Lab Turnaround Time Research Articles

The future is now: Implementation of standard of care, preemptive pharmacogenomic testing in patients with gastrointestinal cancers.

1546 Background: Preemptive germline pharmacogenomic (PGx) testing provides insight into the safety of high-risk chemotherapy and effective use of supportive care medications in gastrointestinal (GI) cancers. Advances in clinical practice guidelines and clinician support have accelerated the appetite for PGx testing, particularly for drugs with severe adverse reactions. The objective of this study was to assess operational outcomes associated with end-to-end electronic health record (EHR) integration of standard of care, preemptive multigene PGx testing in patients with GI cancers. Methods: Patients in two UCHealth GI oncology clinics were tested for five PGx genes related to 5-fluorouracil (5-FU, DPYD), irinotecan ( UGT1A1), and supportive care therapies ( CYP2C19, CYP2D6, CYP2C9). The PGx test order was embedded in all GI oncology treatment plans. Patient samples were genotyped, and PGx results were returned as discrete data to the EHR. Automated clinical decision support (CDS) tools provided PGx-guided recommendations at the point of prescribing. We leveraged the EPIS process framework and evaluated operational outcomes such as number of patients tested, lab turnaround time, patients with actionable phenotypes, and number of CDS alerts and clinical actions. Results: The analysis included 89 patients who received results for DPYD/UGT1A1 and 83 patients who received results for supportive care genes. Among samples tested, DPYD/UGT1A1 and supportive care gene results were returned to the EHR in an average of 4.7 ± 2 days (range 1-8) and 17.3 ± 3 days (range 9-24), respectively. The number of patients with abnormal phenotypes, defined as poor metabolizers for UGT1A1 and any non-normal phenotypes for the other genes, were UGT1A1, n=10 (11.2%); DPYD, n=4 (4.5%); CYP2C19, n=43 (51.8%); CYP2D6, n=31 (41.3%; 8 uninterpretable results); and CYP2C9, n=19 (22.9%). This equated to 14/89 (15.7%) and 68/83 (81.9%) patients having an abnormal result for DPYD/UGT1A1 and at least one supportive care gene, respectively. CDS alerts fired for 32 drug-gene interactions for 25 distinct patients. Of the alerts, 7 (21.9%) were for 5-FU or irinotecan, which showed for 7/89 patients (7.9%); 25 (78.1%) were for supportive care medications, which showed for 23/83 patients (27.7%). There were 9 clinical actions taken in response to the PGx alerts, 7 (77.8%) for 5-FU or irinotecan and 2 (22.2%) for supportive care drugs. Appropriate clinical actions were taken for 100% of patients with 5-FU or irinotecan drug-gene interactions. Conclusions: End-to-end EHR integration of PGx testing and prescribing guidance facilitated clinician adoption of preemptive, standard of care multigene PGx testing, with test results driving important medication changes. Future studies will evaluate the impact of PGx testing on clinical outcomes and cost effectiveness metrics in this population.

Implementing DPYD/UGT1A1testing to prevent treatment related adverse events (TRAE) in patients with gastrointestinal (GI) cancer: Results of a pragmatic implementation trial.

10599 Background: Fluoropyrimidines (FP), 5-FU and capecitabine, are standard treatments for many GI cancers. Irinotecan may be used with FPs in both the curative and palliative settings. 30-40% of patients experience severe TRAEs which can lead to treatment interruption and hospitalization. TRAE risk is higher in patients with pharmacogenetic variants in DPYD and/or UGT1A1. Methods: This is a non-randomized, open-label implementation study at 3 cancer care sites within an academic health system to determine feasibility of integrating DPYD/UGT1A1 testing into clinical care (IMPACT-GI; NCT#04736472). Test ordering and discrete variant resulting were available within the Electronic Health Record. The lab detected 5 DPYD variants with reduced or no function (c.1905+1G>A, c.2846A>T, c.1679T>G, c.1236G>A, c.557A>G) and 2 UGT1A1 (*6, *28) alleles. Patients with a GI cancer initiating treatment with 5-FU, capecitabine, or irinotecan underwent testing along with preemptive chemotherapy dose modifications. Carriers of 1 DPYD variant (i.e., intermediate metabolizers [IM]) and UGT1A1 homozygous carriers (i.e., poor metabolizers [PM]) were recommended a 50% and 30% dose reduction, respectively. The primary endpoints were feasibility (proportion of results available prior to cycle 1) and fidelity (genotype concordant dose modifications). Secondary endpoints included severe TRAE (requiring emergency room visit or hospitalization) comparing variant carriers vs. wildtype over the first 6 cycles. Results: From 3/2021- 12/2022, 224 patients received testing (54% male, 74% White, 18% Black, mean age 62 ±17 years. The most common diagnoses were 47% colorectal and 30% pancreatic cancers. The median lab turnaround time was 10 (IQR 9-13) calendar days with 57.2% of results available prior to cycle 1. Results available prior to cycle 1 varied by distance to lab (64.7% near sites vs. 32.7% far site, p<0.001). We identified 7 (3%) DPYD intermediate metabolizers (IM) and 33 (15%) UGT1A1 poor metabolizers (PM). Four (2%) patients carried a variant in both DPYD and UGT1A1. Chemotherapies were preemptively dose reduced for 6 of 7 DPYD carriers receiving FP and 5 of 8 UGT1A1 PMs receiving irinotecan. 2 (28%) DPYD carriers vs. 71 (33%) wildtype carriers had a severe TRAE. 4 (50%) UGT1A1 PMs vs. 11 (36%) UGT1A1 wildtype carriers experienced a severe TRAE. Conclusions: DPYD/UGT1A1 testing is feasible with oncology providers following the genotype guided dose reductions when results were available prior to cycle 1. Pretreatment DPYD/UGT1A1 testing in conjunction with preemptive dose reductions resulted a similar proportion of severe TRAE as compared with wild-type patients. Further workflow modifications are required to decrease test turnaround time to ensure results are available prior to chemotherapy initiation. Clinical trial information: NCT04736472 .

Real-world experience of an in-house dihydropyrimidine dehydrogenase (DPYD) genotype test to guide fluoropyrimidine (FP) dosing at a multisite cancer hospital.

1534 Background: FPs, including 5-fluorouracil and capecitabine, are widely used to treat solid tumor malignancies like gastrointestinal (GI) cancers. One-third of patients (pts) develop severe toxicities which may lead to treatment delays or hospitalization. Toxicities can be partly due to genetic variations in DPYD. Herein, we describe the implementation of an in-house DPYD test and its impact on FP dosing at a multisite cancer hospital. Methods: This is an observational study of pts starting or continuing FP-based chemotherapy who received DPYD testing as part of routine care. Buccal swabs were collected in clinic and sent to an in-house lab for genotyping using a polymerase chain reaction-based Drug Metabolizing Enzyme assay that interrogates all 5 variants with moderate-to-strong evidence according to the Clinical Pharmacogenetics Implementation Consortium (CPIC) (c.1905+1G>A, c.2846A>T, c.1679T>G, c.1236G>A and c.557A>G). Phenotype translations and dosing were based on CPIC guidelines. Test results and dose recommendations were uploaded to the electronic medical record (EMR) and emailed to the care team. In April 2022, pre- and post-test EMR alerts were built to prompt test ordering and dose modifications. The primary objective was to evaluate the proportion of DPYD variant carriers in tested pts receiving FP. Secondarily, we evaluated turnaround time and impact on FP dosing. Results: From March 2020-December 2022, 491 pts across 14 clinics received DPYD genotyping (54% male, 74% White, 20% Black, median age 53 years). GI cancers (~50% colorectal) represented 90% of the diagnoses. The median lab turnaround time was 3 (IQR 2-6) days. Pretreatment testing was ordered in 389 (79%) pts, of which 360 (93%) had results before cycle 1. Overall, 30 pts (6.1%) were heterozygous carriers (4.9% in pretreatment and 10.8% in reactive testing groups). Variants observed were c.1236G>A (n=13), c.2846A>T (n=8), c.1905+1G>A (*2A) (n=4), c.557A>G (n=4), and c.1679T>G (*13) (n=1). FP dose was modified in 27 (90%) pts (reduced in 25, avoided in 1, discontinued in 1). Of 19 carriers with pretreatment testing, 17 (90%) received an upfront dose reduction (mean reduction 42%; 3 had subsequent dose escalations); 1 avoided FP and 1 declined chemotherapy. Of 11 carriers with reactive testing, 9 had dose reductions (mean reduction 39%) and 2 discontinued FP due to toxicity. The mean FP dose intensity at cycle 1 was 56% in pretreatment carriers, 97% in reactive carriers, and 94% in wild type pts. Conclusions: DPYD genotype-guided FP dosing is feasible at a multisite cancer hospital. In-house rapid turnaround DPYD testing identified variant carriers and resulted in treatment/dose modifications for most carriers, potentially avoiding or mitigating severe toxicities and/or hospitalization, particularly with pretreatment testing. Toxicity evaluation is ongoing.

Evaluation of the Safety and Efficacy of Bivalirudin Anticoagulation in Patients with Heparin-Induced Thrombocytopenia According to Renal Function and Body Mass Index

Background: Heparin-induced thrombocytopenia (HIT) is a life-threatening complication in which antibodies to platelet factor 4 complexed to heparin lead to platelet overactivation resulting in a hypercoagulable state. Treatment begins with stopping all sources of heparin and initiating rapid-acting non-heparin anticoagulation. Bivalirudin is a direct thrombin inhibitor (DTI) used off-label for the prevention and treatment of HIT. It is primarily enzymatically cleared; however, dose reductions are required in renal impairment. Despite its widespread off-label use in HIT, there is a paucity of data for dosing bivalirudin in patients with renal dysfunction and obesity. Here we report the results of a medication use evaluation (MUE) investigating the safety and efficacy of dosing bivalirudin based on renal function and body mass index (BMI). Methods: We conducted a retrospective MUE including patients 18-89 years of age receiving bivalirudin with ≥3 DTI levels between June 2019 and December 2021. Patients receiving bivalirudin for percutaneous coronary intervention were excluded. Creatinine clearance was measured with the Cockcroft-Gault equation. The primary outcome was time to therapeutic anticoagulation (TTA) defined as the time in hours (hr) between bivalirudin initiation and the first of two consecutive therapeutic DTI levels. Secondary outcomes included average initial therapeutic dose, time in therapeutic range (TTR) calculated as the percentage of therapeutic DTI levels, incidence of clinically significant bleeding, and average number of dose changes before reaching therapeutic goal. Results: Thirty-eight patients (21 females, 55%) with a mean (SD) age of 60.3 (13.5) years were included, 12 of which had a history of or confirmed HIT by serotonin release assay. The remaining patients had suspected HIT or coagulation abnormalities precluding the use of heparin. One patient was classified as an outlier and excluded due to requiring an abnormal number of dose adjustments. Among this population, 17 (45%) had normal renal function (CrCl >60 mL/min), 11 (29%) had mild renal impairment (CrCl 30-60 mL/min), 1 (3%) had moderate renal impairment (CrCl <30 mL/min), 4 (10%) were on intermittent hemodialysis (IHD), and 5 (13%) were on continuous renal replacement therapy (CRRT). Stratified by BMI, 2 (5%) were underweight (BMI <18.5 kg/m2), 3 (8%) were healthy (BMI 18.5-24.9 kg/m2), 17 (45%) were overweight (BMI 25.0-29.9 kg/m2), and 16 (42%) were obese (BMI ≥30 kg/m2). There was no statistically significant difference in TTA based on renal function or BMI. However, clinically, patients on IHD or CRRT trended toward having a shorter TTA compared to patients with normal, mildly impaired, and moderately impaired renal function (28.2 ± 9.0 or 28.9 ± 16.3 hr vs. 40.0 ± 27.6, 36.7 ± 31.6, and 42.9 hr, respectively). Obese and overweight patients trended toward a shorter TTA compared to healthy and underweight patients (31.4 ± 28.9 and 32.8 ± 17.4 hr vs. 62.3 ± 35.6 and 54.8 ± 5.0 hr, respectively). The difference in TTA may be affected by lab turnaround time (TAT). To adjust for lab TAT, the average number of dose adjustments was assessed. There was no difference in the number of dose adjustments based on renal function. In contrast, overweight and obese patients trended toward requiring fewer dose changes compared to underweight and healthy patients. This trend aligned with overweight and obese patients achieving a statistically significantly higher TTR compared to underweight and healthy patients (55.5 vs. 34.4%, p = 0.02). Based on bivalirudin's standard renal dose adjustments, patients with a CrCl >60 mL/min had a statistically significantly larger average initial therapeutic dose compared to those with a CrCl ≤60 mL/min (0.114 vs. 0.069 mg/kg/hr, p < 0.001). However, this difference was not observed based on BMI. Incidences of clinically significant bleeding were not observed to have affected TTA, TTR, average initial therapeutic dose, or number of dose changes before reaching therapeutic anticoagulation. Conclusion: While our data are consistent with bivalirudin requiring renal dose adjustments, it was observed that underweight and healthy BMI patients required more dose adjustments and took longer to achieve therapeutic anticoagulation. More studies are needed to determine if these patients would benefit from a higher initial dosing strategy. This study was limited due to the sample size. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Improving Time-to-Treatment for Advanced Non-Small Cell Lung Cancer Patients through Faster Single Gene EGFR Testing Using the Idylla™ EGFR Testing Platform.

Introduction: Patients with advanced-stage non-small cell lung cancer (NSCLC) may benefit from a short time-to-treatment (TTT). Predictive biomarker testing is performed prior to treatment, as recommended by various international expert consensus bodies. Genetic testing is more time-intensive than immunohistochemistry (IHC) and commonly contributes to prolonged TTT. For epidermal growth factor receptor-positive patients (EGFR+), further genetic testing may not be required due to the mutual exclusivity of actionable mutations. Methods: The trial cohort (N = 238) received both BC Cancer NGS panel (Oncopanel) and Idylla EGFR testing. Data were also collected for a control cohort (N = 220) that received Oncopanel testing. For each patient, the time that the lab received the sample, the time taken to report the NGS and Idylla tests, the time of first treatment, and the final treatment regimen were recorded. Results: A concordance frequency of 98.7% (232/235) was observed between the Idylla and NGS panel. The lab turnaround time (TAT) was faster for the Idylla test by an average of 12.4 days (N = 235, p < 0.01). Overall, the average TTT in the trial cohort (N = 114) was 10.1 days faster (p < 0.05) than the control (N = 114), leading to a 25% reduction in TTT. For patients treated based on EGFR positivity, the mean TTT was 16.8 days faster (p < 0.05) in the trial cohort (N = 33) than the control cohort (N = 28), leading to a 48% reduction in TTT. Conclusion: Using the Idylla EGFR test as part of the molecular testing repertoire in advanced-stage NSCLC patients could significantly reduce TTT.

Abstract P3-09-19: The utility of using genomic testing on needle core biopsies during the COVID-19 pandemic: Molecular characterization, risk stratification, neoadjuvant outcome, and future implications

Abstract Introduction: The COVID-19 pandemic has caused an extraordinary challenge for global health. New guidelines were implemented, including postponing non-essential surgical procedures to conserve resources. In response, the COVID19 Pandemic Breast Cancer Consortium expert opinion suggested the use of core biopsies for genomic testing to help triage patients for surgical vs. systemic treatment. To better understand how expedited genomic results could impact peri-operative care, we performed a pre-operative quality project to assess testing Mammaprint (MP), a 70-gene risk of recurrence assay, and Blueprint (BP), an 80-gene molecular subtyping assay, on core biopsies. Here we report our experience with MP and BP testing on core biopsies, and the correlation between test results and response to neoadjuvant therapy.Design: From April to December 2020, all core biopsies with a breast carcinoma diagnosis from our clinic (300 patients) were routinely sent for MP and BP testing as part of a rapid result program that was initiated to see whether test results could be obtained in time and whether they would lead to more informed pre-operative treatment decisions. Unstained slides were sent for genomic and receptor testing concurrently. When genomic results differed from IHC/FISH results or suggested a different treatment plan vs. clinical factors alone, we referred to this as “reclassification.” For those patients who completed their neoadjuvant chemotherapy, we grouped them by their genomic results and by their conventional IHC/FISH/Clinical classification, and compared the outcome.Results: MP and BP results from core biopsy were available for 96.6% of patients (n=290/300). The average time from biopsy to test results was 10 days, and the average lab turnaround time was 5 days. Results were available for tumor conference discussions 100% of the time. MP and BP re-classified 84 of 300 patients (28%) from conventional IHC/FISH subtyping, and reclassified 42 of 195 patients (22%) of patients from their risk category based on traditional clinical factors (Table-1). Of the 38 patients with available post-neoadjuvant therapy outcome, 13 patients (34%) achieved pathologic complete response (pCR). 16 patients were classified as Her-2 enriched by IHC/FISH of which 9 (56%) achieved pCR. MP/BP aligned with the IHC/FISH Her-2 enriched classification in 11/16 patients, while 5 patients were reclassified to Luminal B by MP/BP. Of the 11 patients with concordant IHC/FISH and MP/BP results, 8 achieved pCR (73%), while one of the 5 cases reclassified to Luminal B achieved pCR (20%). Of the patients who were classified Luminal by IHC (9 patients), one patient achieved pCR (11%), and of the patients classified luminal (A or B) by MP/BP (12 patients) two achieved pCR (16%). Of the IHC-triple negative patients and genomic basal patients, three patients achieved pCR in each group (23% and 20%, respectively).Conclusion: Performing MP/BP tests on core needle biopsies hold a high success rate. Incorporating test results into peri-operative discussions may result in better-informed decisions about treatment planning and timing of surgery versus systemic therapy. A higher rate of pCR was seen in the MP/BP Her-2 enriched group compared to the IHC/FISH Her-2 enriched group. Although this workflow was designed to triage patients during the COVID pandemic, this approach has great potential beyond the pandemic. Table-1: Reclassification Rate vs. path IHC/FISH or Clinical FactorsIHC/FISH/Clinical ◊ Genomic# of reclassified patients/total patients in the corresponding traditional category% of patientsLuminal A ◊ Luminal B25/16116%Luminal A ◊ Her-21/1610.6%Luminal B ◊ Luminal A35/7249%Luminal B ◊ Basal4/726%Her-2 ◊ Luminal A1/313%Her-2 ◊ Luminal B10/3132%Her-2 ◊ Basal1/313%Triple negative ◊ Luminal A4/3611%Triple negative ◊ Luminal B3/368%Clinical high risk ◊ Genomic low risk21/8425%Clinical low risk ◊ Genomic high risk21/11119% Citation Format: Hani Katerji, Huina Zhang, Xi Wang, Linda Schiffhauer, Ajay Dhakal, Alissa Huston, Carla Falkson, David Hicks, Bradley Turner. The utility of using genomic testing on needle core biopsies during the COVID-19 pandemic: Molecular characterization, risk stratification, neoadjuvant outcome, and future implications [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-09-19.

EGFR Point of Care Clinical Testing using Idylla Platform Decreases Laboratory Turnaround Time in Advanced Stage Non-Small Cell Lung Cancer, as Compared to New Generation Sequencing

"Background: Patients with advanced-stage non-small cell lung cancer (NSCLC) benefit from a short time-to-treatment (TTT) due to disease severity. Patients at BC Cancer with NSCLC undergo OncoPanel testing, a next-generation sequencing assay, for potential oncogenic drivers prior to treatment as outlined by CAP-AMP-IASLC guidelines. Genetic testing via OncoPanel takes more than two weeks and commonly contributes to an increased TTT. The novel ultra-rapid Idylla EGFR testing platform may decrease TTT in patients who are EGFR mutation positive (M+) due to the mutual exclusivity of actionable mutations. This study evaluates the lab turnaround time (TAT) of the Idylla EGFR testing platform and compares it to that of the OncoPanel. Methods: A group of patients (N = 235) with stage IIIB or stage IV lung adenocarcinoma diagnosed between November 1, 2020 and May 1, 2021 had both OncoPanel and Idylla EGFR testing. The time at which the sample was received in the lab, the time of Idylla EGFR test reporting, and the time of OncoPanel reporting were recorded for each patient. Differences in the lab TAT between the OncoPanel and Idylla EGFR test were compared using a paired t-test within the cohort. Results: The mean lab TAT for the Idylla and OncoPanel tests were 3.4 days (Range: 0-8 days) and 15.8 days (Range: 12-31 days), respectively. It was observed that the lab TAT of the Idylla EGFR test was faster by an average of 12.4 days (Range: 6-29 days, p&lt;0.01, 95% CI: [11.9, 12.8] days) than the OncoPanel TAT (N=235). Conclusions: The lab TAT of the Idylla EGFR test is significantly shorter than of OncoPanel testing. In patients who are EGFR M+, molecular testing could be completed considerably faster using the Idylla EGFR testing platform since further genetic testing is unlikely to yield additional actionable information. Using the Idylla EGFR test as part of a reflexive molecular testing repertoire in advanced-stage NSCLC patients could thus reduce patient TTT."

Benchmarking diagnostic laboratory performance: Survey results for Germany, Austria, and Switzerland

Background and aimsThe need for patient safety through consistent diagnostic performance has increasingly been brought into focus during the last two decades. Around the globe operational efficiency of diagnostic laboratories plays a key role in satisfying this need, which has impressively been shown during the recent months of the SARS-CoV‑2 pandemic. On a global level, however, there has been a lack to collate and benchmark data for diagnostic laboratories. The goals of this study were to design and pilot a questionnaire addressing key aspects of diagnostic laboratory management.MethodsThe questionnaire was designed using an iterative process and taking into consideration information that could be extracted from the literature, author experience and feedback from informal focus groups of laboratory professionals. The resulting tool consisted of 50 items, either relating to general information or more specifically addressing the topics of “operational performance”, “integrated clinical care performance”, and “financial sustainability”. A limited number of laboratories were surveyed to be able to further improve the newly developed tool and motivate the global laboratory community to participate in further benchmarking activity.Results and conclusionAltogether, 65 laboratories participated in the survey, 42 were hospital laboratories and 23 were commercial laboratories. Potential for further improvement and standardization became apparent across the board, e.g. use of IT for order management, auto-validation, or turn-around time (TAT) monitoring. Notably, a gap was identified regarding services provided to physicians, in particular “reflexive test suggestions”, “proactive consultation on complex cases”, and “diagnostic pathways guidance”, which were only provided by about two thirds of laboratories. Concordantly, within-laboratory TAT (Lab TAT) was monitored by about 80% of respondents, while sample-to-result TAT, which is arguably the TAT most relevant to clinicians, was only monitored by 32% of respondents. Altogether, the need for stronger integration of the laboratory into the clinical care process became apparent and should be a main trajectory of future laboratory management.Supplementary InformationThe online version of this article (10.1007/s00508-021-01962-4) contains supplementary material, which is available to authorized users.

COVID-19 outbreak in a personal service setting in Kingston, Ontario, 2020.

During the coronavirus disease 2019 (COVID-19) pandemic, Ontario created a three-phase reopening framework for the economy. Outbreaks were expected at each phase. One week after Phase Two of reopening in the provincial public health administration region of Kingston, Frontenac, Lennox and Addington (KFL&A), a positive case was reported after three weeks of zero new COVID-19 cases. The objective of this report is to describe this COVID-19 outbreak, linked to a personal service setting (PSS), and the public health response to contain the outbreak. The outbreak investigation included all COVID-19 cases in KFL&A between June 20, 2020 and July 3, 2020. Public health inspectors and nurses were rapidly deployed to inspect the PSS. A multimodal approach to high-volume testing involved fixed assessment centres, drive-through testing capacity and targeted testing at the outbreak site. Testing was conducted through a real-time polymerase chain reaction assay at the local Public Health Ontario laboratory. Thirty-seven cases were associated with the outbreak: 38% through direct PSS exposure; 32% through household contact; and 30% through social and workplace contact. A superspreading event contributed to 38% of total cases. The majority of cases were in the low to mid-quintiles when analyzed for material deprivation. Testing rates increased four-fold compared to the prior baseline weeks in response to media attention and public health messaging, resulting in a low percent positivity. The interplay of aggressive accessible testing, quick lab turnaround time, contact tracing within 24 hours of positive laboratory results as per provincial standards, frequent public communication, rapid inspections, mandatory self-isolation and face coverings were measures successful in halting the outbreak. Inspections or self-audits should be required at all PSSs prior to reopening and outbreak management must work with PSSs to reduce the possibility of superspreading events.

Infectious Disease Hospital Preparedness: Lessons Learned From the 2019 Measles Outbreak.

This paper: (1) explores the real and perceived threats to Emergency Departments (EDs) in addressing infectious disease cases in the US, like measles, and (2) identifies priorities for protecting employees, patients, and others stakeholders through hospital preparedness while streamlining processes and managing costs. A case study approach was used to describe the events that triggered an infectious disease emergency response in 1 ED in the southeast. Development of the case study was informed by emergency preparedness literature on Homeland Security Exercise and Evaluation Program processes. Hospital staff and administrators identified a number of factors that either positively contributed to disease containment or exacerbated conditions for disease transmission. Successes included early recognition of the potential threat, development of a multidisciplinary taskforce, and implementation of a pre-incident response plan. Challenges comprised of patient flow in crisis response, lab turnaround time, and employee records. The threat of exposure challenged daily operations and raised situational awareness among administrators and providers to issues that might arise during an infectious disease exposure. Recording emergency preparedness successes, remediating challenges, and sharing information with others may help minimize the threat of communicable diseases within hospital settings in the future.

Orca-T, a Precision Treg-Engineered Donor Product, Prevents Acute Gvhd with Less Immunosuppression in an Early Multicenter Experience with Myeloablative HLA-Matched Transplants

Orca-T, a Precision Treg-Engineered Donor Product, Prevents Acute Gvhd with Less Immunosuppression in an Early Multicenter Experience with Myeloablative HLA-Matched Transplants

Potential Factors That Impact Lenalidomide/R-CHOP Efficacy in Previously Untreated Diffuse Large B-Cell Lymphoma in the ROBUST and ECOG-ACRIN 1412 Studies

Potential Factors That Impact Lenalidomide/R-CHOP Efficacy in Previously Untreated Diffuse Large B-Cell Lymphoma in the ROBUST and ECOG-ACRIN 1412 Studies

THE ROLE OF PNEUMATIC TUBE SYSTEM IN EFFICIENCY OF EMERGENCY LABORATORY SERVICE OF THE HOSPITAL

Laboratory tests are one of the most commonly ordered tests in the ED and often the rate-limiting factor in the workup of a patient. The pneumatic tube system (PTS) can use to provide quick specimen delivery. First aim of this study was to assess PTS by comparing routine chemistry, hematology, coagulation blood test results and sample integrity indices between duplicate samples transported either manually or automatically. Also we tried to assess the contribution of PTS to reduction in lab turnaround times.

P002 Assessing the impact of individualised treatment: an individual-based mathematical modelling study of antimicrobial resistant neisseria gonorrhoeae transmission, diagnosis and treatment in men who have sex with men

IntroductionAntimicrobial resistant (AMR) gonorrhoea is a global public health threat. In London, diagnoses in men who have sex with men (MSM) have more than quadrupled from 2010 to 2015. Importantly, our last-line treatment (ceftriaxone) is used in first-line dual therapy. However, over half of tested isolates are still sensitive to older drugs, e.g. ciprofloxacin. Discriminatory point-of-care tests (POCT) to detect drug sensitivity are under development, enabling individualised treatment decisions.MethodsAn individual-based transmission model of gonorrhoea infection in MSM was developed, incorporating ciprofloxacin-sensitive and resistant strains, using novel heuristic approach to capture partnership dynamics. We explored different strategies to improve treatment selection including a) discriminatory POCT, b) partner treatment based on index case susceptibility, and c) variably delayed positivity testing prior to treatment (pre-screening).ResultsThe flexible model structure enabled us to credibly simulate London gonorrhoea transmission dynamics - assuming 2–10% prevalence and 10–50 daily diagnoses per 100,000 MSM. Simulations show that a) using POCT to detect ciprofloxacin sensitive infections resulted in a 70% decrease in ceftriaxone doses, and b) using index case sensitivity profile to direct treatment of partners could reduce ceftriaxone use by 27%.DiscussionPOCT are likely to dramatically reduce reliance on ceftriaxone. In the meantime, we could use existing data more informatively. If lab turnaround times are fast enough, index case sensitivity profiles could be used to select effective treatments for partners. This new framework addresses limitations of previous models and provides a flexible platform for exploring control options for AMR gonorrhoea.

Algal bloom response and risk management: On-site response tools

Harmful algal blooms caused by cyanobacteria can present a risk to the safety of drinking- and recreational waters and beachfronts through the production of toxins, particularly microcystin, which are highly resilient to degradation. These blooms are difficult to predict, vary in appearance and toxicity, and can show significant spatial heterogeneity: wind- and current-borne scums can produce an order of magnitude range in toxin levels along shorelines. The growing demand for reliable, cost-effective and rapid methods to detect toxins in bloom material and reduce the risk of public exposure cannot be met by most analytical lab turnaround times. Commercial microcystin test kits are now available, but few have been rigorously field-tested or incorporated into monitoring programmes. Working with a local health agency, we evaluated two kits with different operative ranges of detection, applied to samples covering a wide range of water quality, sample matrices, and bloom composition. We compared their performance against lab analyses using Enzyme-Linked Immunosorbent and Protein Phosphatase Inhibition assays. Both kits could resolve samples with high (<10 μg/L microcystin equivalents (MCequiv)) and low/no toxins, but failed to reliably detect toxin levels between 1 and 5 μg/L, at which threshold there were few false negatives (8%) but ∼ one third of the samples (32%) yielded false positives. We conclude that these kits are potentially useful for screening and informed risk management decisions e.g. on beach closures, but should be followed up with more rigorous tests where needed. We describe how, based on these results, the kits have been successfully incorporated into the routine municipal beach monitoring and advisory programme by the Hamilton Public Health Services (Ontario).

Ambulatory redesign: Strategies for quality improvement in patient care.

85 Background: Growing outpatient volume poses patient flow challenges, making it difficult to accommodate the complexities of academic medical practice. Volume increases create operational inefficiencies like delays in lab turnaround time (TAT) and limited rooming capacity resulting in delays in patient access and reduced provider productivity. These bottlenecks negatively impact patient satisfaction. Methods: Four multidisciplinary teams assessed barriers to patient flow in the lab, rooming and scheduling process. We sought to maximize the Advanced Practice Provider (APP) role within clinical programs. Each team was led jointly by an MD and RN and included subject matter experts, advisors and facilitators. The groups met regularly for 2 months to evaluate operational data, national benchmarks and surveyed staff. Monthly progress was presented during the Ambulatory Clinic Committee (ACC) meetings. Number of labs not completed on time, wait-time and APP visit volume were tracked. Results: Recommendations included provider education on lab order process, purchasing a second instrument for chemistries, APP independent visits standards, and realistic scheduling times. Preliminary findings indicate that the lab reduced their average TAT defect rate by 52.3% (CBC) and 76.1% (CMP) compared to January 2014 (baseline) and January 2015 (post implementation). This difference was statistically significant at a 95% CI, with p &lt; .001 for both CBCs and CMPs. In addition, APP total visit volume increased by 81% from FY 2014 to FY 2015. Finally, the overall Press-Ganey mean in patient satisfaction with physician wait time increased from 81.7 to 82.7 (2014 vs. 2015). Conclusions: Multidisciplinary teams recommended valuable process improvement changes to reduce the TAT in the lab and to promote that APPs work within the full scope of their license. Implementation requires extensive project management support and continuous tracking to evaluate outcomes. Opportunities exist to maximize space and room utilization and optimize the scheduling process as the outpatient volume continues to increase.

Abstract T P247: An Interdisciplinary Approach Using a Root Cause Analysis to Decrease Door to IV tPA Times

Background and Issues: The benchmark goal for stroke treatment is door to IV tPA in 60 minutes. In 2010, average door to IV tPA treatment time for acute stroke patients at our acute care, tertiary teaching hospital was 87 minutes. Purpose: As a TJC certified primary stroke center, our purpose was to improve door to IV tPA times. Methods: Causes for lengthy tPA treatment times were identified by the stroke interdisciplinary team using a root cause analysis approach. Identified delays included: lab turn-around times, order entry, clinical decision making time, and tPA preparation, delivery, and administration. Process improvement initiatives for order entry included revisions to electronic order sets to auto-populate and enhance efficiency and safety of order entry. Lab audits revealed that the BMP took the most time to process, resulting in initiation of point of care testing. For clinical decision making delays by neurology, immediate feedback was provided to the neurologist after each tPA administration. A year end summary was compiled showing door to tPA times for each attending neurologist. In addition, 3 APNs completed a neurovascular advanced practice fellowship program. Pharmacy instituted a tracking log to audit prep-to-delivery time which encouraged earlier notification and faster delivery times. Mixing of tPA was changed from (2) 50mg vials to reconstitution of (1) 100mg vial. Nurses who administer tPA were re-competencied using a simulation lab. Patients were triaged to a room in ED closer to the CT scanner. And, a count-down clock was initiated upon patient arrival to ED to enhance time awareness for all stroke team members. Results: Average door to tPA time has decreased from 87 minutes in 2010 to 50 minutes YTD 2013, a 37 minute improvement. In addition, volume increased by 25 more tPA administrations in 2012. Chi square comparisons of discharge dispositions showed no statistical differences for 2010 vs 2013 (p=.56) or 2012 vs 2013 (p= .18). Our hospital has received the American Stroke Association’s Target Stroke award for the past 2 years. Conclusions: An interdisciplinary approach using a root cause analysis is effective in identifying and implementing process improvements, ultimately leading to decreased door to IV tPA times.

Reducing Ambulance Diversion at the Hospital and Regional Levels: Systemic Review of Insights from Simulation Models

Introduction:Optimal solutions for reducing diversion without worsening emergency department (ED) crowding are unclear. We performed a systematic review of published simulation studies to identify: 1) the tradeoff between ambulance diversion and ED wait times; 2) the predicted impact of patient flow interventions on reducing diversion; and 3) the optimal regional strategy for reducing diversion.Methods:Data Sources: Systematic review of articles using MEDLINE, Inspec, Scopus. Additional studies identified through bibliography review, Google Scholar, and scientific conference proceedings. Study Selection: Only simulations modeling ambulance diversion as a result of ED crowding or inpatient capacity problems were included. Data extraction: Independent extraction by two authors using predefined data fields.Results:We identified 5,116 potentially relevant records; 10 studies met inclusion criteria. In models that quantified the relationship between ED throughput times and diversion, diversion was found to only minimally improve ED waiting room times. Adding holding units for inpatient boarders and ED-based fast tracks, improving lab turnaround times, and smoothing elective surgery caseloads were found to reduce diversion considerably. While two models found a cooperative agreement between hospitals is necessary to prevent defensive diversion behavior by a hospital when a nearby hospital goes on diversion, one model found there may be more optimal solutions for reducing region wide wait times than a regional ban on diversion.Conclusion:Smoothing elective surgery caseloads, adding ED fast tracks as well as holding units for inpatient boarders, improving ED lab turnaround times, and implementing regional cooperative agreements among hospitals are promising avenues for reducing diversion.

Decreasing Lab Turnaround Time Improves Emergency Department Throughput and Decreases Emergency Medical Services Diversion: A Simulation Model

The effect of decreasing lab turnaround times on emergency department (ED) efficiency can be estimated through system-level simulation models and help identify important outcome measures to study prospectively. Furthermore, such models may suggest the advantage of bedside or point-of-care testing and how they might affect efficiency measures. The authors used a sophisticated simulation model in place at an adult urban ED with an annual census of 55,000 patient visits. The effect of decreasing turnaround times on emergency medical services (EMS) diversion, ED patient throughput, and total ED length of stay (LOS) was determined. Data were generated by using system dynamics analytic modeling and simulation approach on 90 separate days from December 2, 2007, through February 29, 2008. The model was a continuous simulation of ED flow, driven by real-time actual patient data, and had intrinsic error checking to assume reasonable goodness-of-fit. A return of complete laboratory results incrementally at 120, 100, 80, 60, 40, 20, and 10 minutes was compared. Diversion calculation assumed EMS closure when more than 10 patients were in the waiting room and 100% ED bed occupancy had been reached for longer than 30 minutes, as per local practice. LOS was generated from data insertion into the patient flow stream and calculation of time to specific predefined gates. The average accuracy of four separate measurement channels (waiting room volume, ED census, inpatient admit stream, and ED discharge stream), all across 24 hours, was measured by comparing the area under the simulated curve against the area under the measured curve. Each channel's accuracy was summed and averaged for an overall accuracy rating. As lab turnaround time decreased from 120 to 10 minutes, the total number of diversion days (maximum 57 at 120 minutes, minimum 29 at 10 minutes), average diversion hours per day (10.8 hours vs. 6.0 hours), percentage of days with diversion (63% vs. 32%), and average ED LOS (2.77 hours vs. 2.17 hours) incrementally decreased, while average daily throughput (104 patients vs. 120 patients) increased. All runs were at least 85% accurate. This simulation model suggests compelling improvement in ED efficiency with decreasing lab turnaround time. Outcomes such as time on EMS diversion, ED LOS, and ED throughput represent important but understudied areas that should be evaluated prospectively. EDs should consider processes that will improve turnaround time, such as point-of-care testing, to obtain these goals.

El Camino Hospital: Using Health Information Technology to Promote Patient Safety

El Camino Hospital is a leader in the use of health information technology to promote patient safety, including bar coding, computerized order entry, electronic medical records, and wireless communications. Each year, El Camino Hospital's board of directors sets performance expectations for the chief executive officer, which are tied to achievement of local, regional, and national safety and quality standards, including the six Institute of Medicine quality dimensions. He then determines a set of explicit quality goals and measurable actions, which serve as guidelines for the overall hospital. The goals and progress reports are widely shared with employees, medical staff, patients and families, and the public. For safety, for example, the medication error reduction team tracks and reviews medication error rates. The hospital has virtually eliminated transcription errors through its 100% use of computerized physician order entry. Clinical pathways and standard order sets have reduced practice variation, providing a safer environment. Many projects focused on timeliness, such as emergency department wait time, lab turnaround time, and pneumonia time to initial antibiotic. Results have been mixed, with projects most successful when a link was established with patient outcomes, such as in reducing time to percutaneous transluminal coronary angioplasty for patients with acute myocardial infarction.