Publications by authors named "Julie George"

83 Publications

MAPK-pathway inhibition mediates inflammatory reprogramming and sensitizes tumors to targeted activation of innate immunity sensor RIG-I.

Nat Commun 2021 Sep 17;12(1):5505. Epub 2021 Sep 17.

Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931, Cologne, Germany.

Kinase inhibitors suppress the growth of oncogene driven cancer but also enforce the selection of treatment resistant cells that are thought to promote tumor relapse in patients. Here, we report transcriptomic and functional genomics analyses of cells and tumors within their microenvironment across different genotypes that persist during kinase inhibitor treatment. We uncover a conserved, MAPK/IRF1-mediated inflammatory response in tumors that undergo stemness- and senescence-associated reprogramming. In these tumor cells, activation of the innate immunity sensor RIG-I via its agonist IVT4, triggers an interferon and a pro-apoptotic response that synergize with concomitant kinase inhibition. In humanized lung cancer xenografts and a syngeneic Egfr-driven lung cancer model these effects translate into reduction of exhausted CD8 T cells and robust tumor shrinkage. Overall, the mechanistic understanding of MAPK/IRF1-mediated intratumoral reprogramming may ultimately prolong the efficacy of targeted drugs in genetically defined cancer patients.
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http://dx.doi.org/10.1038/s41467-021-25728-8DOI Listing
September 2021

Ferroptosis response segregates small cell lung cancer (SCLC) neuroendocrine subtypes.

Nat Commun 2021 04 6;12(1):2048. Epub 2021 Apr 6.

Department of Translational Genomics, Medical Faculty, University of Cologne, Cologne, Germany.

Loss of TP53 and RB1 in treatment-naïve small cell lung cancer (SCLC) suggests selective pressure to inactivate cell death pathways prior to therapy. Yet, which of these pathways remain available in treatment-naïve SCLC is unknown. Here, through systemic analysis of cell death pathway availability in treatment-naïve SCLC, we identify non-neuroendocrine (NE) SCLC to be vulnerable to ferroptosis through subtype-specific lipidome remodeling. While NE SCLC is ferroptosis resistant, it acquires selective addiction to the TRX anti-oxidant pathway. In experimental settings of non-NE/NE intratumoral heterogeneity, non-NE or NE populations are selectively depleted by ferroptosis or TRX pathway inhibition, respectively. Preventing subtype plasticity observed under single pathway targeting, combined treatment kills established non-NE and NE tumors in xenografts, genetically engineered mouse models of SCLC and patient-derived cells, and identifies a patient subset with drastically improved overall survival. These findings reveal cell death pathway mining as a means to identify rational combination therapies for SCLC.
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http://dx.doi.org/10.1038/s41467-021-22336-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024350PMC
April 2021

Safety of apixaban compared to warfarin in hemodialysis patients: Do antiplatelets make a difference?

Eur J Haematol 2021 May 8;106(5):689-696. Epub 2021 Mar 8.

Department of Nephrology, Beaumont Health System, Royal Oak, OUWB School of Medicine, Royal Oak, MI, USA.

Background: Data on the safety of apixaban compared to warfarin in hemodialysis (HD) patients are accumulating, but the impact of concomitant antiplatelet use is unknown.

Objectives: Compare hemorrhagic risk and impact of antiplatelets in HD patients receiving oral anticoagulants (OAC).

Methods: Retrospective, multi-center study of HD patients started on OAC inpatient over 5 years.

Results: 707 patients were included: 563 received warfarin, and 144 received apixaban. 197 had bleeding, most in the warfarin group (173 [30.1%] vs 24 [16.7%] in the apixaban group), P-value < .01). However, with concomitant antiplatelet use, frequencies were similar (31.4% vs 25.0%; P-value = .292). Cumulative incidence using bleeding as event of interest and death as competing risk showed higher rates of bleeding with warfarin. In a multivariate model, apixaban was associated with a lower hemorrhagic risk (hazard ratio [HR] 0.55 [95% confidence interval {CI} 0.35-0.86}). Apixaban showed lower hemorrhagic risk alone (HR 0.24, 95% CI 0.10-0.55) and similar risk when administered with antiplatelets (HR 0.93, 95% CI 0.55-1.56).

Conclusions: Apixaban is associated with less bleeding in HD patients compared to warfarin, but concomitant antiplatelet use may negate the safety advantage. Prospective trials are warranted to determine the impact of antiplatelets on apixaban safety.
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http://dx.doi.org/10.1111/ejh.13599DOI Listing
May 2021

Protocol driven periprocedural anticoagulation for left atrial ablation.

J Cardiovasc Electrophysiol 2021 03 2;32(3):639-646. Epub 2021 Feb 2.

Department of Cardiovascular Medicine, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, USA.

Introduction: A weight-based heparin dosing policy adjusted for preprocedural oral anticoagulation was implemented to reduce the likelihood of subtherapeutic dosing during left atrial catheter ablation procedures. We hypothesized that initiation of the protocol would result in a greater prevalence of therapeutic activated clotting time (ACT) values and decreased time to therapeutic ACT during left atrial ablation procedures.

Methods: A departmental protocol was initiated for which subjects received intravenous unfractionated heparin (UFH) to achieve and maintain a goal of ACT >300 s. Initial bolus dose was adjusted for pre-procedure oral anticoagulation and weight as follows: 50 units/kg for those receiving warfarin, 75 units/kg for those not anticoagulated, and 120 units/kg for those on direct oral anticoagulants (DOACs). A UFH infusion was initiated at 10% of the bolus per hour. One hundred consecutive left atrial ablation procedures treated with Protocol Guided heparin dosing were compared with a retrospective consecutive cohort of Usual Care heparin dosing.

Results: When the Usual Care and Protocol Guided cohorts were compared, significant findings were limited to those on pre-procedure DOAC. The initial UFH bolus increased from 99.3 ± 24.8 to 118.2 ± 22.8 units/kg (p < .001), the proportion of therapeutic ACT on the first draw after heparin administration increased from 57.7% to 76.6% (p = .010), and the time to therapeutic ACT after UFH administration decreased from 37.8 ± 19.8 to 30.2 ± 16.4 min (p = .032).

Conclusion: A weight-based protocol for periprocedural UFH administration resulted in a higher proportion of therapeutic ACT values and decreased the time to therapeutic ACT for those on pre-procedure DOAC.
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http://dx.doi.org/10.1111/jce.14892DOI Listing
March 2021

The costs of treating and not treating patients with chronic myeloid leukemia with tyrosine kinase inhibitors among Medicare patients in the United States.

Cancer 2021 01 29;127(1):93-102. Epub 2020 Oct 29.

Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.

Background: Patients with high cost-sharing of tyrosine kinase inhibitors (TKIs) experience delays in treatment for chronic myeloid leukemia (CML). To the authors' knowledge, the clinical outcomes among and costs for patients not receiving TKIs are not well defined.

Methods: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, the authors evaluated differences in TKI initiation, health care use, cost, and survival among patients with CML with continuous Medicare Parts A and B and Part D coverage who were diagnosed between 2007 and 2015.

Results: A total of 941 patients were included. Approximately 29% of all patients did not initiate treatment with TKIs within 6 months (non-TKI users), and had lower rates of BCR-ABL testing and more hospitalizations compared with TKI users. Approximately 21% were not found to have any TKI claims at any time. TKI initiation rates within 6 months of diagnosis increased for all patients over time (61% to 85%), with greater improvements observed in patients receiving subsidies (55% to 90%). Total Medicare costs were greater in patients treated with TKIs, with approximately 50% because of TKI costs. Non-TKI users had more inpatient costs compared with TKI users. Trends in cost remained significant when adjusting for age and comorbidities. The median overall survival was 40 months (95% confidence interval [95% CI], 34-48 months) compared with 86 months (95% CI, 73 months to not reached), respectively, for non-TKI users versus TKI users, a finding that remained consistent when adjusting for age, comorbidities, and subsidy status (hazard ratio, 2.23; 95% CI, 1.77-2.81).

Conclusions: Approximately 21% of all patients with CML did not receive TKIs at any time. Cost-sharing subsidies consistently are found to be associated with higher initiation rates. Non-TKI users had higher inpatient costs and poorer survival outcomes. Interventions to lower TKI costs for all patients are desirable.
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http://dx.doi.org/10.1002/cncr.33267DOI Listing
January 2021

Acute hyperhidrosis and postural tachycardia in a COVID-19 patient.

Clin Auton Res 2020 12 24;30(6):571-573. Epub 2020 Sep 24.

Department of General Medicine, Tan Tock Seng Hospital, Singapore, Singapore.

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http://dx.doi.org/10.1007/s10286-020-00733-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511524PMC
December 2020

Importance of measurement site on assessment of lesion-specific ischemia and diagnostic performance by coronary computed tomography Angiography-Derived Fractional Flow Reserve.

J Cardiovasc Comput Tomogr 2021 Mar-Apr;15(2):114-120. Epub 2020 Aug 29.

Department of Cardiovascular Medicine, Beaumont Hospital-Royal Oak, Royal Oak, MI, USA. Electronic address:

Background: Values of fractional flow reserve (FFR) by coronary computed tomography angiography (CTA) decline from the ostium to the terminal vessel, irrespective of stenosis severity. The purpose of this study is to determine if the site of measurement of FFR impacts assessment of ischemia and its diagnostic performance relative to invasive FFR (FFR).

Methods: 1484 patients underwent FFR; 1910 vessels were stratified by stenosis severity (normal; <25%, 25-50%, 50-70%, and >70% stenosis). The rates of positive FFR (≤0.8) were determined by measuring FFR from the terminal vessel and from distal-to-the-lesion. Reclassification rates from positive to negative FFR were calculated. Diagnostic performance of FFR relative to FFR was evaluated in 182 vessels using linear regression, Bland Altman analysis, and receiver operating characteristic (ROC) curves.

Results: Positive FFR was identified in 24.9% of vessels using terminal vessel FFR and 10.1% using FFR distal-to-the-lesion (p ​< ​0.001). FFR obtained distal-to-the-lesion resulted in reclassification of 59.6% of positive terminal FFR to negative FFR. Relative to FFR, there were improvements in specificity (50% to 86%, p ​< ​0.001), diagnostic accuracy (65% to 88%, p ​< ​0.001), positive predictive value (50% to 78%, p ​< ​0.001), and area-under-the-curve (AUC, 0.83 to 0.91, p ​< ​0.001) when FFR was measured distal-to-the-lesion.

Conclusion: FFR values from the terminal vessel should not be used to assess lesion-specific ischemia due to high rates of false positive results. FFR measured distal-to-the-lesion improves the diagnostic performance of FFR relative to FFR, ensures that FFR values are due to lesion-specific ischemia, and could reduce the rate of unnecessary invasive procedures.
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http://dx.doi.org/10.1016/j.jcct.2020.08.005DOI Listing
July 2021

Concomitant use of direct oral anticoagulants and aspirin versus direct oral anticoagulants alone in atrial fibrillation and flutter: a retrospective cohort.

BMC Cardiovasc Disord 2020 06 1;20(1):263. Epub 2020 Jun 1.

General Internal Medicine Division, Beaumont Health, Royal Oak, MI, USA.

Background: The benefit of combining aspirin and direct oral anticoagulants on the reduction of cardiovascular events in atrial fibrillation or flutter is not well studied. We aimed to assess whether concurrent aspirin and direct oral anticoagulant therapy for atrial fibrillation or flutter will result in less coronary, cerebrovascular and systemic ischemic events compared to direct oral anticoagulant therapy alone.

Methods: Retrospective study of adult patients between 18 and 100 years old who have nonvalvular atrial fibrillation or flutter and were started on a direct oral anticoagulant (apixaban, rivaroxaban, or dabigatran), between January 1, 2010 and September 1, 2015 within the Beaumont Health System. Exclusions were history of venous thromboembolic disease and use of other antiplatelet therapies such as P2Y12 inhibitors. Patients were classified into two groups based on concurrent aspirin use and observed for a minimum of 2 years. Primary outcome was major adverse cardiac events, defined as acute coronary syndromes, ischemic strokes, and embolic events. Secondary outcomes were bleeding and death.

Results: Six thousand four patients were in the final analysis, 57% males and 80% Caucasians, median age 71, interquartile range (63-80). The group exposed to aspirin contained 2908 subjects, and the group unexposed to aspirin contained 3096 subjects. After using propensity scores to balance the baseline characteristics in both groups, the analysis revealed higher rate of major adverse cardiac events in the exposed group compared to the unexposed group, (HR 2.11, 95% CI (1.74-2.56)) with a number needed to harm of 11 (95% CI [9-11]). The rate of bleeding was also higher in the exposed group, (HR 1.30, 95% CI (1.11-1.52)). The rate of death was not statistically different between the groups, (HR 0.87, 95% CI (0.61-1.25)).

Conclusions: In this observational analysis of patients with atrial fibrillation and flutter, the concomitant use of direct oral anticoagulants and aspirin was associated with an increased risk of both major adverse cardiac and bleeding events when compared to the use of direct oral anticoagulants alone. These findings underscore the potential harm of this combination therapy when used without a clear indication.
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http://dx.doi.org/10.1186/s12872-020-01509-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268433PMC
June 2020

Developing a Workforce for Health in North Carolina: Planning for the Future.

N C Med J 2020 May-Jun;81(3):185-190

chancellor for health affairs, Duke University, Durham, North Carolina; president and CEO, Duke University Health System, Durham, North Carolina.

Among the many trends influencing health and health care delivery over the next decade, three are particularly important: the transition to value-based care and increased focus on population health; the shift of care from acute to community-based settings; and addressing the vulnerability of rural health care systems in North Carolina.
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http://dx.doi.org/10.18043/ncm.81.3.185DOI Listing
July 2020

Depletion of histone methyltransferase KMT9 inhibits lung cancer cell proliferation by inducing non-apoptotic cell death.

Cancer Cell Int 2020 17;20:52. Epub 2020 Feb 17.

1Klinik für Urologie und Zentrale Klinische Forschung, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Universitätsklinikum Freiburg, Freiburg, Germany.

Background: Lung cancer is the leading cause of cancer related death worldwide. Over the past 15 years no major improvement of survival rates could be accomplished. The recently discovered histone methyltransferase KMT9 that acts as epigenetic regulator of prostate tumor growth has now raised hopes of enabling new cancer therapies. In this study, we aimed to identify the function of KMT9 in lung cancer.

Methods: We unraveled the KMT9 transcriptome and proteome in A549 lung adenocarcinoma cells using RNA-Seq and mass spectrometry and linked them with functional cell culture, real-time proliferation and flow cytometry assays.

Results: We show that KMT9α and -β subunits of KMT9 are expressed in lung cancer tissue and cell lines. Importantly, high levels of KMT9α correlate with poor patient survival. We identified 460 genes that are deregulated at the RNA and protein level upon knock-down of KMT9α in A549 cells. These genes cluster with proliferation, cell cycle and cell death gene sets as well as with subcellular organelles in gene ontology analysis. Knock-down of KMT9α inhibits lung cancer cell proliferation and induces non-apoptotic cell death in A549 cells.

Conclusions: The novel histone methyltransferase KMT9 is crucial for proliferation and survival of lung cancer cells harboring various mutations. Small molecule inhibitors targeting KMT9 therefore should be further examined as potential milestones in modern epigenetic lung cancer therapy.
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http://dx.doi.org/10.1186/s12935-020-1141-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027090PMC
February 2020

A community-driven and evidence-based approach to developing mental wellness strategies in First Nations: a program protocol.

Res Involv Engagem 2020 12;6. Epub 2020 Feb 12.

1Centre for Addiction and Mental Health, Toronto and London, Ontario Canada.

Background: Mental health, substance use/addiction and violence (MSV) are important issues affecting the well-being of Indigenous People in Canada. This paper outlines the protocol for a research-to-action program called the Mental Wellness Program (MWP). The MWP aims to increase community capacity, promote relationship-building among communities, and close gaps in services through processes that place value on and supports Indigenous communities' rights to self-determination and control. The MWP involves collecting and using local data to develop and implement community-specific mental wellness strategies in five First Nations in Ontario.

Methods: The MWP has four key phases. Phase 1 (data collection) includes a community-wide survey to understand MSV issues, service needs and community strengths; in-depth interviews with individuals with lived experiences with MSV issues to understand, health system strengths, service gaps and challenges, as well as individual and community resilience factors; and focus groups with service providers to improve understanding of system weaknesses and strengths in addressing MSV. Phase 2 (review and synthesis) involves analysis of results from these local data sources and knowledge-sharing events to identify a priority area for strategic development based on local strengths and need. Phase 3 (participatory action research approach) involves community members, including persons with lived experience, working with the community and local service providers to develop, implement, and evaluate the MWP to address the selected priority area. Phase 4 (share) is focused on developing and implementing effective knowledge-sharing initiatives. Guidelines and models for building the MWP are shared regionally and provincially through forums, webinars, and social media, as well as cross-community mentoring.

Discussion: MWP uses local community data to address MSV challenges by building on community supports and resilience factors. Drawing on local data and each community's system of formal and informal supports, the program includes sharing exemplary knowledge-to-action models and wellness strategies developed and First Nations people that can be used by other First Nations to identify shared wellness priorities in each community, and determine and execute next steps in addressing areas of main concern.
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http://dx.doi.org/10.1186/s40900-020-0176-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017570PMC
February 2020

Using telemedicine to improve access, cost and quality of secondary care for people in prison in England: a hybrid type 2 implementation effectiveness study.

BMJ Open 2020 02 18;10(2):e035837. Epub 2020 Feb 18.

Collaborative Centre for Inclusion Health, University College London, London, UK.

Introduction: People in prison tend to experience poorer health, access to healthcare services and health outcomes than the general population. Use of video consultations (telemedicine) has been proven effective at improving the access, cost and quality of secondary care for prisoners in the USA and Australia. Implementation and use in English prison settings has been limited to date despite political drivers for change. We plan to research the implementation of a new prison-hospital telemedicine model in an English county to understand what factors drive or hinder implementation and whether the model can improve healthcare outcomes as demonstrated in other contextual settings.

Methods And Analysis: We will undertake a hybrid type 2 implementation effectiveness study to gather evidence on both clinical and implementation outcomes. Data collection will be guided by the theoretical constructs of Normalisation Process Theory. We will prospectively collect data through: (1) prisoner/patient focus groups, interviews and questionnaires, (2) prison healthcare, hospital and wider prison staff interviews and questionnaires, (3) routine quality improvement and service evaluation data. Up to four prisons and three hospital settings in Surrey (England) will be included in the telemedicine research, dependent on their telemedicine readiness during the study period. Prisons proposed include male and female prisoners, remand (not yet sentenced) and sentenced individuals and different security categorisations. In addition, focus groups in five telemedicine naïve prisons will provide information on patient preconceptions and concerns surrounding telemedicine.

Ethics And Dissemination: This study has received National Health Service Research Ethics Committee, Her Majesty's Prison and Probation Service National Research Committee and Health Research Authority approval. Dissemination of results will take place through peer-reviewed journals, conferences and existing health and justice networks.
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http://dx.doi.org/10.1136/bmjopen-2019-035837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044812PMC
February 2020

New Approaches to SCLC Therapy: From the Laboratory to the Clinic.

J Thorac Oncol 2020 04 1;15(4):520-540. Epub 2020 Feb 1.

University of Virginia, Charlottesville, Virginia.

The outcomes of patients with SCLC have not yet been substantially impacted by the revolution in precision oncology, primarily owing to a paucity of genetic alterations in actionable driver oncogenes. Nevertheless, systemic therapies that include immunotherapy are beginning to show promise in the clinic. Although, these results are encouraging, many patients do not respond to, or rapidly recur after, current regimens, necessitating alternative or complementary therapeutic strategies. In this review, we discuss ongoing investigations into the pathobiology of this recalcitrant cancer and the therapeutic vulnerabilities that are exposed by the disease state. Included within this discussion, is a snapshot of the current biomarker and clinical trial landscapes for SCLC. Finally, we identify key knowledge gaps that should be addressed to advance the field in pursuit of reduced SCLC mortality. This review largely summarizes work presented at the Third Biennial International Association for the Study of Lung Cancer SCLC Meeting.
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http://dx.doi.org/10.1016/j.jtho.2020.01.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263769PMC
April 2020

Predictors of Cytoreductive Nephrectomy for Metastatic Kidney Cancer in SEER and Metropolitan Detroit Databases.

J Kidney Cancer VHL 2019 28;6(1):13-25. Epub 2019 Oct 28.

Department of Oncology, Karmanos Cancer Center, Wayne State University, Detroit, MI, USA.

Patients without cytoreductive nephrectomy (CN) are inadequately represented in metastatic renal cell carcinoma (RCC) clinical trials. The characteristics that impact the decision of CN were explored in the SEER database. Data on primary, regional, or distant (metastatic) stage kidney cancer over the period 2000-2013 were extracted from the National Cancer Institute Surveillance, Epidemiology, and End Results Program (SEER-18) database. A sub-analysis of Metropolitan Detroit cases, to evaluate the influence of comorbidities, was conducted. Logistic regression was used to calculate the odds ratios, and Cox model was used to calculate hazard ratios; 37% of 21,052 metastatic RCC cases had CN performed. CN demonstrated significant survival advantage (HR = 0.31, 95% confidence interval [CI]: 0.30-0.33). Comorbidity data were available on 76% of distant RCC cases from the Detroit SEER database. Neither hypertension, diabetes mellitus nor the number of comorbidities (0, 1 or 2) had a statistically significant impact on the likelihood of CN. Majority of patients (63%) with distant-stage RCC do not undergo CN and have a median overall survival (OS) of 3 months as compared to a median OS of 18 months for patients who have undergone CN. Patient demographics and tumor characteristics make a significant impact on the incidence of CN. The impact of comorbidities (number and type) was modest and not statistically significant. The optimal management of patients with synchronous primary and metastatic RCC needs to be prospectively evaluated in the setting of contemporary systemic therapy.
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http://dx.doi.org/10.15586/jkcvhl.2019.121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839034PMC
October 2019

Health and social care costs at the end of life: a matched analysis of linked patient records in East London.

Age Ageing 2019 12;49(1):82-87

Institute of Health Informatics, University College London, London NW1 2DA, UK.

Background: care in the final year of life accounts for 10% of inpatient hospital costs in UK. However, there has been little analysis of costs in other care settings. We investigated the publicly funded costs associated with the end of life across different health and social care settings.

Method: we performed cross-sectional analysis of linked electronic health records of residents aged over 50 in a locality in East London, UK, between 2011 and 2017. Those who died during the study period were matched to survivors on age group, sex, deprivation, number of long-term conditions and time period. Mean costs were calculated by care setting, age and months to death.

Results: across 8,720 matched patients, the final year of life was associated with £7,450 (95% confidence interval £7,086-£7,842, P < 0.001) of additional health and care costs, 57% of which related to unplanned hospital care. Whilst costs increased sharply over the final few months of life in emergency and inpatient hospital care, in non-acute settings costs were less concentrated in this period. Patients who died at older ages had higher social care costs and lower healthcare costs than younger patients in their final year of life.

Conclusions: the large proportion of costs relating to unplanned hospital care suggests that end-of-life planning could direct care towards more appropriate settings and lead to system efficiencies. Death at older ages results in an increasing proportion of care costs relating to social care than to healthcare, which has implications for an ageing society.
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http://dx.doi.org/10.1093/ageing/afz137DOI Listing
December 2019

Improving care quality with prison telemedicine: The effects of context and multiplicity on successful implementation and use.

J Telemed Telecare 2021 Jul 22;27(6):325-342. Epub 2019 Oct 22.

UCL Institute of Epidemiology and Health Care, London, UK.

Background: Prison telemedicine can improve the access, cost and quality of healthcare for prisoners, however adoption in prison systems worldwide has been variable despite these demonstrable benefits. This study examines anticipated and realised benefits, barriers and enablers for prison telemedicine, thereby providing evidence to improve the chances of successful implementation.

Methods: A systematic search was conducted using a combination of medical subject headings and text word searches for prisons and telemedicine. Databases searched included: PubMed, Embase, CINAHL Plus, PsycINFO, Web of Science, Scopus and International Bibliography of the Social Sciences. Articles were included if they reported information regarding the use of/advocacy for telemedicine, for people residing within a secure correctional facility. A scoping summary and subsequent thematic qualitative analysis was undertaken on articles selected for inclusion in the review, to identify issues associated with successful implementation and use.

Results: One thousand, eight hundred and eighty-two non-duplicate articles were returned, 225 were identified for full text review. A total of 163 articles were included in the final literature set. Important considerations for prison telemedicine implementation include: differences between anticipated and realised benefits and barriers, differing wants and needs of prison and community healthcare providers, the importance of top-down and bottom-up support and consideration of logistical and clinical compatibility.

Conclusions: When implemented well, patients, prison and hospital staff are generally satisfied with telemedicine. Successful implementation requires careful consideration at outset of the partners to be engaged, the local context for implementation and the potential benefits that should be communicated to encourage participation.
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http://dx.doi.org/10.1177/1357633X19869131DOI Listing
July 2021

Clinical Use of CT-Derived Fractional Flow Reserve in the Emergency Department.

JACC Cardiovasc Imaging 2020 02 17;13(2 Pt 1):452-461. Epub 2019 Jul 17.

Department of Cardiovascular Medicine, Beaumont Health, Royal Oak, Michigan.

Objectives: This study sought to examine the feasibility, safety, clinical outcomes, and costs associated with computed tomography-derived fractional flow reserve (FFR) in acute chest pain (ACP) patients in a coronary computed tomography angiography (CTA)-based triage program.

Background: FFR is useful in determining lesion-specific ischemia in patients with stable ischemic heart disease, but its utility in ACP has not been studied.

Methods: ACP patients with no known coronary artery disease undergoing coronary CTA and coronary CTA with FFR were studied. FFR ≤0.80 was considered positive for hemodynamically significant stenosis.

Results: Among 555 patients, 297 underwent coronary CTA and FFR (196 negative, 101 positive), whereas 258 had coronary CTA only. The rejection rate for FFR was 1.6%. At 90 days, there was no difference in major adverse cardiac events (including death, nonfatal myocardial infarction, and unexpected revascularization after the index visit) between the coronary CTA and FFR groups (4.3% vs. 2.7%; p = 0.310). Diagnostic failure, defined as discordance between the coronary CTA or FFR results with invasive findings, did not differ between the groups (1.9% vs. 1.68%; p = NS). No deaths or myocardial infarction occurred with negative FFR when revascularization was deferred. Negative FFR was associated with higher nonobstructive disease on invasive coronary angiography (56.5%) than positive FFR (8.0%) and coronary CTA (22.9%) (p < 0.001). There was no difference in overall costs between the coronary CTA and FFR groups ($8,582 vs. $8,048; p = 0.550).

Conclusions: In ACP, FFR is feasible, with no difference in major adverse cardiac events and costs compared with coronary CTA alone. Deferral of revascularization is safe with negative FFR, which is associated with higher nonobstructive disease on invasive angiography.
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http://dx.doi.org/10.1016/j.jcmg.2019.05.025DOI Listing
February 2020

Buffering effects of social support for Indigenous males and females living with historical trauma and loss in 2 First Nation communities.

Int J Circumpolar Health 2019 Jan-Dec;78(2):1542931

a Institute for Mental Health Policy Research, Centre for Addiction and Mental Health , London , Ontario , Canada.

Globally, Indigenous mental health research has increasingly focused on strengths-based theory to understand how positive factors influence wellness. However, few studies have examined how social support buffers the effects of trauma and stress on the mental health of Indigenous people. Using survey data from 207 males and 279 females in 2 Ontario First Nations we examined whether social support diminished the negative effects of perceived racism, historical trauma and loss on depression and/or anxiety. Among females, having more social supports was significantly related to a lower likelihood of depression/anxiety, whereas greater perceived racism and historical losses were associated with a greater likelihood of depression/anxiety. For both males and females, childhood adversity was significantly related to a greater likelihood of depression/anxiety. Among females, a significant interaction was found between social support and childhood adversities. For females with low social support, depression/anxiety was significantly higher among those who had experienced childhood adversities versus those with none; however, for those with high level of social support, the association was not significant. The same relationships were not found for males. Possible reasons are that males and females might experience depression/anxiety differently, or the social support measure might not adequately capture social support for First Nations males.
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http://dx.doi.org/10.1080/22423982.2018.1542931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6508050PMC
January 2020

Buffering effects of social support for Indigenous males and females living with historical trauma and loss in 2 First Nation communities.

Int J Circumpolar Health 2019 Jan-Dec;78(2):1542931

a Institute for Mental Health Policy Research, Centre for Addiction and Mental Health , London , Ontario , Canada.

Globally, Indigenous mental health research has increasingly focused on strengths-based theory to understand how positive factors influence wellness. However, few studies have examined how social support buffers the effects of trauma and stress on the mental health of Indigenous people. Using survey data from 207 males and 279 females in 2 Ontario First Nations we examined whether social support diminished the negative effects of perceived racism, historical trauma and loss on depression and/or anxiety. Among females, having more social supports was significantly related to a lower likelihood of depression/anxiety, whereas greater perceived racism and historical losses were associated with a greater likelihood of depression/anxiety. For both males and females, childhood adversity was significantly related to a greater likelihood of depression/anxiety. Among females, a significant interaction was found between social support and childhood adversities. For females with low social support, depression/anxiety was significantly higher among those who had experienced childhood adversities versus those with none; however, for those with high level of social support, the association was not significant. The same relationships were not found for males. Possible reasons are that males and females might experience depression/anxiety differently, or the social support measure might not adequately capture social support for First Nations males.
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http://dx.doi.org/10.1080/22423982.2018.1542931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6508050PMC
January 2020

Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data.

Nat Rev Cancer 2019 05;19(5):289-297

University of Texas Southwestern Medical Center, Dallas, TX, USA.

Small cell lung cancer (SCLC) is an exceptionally lethal malignancy for which more effective therapies are urgently needed. Several lines of evidence, from SCLC primary human tumours, patient-derived xenografts, cancer cell lines and genetically engineered mouse models, appear to be converging on a new model of SCLC subtypes defined by differential expression of four key transcription regulators: achaete-scute homologue 1 (ASCL1; also known as ASH1), neurogenic differentiation factor 1 (NeuroD1), yes-associated protein 1 (YAP1) and POU class 2 homeobox 3 (POU2F3). In this Perspectives article, we review and synthesize these recent lines of evidence and propose a working nomenclature for SCLC subtypes defined by relative expression of these four factors. Defining the unique therapeutic vulnerabilities of these subtypes of SCLC should help to focus and accelerate therapeutic research, leading to rationally targeted approaches that may ultimately improve clinical outcomes for patients with this disease.
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http://dx.doi.org/10.1038/s41568-019-0133-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538259PMC
May 2019

Less Common Gynecologic Malignancies: An Integrative Review.

Semin Oncol Nurs 2019 Apr 11;35(2):175-181. Epub 2019 Mar 11.

Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.

Objective: To review current data on vaginal, vulvar, and fallopian tube cancers, including incidence, diagnosis, staging, risk reduction measures, and management.

Data Sources: A review of retrieved articles dated 2006-2018 from PubMed.

Conclusion: Early diagnosis and treatment of rare gynecologic cancers is dependent on a thorough history and examination. Of particular interest is the role of fallopian tube as the location of primary origin of ovarian and peritoneal cancers as well as the potential for vaccination prevention of vaginal and vulvar cancers.

Implications For Nursing Practice: Nurses in diverse roles should have an understanding of these rare tumor types to support assessment and early identification with their patients.
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http://dx.doi.org/10.1016/j.soncn.2019.02.004DOI Listing
April 2019

Code sets for respiratory symptoms in electronic health records research: a systematic review protocol.

BMJ Open 2019 03 3;9(3):e025965. Epub 2019 Mar 3.

Institute of Health Informatics, University College London, London, UK.

Introduction: Asthma and chronic obstructive pulmonary disease (COPD) are common respiratory conditions, which result in significant morbidity worldwide. These conditions are associated with a range of non-specific symptoms, which in themselves are a target for health research. Such research is increasingly being conducted using electronic health records (EHRs), but computable phenotype definitions, in the form of code sets or code lists, are required to extract structured data from these large routine databases in a systematic and reproducible way. The aim of this protocol is to specify a systematic review to identify code sets for respiratory symptoms in EHRs research.

Methods And Analysis: MEDLINE and Embase databases will be searched using terms relating to EHRs, respiratory symptoms and use of code sets. The search will cover all English-language studies in these databases between January 1990 and December 2017. Two reviewers will independently screen identified studies for inclusion, and key data will be extracted into a uniform table, facilitating cross-comparison of codes used. Disagreements between the reviewers will be adjudicated by a third reviewer. This protocol has been produced in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol guidelines.

Ethics And Dissemination: As a review of previously published studies, no ethical approval is required. The results of this review will be submitted to a peer-reviewed journal for publication and can be used in future research into respiratory symptoms that uses electronic healthcare databases.

Prospero Registration Number: CRD42018100830.
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http://dx.doi.org/10.1136/bmjopen-2018-025965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443061PMC
March 2019

Exploring the Outcomes of Portal Vein Thrombosis in the Clinical Setting of Cirrhosis, Malignancy, and Intra-abdominal Infections with and without Anticoagulation: A Retrospective 5-Year Study.

Int J Angiol 2018 Dec 4;27(4):208-212. Epub 2017 Oct 4.

Department of General Medicine, Tan Tock Seng Hospital, Singapore.

The aim of this study was to understand the differences in clinical outcomes in portal vein thrombosis (PVT) patients with cirrhosis, malignancy, and abdominal infections, with or without anticoagulation. This study was approved by ethics committee. Data were collected from 2011 to 2016. Patients were classified into three groups: PVT with cirrhosis, malignancy, and infections. Primary outcomes measures collected were clot resolution, bleeding, recurrence, and death. Frequency, means, and percentages were calculated. In total, 30 patients were analyzed in this study. Mean age was 60.8 years (range of 30-91 years). There were 19 (63.3%) males and 11 (36.7%) females with ethnicity: 21 (70.0%) Chinese, 2 (6.7%) Malay, 2 (6.7%) Indian, and 5 (16.7%) other race. Fifteen patients received anticoagulation and 15 did not receive anticoagulation. Of the 15 patients who received anticoagulation, there was complete resolution of thrombus in 5 (33.3%), partial resolution in 1 (6.7%), and no resolution in 9 (60.0%). Of these 15 patients, there was bleeding in 3 (20.0%), there was no recurrence in 9 (60.0%), and 3 (20.0%) died during the period of follow-up. Of the 15 patients who did not receive anticoagulation, there was complete resolution of thrombus in 2 (13.3%), partial resolution in 0 (0.0%), and no resolution in 13 (86.7%). Of these 15 patients, there was bleeding in 0 (0%), there was recurrence in 2 (13.3%), and 6 (40.0%) died during the period of follow-up. Anticoagulation is effective in PVT. It reduces mortality with lower rate of recurrence. However, it is associated with increased risk of bleeding.
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http://dx.doi.org/10.1055/s-0037-1607049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221800PMC
December 2018

Author Correction: LSD1 modulates the non-canonical integrin β3 signaling pathway in non-small cell lung carcinoma cells.

Sci Rep 2018 Nov 1;8(1):16452. Epub 2018 Nov 1.

Institute of Pathology, University Hospital of Cologne, 50931, Cologne, Germany.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-018-31451-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210192PMC
November 2018

Colorado Healthy Eating and Active Living Cities and Towns Campaign.

Am J Prev Med 2018 05;54(5 Suppl 2):S145-S149

Community Benefit and Relations, Kaiser Permanente Colorado, Denver, Colorado.

The goal of the Healthy Eating/Active Living (HEAL) Cities and Towns Campaign is to provide municipal leaders with the information, tools, and personalized assistance they need to promote and adopt policies that advance population health. Colorado is composed of 271 cities and towns and has one of the fastest-growing obesity rates in the nation. Colorado's Campaign began in 2012 with a partnership between LiveWell Colorado and the Colorado Municipal League. As a grantee of a regional public health organization, the Campaign Coordinator provides technical assistance to municipal leaders and recognizes cities and towns that adopt varied HEAL policies with four designations: Eager, Active, Fit, and Elite. These designations are based on the total number of policies the municipality currently has and how many they are willing to adopt to move up in status, ranging from Eager (working on one policy) to Elite (at least five policies adopted). Since 2012, there have been 50 Colorado cities and towns that have joined the Campaign reaching more than 2.9 million Colorado residents (more than 50% of the population). Sixteen percent of Colorado's population lives in a city or town with at least five HEAL policies. The purpose of this special article is to describe how the Campaign in Colorado uses tailored technical assistance to help municipalities adopt HEAL-related policies and share some lessons learned for other public health organizations working on similar campaigns.

Supplement Information: This article is part of a supplement entitled Building Thriving Communities Through Comprehensive Community Health Initiatives, which is sponsored by Kaiser Permanente, Community Health.
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http://dx.doi.org/10.1016/j.amepre.2017.11.014DOI Listing
May 2018

Causes of death in long-term survivors of non-small cell lung cancer: A regional Surveillance, Epidemiology, and End Results study.

Ann Thorac Med 2018 Apr-Jun;13(2):76-81

Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University, Detroit, Michigan, USA.

Introduction: Survival from lung cancer is improving. There are limited data on the causes of death in 5-year survivors of lung cancer. The aim of this study is to explore the causes of death in long-term survivors of non-small cell lung cancer (NSCLC) and describe the odds of dying from causes other than lung cancer in this patient population.

Methods: An analysis of 5-year survivors of newly diagnosed NSCLC from 1996 to 2007, in Metropolitan Detroit included in Surveillance, Epidemiology, and End Results program, was done.

Results: Of 23,059 patients identified, 3789 (16.43%) patients were alive at 5-year period (long-term survivors) and 1897 (50.06%) patients died in the later follow-up period (median 88 months; range 1-219 months). The causes of death besides lung cancer were observed in 55.2% of these patients. The most common causes of death were cardiovascular diseases (CVDs) (16%), chronic obstructive pulmonary diseases (11%), and other malignancies (8%). Patients older than 65 years, males, and those who underwent surgery for treatment of lung cancer faced a greater likelihood of death by other causes as compared to lung cancer (OR: 1.45, 95% confidence interval [CI]: 1.18-1.77; OR: 1.24, 95% CI: 1.02-1.51; and OR: 1.39, 95% CI: 1.06-1.82, respectively).

Conclusions: Five-year survivors of NSCLC more commonly die from causes such as CVDs, lung diseases, and other malignancies. Aggressive preventive and therapeutic measures of these diseases may further improve the outcome in this patient population.
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http://dx.doi.org/10.4103/atm.ATM_243_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892092PMC
April 2018

Comparing Treatment Strategies for Stage I Small-cell lung Cancer.

Clin Lung Cancer 2018 09 23;19(5):e559-e565. Epub 2018 Mar 23.

Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.

Introduction: The diagnosis of stage I small-cell lung cancer (SCLC) is increasing in incidence with the advent of low-dose screening computed tomography. Surgery is considered the standard of care but there are very few data to guide clinical decision-making. The purpose of this study was to compare outcomes for patients receiving definitive surgery, stereotactic body radiation therapy (SBRT), or external beam radiation therapy (EBRT) for stage I SCLC.

Patients And Methods: Patients with a primary diagnosis of stage I SCLC were identified in the National Cancer Database. Patients were defined as having a first course of treatment of either surgery, EBRT, or SBRT. Overall survival (OS) was determined using the Kaplan-Meier method and Cox proportional hazards regression methods were used to estimate risk of overall mortality.

Results: A total of 2678 patients were included in the analysis. The 2- and 3-year OS for the whole cohort was 62% and 50%. Comparing treatment strategies in a multivariate model, surgical resection showed improved OS over EBRT (P < .001) and SBRT (P < .001), however, the OS benefit over SBRT did not persist for patients who underwent limited resection. When excluding patients who underwent surgery, SBRT showed improved OS compared with EBRT (P = .04). Additional use of chemotherapy with any treatment modality resulted in improved OS (P < .001).

Conclusion: In this hospital-based registry study, definitive surgical resection and use of chemotherapy resulted in improved survival for patients with early stage SCLC. For patients who are not candidates for surgery, SBRT may offer a survival benefit compared with standard EBRT.
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http://dx.doi.org/10.1016/j.cllc.2018.03.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152878PMC
September 2018

Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors.

Nat Commun 2018 03 13;9(1):1048. Epub 2018 Mar 13.

Genetic Cancer Susceptibility Group, Section of Genetics, International Agency for Research on Cancer (IARC-WHO), Lyon, 69008, France.

Pulmonary large-cell neuroendocrine carcinomas (LCNECs) have similarities with other lung cancers, but their precise relationship has remained unclear. Here we perform a comprehensive genomic (n = 60) and transcriptomic (n = 69) analysis of 75 LCNECs and identify two molecular subgroups: "type I LCNECs" with bi-allelic TP53 and STK11/KEAP1 alterations (37%), and "type II LCNECs" enriched for bi-allelic inactivation of TP53 and RB1 (42%). Despite sharing genomic alterations with adenocarcinomas and squamous cell carcinomas, no transcriptional relationship was found; instead LCNECs form distinct transcriptional subgroups with closest similarity to SCLC. While type I LCNECs and SCLCs exhibit a neuroendocrine profile with ASCL1/DLL3/NOTCH, type II LCNECs bear TP53 and RB1 alterations and differ from most SCLC tumors with reduced neuroendocrine markers, a pattern of ASCL1/DLL3/NOTCH, and an upregulation of immune-related pathways. In conclusion, LCNECs comprise two molecularly defined subgroups, and distinguishing them from SCLC may allow stratified targeted treatment of high-grade neuroendocrine lung tumors.
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http://dx.doi.org/10.1038/s41467-018-03099-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849599PMC
March 2018
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