pandemic and its association with their health beliefs toward this health crisis.

Methods: A cross-sectional descriptive study was conducted. A quota sample of 1000 adults was recruited in Hong Kong in April 2020. Guided by the Health Belief Model, the subjects were invited to answer questions on their practice of reusing face masks and health beliefs toward COVID-19 through telephone interview. Their practice on reuse, storage, and decontamination of used face masks were summarized by descriptive statistics. The difference in health beliefs between the subjects who reused and did not reuse face masks was examined by conducting an independent t test. The association between health beliefs and reuse of face masks was determined by conducting a logistic regression analysis.

Results: One-third (n = 345, 35.4%) of the subjects reused face masks in an average of 2.5 days. Among them, 207 subjects stored and 115 subjects decontaminated their used face masks by using various methods. The subjects who reused face masks significantly perceived having inadequate face masks (t = 3.905; p <  0.001). Having a higher level of perception of having inadequate face masks increased the likelihood of reusing face masks (OR = 0.784; CI 95%: 0.659-0.934; p = 0.006).

Conclusion: Despite having 90 face masks in stock, the adults who reused face masks significantly perceived that they had inadequate face masks. Concerted effort of health care professionals, community organizations, and the government will improve individuals' practice in use of face masks and alleviate their actual and perceived feeling of having inadequate face masks, which lead them to reuse.
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http://dx.doi.org/10.1186/s12889-021-11346-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240770PMC
June 2021

Stage dependent recurrence patterns and post-recurrence outcomes in non-metastatic colon cancer.

Acta Oncol 2021 Sep 29;60(9):1106-1113. Epub 2021 Jun 29.

Personalised Oncology Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, Australia.

Background: Multiple meta-analyses have demonstrated that routine surveillance following colorectal cancer surgery improves survival outcomes. There is limited data on how recurrence patterns and post-recurrence outcomes vary by individual tumor stage.

Methods: Using a multi-site community cohort study, we examined the potential impact of primary tumor stage on the sites of recurrence, management of recurrent disease with curative intent, and post-resection survival. We also explored changes over time.

Results: Of 4257 new colon cancers diagnosed 2001 through 2016, 789 (21.1%) had stage I, 1584 (42.4%) had stage II, and 1360 (36.4%) had stage III colon cancer. For consecutive 5-year periods (2001-2005, 2006-2010, 2011-2016), recurrence rates have declined (23.4 17.1 13.6%,  < 0.001), however, the resection rates of metastatic disease (29.3 38.6 35.0%,  = 0.21) and post-resection 5-year survival (52.0 51.8 64.2%,  = 0.12) have remained steady. Primary tumor stage impacted recurrence rate (3.8 12 28%,  < 0.0001 for stage 1, 2, and 3), patterns of recurrence, resection of metastatic disease, (50 42 30%,  < 0.0001) and post-resection 5-year survival (92 64 44%,  < 0.001).

Conclusion: In this community cohort we defined significant differences in recurrence patterns and post-resection survival by tumor stage, with a diminishing rate of recurrence over time. While recurrence rates were lower with stage I and II disease, the high rate of metastatic disease resection and excellent post-resection outcomes help to justify routine surveillance in these patients.
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http://dx.doi.org/10.1080/0284186X.2021.1943519DOI Listing
September 2021

Circulating Tumour DNA as a Potential Cost-Effective Biomarker to Reduce Adjuvant Chemotherapy Overtreatment in Stage II Colorectal Cancer.

Pharmacoeconomics 2021 08 5;39(8):953-964. Epub 2021 Jun 5.

Personalised Oncology Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Melbourne, VIC, 3052, Australia.

Background And Objective: Substantial adjuvant chemotherapy (AC) overtreatment for stage II colorectal cancer results in a health and financial burden. Circulating tumour DNA (ctDNA) can improve patient selection for AC by detecting micro-metastatic disease. We estimated the health economic potential of ctDNA-guided AC for stage II colorectal cancer.

Methods: A cost-utility analysis was performed to compare ctDNA-guided AC to standard of care, where 22.6% of standard of care patients and all ctDNA-positive patients (8.7% of tested patients) received AC and all ctDNA-negative patients (91.3%) did not. A third preference-sensitive ctDNA strategy was included where 6.8% of ctDNA-negative patients would receive AC. A state-transition model was populated using data from a prospective cohort study and clinical registries. Health and economic outcomes were discounted at 5% over a lifetime horizon from a 2019 Australian payer perspective. Extensive scenario and probabilistic analyses quantified model uncertainty.

Results: Compared to standard of care, the ctDNA and preference-sensitive ctDNA strategies increased quality-adjusted life-years by 0.20 (95% confidence interval - 0.40 to 0.81) and 0.19 (- 0.40 to 0.78), and resulted in incremental costs of AUD - 4055 (- 16,853 to 8472) and AUD - 2284 (- 14,685 to 10,116), respectively. Circulating tumour DNA remained cost effective at a willingness to pay of AUD 20,000 per quality-adjusted life-year gained throughout most scenario analyses in which the proportion of ctDNA-positive patients cured by AC and compliance to a ctDNA-negative test results were decreased.

Conclusions: Circulating tumour-guided AC is a potentially cost-effective strategy towards reducing overtreatment in stage II colorectal cancer. Results from ongoing randomised clinical studies will be important to reduce uncertainty in the estimates.
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http://dx.doi.org/10.1007/s40273-021-01047-0DOI Listing
August 2021

A high-density narrow-field inhibitory retinal interneuron with direct coupling to Müller glia.

J Neurosci 2021 Jun 1. Epub 2021 Jun 1.

Department of Physiology and Biophysics, University of Washington, Seattle, WA.

Amacrine cells are interneurons composing the most diverse cell class in the mammalian retina. They help encode visual features such as edges or directed motion by mediating excitatory and inhibitory interactions between input (i.e. bipolar) and output (i.e. ganglion) neurons in the inner plexiform layer (IPL). Like other brain regions, the retina also contains glial cells that contribute to neurotransmitter uptake, metabolic regulation and neurovascular control. Here, we report that in mouse retina (of either sex), an abundant, though previously unstudied inhibitory amacrine cell is coupled directly to Müller glia. Electron microscopic reconstructions of this amacrine type revealed chemical synapses with known retinal cell types and extensive associations with Müller glia, the processes of which often completely ensheathe the neurites of this amacrine cell. Microinjecting small tracer molecules into the somas of these amacrine cells led to selective labelling of nearby Müller glia, leading us to suggest the name "Müller glia-coupled amacrine cell," or MAC. Our data also indicate that MACs release glycine at conventional chemical synapses, and viral retrograde transsynaptic tracing from the dorsal lateral geniculate nucleus (dLGN) showed selective connections between MACs and a subpopulation of RGC types. Visually-evoked responses revealed a strong preference for light increments; these "ON" responses were primarily mediated by excitatory chemical synaptic input and direct electrical coupling with other cells. This initial characterization of the MAC provides the first evidence for neuron-glia coupling in the mammalian retina and identifies the MAC as a potential link between inhibitory processing and glial function.Gap junctions between pairs of neurons or glial cells are commonly found throughout the nervous system and play multiple roles, including electrical coupling and metabolic exchange. In contrast, gap junctions between neurons and glia cells have rarely been reported and are poorly understood. Here we report the first evidence for neuron-glia coupling in the mammalian retina, specifically between an abundant (but previously unstudied) inhibitory interneuron and Müller glia. Moreover, viral tracing, optogenetics and serial electron microscopy provide new information about the neuron's synaptic partners and physiological responses.
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http://dx.doi.org/10.1523/JNEUROSCI.0199-20.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276741PMC
June 2021

Predictors of mortality for patients admitted to the intensive care unit with obstructing septic stones.

Can Urol Assoc J 2021 Nov;15(11):E593-E597

Section of Urology, Department of Surgery, University of Manitoba, Winnipeg, MB, Canada.

Introduction: Patients diagnosed with septic stone are at significant risk of morbidity and mortality should source control through drainage be delayed, and they are often admitted to intensive care units (ICU) for hemodynamic support. The purpose of this study was to determine patient factors that may predict mortality in patients admitted to ICU with septic stone, particularly whether rural patients at a greater distance from a tertiary care center were at greater risk of mortality given the inherent delay in intervention.

Methods: The Manitoba Intensive Care Unit prospective registry began in 1999 and includes all patients admitted to ICU across Manitoba. Baseline characteristics, such as age, gender, vital signs, creatinine, Charlson comorbidity index (CCI), mortality outcomes, and location of residency were obtained for those admitted to ICU for septic stone. Association between death and clinical/demographic variables was performed with adjusted multivariable logistical regression analysis.

Results: A total of 342 patients admitted to the ICU were analyzed, with a mean age of 63.5±15.5 years. Baseline characteristics were similar between groups (p>0.05). On multivariable adjusted logistical regression, the presence of acute kidney injury (AKI) (p<0.001) and intubation (p<0.001) were associated with mortality. There was no difference in mortality attributable to location of residency, vital signs, or CCI.

Conclusions: Among patients admitted to the ICU for septic stones in Manitoba, we demonstrate an association between AKI and intubation with mortality. Other factors, such as whether patients were from a rural region and baseline patient characteristics, were not predictive of mortality.
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http://dx.doi.org/10.5489/cuaj.7118DOI Listing
November 2021

Bridging the gap: a pre-post feasibility study of embedding exercise therapy into a co-located cancer unit.

Support Care Cancer 2021 Nov 8;29(11):6701-6711. Epub 2021 May 8.

School of Allied Health, Human Services and Sport, La Trobe University, Melbourne, VIC, Australia.

Purpose: To establish the feasibility of embedding a flexible, exercise-based rehabilitation program into a cancer treatment unit to allow cancer survivors early exercise support.

Method: A pre-post study was conducted using Bowen's Framework to describe key domains of feasibility: demand (referrals), acceptability (uptake, attendance, satisfaction), implementation (resources), practicality (adverse events, costs) and limited-efficacy (function, quality of life, self-efficacy). Participants were medically stable, adult cancer survivors receiving curative or palliative treatment for cancer at the health service. Participants completed an 8-week home or hospital-based exercise program. Data were analysed descriptively. Standardised mean differences (Hedge's g) and mean differences were calculated to determine effect size and clinical significance.

Results: The exercise-based rehabilitation service received 155 referrals over 6 months. Of those eligible, 73/119 (61%) commenced. Participants opting for twice-weekly, hospital-based exercise attended 9/16 (56%) sessions. Participants reported high satisfaction and there were no major adverse events. The program utilised existing resources, with the predominant cost being staff. The average health service cost per participant was AUD $1,104. Participants made clinically significant gains in function (6-min walk distance; + 73 m, 95% confidence interval 49 to 96) and quality of life (EORTC QLQ-C30 Global quality of life; + 8 units, 95% confidence interval 3 to 13).

Conclusion: Implementation of exercise-based rehabilitation in a co-located cancer unit was safe and feasible. Access, patient and staff education and establishing funding streams are important implementation considerations. Implications for cancer survivors Access to exercise in a cancer unit provides opportunity for early intervention to optimise function during treatment.
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http://dx.doi.org/10.1007/s00520-021-06261-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105143PMC
November 2021

The Impact of Theory in HPV Vaccination Promotion Research: A Systematic Review and Meta-Analysis.

Am J Health Promot 2021 09 5;35(7):1002-1014. Epub 2021 May 5.

The Edward R. Murrow College of Communication, 6760Washington State University, Pullman, WA, USA.

Objective: Numerous studies examined HPV vaccination promotional strategies. However, an overview of theory use, a synthesis of strategies' effectiveness and an examination of the moderating influence of theory are absent.

Data Source: We retrieved studies from Academic Search Complete, Business Source Complete, PubMed, PsycINFO, Web of Science, CMMC, CINAHL, and MEDLINE.

Study Inclusion And Exclusion Criteria: 1) peer-reviewed articles written in English, 2) experimental or quasi-experimental, 3) measure HPV vaccination-related outcomes, 4) had to contain a control condition and report statistics necessary for conversion (for meta-analysis only).

Data Extraction: 70 and 30 studies were included for the systematic review and meta-analysis respectively.

Data Synthesis: Four major categories were coded: study information, theory use, type of theory, and outcomes. Two independent coders coded the sample (Cohen's Kappa ranged from .8 to 1).

Results: Most of the studies were based in the U.S. (77%, k = 54) with convenient samples (80%, k = 56), targeted toward females (46%, k = 32), and around a quarter did not employ any theories (47%, k = 33). Among theory-driven studies, the most commonly used were Framing (22%, k = 19), Health Belief Model (HBM; 13%, k = 12), and Narrative (7%, k = 6). Among controlled studies, promotional strategies were significantly more effective compared to the control (r+ = .25, p < .001). Strategies guided by the information, motivation, behavioral skills model (IMB) were more effective (r+ = .75, p < .001) than studies guided by framing theory (r+ = -.23, p < .001), HBM (r+ = .01, p < .001), and other theories (r+ = .11, p < .001).

Conclusion: This review contributes to HPV vaccination promotion literature by offering a comprehensive overview of promotional strategies and practical suggestions for future research and practices.
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http://dx.doi.org/10.1177/08901171211012524DOI Listing
September 2021

Circulating tumor DNA dynamics and recurrence risk in patients undergoing curative intent resection of colorectal cancer liver metastases: A prospective cohort study.

PLoS Med 2021 05 3;18(5):e1003620. Epub 2021 May 3.

The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.

Background: In patients with resectable colorectal liver metastases (CRLM), the role of pre- and postoperative systemic therapy continues to be debated. Previous studies have shown that circulating tumor DNA (ctDNA) analysis, as a marker of minimal residual disease, is a powerful prognostic factor in patients with nonmetastatic colorectal cancer (CRC). Serial analysis of ctDNA in patients with resectable CRLM could inform the optimal use of perioperative chemotherapy. Here, we performed a validation study to confirm the prognostic impact of postoperative ctDNA in resectable CRLM observed in a previous discovery study.

Methods And Findings: We prospectively collected plasma samples from patients with resectable CRLM, including presurgical and postsurgical samples, serial samples during any pre- or postoperative chemotherapy, and serial samples in follow-up. Via targeted sequencing of 15 genes commonly mutated in CRC, we identified at least 1 somatic mutation in each patient's tumor. We then designed a personalized assay to assess 1 mutation in plasma samples using the Safe-SeqS assay. A total of 380 plasma samples from 54 patients recruited from July 2011 to Dec 2014 were included in our analysis. Twenty-three (43%) patients received neoadjuvant chemotherapy, and 42 patients (78%) received adjuvant chemotherapy after surgery. Median follow-up was 51 months (interquartile range, 31 to 60 months). At least 1 somatic mutation was identified in all patients' tumor tissue. ctDNA was detectable in 46/54 (85%) patients prior to any treatment and 12/49 (24%) patients after surgery. There was a median 40.93-fold (19.10 to 87.73, P < 0.001) decrease in ctDNA mutant allele fraction with neoadjuvant chemotherapy, but ctDNA clearance during neoadjuvant chemotherapy was not associated with a better recurrence-free survival (RFS). Patients with detectable postoperative ctDNA experienced a significantly lower RFS (HR 6.3; 95% CI 2.58 to 15.2; P < 0.001) and overall survival (HR 4.2; 95% CI 1.5 to 11.8; P < 0.001) compared to patients with undetectable ctDNA. For the 11 patients with detectable postoperative ctDNA who had serial ctDNA sampling during adjuvant chemotherapy, ctDNA clearance was observed in 3 patients, 2 of whom remained disease-free. All 8 patients with persistently detectable ctDNA after adjuvant chemotherapy have recurred. End-of-treatment (surgery +/- adjuvant chemotherapy) ctDNA detection was associated with a 5-year RFS of 0% compared to 75.6% for patients with an undetectable end-of-treatment ctDNA (HR 14.9; 95% CI 4.94 to 44.7; P < 0.001). Key limitations of the study include the small sample size and the potential for false-positive findings with multiple hypothesis testing.

Conclusions: We confirmed the prognostic impact of postsurgery and posttreatment ctDNA in patients with resected CRLM. The potential utility of serial ctDNA analysis during adjuvant chemotherapy as an early marker of treatment efficacy was also demonstrated. Further studies are required to define how to optimally integrate ctDNA analyses into decision-making regarding the use and timing of adjuvant therapy for resectable CRLM.

Trial Registration: ACTRN12612000345886.
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http://dx.doi.org/10.1371/journal.pmed.1003620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128260PMC
May 2021

Orchestral manoeuvres in the light: crosstalk needed for regulation of the Chlamydomonas carbon concentration mechanism.

J Exp Bot 2021 06;72(13):4604-4624

Department of Plant Sciences, Downing Street, University of Cambridge, Cambridge, UK.

The inducible carbon concentration mechanism (CCM) in Chlamydomonas reinhardtii has been well defined from a molecular and ultrastructural perspective. Inorganic carbon transport proteins, and strategically located carbonic anhydrases deliver CO2 within the chloroplast pyrenoid matrix where Rubisco is packaged. However, there is little understanding of the fundamental signalling and sensing processes leading to CCM induction. While external CO2 limitation has been believed to be the primary cue, the coupling between energetic supply and inorganic carbon demand through regulatory feedback from light harvesting and photorespiration signals could provide the original CCM trigger. Key questions regarding the integration of these processes are addressed in this review. We consider how the chloroplast functions as a crucible for photosynthesis, importing and integrating nuclear-encoded components from the cytoplasm, and sending retrograde signals to the nucleus to regulate CCM induction. We hypothesize that induction of the CCM is associated with retrograde signals associated with photorespiration and/or light stress. We have also examined the significance of common evolutionary pressures for origins of two co-regulated processes, namely the CCM and photorespiration, in addition to identifying genes of interest involved in transcription, protein folding, and regulatory processes which are needed to fully understand the processes leading to CCM induction.
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http://dx.doi.org/10.1093/jxb/erab169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320531PMC
June 2021

Patient demographics and management landscape of metastatic colorectal cancer in the third-line setting: Real-world data in an australian population.

Asia Pac J Clin Oncol 2021 Apr 18. Epub 2021 Apr 18.

Macarthur Cancer Therapy Centre, Campbelltown, New South Wales, Australia.

Background: Colorectal cancer is the third most common cancer and second leading cause of cancer mortality in Australia, thus carrying a significant disease burden.

Aims: This analysis aims to explore real-world treatment landscape of metastatic colorectal cancer in the third-line setting.

Methods: We retrospectively analysed treatment of recurrent and advanced colorectal cancer (TRACC) registry database from 2009 onwards. Patients treated with palliative intent who progressed after two lines of therapies were included. One treatment line was defined as any combination of systemic therapy given until progression.

Results: Out of 1820 patients treated palliatively, 32% (590 patients) met study criteria. Of these, 43% (254 patients) proceeded to third-line therapy, equating to 14% of all metastatic patients. In KRAS mutant or unknown tumours (97 patients), fluoropyrimidine (FP)-oxaliplatin combination was the most common choice (51%), followed by FP-irinotecan (15%), trifluridine/tipiracil (11%), mono-chemotherapy (10%), regorafenib (5%) and others (7%). Majority of FP-doublet (83%) was given as rechallenge. In 157 patients with KRAS wildtype disease, monotherapy with EGFR inhibitor was most commonly used (41%), followed by EGFR inhibitor with chemotherapy (20%), FP-doublet (18%), mono-chemotherapy (6%), trifluridine/tipiracil (6%), regorafenib (1%) and others (8%). Median overall survival was 7.1 months (range 0.4-41.2), and median time on third-line treatment was 3 months (range 0.1-40).

Conclusions: In real-world Australian population, treatment choices differed based on KRAS status and will likely change with the availability of newer drugs on the pharmaceutical benefits scheme. Survival outcomes are comparable to newer agents in clinical trials for select patients.
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http://dx.doi.org/10.1111/ajco.13553DOI Listing
April 2021

Predicting Protein and Fat Content in Human Donor Milk Using Machine Learning.

J Nutr 2021 Jul;151(7):2075-2083

Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, Canada.

Background: Donor milk is the standard of care for hospitalized very low birth weight (VLBW) infants when mother's milk is unavailable; however, growth of donor milk-fed infants is frequently suboptimal. Variability in nutrient composition of donated milk complicates the production of a uniform pooled product and, subsequently, the provision of adequate nutrition to promote optimal growth and development of VLBW infants. We reasoned a machine learning approach to construct batches using characteristics of the milk donation might be an effective strategy in reducing the variability in donor milk product composition.

Objective: The objective of this study was to identify whether machine learning models can accurately predict donor milk macronutrient content. We focused on predicting fat and protein, given their well-established importance in VLBW infant growth outcomes.

Methods: Samples of donor milk, consisting of 272 individual donations and 61 pool samples, were collected from the Rogers Hixon Ontario Human Milk Bank and analyzed for macronutrient content. Four different machine learning models were constructed using independent variable groups associated with donations, donors, and donor-pumping practices. A baseline model was established using lactation stage and infant gestational status. Predictions were made for individual donations and resultant pools.

Results: Machine learning models predicted protein of individual donations and pools with a mean absolute error (MAE) of 0.16 g/dL and 0.10 g/dL, respectively. Individual donation and pooled fat predictions had an MAE of 0.91 g/dL and 0.42 g/dL, respectively. At both the individual donation and pool levels, protein predictions were significantly more accurate than baseline, whereas fat predictions were competitive with baseline.

Conclusions: Machine learning models can provide accurate predictions of macronutrient content in donor milk. The macronutrient content of pooled milk had a lower prediction error, reinforcing the value of pooling practices. Future research should examine how macronutrient content predictions can be used to facilitate milk bank pooling strategies.
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http://dx.doi.org/10.1093/jn/nxab069DOI Listing
July 2021

Immunohistochemical evaluation of the prognostic and predictive power of epidermal growth factor receptor ligand levels in patients with metastatic colorectal cancer.

Growth Factors 2020 Jun-Jul;38(3-4):127-136. Epub 2021 Mar 27.

Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.

For patients with metastatic colorectal cancer (mCRC), epidermal growth factor receptor (EGFR) inhibitors are limited to patients with wild-type tumours. Not all patients will benefit from treatment and better predictive biomarkers are needed. Here we investigated the prognostic and predictive impact of the EGFR ligands amphiregulin (AREG) and epiregulin (EREG). Expression levels were assessed by immunohistochemistry on 99 wild-type tumours. AREG and EREG positivity was seen in 49% and 50% of cases, respectively. No difference in expression was observed by primary tumour side. There was no significant difference in OS by AREG or EREG expression. In the subset of patients who received an EGFR inhibitor, EREG positivity was associated with longer OS (median 34.0 vs. 27.0 months,  = 0.033), driven by a difference in patients with a left-sided primary (HR 0.37,  = 0.015). Our study supports further investigation into EREG as a predictive biomarker in mCRC.
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http://dx.doi.org/10.1080/08977194.2021.1878166DOI Listing
March 2021

Exploring exercise participation and the usability of the adaptive rower and arm crank ergometer through wheelchair users' perspectives.

Disabil Rehabil 2021 Mar 17:1-10. Epub 2021 Mar 17.

Department of Occupational Science and Occupational Therapy, University of British Columbia, Vancouver, Canada.

Purpose: Arm crank ergometry and adaptive rowing are existing exercise options for wheelchairs users, but not commonly available. This study was conducted to explore exercise participation of wheelchair users, as well as the usability of the adaptive rowing ergometer (aROW) and arm crank ergometer (ACE).

Methods: This mixed-methods study used a concurrent triangulation design. Following completion of both exercise sessions (5 min each), participants ( = 14) with spinal cord injury/disease (SCI/D) completed the System Usability Scale (SUS), and a semi-structured interview. Participants were asked about the use of both exercise modalities, and general exercise participation. SUS data were analyzed using a paired sample -test and qualitative data were analyzed through conventional content analysis.

Results: Wheelchair users exercised for improved physical and mental health, as well as for functional independence, and community participation; however, lack of accessible equipment was a prominent barrier. Both the aROW and ACE have high usability, but the aROW was perceived as more enjoyable and effective for cardiovascular exercise.

Conclusions: The implementation of the aROW into community gyms has the potential to help close the existing gap in inclusive equipment and may help people with disabilities to be more fully included in their community and lead healthier lives.Implications for rehabilitationWheelchair users perceive exercise as a meaningful activity that enhances physical health and risk of disease, functional independence, community participation, and overall social and emotional health.The adapted rowing machine was perceived as highly usable and was felt to be more enjoyable and effective for cardiovascular exercise compared to traditional arm crank ergometers.The adaptive rower provides an additional accessible equipment option for wheelchair users to obtain effective cardiovascular exercise.More available equipment may increase community participation and promote inclusion for wheelchair users.
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http://dx.doi.org/10.1080/09638288.2021.1894245DOI Listing
March 2021

Cancer clinical trial vs real-world outcomes for standard of care first-line treatment in the advanced disease setting.

Int J Cancer 2021 07 13;149(2):409-419. Epub 2021 Apr 13.

Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia.

Clinical trials have strict eligibility criteria, potentially limiting external validity. However, while often discussed this has seldom been explored, particularly across cancer types and at variable time frames posttrial completion. We examined comprehensive registry data (January 2014 to June 2019) for standard first-line treatments for metastatic colorectal cancer (CRC), advanced pancreatic cancer (PC), metastatic HER2-amplified breast cancer (BC) and castrate-resistant prostate cancer (CaP). Registry patient characteristics and outcomes were compared to the practice-changing trial. Registry patients were older than the matched trial cohort by a median of 2-6 years (all P = <.01) for the CRC, BC and PC cohorts. The proportion of Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 patients was lower for CRC (94.1% vs 99.2%, P = .001) and BC (94.9% vs 99.3%, P = .001). Progression-free survival (PFS) for registry patients was similar to the trial patients or significantly longer (CaP, Hazard Ratio [HR] = 0.65, P = <.001). Overall survival (OS) was also similar or significantly longer (CaP, HR 0.49, P = <.001). In conclusion, despite real-world patients sometimes being older or having inferior PS to trial cohorts, the survival outcomes achieved were consistently equal or superior to those reported for the same treatment in the trial. We suggest that this is potentially due to optimised use of each treatment over time, improved multidisciplinary care and increased postprogression options. We can reassure clinicians and patients that outcomes matching or exceeding those reported in trials are possible. The potential for survival gains over time should routinely be factored into future trial statistical plans.
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http://dx.doi.org/10.1002/ijc.33568DOI Listing
July 2021

BRAFV600E Mutations Arising from a Left-Side Primary in Metastatic Colorectal Cancer: Are They a Distinct Subset?

Target Oncol 2021 03 18;16(2):227-236. Epub 2021 Feb 18.

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.

Background: B-Raf proto-oncogene (BRAF)-V600E mutations (BRAFmt) in colorectal cancer (CRC) predominantly occur in right-side (RS) primaries. In metastatic CRC (mCRC), there is substantial overlap between the reported features of BRAFmt and of an RS primary.

Objectives: To explore the significance of BRAFmt in a left-side (LS) primary, we analysed data from a multi-site mCRC registry. Tumours distal to the splenic flexure were considered LS.

Results: Of 3380 patients enrolled from June 2009 to June 2020, 214 (13%) of 1657 with known status were BRAFmt: 127 (24%) of 524 RS and 87 (8%) of 1133 LS. LS versus RS BRAFmt were younger (mean 59.5 vs. 65.1 years; p = 0.01), whereas sex (48 vs. 59% female; p = 0.13), mismatch repair-deficiency (dMMR) (16 vs. 21%; p = 0.47), and overall survival (OS) (median 15.1 vs. 17.7 months; p = 0.98) were similar. LS BRAFmt versus LS BRAF wildtype (wt) were of similar age (59.5 vs. 61.3 years; p = 0.28) with more females (48 vs. 37%; p = 0.04), more dMMR (16 vs. 1%; p < 0.0001), and inferior OS (median 15.1 vs. 36.6 months; p < 0.0001). Initial treatment with chemotherapy plus an epidermal growth factor receptor inhibitor produced median progression-free survival (PFS) of 4.3 versus 12.3 months (p = 0.20) for LS BRAFmt (n = 9) versus LS BRAFwt (n = 104). Initial chemotherapy and bevacizumab produced a median PFS of 7.6 versus 11.6 months (p = 0.02) for LS BRAFmt (n = 36) versus LS BRAFwt (n = 438), respectively.

Conclusion: LS BRAFmt cancers share many features with RS BRAFmt cancers, including poor survival outcomes. Mature data on the activity of BRAF-targeted therapies in the first-line setting are eagerly awaited.
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http://dx.doi.org/10.1007/s11523-021-00793-7DOI Listing
March 2021

Dual Antiangiogenesis Agents Bevacizumab Plus Trebananib, without Chemotherapy, in First-line Treatment of Metastatic Colorectal Cancer: Results of a Phase II Study.

Clin Cancer Res 2021 04 29;27(8):2159-2167. Epub 2021 Jan 29.

Olivia Newton-John Cancer Research Institute, Melbourne, Victoria, Australia.

Purpose: To assess the efficacy and safety of dual antiangiogenesis agents, bevacizumab plus trebananib, without chemotherapy, in first-line treatment of metastatic colorectal cancer (mCRC).

Patients And Methods: This open-label phase II study enrolled patients with unresectable mCRC with no prior systemic treatment. All patients received bevacizumab 7.5 mg/kg 3-weekly and trebananib 15 mg/kg weekly. The primary endpoint was disease control [stable disease, partial response (PR), or complete response (CR)] at 6 months (DC6m). Secondary endpoints included toxicity, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Exploratory biomarkers in plasma angiogenesis-related proteins, tumor gene expression, and plasma antibodies to tumor antigens were examined.

Results: Forty-five patients were enrolled from four Australian sites. DC6m was 63% [95% confidence interval (CI), 47-77]. ORR was 17% (95% CI, 7-32), comprising of seven PRs. Median duration of response was 20 months (range, 10-48 months). Median PFS was 8.4 months and median OS 31.4 months. Grade 1-2 peripheral edema and joint-related symptoms were common. Overall incidence of grade 3-4 adverse events (AE) of any type was 33% ( = 15). Expected AEs of bevacizumab treatment did not appear to be increased by the addition of trebananib.

Conclusions: In a first-line mCRC population, the dual antiangiogenic combination, bevacizumab plus trebananib, without chemotherapy, was efficacious with durable responses. The toxicity profile of the combination was manageable and did not exceed that expected with bevacizumab +/- chemotherapy. Exploratory biomarker results raise the hypothesis that the antiangiogenic combination may enable the antitumor immune response in immunotolerant colorectal cancer.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-2714DOI Listing
April 2021

Indexing Cerebrovascular Health Using Transcranial Doppler Ultrasound.

Ultrasound Med Biol 2021 04 22;47(4):919-927. Epub 2021 Jan 22.

School of Electrical Engineering & Computing, University of Newcastle, Callaghan, New South Wales, Australia.

Transcranial Doppler (TCD) blood flow velocity has been extensively used in biomedical research as it provides a cost-effective and relatively simple approach to assess changes in cerebral blood flow dynamics and track cerebrovascular health status. In this article we introduce a new TCD-based timing index, TI, as an indicator of vascular stiffening and vascular health. We investigate the correlations of the new index and the existing indices, namely the pulsatility index and the augmentation index, with age, cardiorespiratory fitness (CRF) and magnetic resonance imaging (MRI) blood flow pulsatility index (PI). Notably, the new index showed stronger correlations with CRF (r = -0.79) and PI (r = 0.53) compared with the augmentation index (r = -0.65 with CRF and no significant correlation with PI) and the pulsatility index (no significant correlations with CRF or PI), and a similar correlation with age as the augmentation index. The clearer relationship of the proposed timing index with vascular aging factors underlines its utility as an early indicator of vascular stiffening.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2020.12.022DOI Listing
April 2021

Prioritizing health outcomes when assessing the effects of exposure to radiofrequency electromagnetic fields: A survey among experts.

Environ Int 2021 01 11;146:106300. Epub 2020 Dec 11.

Department of Environment, Climate Change and Health, World Health Organization, Geneva, Switzerland.

Exposure to radiofrequency (RF) electromagnetic fields (EMF) (frequencies of 100 kHz to 300 GHz) has been steadily increasing. In addition to heat-related effects of RF EMF, other yet-unspecified biological effects, might exist which could possibly lead to health effects. Given the large number of health endpoints that have been studied, we wanted to prioritize those that would merit systematic reviews. We developed a survey listing of all health endpoints reported in the literature and we asked 300 RF EMF experts and researchers to prioritize these health effects for systematic review as critical, important or unimportant. We also asked the experts to provide the rationale for their prioritization. Of the 300 RF EMF experts queried, 164 (54%) responded. They rated cancer, heat-related effects, adverse birth outcomes, electromagnetic hypersensitivity, cognitive impairment, adverse pregnancy outcomes and oxidative stress as outcomes most critical regarding RF EMF exposure. For these outcomes, systematic reviews are needed. For heat-related outcomes, the experts based their ranking of the critical outcomes on what is known from human or animal studies, and for cancer and other outcomes, they based their rating also on public concern. To assess health risks of an exposure in a robust manner, it is important to prioritize the health outcomes that should be systematically reviewed. Here we have shown that it feasible to do so in an inclusive and transparent way.
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http://dx.doi.org/10.1016/j.envint.2020.106300DOI Listing
January 2021

Expanding Telehealth Competencies in Primary Care: A Longitudinal Interdisciplinary Simulation to Train Internal Medicine Residents in Complex Patient Care.

J Grad Med Educ 2020 Dec 4;12(6):745-752. Epub 2020 Dec 4.

Assistant Professor, Department of Family, Population and Preventive Medicine, Stony Brook University Hospital.

Background: Despite increasing use of telehealth, there are limited published curricula training primary care providers in utilizing telehealth to deliver complex interdisciplinary care.

Objective: To describe and evaluate a telehealth curriculum with a longitudinal objective structured clinical examination (OSCE) to improve internal medicine residents' confidence and skills in coordinating complex interdisciplinary primary care via televisits, electronic consultation, and teleconferencing.

Methods: In 2019, 56 first- and third-year residents participated in a 3-part, 5-week OSCE training them to use telehealth to manage complex primary care. Learners conducted a standardized patient (SP) televisit in session 1, coordinated care via inter-visit e-messaging, and led a simulated interdisciplinary teleconference in session 2. Surveys measured confidence before session 1 (pre), post-session 1 (post-1), and post-session 2 (post-2). SP televisit checklists and investigators' assessment of e-messages evaluated residents' telehealth skills.

Results: Response rates were pre 100%, post-1 95% (53 of 56), and post-2 100%. Post-intervention, more residents were "confident/very confident" in adjusting their camera (33%, 95% CI 20-45 vs 85%, 95% CI 75-95, < .0001), e-messaging (pre 36%, 95% CI 24-49 vs post-2 80%, 95% CI 70-91, < .0001), and coordinating interdisciplinary care (pre 35%, 95% CI 22-47 vs post-2 84%, 95% CI 74-94, < .0001). More residents were "likely/very likely" to use telemedicine in the future (pre 56%, 95% CI 43-69, vs post-2 79%, 95% CI 68-89, = .001).

Conclusions: A longitudinal, interdisciplinary telehealth simulation is feasible and can improve residents' confidence in using telemedicine to provide complex patient care.
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http://dx.doi.org/10.4300/JGME-D-20-00030.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771597PMC
December 2020
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