Early Testing Research Articles

Costs of colorectal cancer screening with colonoscopy, including post-endoscopy events, among adults with Medicaid insurance

Objective To examine the healthcare utilization and costs associated with colorectal cancer (CRC) screening by colonoscopy, including costs associated with post-endoscopy events, among average-risk adults covered by Medicaid insurance. Methods This cohort study evaluated a population of adults (ages 50–75 years) with CRC screening between 1/1/2014 and 12/31/2018 (index = earliest test) from the IBM MarketScan Multi-State Medicaid database. Individuals at above-average risk for CRC or with prior CRC screening were excluded. CRC screening was reported by screening type: colonoscopy, fecal immunochemical test [FIT], fecal occult blood test [FOBT], multi-target stool DNA [mt-sDNA]. Frequency and costs of events potentially related to colonoscopy (defined as occurring within 30 days post-endoscopy) were reported overall, by event type, and by individual event. Results We identified a total of 13,134 average-risk adults covered by Medicaid insurance who received screening by colonoscopy; 63.6% (8350) had Medicare dual-eligibility while 36.4% (4785) did not have Medicare dual-eligibility. The mean (SD) cost of a colonoscopy procedure was $684 ($907) and mean (SD) out-of-pocket costs were $6 ($132). Serious gastrointestinal (GI) events (perforation and bleeding) were observed in 4.6% of individuals with colonoscopy, 4.3% had other GI events, and 3.0% had an incident cardiovascular/cerebrovascular event. Mean (SD) event-related costs were $1233 ($5784) among individuals with a serious GI event, $747 ($1961) among individuals with other GI events, and $4398 ($19,369) among individuals with a cardiovascular/cerebrovascular event. Conclusions This large, claims-based cohort study reports average (SD) out-of-pocket costs for Medicaid beneficiaries at $6 ($132), which could be one factor contributing to the accessibility of CRC screening by colonoscopy. The incidence of events potentially associated with colonoscopy (i.e. within 30 days after the screening) was 3–4%, and the event-related costs were considerable.

Overview of Nuclear Piping Seismic Verification

Abstract Nuclear power has gone through several transitional phases worldwide with early development, design, and construction in 1960s,1970s, and 1980s, particularly in Japan and US. There were some major research programs conducted during those years to develop methodology and prove the technology. Much of this knowledge is still very relevant and applicable and would be useful to young engineers and new professional coming to the nuclear industry. One of such programs is seismic verification of major structures, systems, and components (SSCs) by tests in Japan during the period of 1981 through 2004 at a large shaking table facility. Opportunities for conducting such large tests are not likely in the current environment of the industry and, therefore, one of the objectives of this paper is to summarize some earlier tests to raise awareness for the newcomers to the industry. This paper discusses on Seismic verification tests of PWR and BWR Primary Loop, Main Steam and Feed Water line, Ultimate Strength of Piping and eroded piping , conducted in Japan. In particular, this paper focuses on: insights obtained from the test results; comparisons of test results with responses during actual earthquakes; collaboration of Japan and US in these tests; observations on robustness of Japanese seismic design; how the results relate to current issues; and use of these results from the future perspectives.

Healthcare costs of colorectal cancer screening and events following colonoscopy among commercially insured average-risk adults in the United States

Objective To examine the healthcare costs associated with colorectal cancer (CRC) screening and the frequency and costs of events potentially related to colonoscopy among average-risk adults. Methods In this cohort study, adults (ages 50–75 years) with CRC screening between 1/1/2014 and 6/30/2019 (index = earliest test) were selected from the IBM MarketScan Research databases. Individuals at above-average risk for CRC or with prior CRC screening were excluded. Frequency of utilization was reported by screening type: colonoscopy, fecal immunochemical test (FIT), fecal occult blood test (FOBT), multi-target stool DNA (mt-sDNA). For colonoscopy, frequency and costs of potential events were reported overall, by event type, and by an individual event in the 30 days after colonoscopy. Results Among the 333,306 average-risk adults, colonoscopy was the most common CRC screening modality (70.6%), followed by FIT (17.7%), FOBT (8.1%), and mt-sDNA (3.2%). The mean cost of a colonoscopy procedure was $2,125 and the mean out-of-pocket costs were $79. Serious gastrointestinal (GI) events were observed in 1.3% of individuals with colonoscopy, 1.9% had other GI events, and 1.2% had an incident cardiovascular event. Mean event-related costs were $2,631 among individuals with a serious GI event, $1,774 among individuals with any other GI event, and $4,234 among individuals with a cardiovascular event. Conclusions This study provides updated and more detailed information regarding the costs of CRC screening and potential colonoscopy events based on a comprehensive review of a robust claims dataset.

Evaluating the Efficacy of a Screening Protocol for Severe Acute Respiratory Syndrome Coronavirus 2 Virus in Asymptomatic Preoperative/Preprocedural Patients at a Military Hospital.

ABSTRACTIntroductionFacing the COVID-19 pandemic, many hospitals implemented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening protocols before aerosol-generating procedures (AGPs) in an effort to protect patients and health care workers. Given the limited prior evidence on the effectiveness of such protocols, we report the process improvement experience at a military treatment facility.Materials and MethodsWe evaluated the outcomes of patients undergoing AGPs from March to September 2020, divided into three cohorts: a preprotocol (PP) cohort who did not receive screening, an early testing (ET) cohort representing the early months of the screening protocol, and a late testing (LT) cohort managed under adaptive modifications to the screening protocol. We recorded identifiable post-procedure COVID-19 diagnoses. The study was approved as a process improvement protocol and was determined not to meet criteria for human subject research through an institutional approval process.ResultsAcross the three cohorts, 4520 procedures were performed: 422 PP, 1297 ET, and 2801 LT. Among 4098 procedures in the ET and LT cohorts, 12 asymptomatic patients tested positive for SARS-CoV-2 (0.29% positivity rate). One left the health system before completing the procedure and another proceeded urgently under COVID precautions, while 10 were rescheduled and completed at a later date; 7 were cleared using a test-based strategy, while 3 were cleared using a time-based strategy. Of 445 patients who had SARS-CoV-2 tests performed within 30 days following their procedures, three patients with negative preoperative tests had a positive test within 30 days, all in the LT cohort but had evidence of acquiring the infection after the procedure or had a false-positive test.ConclusionsOur strategy of preprocedural SARS-CoV-2 testing successfully identified asymptomatic infected patients before surgery. Care was delayed for most of these patients without apparent detriment. Adaptation to a time-based strategy for clearance might reduce such delays, but other considerations may still influence how soon procedures should be completed after a positive test.

ARDL as an Elixir Approach to Cure for Spurious Regression in Nonstationary Time Series

In conventional Econometrics, the unit root and cointegration analysis are the only ways to circumvent the spurious regression which may arise from missing variable (lag values) rather than the nonstationarity process in time series data. We propose the Ghouse equation solution of autoregressive distributed lag mechanism which does not require additional work in unit root testing and bound testing. This advantage makes the proposed methodology more efficient compared to the existing cointegration procedures. The earlier tests weaken their position in comparison to it, as they had numerous linked testing procedures which further increase the size of the test and/or reduce the test power. The simplification of the Ghouse equation does not attain any such type of error, which makes it a more powerful test as compared to widely cited exiting testing methods in econometrics and statistics literature.

Overview of Inception and Viability of Genetic Amniocentesis

Clinical procedures that took both time and effort in terms of prior diagnosis are being aided by technology and significant advancements in recognizing and predicting outcomes long before they actually take place. The aim of prenatal diagnosis is to detect fetal structural and genetic abnormalities. That is why it is possible to talk in the unborn fetus about preventing and detecting inherited and congenital illnesses. The most comprehensive and intrinsic makeup shared by all and therefore a vital subject to comparative analysis even before birth is the unmistakable nucleotide sequence that directs all physical and chemical changes. Amniocentesis involves taking out a small sample of amniotic fluid from the sac surrounding the fetus and analysis of its composition, so in essence genetic amniocentesis refers to examination of genetic abnormalities that might be prevalent in the developing fetus This permits taking decisions concerning about the progress of pregnancy to be made before viability. Comparatively less commonly, amniocentesis is performed in the beginning of third trimester instead of earlier testing. Advanced genomic study technologies such as Chromosomal Microarray Analysis (CMA) provide much more accurate and detailed information about the fetus. The ideal site for amniocentesis for localization should be determined by an ultrasound scan but in the absence of this facility, a site may be selected after careful palpation of the gravid uterus. Trisomy, Micro deletions/ micro substitutions can be detected by genetic amniocentesis. Fluorescence in Situ Hybridization is a dependable and brief technique for identifying maximum chromosomal variations and has now been carried out as a routine symptomatic strategy for the discovery of fetal irregularities.

A-153 Neuropsychological Effects Assessed Using WISC-IV and WISC-V

Abstract Objective This review explores The Weschler Intelligence Scale for Children – Fourth Edition (WISC-IV) and the Weschler Intelligence Scale for Children – Fifth Edition (WISC-V) administered to children with various medical histories including traumatic brain injury, vascular conditions, brain tumor, epilepsy, strokes, sickle cell disease, down syndrome, and neurotoxicity on neurodevelopment. This review aims to explore neuropsychological effects of these medical conditions derived from final scores and scale comparisons. Data Selection Peer-reviewed studies between 2000 and 2020 were gathered from EBSCO, Google Scholar, and Science Direct. Criteria was limited to neurological conditions present in children, who were required to be assessed using either WISC-IV or WISC-V. Children with other developmental or learning disabilities were excluded. Data on Weschler Adult Intelligence Scale (WAIS) were excluded along with any other assessment administered to children. Thirteen articles were included based on the criteria along with two articles that discuss the validity of WISC. Data Synthesis The components of the WISC-IV or WISC-V demonstrated low average or below average scores on many scales, especially overall FSIQ. The largest impairments were present in Processing Speed Index, Verbal Comprehension Index, Working Memory Index, Visual Spatial Index, and overall FSIQ. All children assessed with preexisting neurological conditions demonstrated deficits in neuropsychological domains. The severity of the neurological condition significantly impacted scores when compared to children with no conditions. Conclusions The administration of WISC-IV and WISC-V demonstrated neuropsychological and functioning impairments in children with preexisting neurological conditions. The assessment successfully identified deficit areas and earlier testing can encourage earlier treatments.

Mechanical properties and microstructure of directionally solidified Fe-4.25%C eutectic alloy

An analysis of mechanical properties of directionally solidified Fe-4.25%C eutectic alloy and its microstructure and fracture mechanisms is presented. Tests were conducted for macro-samples made with different growth rates. Strength tests were performed with the use of micro-samples taken from different cross-sections of macro-samples. Fe-4.25%C eutectic alloy finds application mainly in construction of structures exposed to abrasion under significant compression loads. As specified by the metastable phase diagram, Fe–Fe3C, the white eutectic or austenitic (γ) iron carbide Fe3C can be formed. The type of obtained morphology depends mostly on the temperature gradient G, the chemical composition, and growth rate, which has a substantial impact on the morphology of the γ-Fe3C eutectic. As earlier tests have proven, interphase spacing λ decreases as grow rate v increases, which improves fine-graining of the alloy. We show that directional solidification with controlled growth rate improves mechanical properties of the Fe-4.25%C eutectic alloy, enabling its use as a structural element in a significantly expanded range of applications.

Reply to comment on Peto et al. (2020): Weekly COVID-19 testing with household quarantine and contact tracing is feasible and would probably end the epidemic.

Open AccessMoreSectionsView PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail Cite this article Peto Julian 2021Reply to comment on Peto et al. (2020): Weekly COVID-19 testing with household quarantine and contact tracing is feasible and would probably end the epidemicR. Soc. open sci.8210467210467http://doi.org/10.1098/rsos.210467SectionSupplemental MaterialOpen AccessInvited replyReply to comment on Peto et al. (2020): Weekly COVID-19 testing with household quarantine and contact tracing is feasible and would probably end the epidemic Julian Peto Julian Peto http://orcid.org/0000-0002-1685-8912 London School of Hygiene and Tropical Medicine, London, UK [email protected] Google Scholar Find this author on PubMed Search for more papers by this author Julian Peto Julian Peto http://orcid.org/0000-0002-1685-8912 London School of Hygiene and Tropical Medicine, London, UK [email protected] Google Scholar Find this author on PubMed Search for more papers by this author Published:23 June 2021https://doi.org/10.1098/rsos.210467 Review history Reply to comment on Peto et al. (2020): Weekly COVID-19 testing with household quarantine and contact tracing is feasible and would probably end the epidemic An epidemic model is a hypothesis, not an observation. Few scientists would question our statement that the impact of ‘the combination of weekly SARS-CoV-2 testing with an earlier test if symptoms appear, strict household quarantine and contact tracing … cannot be reliably predicted by further modelling’ [1, p. 3]; yet Planck and colleagues [2] claim that their simple model shows that mass weekly testing and household quarantine, even if it were perfectly achievable, would not be sufficient to control the spread of COVID-19. This is contradicted by the transient reversal of rising prevalence in Slovakia after two rounds of weekly national testing and household quarantine. Prevalence fell by 58% within a week, and a microsimulation calibrated to the observed results confirms that quarantining the whole household following a positive test made a dominant contribution, with an estimated weekly reduction in the prevalence of 59% with and only 10% without household quarantine [3]. We need real data on the effects of different population testing protocols in whole cities [4], not uncalibrated simulations predicting that it cannot work.FootnotesThe accompanying comment can be viewed at http://doi.org/10.1098/rsos.201546.© 2021 The Authors.Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

Does the law require reinterpretation and return of revised genomic results?

Does the law require reinterpretation and return of revised genomic results?

Reducing travel-related SARS-CoV-2 transmission with layered mitigation measures: symptom monitoring, quarantine, and testing

BackgroundBalancing the control of SARS-CoV-2 transmission with the resumption of travel is a global priority. Current recommendations include mitigation measures before, during, and after travel. Pre- and post-travel strategies including symptom monitoring, antigen or nucleic acid amplification testing, and quarantine can be combined in multiple ways considering different trade-offs in feasibility, adherence, effectiveness, cost, and adverse consequences.MethodsWe used a mathematical model to analyze the expected effectiveness of symptom monitoring, testing, and quarantine under different estimates of the infectious period, test-positivity relative to time of infection, and test sensitivity to reduce the risk of transmission from infected travelers during and after travel.ResultsIf infection occurs 0–7 days prior to travel, immediate isolation following symptom onset prior to or during travel reduces risk of transmission while traveling by 30–35%. Pre-departure testing can further reduce risk, with testing closer to the time of travel being optimal even if test sensitivity is lower than an earlier test. For example, testing on the day of departure can reduce risk while traveling by 44–72%. For transmission risk after travel with infection time up to 7 days prior to arrival at the destination, isolation based on symptom monitoring reduced introduction risk at the destination by 42–56%. A 14-day quarantine after arrival, without symptom monitoring or testing, can reduce post-travel risk by 96–100% on its own. However, a shorter quarantine of 7 days combined with symptom monitoring and a test on day 5–6 after arrival is also effective (97--100%) at reducing introduction risk and is less burdensome, which may improve adherence.ConclusionsQuarantine is an effective measure to reduce SARS-CoV-2 transmission risk from travelers and can be enhanced by the addition of symptom monitoring and testing. Optimal test timing depends on the effectiveness of quarantine: with low adherence or no quarantine, optimal test timing is close to the time of arrival; with effective quarantine, testing a few days later optimizes sensitivity to detect those infected immediately before or while traveling. These measures can complement recommendations such as social distancing, using masks, and hand hygiene, to further reduce risk during and after travel.

A Constellation of Satellites Hunting Methane Leaks Is Launching Soon

A blowout in Ohio in 2018 was the first ever where the emissions could be measured from space, though it was at best a rough estimate based on data gathered on the 13th day after the XTO Energy well control event began. A year later, a blowout of a Devon well near Victoria, Texas, was measured starting the day after it occurred, with data collected on 3 days over the next 2 weeks. Using the measurement of carbon dioxide, it was estimated that the flare was 87% effective in burning about 4,800 metric tons of the leaking methane gas. Emission estimates varied wildly, and both the Ohio (Pandey et al. 2019) and Texas (Cusworth, Duren, Thorpe et al. 2020) efforts to use satellites led to technical papers to consider how they addressed this challenge. For those with blowouts next year, chances are a lot better methane-emission data would be available because of the launch of a constellation of specialized methane-measurement satellites by the two groups that played a key role in the earlier tests. In presentations at CERAWeek by IHS Markit, GHGSat said it has two methane-detection satellites in orbit and plans the launch of eight more, and the Environmental Defense Fund (EDF) said it is moving forward with the launch of its first one next year. Both are aiming to cover the lion’s share of oil and gas operations and measure the flow rate of the gas rather than concentrations in the atmosphere. They said they can do that far more accurately than was possible with the general-purpose climate observation satellites by focusing their equipment on the wavelength of methane. GHGSat said its satellites, which are about the size of a microwave oven, can measure the potent greenhouse gas from an elevation of 500 km and up. They are placed in polar orbit, which allows them to cover the globe every 2 weeks as the Earth rotates. Launching more satellites will allow more frequent looks. There are differences in the GHGSat and EDF designs, reflecting their contrasting missions. The Canadian company GHGSat, whose satellite initiative was initially supported by Schlumberger and the Oil and Gas Climate Initiative, is building tiny satellites with extremely high resolution to serve clients in the oil and mining businesses. During the presentation, Stéphane Germain, chief executive officer of GHGSat, displayed an image and said its satellites can tell if the methane is “coming from a particular facility and even tell what part of the facility it is coming from.” The company also sells the services of similarly equipped planes that can create more-detailed images using similar equipment at elevations of 3000 m and higher. EDF raised $100 million from donors, including Elon Musk, and has hired Raytheon to build a satellite equipped with a detector from Ball Aerospace. It can survey an area that is 260 km wide. That is far wider than the GHGSat satellites, which have the advantage of being able to zero in on smaller details when looking for leaks. The environmental group points out its device is more sensitive to methane emissions, detecting levels down to two parts per billion.

Retention of Molten Corium in Calandria Vessel of PHWR With Moderator Drain Pipe

Abstract Retention of molten corium inside calandria vessel is crucial for arresting accident progression in pressurized heavy water reactors (PHWRs) during severe accidents. Our earlier tests have demonstrated corium retention and its cooling inside the calandria vessel of PHWRs through external cooling by vault water. However, the presence of nozzles and moderator drain pipe at the bottom of calandria vessel has not been considered in these studies. These nozzles and drain pipes used for moderator circulation can make the viability of corium retention even more challenging. Once the moderator has evaporated, debris reheating, compacting, and finally melting can cause the release of molten corium into the moderator recirculation system. This can lead to the relocation of corium beyond calandria vessel. The corium might reach the pump room or calandria vault after the failure of moderator drain pipe and/or moderator pump seals. This has severe consequences on containment integrity due to molten corium concrete interaction (MCCI). The risks posed by MCCI can be avoided if corium can be contained inside calandria vessel even with the presence of nozzles (at the bottom of the vessel) or if at all it enters into the drain line, does not cause its failure. Thus, it becomes crucial to evaluate the challenges faced by “in-vessel retention” (IVR) as a severe accident management strategy due to the presence of openings in the calandria vessel. Relatively colder debris present near the bottom of calandria vessel might help in obstructing the nozzles of the moderator drain line and can prevent the entry of hot molten corium into the moderator cooling line. The role of debris, therefore, becomes important under such scenarios for not just insulation of calandria vessel from hot corium but also for retention of corium within the vessel. In this article, these issues are addressed by conducting two sets of experiments for assessment of retention capability (IVR) of calandria vessel: (i) with the presence of debris and (ii) without debris at the bottom of calandria vessel. The moderator recirculation line was scaled to simulate the heat transfer from corium to vault water and solidification of corium simulant while flowing through the moderator drain pipe. It was observed that debris bed present at the bottom of the vessel helps in arresting the molten corium front and thus prevents corium from entering into moderator drain pipe. When experiments were conducted without debris, molten corium was found to be relocating in the moderator drain pipe. The drain pipe, however, did not fail under the thermal load.

EP08 A case of granulomatosis with polyangiitis complicated by COVID-19: challenges in diagnosis and management

EP08 A case of granulomatosis with polyangiitis complicated by COVID-19: challenges in diagnosis and management

S0577 Healthcare Costs of Colonoscopy With and Without Complications Among Patients at Average Risk for Colorectal Cancer in the United States (US)

INTRODUCTION: Screening is recommended for individuals aged 50-75 years at average risk for colorectal cancer (CRC). Although several non-invasive options are available, colonoscopy remains the most commonly used screening test. This study assessed costs of colonoscopy for patients at average risk for CRC in the US. METHODS: The IBM MarketScan administrative claims databases were used to select adults (age ≥45–75 years) with a claim for CRC screening during 1/1/2014-6/30/2019 (index = earliest test). Patients were required to have 10 years of continuous health plan enrollment prior to and for 30 days following index. Patients at high-risk for CRC, with prior CRC screening (already up to date), < 50 years old at index, and with a CRC screening test other than colonoscopy on index were excluded. Subsets with and without a complication related to colonoscopy (defined as a new diagnosis for a gastrointestinal, cardiovascular, or cerebrovascular condition within 30 days of the colonoscopy) were identified. Costs of colonoscopy (total, plan paid, out of pocket) were measured during the ±30 days from the colonoscopy date (inclusive of procedure costs, pathology costs, anesthesia costs, and bowel preparation prescription costs). Mean costs were reported overall, and for colonoscopies with and without complications. RESULTS: The study population included 228,409 average risk patients with colonoscopy (9,381 [4.1%] with complications and 219,028 [95.9%] without complications). Mean age was 56.8 years, 49.8% were male, and the mean (standard deviation [SD]) Deyo-Charlson comorbidity score was 0.38 (SD 0.86). Overall, 47.6% had a bowel preparation prescription, 82.9% had anesthesia, and 60.4% had a pathology claim associated with their colonoscopy. Mean (SD) costs of colonoscopy among all patients were $2125 ($1369) and out of pocket costs comprised 3.7% of the total. Colonoscopy costs for patients with bowel preparation, anesthesia, and pathology were $2185 ($1397), $2228 ($1386), and $2367 ($1507) respectively (Figure 1). Colonoscopy costs were similar for patients with and without complications (mean $2,128 [SD $1,695] and mean $2,125 [SD $1,353]), but out of pocket costs were higher (with vs without complications; P < 0.001) (Table 1). CONCLUSION: This study provides further clarity regarding the costs of colonoscopy based on comprehensive review of a robust claims dataset. These findings will better inform analyses and assessments of endorsed CRC screening options.Figure 1.: Colonoscopy Costs, Overall, With Bowel Preparation, With Anesthesia, with Pathology.Table 1.: Colonoscopy Costs, Overall, With Complications and Without Complications *Serious gastrointestinal (perforation and bleeding), other gastrointestinal (paralytic ileus, nausea/vomiting/dehydration, abdominal pain), cardiovascular/cerebrovascular (myocardial infarction/angina, arrythmia, heart failure, cardiac/respiratory arrest, syncope/hypotension/shock, stroke, transient ischemic attack)

Drugging the undruggable: A market readiness analysis for KRAS-G12C.

e15667 Background: KRAS G12C is a distinctively aggressive, poor survival, tumor genotype conferring resistance to anti-EGFR therapies in lung, colorectal (CRC) and pancreatic cancers. Prospective therapies targeting G12C have demonstrated promising activity in Phase I trials. In the advent of potentially transformative novel inhibitor therapies, we assess the need for earlier and repeated tumor profiling between treatments to accurately guide further therapeutics and assess market readiness for specified testing. Methods: Treatment-naïve patients and cell-lines were assessed for genomic change by consensus molecular classification in CRC pre/post treatment with standard chemotherapy. Assessing mutation occurrence, prevalence and testing rates, we aimed to identify areas of translational potential for testing within common cancers. A laboratory and prescriber mapping of the US across lung, CRC and pancreatic cancer types, was carried out using Diaceutics’ proprietary Global Diagnostics Index (GDI), a real-world data diagnostic database, to determine market readiness for companion diagnostic (CDx) and follow-on testing in the dawn of transformative therapies. Potential barriers to test adoption were explored including reimbursement analysis. Results: Genomic analysis shows CRC tumors change after treatment with first-line therapies rendering the primary tumor profile result less reliable. This highlights a distinct need for repeated testing post-treatment for continued efficacy in therapeutics. Patients with pancreatic cancer would benefit the most from increased testing for G12C particularly earlier testing as KRAS mutants occur before neoplastic transformation. Although the market appears ready, reimbursement for KRAS G12C remains a challenge for pancreatic cancer compared to either lung or CRC. Conclusions: This study provides genomic evidence of the necessity for more frequent tumor testing post-treatment with chemotherapy, and earlier testing in pancreatic cancer to enhance efficacy of targeted therapies. The market is ready for increased testing volumes, yet problems surrounding reimbursement and stage of testing remain. Earlier testing may increase survival and decrease cost of patient care, suggesting more frequent testing is imperative across cancer types.

NOMINATOR: Feasibility of genomic testing of rare cancers to match cancer to treatment.

103 Background: Rare cancers (RCs) often lack proven treatments and consequently have poorer outcomes. Identification of molecular biomarkers can facilitate treatment selection and trials access for RC patients (pts) where histology-based trials are not feasible. We assessed the potential for next-generation sequencing (NGS) to impact RC care. Methods: Pts with a rare histology, poor-prognosis solid-tumor and no standard of care therapy underwent NGS genomic profiling of paired FFPE tumor and blood (PMCC comprehensive cancer panel; 391 genes). A virtual molecular tumour board (MTB) reviewed curated results regarding diagnosis, actionability (OncoKB) and treatment recommendations. Results: Between July 2017 and Nov 2019, 121 pt were prospectively enrolled across 4 Australian sites. 109 (91%) pts had a tumour with an incidence of &lt; 1/100,000 person/years with 83 diverse RC histologies represented. 100 (83%) cases were successfully sequenced. The most commonly aberrant genes ( &gt; 10%) were: TP53 (45%), CDKN2A/B, RB1, PTEN and NF1. 51 (51%) had at least one potentially actionable finding, with 27 matched to a clinically validated drug (OncoKB level 3 or better) [Table]. In 6 cases NGS resulted in a revised diagnosis (includes 4 with FDA approved therapy). Actionable germline mutations were detected in 3 individuals of which 2 were previously known. The majority of pts remain in follow-up, however, 8 died prior to or within 28 days of NGS result availability. Drug access remains a limitation with only 12 receiving therapy based on NGS/MTB guidance. Clinical trial information: ACTRN12616001000493 . Conclusions: NGS in RCs is feasible with potential impact in half of cases. Earlier testing and improved off-label/trial drug access is necessary to increase the likelihood that RC patients may benefit from molecularly guided therapy. [Table: see text]

Injury metrics are altered in spica-casted versus non-casted child ATDs in side-impact collisions with door intrusion

Objective: There is little data defining safe transport protocols for spica-casted children. A single earlier study demonstrated the presence of a body cast alters kinematics and injury metrics during simulated side-impact crashes. Since then, the National Highway Transportation Safety Administration (NHTSA) proposed a new side-impact test protocol for evaluating child restraints. This test is more severe than the earlier tests, as it simulates an impact with a door intruding into the occupant space. As no currently available child restraint system (CRS) able to accommodate a spica-casted child has been evaluated using these updated testing criteria, the objective of this study was to evaluate current restraint options in simulated side-impact collisions using an anthropomorphic test device (ATD) modeled after a 3-year-old.Methods: Four commercially available CRSs able to accommodate a spica-casted Q3s side-impact ATD were selected for testing. Side-impact testing was performed using casted and uncasted ATDs in compliance with the NHTSA proposed side-impact test. High-speed photography and ATD instrumentation were used to measure selected injury criteria.Results: HIC15 values were highest in CRSs with less robust side wings, such as the Merritt WallenburgTM (HIC15 = 1,373), which allow for the occupant to interact with the intruding door panel. Head contact with the door panel was found to correspond with high resultant neck peak force. Pelvic acceleration magnitudes were greatest for the uncasted tests. Casted tests with a CRS that included an armrest were associated with greater torso rotation in the frontal plane with the left shoulder moving toward the door panel.Conclusions: The presence of a spica cast alters injury metrics in side-impact testing. Spica specific child safety seats are not yet optimized for side-impact with door intrusion. This is due to a lack of adequate side cushion wings, which may place both casted and uncasted occupants at increased likelihood for injury through head contact with an intruding door. Additional work is needed to improve the safety of CRSs for both casted and uncasted children in side-impact collisions.

Abstract P1-18-18: PIK3CA mutation testing prevalence among post-menopausal (PM) women with hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer (mBC) using real world data

Abstract Background: Mutation testing has historically been of limited utility in patients with mBC due to the absence of approved treatments directed at specific genetic variants. However, the SOLAR-1 trial found improved progression-free survival with the addition of the PI3K inhibitor, alpelisib, to fulvestrant, versus placebo, among patients with PIK3CA mutated HR+/HER2- mBC, leading to FDA approval of alpelisib and indicating that PIK3CA mutation assessment has significant clinical relevance. The FDA approval for alpelisib after progression on endocrine therapy necessitates that PIK3CA status be ascertained relatively early in the course of disease of patients with HR+/HER2- mBC. We therefore examined the prevalence and timepoint of mutation testing encompassing PIK3CA among PM women with HR+/HER2- mBC in the United States (US). Methods: This retrospective cohort study used administrative claims data from the MarketScan Commercial and Medicare Supplemental Databases, which include longitudinal records of medical services and prescription drugs from 25-30 million employees and dependents annually, covered by a variety of health plans. PM women diagnosed with mBC between 1/1/2012-7/31/2018 (index date = first metastasis diagnosis date) were selected. Patients were required to have HR+/HER2- disease defined by at least one prescription for endocrine therapy and no evidence of anti-HER2 targeted therapy post-index. The follow-up period was from index until inpatient death, disenrollment, or study end. Mutation testing was captured by a Current Procedural Terminology (CPT) code (81404, 81455, 81445) for polymerase chain reaction (PCR) or next generation sequencing (NGS) inclusive of PIK3CA mutation during the study period. The provider type on the BC-related outpatient physician office visit closest to the first mutation testing date was identified. Testing prevalence was calculated as percent of eligible PM women with HR+/HER2- mBC with a procedure code for PCR and/or NGS test. Results: The study population included 8,499 mBC patients with mean (standard deviation [SD]) age 66.5 (10.6) years and an average follow-up duration of 1.9 (1.4) years. In total, 177 (2.1%) patients had NGS or PCR inclusive of the PIK3CA test during the study period. Of patients with a test, 28.8% (N=51) underwent testing prior to the start of first systemic therapy for metastatic disease (first line) and 126 (71.2%) were tested during or after first line (Table). Of patients with a test, 88.1% (N=156) had a BC-related outpatient physician office visit within 30 days prior to the test. The majority (55.1%) of visits (N=156) were with a hematologist-oncologist. N%All eligible PM women with HR+/HER2- mBC8,499Patients with PCR and NGS testing inclusive of PIK3CA mutation177 2.1%Timing of earliest test (among those with testing) Prior to distant metastasis2212.4%From date of distant metastasis to first line2916.4%During first line4726.6%After first line7944.6% Conclusions: Patients with HR+/HER2- mBC are infrequently tested for mutations such as PIK3CA, with majority of patients not being tested before the initiation of first line therapy. The demonstrated benefit of alpelisib in patients with PIK3CA mutations likely necessitates widespread testing for this important predictive factor early in the disease course. Future analyses are needed to determine the temporal trends over time and assess how genotype testing could be more standard. Citation Format: Nicole Princic, Qayyim Said, David Smith, William Johnson, Ayal Aizer. PIK3CA mutation testing prevalence among post-menopausal (PM) women with hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer (mBC) using real world data [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-18.

Fiber push-in failure in carbon fiber epoxy composites

Micromechanical quasi-static and cyclic fiber push-in tests performed with an indenter in-situ in a scanning electron microscope on polished slices (thickness around 300 μm) of carbon-fiber epoxy composites provide information on the effect of fiber density on the fiber-matrix debonding and the fiber failure. Specifically, "close-packed", i.e., fibers surrounded by six nearest neighbor fibers (called "hexagonal" hereafter) versus "isolated" fibers, defined as fibers at least one fiber diameter distant from the next nearest fiber, were compared. In spite of the more compliant behavior of isolated fibers under quasi-static and cyclic indentation loads, initiation of fiber-matrix debonding and push-in failure (fiber splitting into two or three parts) occurred at roughly comparable loads for both, "hexagonal" and "isolated" fibers. Earlier tests on thinner slices of such composites (thickness around 30 μm) had resulted in full debonding and fiber push-out without fiber failure. The fibers in the thicker slices showed first indenter imprints on the surface and an increasing hysteretic behavior in the load-displacement curves before debonding. The analysis of the cyclic load-displacement curves yields the elastic-plastic and the hysteretic (debonding) energy contributions.