Publications by authors named "Vanessa Wong"

95 Publications

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

Evaluating delays for emergent CT scans from a rural British Columbia hospital.

CJEM 2021 Jun 22. Epub 2021 Jun 22.

University of British Columbia, Vancouver, BC, Canada.

Objectives: Computed Tomography (CT) scans help diagnose and triage life-threatening and time-sensitive emergency conditions, but most rural hospitals in British Columbia do not have access to a local CT scanner. We investigate how many transfers from a rural British Columbia hospital were for CT scans and describe the time delays to emergent CT imaging.

Methods: This was a prospective cohort study, over a 1-year period, on all patients requiring a transfer from the Golden and District Hospital, located 247 km from the closest CT scanner. Data collection forms were completed prospectively and the main measurements included age, transport triage level, reason for transfer, referral hospital, transfer request time, and CT scan time. The time interval between the CT request and CT imaging was calculated and represents the 'delay to CT scan' interval.

Results: The study hospital received 8672 emergency department (ED) visits and 220 were transferred to referral centres (2.5%). 61% of all transfers received a CT scan. Transfers for time-sensitive emergencies took an average of 6 h 52 min. Patients with acute stroke experienced a 4 h 44 min time interval. Less urgent and non-urgent conditions entailed an even greater time delay.

Conclusions: This study highlights that the lack of a rural CT scanner is associated with increased transfers and significant time delays. Improving access to CT scanners for rural communities may be one of the many steps in addressing healthcare disparities between rural and urban communities.
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http://dx.doi.org/10.1007/s43678-021-00147-2DOI Listing
June 2021

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

Pharmacoeconomics 2021 Aug 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

The nature of Pu-bearing particles from the Maralinga nuclear testing site, Australia.

Sci Rep 2021 May 21;11(1):10698. Epub 2021 May 21.

School of Earth, Atmosphere and Environment, Monash University, Clayton, Australia.

The high-energy release of plutonium (Pu) and uranium (U) during the Maralinga nuclear trials (1955-1963) in Australia, designed to simulate high temperature, non-critical nuclear accidents, resulted in wide dispersion µm-sized, radioactive, Pu-U-bearing 'hot' particles that persist in soils. By combining non-destructive, multi-technique synchrotron-based micro-characterization with the first nano-scale imagining of the composition and textures of six Maralinga particles, we find that all particles display intricate physical and chemical make-ups consistent with formation via condensation and cooling of polymetallic melts (immiscible Fe-Al-Pu-U; and Pb ± Pu-U) within the detonation plumes. Plutonium and U are present predominantly in micro- to nano-particulate forms, and most hot particles contain low valence Pu-U-C compounds; these chemically reactive phases are protected by their inclusion in metallic alloys. Plutonium reworking was observed within an oxidised rim in a Pb-rich particle; however overall Pu remained immobile in the studied particles, while small-scale oxidation and mobility of U is widespread. It is notoriously difficult to predict the long-term environmental behaviour of hot particles. Nano-scale characterization of the hot particles suggests that long-term, slow release of Pu from the hot particles may take place via a range of chemical and physical processes, likely contributing to on-going Pu uptake by wildlife at Maralinga.
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http://dx.doi.org/10.1038/s41598-021-89757-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139974PMC
May 2021

Uptake of bone modifying agents in patients with HER2+ metastatic breast cancer with bone metastases - prospective data from a multi-site Australian registry.

Intern Med J 2021 May 18. Epub 2021 May 18.

Walter and Eliza Hall Institute of Medical Research, VIC.

Background And Aim: International practice guidelines recommend administration of bone modifying agents (BMA) in metastatic breast cancer (MBC) patients with bone metastases to reduce skeletal related events (SRE). Optimal delivery of BMA in routine clinical practice including agent selection and prescribing intervals remains unclear. We aim to describe real-world practice of Australian breast oncologists.

Methods: Prospective data from February 2015 to July 2020 on BMA delivery to MBC patients with bone metastases was analysed from TABITHA, a multi-site Australian HER2+ MBC registry.

Results: Of 333 HER2+ MBC patients, 171 (51%) had bone metastases at diagnosis, with a mean age of 58.1 years [range 32-87]. 130 (76%) patients received a BMA, with 90 (69%) receiving denosumab and 40 (31%) receiving a bisphosphonate. Patients who received a BMA were more likely to have received concurrent first line systemic anti-HER2 therapy (95% vs 83%, p=0.04), to present with bone-only metastases at diagnosis (24% vs 7%, p=0.02) and less likely to have visceral metastases (51% vs 71%, p=0.03). Ten of 40 (25%) bisphosphonate patients and 45 of 90 (50%) denosumab patients received their BMA at the recommended 4-weekly interval. Prescribing intervals varied over time. Adverse events reported were consistent with clinical trial data.

Conclusion: Three-quarters of Australian HER2+ MBC patients with bone metastases receive a BMA, often at different schedules than guidelines recommend. Further studies, including of all MBC subtypes, are warranted to better understand clinicians' prescribing rationale and potential consequences of current prescribing practice on SRE incidence. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/imj.15376DOI Listing
May 2021

A global resource for genomic predictions of antimicrobial resistance and surveillance of Salmonella Typhi at pathogenwatch.

Nat Commun 2021 05 17;12(1):2879. Epub 2021 May 17.

Centre for Genomic Pathogen Surveillance, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK.

As whole-genome sequencing capacity becomes increasingly decentralized, there is a growing opportunity for collaboration and the sharing of surveillance data within and between countries to inform typhoid control policies. This vision requires free, community-driven tools that facilitate access to genomic data for public health on a global scale. Here we present the Pathogenwatch scheme for Salmonella enterica serovar Typhi (S. Typhi), a web application enabling the rapid identification of genomic markers of antimicrobial resistance (AMR) and contextualization with public genomic data. We show that the clustering of S. Typhi genomes in Pathogenwatch is comparable to established bioinformatics methods, and that genomic predictions of AMR are highly concordant with phenotypic susceptibility data. We demonstrate the public health utility of Pathogenwatch with examples selected from >4,300 public genomes available in the application. Pathogenwatch provides an intuitive entry point to monitor of the emergence and spread of S. Typhi high risk clones.
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http://dx.doi.org/10.1038/s41467-021-23091-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128892PMC
May 2021

Effect of the counter-ion on nanocellulose hydrogels and their superabsorbent structure and properties.

J Colloid Interface Sci 2021 Oct 17;599:140-148. Epub 2021 Apr 17.

Bioresource Processing Research Institute of Australia (BioPRIA) and Department of Chemical Engineering, Monash University, Clayton, VIC 3800, Australia. Electronic address:

Hypothesis: Carboxylated nanocellulose gels and superabsorbents (SAPs) can be engineered by ion exchange of TEMPO treated cellulose fibers with different cations prior to shearing, thus creating a nanofibrous network ionically cross-linked. The structure and properties of these materials are highly influenced by the type counter-ion used as it controls both the degree of fibrillation and crosslinking.

Experiments: Functionalised nanocellulose SAPs were made using TEMPO-mediated oxidation followed by ion-exchange before fibrillation into a hydrogel and freeze-drying. Seven different cations were tested: 4 of valency 1 (H, Na, K, NH), and 3 of valency 2 (Ca, Mg, and Zn). The effect of the counter-ion on the gelation mechanism and the superabsorbent performance was evaluated. The SAP absorption capacity in deionised water was related to the superabsorbent structure and morphology.

Findings: The gel stability of nanocellulose superabsorbents is governed by the counter-ion type and valency. The viscoelastic properties of all nanocellulose hydrogels are controlled by its elastic regime, that is storage modulus (G') > loss modulus (G″). The type of cation dictates the rheology of these gels by altering the fibrillation efficiency due to the extent of ionic cross-links occurring before and after fibrillation. The driving force for gelation in monovalent gels is due to the coupling of nanofibrils by physical interactions, creating an electrostatic stabilisation of the ionised COO groups at high shear forces. Cation - carboxylate interactions dominate the gelation in divalent gels by supressing the repulsive charges generated by the COO and also creating interfibril connections via ionic-crosslinks, as confirmed by the zeta potentials. The superabsorption performance is dominated by the counter-ion and is in the order of: NH > K > Na > Mg > Zn > Ca. NH-SAPs present the slowest kinetics and the highest absorption capacity. Its high pore area, which extends the number of accessible carboxyl groups that participates in hydrogen bonding with water, is responsible for this behaviour. Nanocellulose SAPs are attractive renewable materials, suited for many applications, including as nutrient cation carriers in agriculture.
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http://dx.doi.org/10.1016/j.jcis.2021.04.065DOI Listing
October 2021

Preclinical Proficiency-Based Model of Ultrasound Training.

Anesth Analg 2021 Apr 12. Epub 2021 Apr 12.

From the Department of Anesthesia, Critical Care and Pain Medicine.

Background: Graduate medical education is being transformed from a time-based training model to a competency-based training model. While the application of ultrasound in the perioperative arena has become an expected skill set for anesthesiologists, clinical exposure during training is intermittent and nongraduated without a structured program. We developed a formal structured perioperative ultrasound program to efficiently train first-year clinical anesthesia (CA-1) residents and evaluated its effectiveness quantitatively in the form of a proficiency index.

Methods: In this prospective study, a multimodal perioperative ultrasound training program spread over 3 months was designed by experts at an accredited anesthesiology residency program to train the CA-1 residents. The training model was based on self-learning through web-based modules and instructor-based learning by performing perioperative ultrasound techniques on simulators and live models. The effectiveness of the program was evaluated by comparing the CA-1 residents who completed the training to graduating third-year clinical anesthesia (CA-3) residents who underwent the traditional ultrasound training in the residency program using a designed index called a "proficiency index." The proficiency index was composed of scores on a cognitive knowledge test (20%) and scores on an objective structured clinical examination (OSCE) to evaluate the workflow understanding (40%) and psychomotor skills (40%).

Results: Sixteen CA-1 residents successfully completed the perioperative ultrasound training program and the subsequent evaluation with the proficiency index. The total duration of training was 60 hours of self-based learning and instructor-based learning. There was a significant improvement observed in the cognitive knowledge test scores for the CA-1 residents after the training program (pretest: 71% [0.141 ± 0.019]; posttest: 83% [0.165 ± 0.041]; P < .001). At the end of the program, the CA-1 residents achieved an average proficiency index that was not significantly different from the average proficiency index of graduating CA-3 residents who underwent traditional ultrasound training (CA-1: 0.803 ± 0.049; CA-3: 0.823 ± 0.063, P = .307).

Conclusions: Our results suggest that the implementation of a formal, structured curriculum allows CA-1 residents to achieve a level of proficiency in perioperative ultrasound applications before clinical exposure.
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http://dx.doi.org/10.1213/ANE.0000000000005510DOI Listing
April 2021

Teaching Medical Students to Create Anesthetic Plans Using a Branched-Chain Learning Module.

A A Pract 2021 Apr 1;15(4):e01446. Epub 2021 Apr 1.

Albany Medical College, Albany, New York.

It is challenging to include medical students in the anesthetic decision-making process during their introductory clinical rotation in anesthesiology. Furthermore, the rotation is often too brief to even expose students to the variety inherent in anesthesia practice. We created a web-based, branched-chain learning module (BCLM) for medical students with alternate narratives and patient outcomes based on their anesthetic choices. In semistructured group interviews, students described how the BCLM met its educational objectives and gave constructive feedback on several ways to improve their experience with it, guiding the future use of BCLMs in medical education.
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http://dx.doi.org/10.1213/XAA.0000000000001446DOI Listing
April 2021

Identifying the Gap Between Novices and Experts in Fiberoptic Scope Control.

J Educ Perioper Med 2021 Jan-Mar;23(1):E655. Epub 2021 Jan 1.

Background: Fiberoptic intubation (FOI) is key in managing difficult airways. Good scope control increases efficiency and patient safety. Understanding the gap between novices and experts in scope control would help medical educators develop a feedback-based teaching approach for novices. We designed and used a checklist for evaluating the gap in fiberoptic scope control between novices and experts.

Methods: Twelve first-year anesthesiology residents (novice group) attended a lecture, followed by hands-on practice with a fiberoptic scope on a manikin. Five staff anesthesiologists (expert group) only did the hands-on practice. After practice, each participant was video-recorded while conducting an FOI on the manikin. Two senior anesthesiologists developed and used a 7-item checklist to assess the FOIs. Checklist scores and total times for FOIs were compared between groups using the Mann-Whitney test. Internal consistency of the checklist items, interrater reliability, and the relationship between checklist score and total time for FOI were assessed with Cronbach alpha, Cohen kappa, and the Pearson correlation coefficient, respectively.

Results: Experts had higher checklist scores than novices ( = .0016). The item with the lowest success rate for novices (50%) was keeping the scope straight. Novices spent more time on the FOI than experts ( = .0005). Cronbach alpha, Cohen kappa, and the Pearson correlation coefficient were 0.8699, 0.75, and -0.9454, respectively.

Conclusions: Our checklist was used to detect differences in fiberoptic scope control skills between novices and experts. With a video-based assessment method, it can be used to develop a feedback-based teaching method for fiberoptic scope control.
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http://dx.doi.org/10.46374/volxxiii_issue1_haobomaDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983185PMC
January 2021

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

Int J Cancer 2021 Jul 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

2000 Year-old Bogong moth (Agrotis infusa) Aboriginal food remains, Australia.

Sci Rep 2020 12 17;10(1):22151. Epub 2020 Dec 17.

School of Earth Sciences, University of Melbourne, Parkville, VIC, Australia.

Insects form an important source of food for many people around the world, but little is known of the deep-time history of insect harvesting from the archaeological record. In Australia, early settler writings from the 1830s to mid-1800s reported congregations of Aboriginal groups from multiple clans and language groups taking advantage of the annual migration of Bogong moths (Agrotis infusa) in and near the Australian Alps, the continent's highest mountain range. The moths were targeted as a food item for their large numbers and high fat contents. Within 30 years of initial colonial contact, however, the Bogong moth festivals had ceased until their recent revival. No reliable archaeological evidence of Bogong moth exploitation or processing has ever been discovered, signalling a major gap in the archaeological history of Aboriginal groups. Here we report on microscopic remains of ground and cooked Bogong moths on a recently excavated grindstone from Cloggs Cave, in the southern foothills of the Australian Alps. These findings represent the first conclusive archaeological evidence of insect foods in Australia, and, as far as we know, of their remains on stone artefacts in the world. They provide insights into the antiquity of important Aboriginal dietary practices that have until now remained archaeologically invisible.
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http://dx.doi.org/10.1038/s41598-020-79307-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747710PMC
December 2020

Minimal important difference estimates for patient-reported outcomes: A systematic survey.

J Clin Epidemiol 2021 May 13;133:61-71. Epub 2020 Dec 13.

Department of Health Research Methods, Evidence and Impact, McMaster University, 1280 Main St East, Hamilton, Ontario L8S 4L8, Canada; Department of Medicine, McMaster University, 1280 Main St East, Hamilton, Ontario L8S 4L8, Canada.

Objectives: The objective of the study was to develop an inventory summarizing all anchor-based minimal important difference (MID) estimates for patient-reported outcome measures (PROMs) available in the medical literature.

Study Design And Setting: We searched MEDLINE, EMBASE, CINAHL, PsycINFO, and the Patient-Reported Outcome and Quality of Life Instruments Database internal library (January 1989-October 2018). We included primary studies empirically calculating an anchor-based MID estimate for any PROM in adults and adolescents. Pairs of reviewers independently screened and selected studies, extracted data, and evaluated the credibility of the MIDs.

Results: We identified 585 eligible studies, the majority conducted in Europe (n = 211) and North America (n = 179), reporting 5,324 MID estimates for 526 distinct PROMs. Investigators conducted their studies in the context of patients receiving surgical (n = 105, 18%), pharmacological (n = 85, 15%), rehabilitation (n = 65, 11%), or a combination of interventions (n = 194, 33%). Of all MID estimates, 59% (n = 3,131) used a global rating of change anchor. Major credibility limitations included weak correlation (n = 1,246, 23%) or no information regarding the correlation (n = 3,498, 66%) between the PROM and anchor and imprecision in the MID estimate (n = 2,513, 47%).

Conclusion: A large number of MIDs for assisting in the interpretation of PROMs exist. The MID inventory will facilitate the use of MID estimates to inform the interpretation of the magnitude of treatment effects in clinical research and guideline development.
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http://dx.doi.org/10.1016/j.jclinepi.2020.11.024DOI Listing
May 2021

Formation of an Intraoperative Educational Curriculum for Anesthesiology Residents Using a Systematic Approach.

A A Pract 2020 Oct;14(12):e01330

From the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Anesthesiology residents spend most of their training in operating rooms, but intraoperative teaching is often unstructured. Needs assessment indicated a need to incorporate a more evidence-based approach to education and improvement of our methods of introducing residents to primary anesthesiology literature. Kern's 6-step approach to curriculum development was used to create a robust and innovative curriculum to increase both the evidence-based component of our curriculum and the amount of educational intraoperative discussion among trainees and faculty. Our curriculum uses a structured topic outline, an e-journal club, and other relevant resources to facilitate discussion of the topics.
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http://dx.doi.org/10.1213/XAA.0000000000001330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592885PMC
October 2020

Cardiac and lung endothelial cells in response to fluid shear stress on physiological matrix stiffness and composition.

Microcirculation 2021 01 29;28(1):e12659. Epub 2020 Sep 29.

Bioengineering Program, Fred DeMatteis School of Engineering and Applied Sciences, Hofstra University, Hempstead, NY, USA.

Objective: Preconditioning of endothelial cells from different vascular beds has potential value for re-endothelialization and implantation of engineered tissues. Understanding how substrate stiffness and composition affects tissue-specific cell response to shear stress will aid in successful endothelialization of engineered tissues. We developed a platform to test biomechanical and biochemical stimuli.

Methods: A novel polydimethylsiloxane-based parallel plate flow chamber enabled application of laminar fluid shear stress of 2 dynes/cm for 12 hours to microvascular cardiac and lung endothelial cells cultured on cardiac and lung-derived extracellular matrix. Optical imaging of cells was used to quantify cell changes in cell alignment. Analysis of integrin expression was performed using flow cytometry.

Results: Application of fluid shear stress caused the greatest cell alignment in cardiac endothelial cells seeded on polystyrene and lung endothelial cells on polydimethylsiloxane. This resulted in elongation of the lung endothelial cells. α and β integrin expression decreased after application of shear stress in both cell types.

Conclusion: Substrate stiffness plays an important role in regulating tissue-specific endothelial response to shear stress, which may be due to differences in their native microenvironments. Furthermore, cardiac and lung endothelial cell response to shear stress was significantly regulated by the type of coating used.
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http://dx.doi.org/10.1111/micc.12659DOI Listing
January 2021

Future migration: Key environmental indicators of Pu accumulation in terrestrial sediments of Queensland, Australia.

J Environ Radioact 2020 Nov 12;223-224:106398. Epub 2020 Sep 12.

School of Earth, Atmosphere & Environment, Monash University, Clayton, VIC, 3800, Australia.

Plutonium (Pu) interactions in the environment are highly complex. Site-specific variables play an integral role in determining the chemical and physical form of Pu, and its migration, bioavailability, and immobility. This paper aims to identify the key variables that can be used to highlight regions of radioecological sensitivity and guide remediation strategies in Australia. Plutonium is present in the Australian environment as a result of global fallout and the British nuclear testing program of 1952-1958 in central and west Australia (Maralinga and Montebello islands). We report the first systematic measurements of Pu and Pu activity concentrations in distal (≥1000 km from test sites) catchment outlet sediments from Queensland, Australia. The average Pu activity concentration was 0.29 mBq.g (n = 73 samples) with a maximum of 4.88 mBq.g .Pu/Pu isotope ratios identified a large range (0.02-0.29 (RSD: 74%)) which is congruent with the heterogeneous nuclear material used for the British nuclear testing programme at Maralinga and Montebello Islands. The use of a modified PCA relying on non-linear distance correlation (dCorr) provided broader insight into the impact of environmental variables on the transport and migration of Pu in this soil system. Primary key environmental indicators of Pu presence were determined to be actinide/lanthanide/heavier transition metals, elevation, electrical conductivity (EC), CaO, SiO, SO, landform, geomorphology, land use, and climate explaining 81.7% of the variance of the system. Overall this highlighted that trace level Pu accumulations are associated with the coarse, refractive components of Australian soils, and are more likely regulated by the climate of the region and overall soil type.
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http://dx.doi.org/10.1016/j.jenvrad.2020.106398DOI Listing
November 2020

Applied phyloepidemiology: Detecting drivers of pathogen transmission from genomic signatures using density measures.

Evol Appl 2020 Jul 22;13(6):1513-1525. Epub 2020 May 22.

CIRI INSERM U1111 CNRS UMR5308 ENS Lyon University of Lyon Lyon France.

Understanding the driving forces of an epidemic is key to inform intervention strategies against it. Correlating measures of the epidemic success of a pathogen with ancillary parameters such as its drug resistance profile provides a flexible tool to identify such driving forces. The recently described time-scaled haplotypic density (THD) method facilitates the inference of a pathogen's epidemic success from genetic data. Contrary to demogenetic approaches that define success in an aggregated fashion, the THD computes an independent index of success for each isolate in a collection. Modeling this index using multivariate regression, thus, allows us to control for various sources of bias and to identify independent predictors of success. We illustrate the use of THD to address key questions regarding three exemplary epidemics of multidrug-resistant (MDR) bacterial lineages, namely Beijing, Typhi H58, and ST8 (including ST8-USA300 MRSA), based on previously published, international genetic datasets. In each case, THD analysis allowed to identify the impact, or lack thereof, of various factors on the epidemic success, independent of confounding by population structure and geographic distribution. Our results suggest that rifampicin resistance drives the MDR Beijing epidemic and that fluoroquinolone resistance drives the ST8/USA300 epidemic, in line with previous evidence of a lack of resistance-associated fitness cost in these pathogens. Conversely, fluoroquinolone resistance measurably hampered the success of Typhi H58 and non-H58. These findings illustrate how THD can help leverage the massive genomic datasets generated by molecular epidemiology studies to address new questions. THD implementation for the R platform is available at https://github.com/rasigadelab/thd.
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http://dx.doi.org/10.1111/eva.12991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359849PMC
July 2020

Development of an Endotracheal Intubation Formative Assessment Tool.

J Educ Perioper Med 2020 Jan-Mar;22(1):E635. Epub 2020 Jan 1.

Background: Valid methods for providing detailed formative feedback on direct laryngoscopy and endotracheal intubation (ETI) performance do not exist. We are developing an observation-based assessment tool for measuring performance and providing feedback during ETI.

Methods: Based on the literature and interviews of experts, we proposed an initial ETI metric with 22 items. Six anesthesiology experts used it to assess the quality of ETI performance in videotaped intubations. Following metric revisions, 2 expert groups assessed 2 collections of videos (27 total) using the revised metric. Two reference standards for comparison with metric scores were created with a third and fourth group of experts; (1) an average global rating (1-100) of each ETI performance and (2) average rank-ordered performance from best to worst. Rater agreement and correlations between the 2 methods were calculated. Regression analysis determined items that optimally discriminated quality. When calculating a score based on all clinically important terms, multiple weightings were evaluated.

Results: Metric items had high average rater agreement (80%) with intraclass correlation coefficients averaging 0.83. Correlations of the reference rank and score were high for both video collections (-0.96, < .05, and -0.95, < .05). Regression coefficients for different item weighting methods indicated strong relationships with global ratings (averaging r = 0.89, < .05) and rankings averaging -0.85, < .05). Prediction of global ratings using regression achieved high accuracy ( = 0.8218).

Conclusions: High observer agreement and strong correlations between metric and rank data support the validity of using this metric to assess ETI performance. Different weighting models yielded scores that correlated strongly with the ratings and ranks from global assessment. When using the metric to predict competency, a 3-item regression model is most accurate in predicting a global score.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219026PMC
January 2020

Tool to improve qualitative assessment of left ventricular systolic function.

Echo Res Pract 2020 Mar 17;7(1):1-8. Epub 2020 Feb 17.

Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

Interactive online learning tools have revolutionized graduate medical education and can impart echocardiographic image interpretive skills. We created self-paced, interactive online training modules using a repository of echocardiography videos of normal and various degrees of abnormal left ventricles. In this study, we tested the feasibility of this learning tool. Thirteen anesthesia interns took a pre-test and then had 3 weeks to complete the training modules on their own time before taking a post-test. The average score on the post-test (74.6% ± 11.08%) was higher than the average score on the pre-test (57.7% ± 9.27%) ( < 0.001). Scores did not differ between extreme function (severe dysfunction or hyperdynamic function) and non-extreme function (normal function or mild or moderate dysfunction) questions on both the pre-test ( = 0.278) and post-test ( = 0.093). The interns scored higher on the post-test than the pre-test on both extreme ( = 0.0062) and non-extreme ( = 0.0083) questions. After using an online educational tool that allowed learning on their own time and pace, trainees improved their ability to correctly categorize left ventricular systolic function. Left ventricular systolic function is often a key echocardiographic question that can be difficult to master. The promising performance of this educational resource may lead to more time- and cost-effective methods for improving diagnostic accuracy among learners.
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http://dx.doi.org/10.1530/ERP-19-0053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077518PMC
March 2020

Hypocalcaemia following denosumab in prostate cancer: A clinical review.

Clin Endocrinol (Oxf) 2020 06 16;92(6):495-502. Epub 2020 Feb 16.

Department of Endocrinology, Austin Health, Melbourne, Vic., Australia.

Objectives: Denosumab is often used in men with advanced prostate cancer to prevent skeletal-related events, but can be associated with severe hypocalcaemia. Our objective was to review the pathophysiology, identify risk factors and provide recommendations for prevention and management of denosumab-associated hypocalcaemia.

Design: We reviewed the literature regarding denosumab-associated severe hypocalcaemia, defined as necessitating hospitalization for intravenous calcium treatment, in the context of prostate cancer.

Patients: Men with prostate cancer with severe denosumab-associated hypocalcemia.

Results: We identified 20 men with prostate cancer with severe denosumab-associated hypocalcemia, including the present case. Median age (range) was 70 years (45-86). All had skeletal metastases and presented with symptomatic hypocalcemia 16 days (4-35) after the initial (n = 18) or second (n = 2) denosumab treatment, with a serum total calcium of 1.36 mmol/L (1.13-1.91). The key risk factor was presence of active osteoblastic metastases, evidenced by elevated serum alkaline phosphatase, 838 U/L (58-2620) and supportive imaging. Other risk factors reported in some men included vitamin D deficiency (<50 nmol/L), 25-OH vitamin D 44 nmol/L (22-81), renal impairment, serum creatinine 103 μmol/L (62-1131) and hypomagnesaemia, 0.82 mmol/L (0.29-1.20). Men received intravenous calcium infusions for 16 days (1-90), and median total intravenous elemental calcium requirements were 3.17 g (0.47-26.65).

Conclusions: Denosumab treatment in men with metastatic prostate cancer can be associated with life-threatening hypocalcaemia requiring prolonged hospitalization for intravenous calcium treatment. Modifiable risk factors should be corrected before denosumab administration. In men with active osteoblastic metastases, consideration should be given to delay denosumab treatment until underlying disease activity is controlled, and/or be administered with close monitoring and proactive treatment with calcium and calcitriol.
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http://dx.doi.org/10.1111/cen.14169DOI Listing
June 2020

A mycotic aneurysm related to Salmonella Rissen infection: a case report.

BMC Infect Dis 2020 Jan 31;20(1):97. Epub 2020 Jan 31.

Infectious Diseases Department, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.

Background: Salmonella species commonly causes infection in humans and on occasion leads to serious complications, such as mycotic aneurysms. Here, we present the first case reported of a patient with a mycotic aneurysm likely secondary to Salmonella Rissen infection.

Case Presentation: The patient presented with 4 weeks of lower back pain, chills and a single episode of diarrhoea 2 months prior during a 14-day trip to Hong Kong and Taiwan. Magnetic resonance imaging revealed an aneurysmal left internal iliac artery with adjacent left iliacus rim-enhancing collection. A stool culture was positive for Salmonella Rissen ST 469 EBG 66 on whole genome sequencing. The patient underwent an emergency bifurcated graft of his internal iliac aneurysm and was successfully treated with appropriate antibiotics.

Conclusions: This case highlights the importance of considering the diagnosis of a mycotic aneurysm in an unusual presentation of back pain with features of infection.
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http://dx.doi.org/10.1186/s12879-020-4819-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995202PMC
January 2020

Phylogenetic Analysis Indicates a Longer Term Presence of the Globally Distributed H58 Haplotype of Salmonella Typhi in Southern India.

Clin Infect Dis 2020 11;71(8):1856-1863

Department of Medicine, Univesity of Cambridge, Cambridge, United Kingdom.

Background: Typhoid fever caused by Salmonella Typhi is a major public health concern in low-/middle-income countries. A recent study of 1900 global S. Typhi indicated that South Asia might be the site of the original emergence of the most successful and hypervirulent clone belonging to the 4.3.1 genotype. However, this study had limited samples from India.

Methods: We analyzed 194 clinical S. Typhi, temporal representatives from those isolated from blood and bone marrow cultures in southern India, over 26 years (1991-2016). Antimicrobial resistance (AMR) testing was performed for most common clinical agents. Whole-genome sequencing and SNP-level analysis was conducted. Comparative genomics of Vellore isolates was performed to infer transmission and AMR events.

Results: We identified multidrug-resistance (MDR)-associated clade 4.3.1 as the dominant genotype. We detected 4.3.1 S. Typhi as early as 1991, the earliest to be reported form India, and the majority were fluoroquinolone resistant and not MDR. MDR was not detected at all in other genotypes circulating in Vellore. Comparison with global S. Typhi showed 2 Vellore subgroups (I and II) that were phylogenetically highly related to previously described South Asia (subgroup I, II) and Southeast Asia (subgroup II) clades.

Conclusions: 4.3.1 S. Typhi has dominated in Vellore for 2 decades. Our study would assist public health agencies in better tracking of transmission and persistence of this successful clade in India and globally. It informs clinicians of the AMR pattern of circulating clone, which would add confidence to their prophylactic/treatment decision making and facilitate efficient patient care.
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http://dx.doi.org/10.1093/cid/ciz1112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643746PMC
November 2020

The Indigenous Faculty Forum: A Longitudinal Professional Development Program to Promote the Advancement of Indigenous Faculty in Academic Medicine.

Hawaii J Health Soc Welf 2019 12;78(12 Suppl 3):8-13

Oregon Health & Science University, Portland, OR (EB, AB, MFM, CT, PAC).

American Indian, Alaska Native (AIAN) and Native Hawaiian and other Pacific Islander (NHPI) faculty, are substantially under-represented (<1%) at US medical schools. The Oregon Health & Science University's Northwest Native American Center of Excellence and The University of Hawai'i Native Hawaiian Center of Excellence have created an Indigenous Faculty Forum (IFF), a one-day structured course with flanking social activities, specifically designed to meet the unique needs of AIAN and NHPI academic faculty. It provided: (1) Indigenous space, (2) skill building, (3) networking, and (4) ongoing mentorship, each of which were included to specifically mitigate isolation and tokenism that negatively affects promotion and advancement. Two Forums have been conducted, first in Portland, OR in 2017 and the second in Hilo, Hawai'i in 2018. Nine of eighteen AIAN faculty in the three-state region (CA, OR, WA) attended IFF Session #1, representing 50% of known AIAN faculty in this region. Thirty-four Indigenous faculty from around the world attended IFF Session #2, with twenty-nine completing program evaluations. Respondents were predominantly female (81.6%), under age 44 (52.7%), and either instructors or assistant professors (52.6%). In terms of career choice, both sessions included primary care physicians as the most represented group (55.6% at Session #1 and 62.1% at Session #2). Increasing Indigenous faculty representation in US medical schools, while simultaneously fostering their career advancement and meaning in work, is vitally important. We have begun the work needed to address this problem and look forward to conducting more efforts, including longitudinal evaluation designs to study effectiveness.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949475PMC
December 2019

A positive BAL galactomannan in non-haemato-oncology patients risks harmful overtreatment.

J Med Microbiol 2019 Dec;68(12):1766-1770

Department of Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.

. Evidence for the clinical utility of bronchoalveolar lavage (BAL) galactomannan in the management of fungal disease outside of haemato-oncology patients is limited.. To determine how the introduction of BAL galactomannan testing impacted on the diagnosis and management of invasive aspergillosis and other fungal diseases in non-haemato-oncology patients.. Retrospective review of all adult patients (age ≥16 years) without a diagnosis of haematological malignancy who had a positive BAL galactomannan from 1 November 2014 to 30 April 2018. Using electronic patient records we obtained demographic data, clinical details, laboratory investigations, relevant radiology and antimicrobial history for each case.. In total, 121 episodes with a galactomannan OD index of ≥0.500 were included in the study; 29 cases (24 %) were felt to reflect fungal disease. Antifungal therapy was commenced as a direct consequence of a positive BAL galactomannan result in 13 patients where the ultimate diagnosis was subsequently considered to be non-mycological: associated medication-related side-effects in this group included deranged liver function tests (=3), rash (=1) and fever (=1), related to amphotericin B (=1) and voriconazole (=4).. We show that vigilance is required when interpreting galactomannan results in non-haematology patients to avoid potentially harmful overtreatment.
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http://dx.doi.org/10.1099/jmm.0.001109DOI Listing
December 2019

Ultrasound-guided Intravenous Line Placement Course for Certified Registered Nurse Anesthetists: A Necessary Next Step.

AANA J 2019 Aug;87(4):269-275

is in the Departments of Anesthesia and Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School.

Ultrasonography (US) proficiency has become a desirable skill for anesthesia providers. It is commonly used in the perioperative arena for establishing peripheral and central vascular access. Establishing intravenous access is one of the most common procedures performed by Certified Registered Nurse Anesthetists (CRNAs) as frontline anesthesia providers. However, there is no structured US training program for CRNAs for vascular access at our institution. We designed and implemented a multimodality US training program specifically for the use of surface US for central and peripheral vascular access for CRNAs. The course was conducted over 2 days and consisted of an online self-paced didactic component, integrated proctored hands-on workshops, and a posttraining examina-tion to quantify knowledge gain. Twenty-five CRNAs attended the course, with significant improvement in knowledge (pretest mean (SD) score = 59.13% (15.74%) vs posttest mean score = 70.0% (9.43%), P = .03). Two weeks after the course, each participant reported that they attempted 1.46 (1.56) ultrasound-guided vascular access procedures on average. Therefore, it is feasible to design short, focused, multimodality training programs for proficiency in the use of surface US for obtaining venous access. The CRNA's proficiency in US is likely to improve efficiency, patient experience, and safety.
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August 2019

The Dean's Certificate of Distinction in Native Hawaiian Health.

Aust J Prim Health 2019 Nov;25(5):410-414

John A. Burns School of Medicine, 651 Ilalo Street, 3rd Floor, Honolulu, HI 96813, USA.

Certificates of Distinction at USA medical schools are given to students who have shown additional commitment and effort in areas such as global health and social justice. In 2014, the Dean's Certificate of Distinction in Native Hawaiian Health (COD-NHH), at the John A. Burns School of Medicine (JABSOM), was designed to offer more experience and knowledge in Native Hawaiian health, as well as directly benefiting Native Hawaiian communities through personal and cultural growth, service learning and scholarly projects. The COD-NHH utilises the Department of Native Hawaiian Health 'na pou kihi' framework represented by a hale (house). This framework embodies the Native Hawaiian holistic view of health and incorporates traditional values and cultural strengths, critical to ensure that students can work comfortably and effectively in our communities. Activities focus on four 'pou kihi' (pillars): (1) cultural knowledge and space; (2) community/environmental stewardship; (3) knowledge advancement and dissemination; and (4) social justice. The first cohort received their COD-NHH in May 2017. Interest among JABSOM students is expanding. The COD-NHH, though well received, has required some modification including new technology for data collection of requirements. Feedback from the community is positive and continued community partnerships allow for opportunities of engagement with the student.
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http://dx.doi.org/10.1071/PY19031DOI Listing
November 2019

Negative Memory Engrams in the Hippocampus Enhance the Susceptibility to Chronic Social Defeat Stress.

J Neurosci 2019 09 12;39(38):7576-7590. Epub 2019 Aug 12.

Basic Neuroscience Division, Douglas Hospital Research Centre, Montreal, Quebec H4H 1R3, Canada, and

The hippocampus has been highly implicated in depression symptoms. Recent findings suggest that the expression and susceptibility of depression symptoms are related to the enhanced functioning of the hippocampus. We reasoned that hippocampal engrams, which represent ensembles of neurons with increased activity after memory formation, could underlie some contributions of the hippocampus to depression symptoms. Using the chronic social defeat stress model, we examined social defeat-related hippocampal engrams in mice that are either susceptible or resilient to the stressor. mice were used to label social defeat-related hippocampal ensembles by LacZ. Engram cells correspond to ensembles that were reactivated by the same stressor. Compared with resilient and nonstressed control mice, susceptible mice exhibited a higher reactivation of social defeat-related LacZ-labeled cells (i.e., engram cells) in both the dorsal and ventral hippocampal CA1 regions. The density of CA1 engram cells correlated with the level of social avoidance. Using DREADD and optogenetic approaches to activate and inactivate social defeat-related CA1 engram cells enhanced and suppressed social avoidance, respectively. Increased engram cells in susceptible mice could not be found in the dentate gyrus. Susceptible mice exhibited more negative stimuli-related, but not neutral stimuli-related, CA1 engram cells than resilient mice in the dorsal hippocampus. Finally, chronic, but not a short and subthreshold, social defeat protocol was necessary to increase CA1 engram cell density. The susceptibility to chronic social defeat stress is regulated by hippocampal CA1 engrams for negative memory. Hippocampal negative memory engrams may underlie the vulnerability and expression of cognitive symptoms in depression. We provided evidence that negative memory hippocampal engrams contribute to the susceptibility to developing depression-related behavior after chronic social defeat stress. The activation of positive memory engrams has been shown to alleviate depression-related behaviors, while our findings reveal the pathological roles of negative memory engrams that could lead to those behaviors. Increased negative memory engrams could be a downstream effect of the reported high hippocampal activity in animal models and patients with depression. Unlike affective symptoms, we know much less about the cellular mechanisms of the cognitive symptoms of depression. Given the crucial roles of hippocampal engrams in memory formation, enhanced reactivation of negative memory engrams could be an important cellular mechanism that underlies the cognitive symptoms of depression.
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http://dx.doi.org/10.1523/JNEUROSCI.1958-18.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750945PMC
September 2019

Customizable Curriculum to Enhance Resident Communication Skills.

Anesth Analg 2019 11;129(5):e155-e158

From the Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Communication remains challenging to teach and evaluate. We designed an online patient survey to assess anesthesia residents' communication skills from August 2014 to July 2015. In December 2014, we implemented a customized, simulation-based curriculum. We calculated an overall rating for each survey by averaging the ratings for the individual questions. Based on the Hodges-Lehmann 2-sample aligned rank-sum test, overall ratings, reported as the median (interquartile range) of residents' average overall ratings, differed significantly between the preintervention (3.86 [3.76-3.94]) and postintervention (3.91 [3.84-3.95]) periods (P = .025). Future studies should assess the intervention's effectiveness and generalizability.
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http://dx.doi.org/10.1213/ANE.0000000000004084DOI Listing
November 2019
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