Incorporation of plasma-based next-generation sequencing to improve guideline-concordant molecular testing in patients with newly diagnosed metastatic nonsquamous non-small cell lung cancer.

14 Background: Current NCCN guidelines recommend comprehensive molecular profiling for all newly diagnosed patients with metastatic non-squamous NSCLC to enable the delivery of personalized medicine. We have previously demonstrated that incorporation of plasma based next-generation gene sequencing (NGS) improves detection of clinically actionable mutations in patients with advanced NSCLC (Aggarwal et al, JAMA Oncology, 2018). To increase rates of comprehensive molecular testing at our institution, we adapted our clinical practice to include concurrent use of plasma (P) and tissue (T) based NGS upon initial diagnosis. P NGS testing was performed using a commercial 74 gene assay. We analyzed the impact of this practice change on guideline concordant molecular testing at our institution. Methods: A retrospective cohort study of patients with newly diagnosed metastatic non-squamous NSCLC following the implementation of this practice change in 12/2018 was performed. Tiers of NCCN guideline concordant testing were defined, Tier 1: complete EGFR, ALK, BRAF, ROS1, MET, RET, NTRK testing, Tier 2: included above, but with incomplete NTRK testing, Tier 3: > 2 genes tested, Tier 4: single gene testing, Tier 5: no testing. Proportion of patients with comprehensive molecular testing by modality (T NGS vs. T+P NGS) were compared using one-sided Fisher’s exact test. Results: Between 01/2019, and 12/2019, 170 patients with newly diagnosed metastatic non-Sq NSCLC were treated at our institution. Overall, 98.2% (167/170) patients underwent molecular testing, Tier 1: n = 100 (59%), Tier 2: n = 39 (23%), Tier 3/4: n = 28 (16.5%), Tier 5: n = 3 (2%). Amongst these patients, 43.1% (72/167) were tested with T NGS alone, 8% (15/167) with P NGS alone, and 47.9% (80/167) with T+P NGS. A higher proportion of patients underwent comprehensive molecular testing (Tiers 1+2) using T+P NGS: 95.7% (79/80) compared to T alone: 62.5% (45/72), p < 0.0005. Prior to the initiation of first line treatment, 72.4% (123/170) patients underwent molecular testing, Tier 1: n = 73 (59%), Tier 2: n = 27 (22%) and Tier 3/4: n = 23 (18%). Amongst these, 39% (48/123) were tested with T NGS alone, 7% (9/123) with P NGS alone and 53.6% (66/123) with T+P NGS. A higher proportion of patients underwent comprehensive molecular testing (Tiers 1+2) using T+P NGS, 100% (66/66) compared to 52% (25/48) with T NGS alone (p < 0.0005). Conclusions: Incorporation of concurrent T+P NGS testing in treatment naïve metastatic non-Sq NSCLC significantly increased the proportion of patients undergoing guideline concordant molecular testing, including prior to initiation of first-line therapy at our institution. Concurrent T+P NGS should be adopted into institutional pathways and routine clinical practice.

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Study protocol for COvid-19 Vascular sERvice (COVER) study: The impact of the COVID-19 pandemic on the provision, practice and outcomes of vascular surgery

10.1101/2020.05.27.20114322 ◽

2020 ◽

Author(s):

Ruth A Benson

Keyword(s):

Vascular Surgery ◽

Service Provision ◽

British Society ◽

Tier 2 ◽

Patient Level ◽

Tier 1 ◽

Ethical Approval ◽

The Uk ◽

Tier 3 ◽

The Impact

ABSTRACTBackgroundThe novel Coronavirus Disease 2019 (COVID-19) pandemic is having a profound impact on global healthcare. Shortages in staff, operating theatre space and intensive care beds has led to a significant reduction in the provision of surgical care. Even vascular surgery, often insulated from resource scarcity due to its status as an urgent specialty, has limited capacity due to the pandemic. Furthermore, many vascular surgical patients are elderly with multiple comorbidities putting them at increased risk of COVID-19 and its complications. There is an urgent need to investigate the impact on patients presenting to vascular surgeons during the COVID-19 pandemic.Methods and AnalysisThe COvid-19 Vascular sERvice (COVER) study has been designed to investigate the worldwide impact of the COVID-19 pandemic on vascular surgery, at both service provision and individual patient level. COVER is running as a collaborative study through the Vascular and Endovascular Research Network (VERN) with the support of numerous national (Vascular Society of Great Britain and Ireland, British Society of Endovascular Therapy, British Society of Interventional Radiology, Rouleaux Club) and an evolving number of international organisations (Vascupedia, SingVasc, Audible Bleeding (USA), Australian and New Zealand Vascular Trials Network (ANZVTN)). The study has 3 ‘Tiers’: Tier 1 is a survey of vascular surgeons to capture longitudinal changes to the provision of vascular services within their hospital; Tier 2 captures data on vascular and endovascular procedures performed during the pandemic; and Tier 3 will capture any deviations to patient management strategies from prepandemic best practice. Data submission and collection will be electronic using online survey tools (Tier 1: SurveyMonkey® for service provision data) and encrypted data capture forms (Tiers 2 and 3: REDCap® for patient level data). Tier 1 data will undergo real-time serial analysis to determine longitudinal changes in practice, with country-specific analyses also performed. The analysis of Tier 2 and Tier 3 data will occur on completion of the study as per the prespecified statistical analysis plan.Ethical ApprovalEthical approval from the UK Health Research Authority has been obtained for Tiers 2 and 3 (20/NW/0196 Liverpool Central). Participating centres in the UK will be required to seek local research and development approval. Non-UK centres will need to obtain a research ethics committee or institutional review board approvals in accordance with national and/or local requirements.ISRCTN: 80453162 (https://doi.org/10.1186/ISRCTN80453162)Ethical Approval: 20/NW/0196 Liverpool Central, IRAS: 282224

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Study protocol for COvid-19 Vascular sERvice (COVER) study: The impact of the COVID-19 pandemic on the provision, practice and outcomes of vascular surgery

PLoS ONE ◽

10.1371/journal.pone.0243299 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0243299

Author(s):

Ruth A. Benson ◽

Sandip Nandhra ◽

Keyword(s):

Vascular Surgery ◽

Service Provision ◽

Resource Scarcity ◽

Research Network ◽

Tier 2 ◽

Longitudinal Changes ◽

Patient Level ◽

Tier 1 ◽

Tier 3 ◽

The Impact

Background The novel Coronavirus Disease 2019 (COVID-19) pandemic is having a profound impact on global healthcare. Shortages in staff, operating theatre space and intensive care beds has led to a significant reduction in the provision of surgical care. Even vascular surgery, often insulated from resource scarcity due to its status as an urgent specialty, has limited capacity due to the pandemic. Furthermore, many vascular surgical patients are elderly with multiple comorbidities putting them at increased risk of COVID-19 and its complications. There is an urgent need to investigate the impact on patients presenting to vascular surgeons during the COVID-19 pandemic. Methods and analysis The COvid-19 Vascular sERvice (COVER) study has been designed to investigate the worldwide impact of the COVID-19 pandemic on vascular surgery, at both service provision and individual patient level. COVER is running as a collaborative study through the Vascular and Endovascular Research Network (VERN), an independent, international vascular research collaborative with the support of numerous national and international organisations). The study has 3 ‘Tiers’: Tier 1 is a survey of vascular surgeons to capture longitudinal changes to the provision of vascular services within their hospital; Tier 2 captures data on vascular and endovascular procedures performed during the pandemic; and Tier 3 will capture any deviations to patient management strategies from pre-pandemic best practice. Data submission and collection will be electronic using online survey tools (Tier 1: SurveyMonkey® for service provision data) and encrypted data capture forms (Tiers 2 and 3: REDCap® for patient level data). Tier 1 data will undergo real-time serial analysis to determine longitudinal changes in practice, with country-specific analyses also performed. The analysis of Tier 2 and Tier 3 data will occur on completion of the study as per the pre-specified statistical analysis plan.

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ESMO Management and treatment adapted recommendations in the COVID-19 era: Lung cancer

ESMO Open ◽

10.1136/esmoopen-2020-000820 ◽

2020 ◽

Vol 5 (Suppl 3) ◽

pp. e000820 ◽

Cited By ~ 13

Author(s):

Antonio Passaro ◽

Alfredo Addeo ◽

Christophe Von Garnier ◽

Fiona Blackhall ◽

David Planchard ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Care ◽

Negative Impact ◽

Well Being ◽

Tier 2 ◽

Optimal Care ◽

Tier 1 ◽

Global Spread ◽

Tier 3 ◽

The Impact

The COVID-19 pandemic, characterised by a fast and global spread during the first months of 2020, has prompted the development of a structured set of recommendations for cancer care management, to maintain the highest possible standards. Within this framework, it is crucial to ensure no disruption to essential oncological services and guarantee the optimal care.This is a structured proposal for the management of lung cancer, comprising three levels of priorities, namely: tier 1 (high priority), tier 2 (medium priority) and tier 3 (low priority)—defined according to the criteria of the Cancer Care Ontario, Huntsman Cancer Institute and Magnitude of Clinical Benefit Scale.The manuscript emphasises the impact of the COVID-19 pandemic on lung cancer care and reconsiders all steps from diagnosis, staging and treatment.These recommendations should, therefore, serve as guidance for prioritising the different aspects of cancer care to mitigate the possible negative impact of the COVID-19 pandemic on the management of our patients.As the situation is rapidly evolving, practical actions are required to guarantee the best patients’ treatment while protecting and respecting their rights, safety and well-being. In this environment, cancer practitioners have great responsibilities: provide timely, appropriate, compassionate and justified cancer care, while protecting themselves and their patients from being infected with COVID-19. In case of shortages, resources must be distributed fairly. Consequently, the following recommendations can be applied with significant nuances, depending on the time and location for their use, considering variable constraints imposed to the health systems. An exceptional flexibility is required from cancer caregivers.

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Optimal Timing for Launching Installation of Tier 2 and 3 Systems of School-Wide Positive Behavioral Interventions and Supports

Journal of Positive Behavior Interventions ◽

10.1177/1098300721996084 ◽

2021 ◽

pp. 109830072199608

Author(s):

Angus Kittelman ◽

Sterett H. Mercer ◽

Kent McIntosh ◽

Robert Hoselton

Keyword(s):

Longitudinal Study ◽

Behavioral Interventions ◽

Structural Equation ◽

Equation Modeling ◽

Optimal Timing ◽

First Year ◽

Tier 2 ◽

Positive Behavioral Interventions ◽

Tier 1 ◽

Tier 3

The purpose of this longitudinal study was to examine patterns in implementation of Tier 2 and 3 school-wide positive behavioral interventions and supports (SWPBIS) systems to identify timings of installation that led to higher implementation of advanced tiers. Extant data from 776 schools in 27 states reporting on the first 3 years of Tier 2 implementation and 359 schools in 23 states reporting on the first year of Tier 3 implementation were analyzed. Using structural equation modeling, we found that higher Tier 1 implementation predicted subsequent Tier 2 and Tier 3 implementation. In addition, waiting 2 or 3 years after initial Tier 1 implementation to launch Tier 2 systems predicted higher initial Tier 2 implementation (compared with implementing the next year). Finally, we found that launching Tier 3 systems after Tier 2 systems, compared with launching both tiers simultaneously, predicted higher Tier 2 implementation in the second and third year, so long as Tier 3 systems were launched within 3 years of Tier 2 systems. These findings provide empirical guidance for when to launch Tier 2 and 3 systems; however, we emphasize that delays in launching advanced systems should not equate to delays in more intensive supports for students.

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Global Inland Capture and Culture Finfisheries Follow Different Trends When Evaluated by the Human Development Index

Sustainability ◽

10.3390/su13158420 ◽

2021 ◽

Vol 13 (15) ◽

pp. 8420

Author(s):

Peter W. Sorensen ◽

Maria Lourdes D. Palomares

Keyword(s):

Socioeconomic Factors ◽

Human Development ◽

Human Development Index ◽

Developed Countries ◽

Global Scale ◽

Tier 2 ◽

Development Index ◽

Tier 1 ◽

Catch Reconstruction ◽

Tier 3

To assess whether and how socioeconomic factors might be influencing global freshwater finfisheries, inland fishery data reported to the FAO between 1950 and 2015 were grouped by capture and culture, country human development index, plotted, and compared. We found that while capture inland finfishes have greatly increased on a global scale, this trend is being driven almost entirely by poorly developed (Tier-3) countries which also identify only 17% of their catch. In contrast, capture finfisheries have recently plateaued in moderately-developed (Tier-2) countries which are also identifying 16% of their catch but are dominated by a single country, China. In contrast, reported capture finfisheries are declining in well-developed (Tier-1) countries which identify nearly all (78%) of their fishes. Simultaneously, aquacultural activity has been increasing rapidly in both Tier-2 and Tier-3 countries, but only slowly in Tier-1 countries; remarkably, nearly all cultured species are being identified by all tier groups. These distinctly different trends suggest that socioeconomic factors influence how countries report and conduct capture finfisheries. Reported rapid increases in capture fisheries are worrisome in poorly developed countries because they cannot be explained and thus these fisheries cannot be managed meaningfully even though they depend on them for food. Our descriptive, proof-of-concept study suggests that socioeconomic factors should be considered in future, more sophisticated efforts to understand global freshwater fisheries which might include catch reconstruction.

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Initial Experience in Predicting the Risk of Hospitalization of 496 Outpatients with COVID-19 Using a Telemedicine Risk Assessment Tool

10.1101/2020.07.21.20159384 ◽

2020 ◽

Cited By ~ 1

Author(s):

James B O'Keefe ◽

Elizabeth J Tong ◽

Thomas H Taylor ◽

Ghazala D Datoo O'Keefe ◽

David C Tong

Keyword(s):

Risk Assessment ◽

Assessment Tool ◽

Cox Regression ◽

Risk Assessment Tool ◽

Individual Risk ◽

Tier 2 ◽

Tier 1 ◽

Risk Patients ◽

Tier 3

Objective: To determine whether a risk prediction tool developed and implemented in March 2020 accurately predicts subsequent hospitalizations. Design: Retrospective cohort study, enrollment from March 24 to May 26, 2020 with follow-up calls until hospitalization or clinical improvement (final calls until June 19, 2020) Setting: Single center telemedicine program managing outpatients from a large medical system in Atlanta, Georgia Participants: 496 patients with laboratory-confirmed COVID-19 in isolation at home. Exclusion criteria included: (1) hospitalization prior to telemedicine program enrollment, (2) immediate discharge with no follow-up calls due to resolution. Exposure: Acute COVID-19 illness Main Outcome and Measures: Hospitalization was the outcome. Days to hospitalization was the metric. Survival analysis using Cox regression was used to determine factors associated with hospitalization. Results: The risk-assessment rubric assigned 496 outpatients to risk tiers as follows: Tier 1, 237 (47.8%); Tier 2, 185 (37.3%); Tier 3, 74 (14.9%). Subsequent hospitalizations numbered 3 (1%), 15 (7%), and 17 (23%) and for Tiers 1-3, respectively. From a Cox regression model with age ≥ 60, gender, and self-reported obesity as covariates, the adjusted hazard ratios using Tier 1 as reference were: Tier 2 HR=3.74 (95% CI, 1.06-13.27; P=0.041); Tier 3 HR=10.87 (95% CI, 3.09-38.27; P<0.001). Tier was the strongest predictor of time to hospitalization. Conclusions and Relevance: A telemedicine risk assessment tool prospectively applied to an outpatient population with COVID-19 identified both low-risk and high-risk patients with better performance than individual risk factors alone. This approach may be appropriate for optimum allocation of resources.

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The Impact of Clonal Hematopoiesis of Indeterminate Potential on Survival in Patients with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽

10.1182/blood-2018-99-116240 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4359-4359

Author(s):

Koji Sasaki ◽

Rashmi Kanagal-Shamanna ◽

Guillermo Montalban-Bravo ◽

Rita Assi ◽

Kiran Naqvi ◽

...

Keyword(s):

Next Generation Sequencing ◽

Myeloid Leukemia ◽

Research Funding ◽

Newly Diagnosed ◽

Next Generation ◽

Risk Of Death ◽

Genetics Research ◽

The Impact ◽

Generation Sequencing

Abstract Introduction: Clearance of detected somatic mutations at complete response by next-generation sequencing is a prognostic marker for survival in patients with acute myeloid leukemia (AML). However, the impact of allelic burden and persistence of clonal hematopoiesis of indeterminate potential (CHIP)-associated mutations on survival remains unclear. The aim of this study is to evaluate the prognostic impact of allelic burden of CHIP mutations at diagnosis, and their persistence within 6 months of therapy. Methods: From February 1, 2012 to May 26, 2016, we reviewed 562 patients with newly diagnosed AML. Next-generation sequencing was performed on the bone marrow samples to detect the presence of CHIP-associated mutations defined as DNMT3A, TET2, ASXL1, JAK2 and TP53. Overall survival (OS) was defined as time period from the diagnosis of AML to the date of last follow-up or death. Univariate (UVA) and multivariate Cox proportional hazard regression (MVA) were performed to identify prognostic factors for OS with p value cutoff of 0.020 for the selection of variables for MVA. Landmark analysis at 6 months was performed for the evaluation of the impact of clearance of CHIP, FLT3-ITD, FLT3D835, and NPM1 mutations. Results: We identified 378 patients (74%) with AML with CHIP mutations; 134 patients (26%) with AML without CHIP mutations. The overall median follow-up of 23 months (range, 0.1-49.0). The median age at diagnosis was 70 years (range, 17-92) and 66 years (range, 20-87) in CHIP AML and non-CHIP AML, respectively (p =0.001). Of 371 patients and 127 patients evaluable for cytogenetic in CHIP AML and non-CHIP AML, 124 (33%) and 25 patients (20%) had complex karyotype, respectively (p= 0.004). Of 378 patients with CHIP AML, 183 patients (48%) had TET2 mutations; 113 (30%), TP53; 110 (29%), ASXL1; 109 (29%), DNMT3A; JAK2, 46 (12%). Of 378 patients, single CHIP mutations was observed in 225 patients (60%); double, 33 (9%); triple, 28 (7%); quadruple, 1 (0%). Concurrent FLT3-ITD mutations was detected in 47 patients (13%) and 12 patients (9%) in CHIP AML and non-CHIP AML, respectively (p= 0.287); FLT3-D835, 22 (6%) and 8 (6%), respectively (p= 0.932); NPM1 mutations, 62 (17%) and 13 (10%), respectively (p= 0.057). Of 183 patients with TET2-mutated AML, the median TET2 variant allele frequency (VAF) was 42.9% (range, 2.26-95.32); of 113 with TP53-mutated AML, the median TP53 VAF, 45.9% (range, 1.15-93.74); of 109 with ASXL1-mutated AML, the median ASXL1 VAF was 34.5% (range, 1.17-58.62); of 109 with DNMT3A-mutated AML, the median DNMT3A VAF was 41.8% (range, 1.02-91.66); of 46 with JAK2-mutated AML, the median JAK2 VAF was 54.4% (range, 1.49-98.52). Overall, the median OS was 12 months and 11 months in CHIP AML and non-CHIP AML, respectively (p= 0.564); 16 months and 5 months in TET2-mutated AML and non-TET2-mutated AML, respectively (p <0.001); 4 months and 13 months in TP53-mutated and non-TP53-mutated AML, respectively (p< 0.001); 17 months and 11 months in DNMT3A-mutated and non-DNMT3A-mutated AML, respectively (p= 0.072); 16 months and 11 months in ASXL1-mutated AML and non-ASXL1-mutated AML, respectively (p= 0.067); 11 months and 12 months in JAK2-murated and non-JAK2-mutated AML, respectively (p= 0.123). The presence and number of CHIP mutations were not a prognostic factor for OS by univariate analysis (p=0.565; hazard ratio [HR], 0.929; 95% confidence interval [CI], 0.722-1.194: p= 0.408; hazard ratio, 1.058; 95% confidence interval, 0.926-1.208, respectively). MVA Cox regression identified age (p< 0.001; HR, 1.036; 95% CI, 1.024-1.048), TP53 VAF (p= 0.007; HR, 1.009; 95% CI, 1.002-1.016), NPM1 VAF (p=0.006; HR, 0.980; 95% CI, 0.967-0.994), and complex karyotype (p<0.001; HR, 1.869; 95% CI, 1.332-2.622) as independent prognostic factors for OS. Of 33 patients with CHIP AML who were evaluated for the clearance of VAF by next generation sequencing , landmark analysis at 6 months showed median OS of not reached and 20.3 months in patients with and without CHIP-mutation clearance, respectively (p=0.310). Conclusion: The VAF of TP53 and NPM1 mutations by next generation sequencing can further stratify patients with newly diagnosed AML. Approximately, each increment of TP53 and NPM1 VAF by 1% is independently associated with 1% higher risk of death, and 2% lower risk of death, respectively. The presence of CHIP mutations except TP53 does not affect outcome. Disclosures Sasaki: Otsuka Pharmaceutical: Honoraria. Short:Takeda Oncology: Consultancy. Ravandi:Macrogenix: Honoraria, Research Funding; Seattle Genetics: Research Funding; Sunesis: Honoraria; Xencor: Research Funding; Jazz: Honoraria; Seattle Genetics: Research Funding; Abbvie: Research Funding; Macrogenix: Honoraria, Research Funding; Bristol-Myers Squibb: Research Funding; Orsenix: Honoraria; Abbvie: Research Funding; Jazz: Honoraria; Xencor: Research Funding; Orsenix: Honoraria; Sunesis: Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Astellas Pharmaceuticals: Consultancy, Honoraria. Kadia:BMS: Research Funding; Abbvie: Consultancy; Takeda: Consultancy; Jazz: Consultancy, Research Funding; Takeda: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Research Funding; Novartis: Consultancy; Amgen: Consultancy, Research Funding; BMS: Research Funding; Jazz: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy; Abbvie: Consultancy; Celgene: Research Funding. DiNardo:Karyopharm: Honoraria; Agios: Consultancy; Celgene: Honoraria; Medimmune: Honoraria; Bayer: Honoraria; Abbvie: Honoraria. Cortes:Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Arog: Research Funding.

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SFBT Within the Tier 2 Framework

10.1093/acprof:oso/9780190607258.003.0005 ◽

2017 ◽

Author(s):

Michael S. Kelly ◽

Johnny S. Kim ◽

Cynthia Franklin

Keyword(s):

Classroom Climate ◽

Tier 2 ◽

Social Emotional ◽

Prevention Services ◽

Coaching Intervention ◽

Tier 1 ◽

American Schools ◽

Tier 2 Intervention ◽

Tier 3 ◽

Teacher Coaching

The educational policy changes of the past 20 years have increased the focus on the provision of prevention services within schools, both for individual students and for social-emotional programming delivered in their classroom. Whether characterized as Response to Intervention (RTI), Positive Behavior Intervention and Supports (PBIS), or Multi-Tiered Systems of Supports (MTSS), the focus on a 3-tier framework of universal (Tier 1), selective (Tier 2) and indicated (Tier 3) has become one of the largest evidence-based framework ever scaled up within American schools, with over 19,000 schools across all 50 states having implemented PBIS by this writing. This chapter focuses on an example of a SFBT Tier 2 intervention, the Working on What Works (WOWW) teacher coaching intervention, that strives to create a better classroom climate for teachers and their students.

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Quantifying the Benefits of a Solar Home System-Based DC Microgrid for Rural Electrification

Energies ◽

10.3390/en12050938 ◽

2019 ◽

Vol 12 (5) ◽

pp. 938 ◽

Cited By ~ 4

Author(s):

Nishant Narayan ◽

Ali Chamseddine ◽

Victor Vega-Garita ◽

Zian Qin ◽

Jelena Popovic-Gerber ◽

...

Keyword(s):

Energy Deficit ◽

Rural Electrification ◽

Tier 2 ◽

Dc Microgrid ◽

Dc Microgrids ◽

Solar Home System ◽

Tier 3 ◽

Electricity Access ◽

The Impact ◽

Adequate Power

Off-grid solar home systems (SHSs) currently constitute a major source of providing basic electricity needs in un(der)-electrified regions of the world, with around 73 million households having benefited from off-grid solar solutions by 2017. However, in and of itself, state-of-the-art SHSs can only provide electricity access with adequate power supply availability up to tier 2, and to some extent, tier 3 levels of the Multi-tier Framework (MTF) for measuring household electricity access. When considering system metrics of loss of load probability (LLP) and battery size, meeting the electricity needs of tiers 4 and 5 is untenable through SHSs alone. Alternatively, a bottom-up microgrid composed of interconnected SHSs is proposed. Such an approach can enable the so-called climb up the rural electrification ladder. The impact of the microgrid size on the system metrics like LLP and energy deficit is evaluated. Finally, it is found that the interconnected SHS-based microgrid can provide more than 40% and 30% gains in battery sizing for the same LLP level as compared to the standalone SHSs sizes for tiers 4 and 5 of the MTF, respectively, thus quantifying the definite gains of an SHS-based microgrid over standalone SHSs. This study paves the way for visualizing SHS-based rural DC microgrids that can not only enable electricity access to the higher tiers of the MTF with lower battery storage needs but also make use of existing SHS infrastructure, thus enabling a technologically easy climb up the rural electrification ladder.

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HSR19-085: A Real World Observational Assessment of the Impact of Immunotherapy on the Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2018.7202 ◽

2019 ◽

Vol 17 (3.5) ◽

pp. HSR19-085

Author(s):

Belqis El Ferjani ◽

Sheenu Chandwani ◽

Meita Hirschmann ◽

Seydeh Dibaj ◽

Emily Roarty ◽

...

Keyword(s):

Clinical Practice ◽

Real World ◽

Performance Status ◽

Single Agent ◽

Small Cell ◽

Cancer Center ◽

Small Cell Lung ◽

First Line ◽

Treatment Choices ◽

The Impact

Background: NSCLC is the leading cause of cancer-related mortality worldwide. Recently reported clinical trials have firmly established the role of PD-1 and PD-L1 inhibitors in the treatment of patients (pts) with metastatic NSCLC (mNSCLC). We have established the prospective, observational, real-world Advanced Non-Small Cell Lung Holistic Registry (ANCHoR) to understand how the advent of immunotherapy impacts treatment choices and clinical outcomes. Objectives: The aim of this analysis is to measure the impact of immunotherapy on the treatment choice for the first-line treatment of mNSCLC and to determine the link between PD-L1 expression and the treatment choices made in routine clinical practice at the MD Anderson Cancer Center (MDA). Methods: From May 1, 2017, to June 30, 2018, English-speaking pts with mNSCLC at MDA who provided written informed consent were enrolled in ANCHoR and longitudinally followed. The PD-L1 testing rates were captured and the treatment decisions made were also captured and tabulated. The time of data cutoff for this study is June 30, 2018. Results: Of the 296 pts enrolled in the registry at the time of data cutoff, there were 49.7% males, 82.1% white, 45.9% ≥65 years old, 69.3% smokers, 83.1% with an initial stage IV diagnosis, 87.2% with nonsquamous histology, 36.1% with bone metastasis, 29.4% with brain metastasis, 43.2% with 0–1 performance status, and 21.6% with a known EGFR or ALK mutation. A total of 233 pts had been tested for PD-L1 (78.7%). Predominant reasons for not testing (63 pts) include not having available tissue (26 pts) or the test was not requested by the physician (31 pts). As of June 30, 2018, 38.5% of patients received immunotherapy as first-line therapy either as a single agent (18.9%, 56 pts) or in combination with chemotherapy (19.6%, 58 pts). Only 35.8% of the patients received platinum doublet chemotherapy alone. Two pts received chemotherapy combined with an anti-angiogenesis agent (0.68%). Targeted therapy was utilized either as a single agent (20.6%) or in combination with immunotherapy (2.4%). Conclusion: Immunotherapy is now utilized as a single agent or in combination in more than one-third of patients with mNSCLC. These numbers are expected to increase as data from recently reported studies get incorporated into common clinical practice. Compared to historic experience, there has been a dramatic decline in the use of chemotherapy with an anti-angiogenesis agent.

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