S1975 Multiplex Gastrointestinal Pathogen Panel Testing Is Associated With Higher Diagnostic Yield and Identification of Pathogenic E. coli Species in Patients With Travelers’ Diarrhea

AbstractObjective:To evaluate the impact of a hard stop in the electronic health record (EHR) on inappropriate gastrointestinal pathogen panel testing (GIPP).Design:We used a quasi-experimental study to evaluate testing before and after the implementation of an EHR alert to stop inappropriate GIPP ordering.Setting:Midwest academic medical center.Participants:Hospitalized patients with diarrhea for which GIPP testing was ordered, between January 2016 through March 2017 (period 1) and April 2017 through June 2018 (period 2).Intervention:A hard stop in the EHR prevented clinicians from ordering a GIPP more than once per admission or in patients hospitalized for >72 hours.Results:During period 1, 1,587 GIPP tests were ordered over 212,212 patient days, at a rate of 7.48 per 1,000 patient days. In period 2, 1,165 GIPP tests were ordered over 222,343 patient days, at a rate of 5.24 per 1,000 patient days. The Poisson model estimated a 30% reduction in total GIPP ordering rates between the 2 periods (relative risk, 0.70; 95% confidence interval [CI], 0.63–0.78; P < .001). The rate of inappropriate tests ordered decreased from 21.5% to 4.9% between the 2 periods (P < .001). The total savings calculated factoring only GIPP orders that triggered the hard stop was ∼$67,000, with potential savings of $168,000 when factoring silent best-practice alert data.Conclusions:A simple hard stop alert in the EHR resulted in significant reduction of inappropriate GIPP testing, which was associated with significant cost savings. Clinicians can practice diagnostic stewardship by avoiding ordering this test more than once per admission or in patients hospitalized >72 hours.

Download Full-text

Development, technical validation, and clinical application of a multigene panel for hereditary gastrointestinal cancer and polyposis

Tumori Journal ◽

10.1177/0300891619847085 ◽

2019 ◽

Vol 105 (4) ◽

pp. 338-352 ◽

Cited By ~ 2

Author(s):

Maria Teresa Ricci ◽

Sara Volorio ◽

Stefano Signoroni ◽

Paolo Mariani ◽

Frederique Mariette ◽

...

Keyword(s):

Gastrointestinal Cancer ◽

Diagnostic Yield ◽

Clinical Impact ◽

Clinical Genetics ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Panel Testing ◽

Technical Validation ◽

Sensitivity Specificity ◽

Multigene Panel

Introduction: Recent advances in technology and research are rapidly changing the diagnostic approach to hereditary gastrointestinal cancer (HGIC) syndromes. Although the practice of clinical genetics is currently transitioning from targeted criteria-based testing to multigene panels, important challenges remain to be addressed. The aim of this study was to develop and technically validate the performance of a multigene panel for HGIC. Methods: CGT-colon-G14 is an amplicon-based panel designed to detect single nucleotide variants and small insertions/deletions in 14 well-established or presumed high-penetrance genes involved in HGIC. The assay parameters tested were sensitivity, specificity, accuracy, and inter-run and intra-run reproducibility. Performance and clinical impact were determined using 48 samples of patients with suspected HGIC/polyposis previously tested with the targeted approach. Results: The CGT-colon-G14 panel showed 99.99% accuracy and 100% inter- and intra-run reproducibility. Moreover, panel testing detected 1 actionable pathogenic variant and 16 variants with uncertain clinical impact that were missed by the conventional approach because they were located in genes not previously analyzed. Conclusion: Introduction of the CGT-colon-G14 panel into the clinic could provide a higher diagnostic yield than a step-wise approach; however, results may not always be straightforward without the implementation of new genetic counseling models.

Download Full-text

Comparison of the Patient Diagnostic Yield of Fibre-optic Bronchoscopy with Conventional Tracheal Aspirate

Journal of BP Koirala Institute of Health Sciences ◽

10.3126/jbpkihs.v3i1.30329 ◽

2020 ◽

Vol 3 (1) ◽

pp. 66-72

Author(s):

Subodh Sagar Dhakal ◽

Navin Kumar Mishra ◽

Karuna Bhatta ◽

Milan Shrestha ◽

Rohit Karna ◽

...

Keyword(s):

Diagnostic Yield ◽

Tracheal Aspirate ◽

P Value ◽

Infectious Agents ◽

Single Center ◽

Acinetobacter Baumanii ◽

E Coli ◽

Baseline Characteristics ◽

Staphyloccus Aureus ◽

Overall Health Status

Objective: To know the efficacy of Bronchoalveolar Lavage (BAL) in establishing diagnosis and its impact on overall health status of the patients. Methods: A single center, longitudinal study involving 40 patients aged > 18 years old with septic shock with similar baseline characteristics was conducted. Two study arms, 20 patients in intervention arm - patient with utilization of Bronchoscopy and BAL in aiding diagnosis and 20-patients in conservative- arm without Bronchoscopy were compared in terms of establishing diagnosis primarily and secondarily in terms of length of stay and 30-day mortality. We were able to identify following organisms in BAL sample: Mycobacterium tuberculosis- 4, Acinetobacter baumanii- 3, Pseudomonasaeruginosa- 2, Klebsiella oxytica- 2, E. coli- 2, Streptococcus pneumoniae- 2, Staphyloccus aureus- Results: We were able to identify various infectious agents as mentioned above 16/20 in BAL group compared to 8/20 in conventional arm; neoplasm in 4 out of 20 subjects in BAL group. In 80% of cases, BAL helped in identifying the organisms compared to only 40% in tracheal aspirate group. In addition, six cases in Intervention arm vs. nine cases in conventional arm had more than > 14 days hospital stay with the p-value 0 .492091. Interventional arm had lesser mortality 5 cases vs. 7 cases in Conventional arm with the p-value of 0.490153 which was not statistically significant. Conclusion: We conclude that the diagnostic bronchoscope and related procedures among critically ill patients are helpful in identifying the pathogens and in detecting malignancy.

Download Full-text

Diagnostic Yield of Epilepsy Panel Testing in Patients With Seizure Onset Within the First Year of Life

Frontiers in Neurology ◽

10.3389/fneur.2019.00988 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 8

Author(s):

Se Song Jang ◽

Soo Yeon Kim ◽

Hunmin Kim ◽

Hee Hwang ◽

Jong Hee Chae ◽

...

Keyword(s):

Diagnostic Yield ◽

First Year ◽

Seizure Onset ◽

Panel Testing ◽

First Year Of Life

Download Full-text

Benefits and safety of multigene panel testing in patients at risk for hereditary breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.28_suppl.16 ◽

2015 ◽

Vol 33 (28_suppl) ◽

pp. 16-16

Author(s):

Nimmi S. Kapoor ◽

Lisa D. Curcio ◽

Carlee A. Blakemore ◽

Amy K. Bremner ◽

Rachel E. McFarland ◽

...

Keyword(s):

Breast Cancer ◽

At Risk ◽

Genetic Testing ◽

Hereditary Breast Cancer ◽

Diagnostic Yield ◽

Gene Panel ◽

Panel Testing ◽

Gene Testing ◽

Gene Panel Testing ◽

Patients At Risk

16 Background: Recently introduced multi-gene panel testing including BRCA1 and BRCA2 genes (BRCA1/2) for hereditary cancer risk has raised concerns with the ability to detect all deleterious BRCA1/2 mutations compared to older methods of sequentially testing BRCA1/2 separately. The purpose of this study is to evaluate rates of pathogenic BRCA1/2mutations and variants of uncertain significance (VUS) between previous restricted algorithms of genetic testing and newer approaches of multi-gene testing. Methods: Data was collected retrospectively from 966 patients who underwent genetic testing at one of three sites from a single institution. Test results were compared between patients who underwent BRCA1/2testing only (limited group, n = 629) to those who underwent multi-gene testing with 5-43 cancer-related genes (panel group, n = 337). Results: Deleterious BRCA1/2 mutations were identified in 37 patients, with equivalent rates between limited and panel groups (4.0% vs 3.6%, respectively, p = 0.86). Thirty-nine patients had a BRCA1/2 VUS, with similar rates between limited and panel groups (4.5% vs 3.3%, respectively, p = 0.49). On multivariate analysis, there was no difference in detection of either BRCA1/2 mutations or VUS between both groups. Of patients undergoing panel testing, an additional 3.9% (n = 13) had non-BRCA pathogenic mutations and 13.4% (n = 45) had non-BRCA VUSs. Mutations in PALB2, CHEK2, and ATM were the most common non-BRCA mutations identified. Conclusions: Multi-gene panel testing detects pathogenic BRCA1/2 mutations at equivalent rates as limited testing and increases the diagnostic yield. Panel testing increases the VUS rate, mainly due to non-BRCA genes. Patients at risk for hereditary breast cancer can safely benefit from upfront, more efficient, multi-gene panel testing.

Download Full-text

Expanded yield of multiplex panel testing in fully accrued prospective trial.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.1525 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 1525-1525

Author(s):

Gregory Idos ◽

Allison W. Kurian ◽

Charite Nicolette Ricker ◽

Duveen Sturgeon ◽

Julie Culver ◽

...

Keyword(s):

Risk Assessment ◽

Genetic Testing ◽

Cancer Risk ◽

Clinical Utility ◽

Diagnostic Yield ◽

Pathogenic Mutation ◽

Gene Panel ◽

Cancer Risk Assessment ◽

Panel Testing ◽

Gene Panel Testing

1525 Background: Genetic testing is a powerful tool for stratifying cancer risk. Multiplex gene panel (MGP) testing allows simultaneous analysis of multiple high- and moderate- penetrance genes. However, the diagnostic yield and clinical utility of panels remain to be further delineated. Methods: A report of a fully accrued trial (N = 2000) of patients undergoing cancer-risk assessment. Patients were enrolled in a multicenter prospective cohort study where diagnostic yield and off-target mutation detection was evaluated of a 25 gene MGP comprised of APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53. Patients were enrolled if they met standard testing guidelines or were predicted to have a ≥2.5% mutation probability by validated models. Differential diagnoses (DDx) were generated after expert clinical genetics assessment, formulating up to 8 inherited cancer syndromes ranked by estimated likelihood. Results: 1998/2000 patients had reported MGP test results. Women constituted 81% of the sample, and 40% were Hispanic; 241 tested positive for at least 1 pathogenic mutation (12.1%) and 689 (34.5%) patients carried at least 1 variant of uncertain significance. The most frequently identified mutations were in BRCA1 (17%, n = 41), BRCA2 (15%, n = 36), APC (8%, n = 19), CHEK2 (7%, n = 17), ATM (7%, n = 16). 39 patients (16%) had at least 1 pathogenic mutation in a mismatch repair (MMR) gene ( MLH1, n = 10; MSH2, n = 10; MSH6, n = 8; PMS2, n = 11). 43 individuals (18%) had MUTYH mutations – 41 were monoallelic. Among 19 patients who had mutations in APC – 16 were APC I1307K. Only 65% (n = 159) of PV results were included in the DDx, with 35% (n = 86) of mutations not clinically suspected. Conclusions: In a diverse cohort, multiplex panel use increased genetic testing yield substantially: 35% carried pathogenic mutations in unsuspected genes, suggesting a significant contribution of expanded multiplex testing to clinical cancer risk assessment. The identification of off-target mutations broadens our understanding of cancer risk and genotype-phenotype correlations. Follow-up is ongoing to assess the clinical utility of multiplex gene panel testing. Clinical trial information: NCT02324062.

Download Full-text

Rapid Multiplex Gastrointestinal Pathogen Panel Testing Improves Antibiotic Stewardship in Patients with Suspected Infectious Diarrhea Compared with Conventional Methods

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.1652 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S624-S624 ◽

Cited By ~ 1

Author(s):

Norman Beatty ◽

David Nix ◽

Jessica August ◽

Roberto Swazo ◽

Kyle Mckeown ◽

...

Keyword(s):

Antibiotic Stewardship ◽

Infectious Diarrhea ◽

Panel Testing ◽

Gastrointestinal Pathogen ◽

Conventional Methods

Download Full-text

Diagnostic Yield of Bone Marrow and Peripheral Blood FISH Panel Testing in Clinically Suspected Myelodysplastic Syndromes and/or Acute Myeloid Leukemia

American Journal of Clinical Pathology ◽

10.1309/ajcpw10ybrmwswye ◽

2011 ◽

Vol 135 (6) ◽

pp. 915-920 ◽

Cited By ~ 38

Author(s):

Joshua F. Coleman ◽

Karl S. Theil ◽

Raymond R. Tubbs ◽

James R. Cook

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Myelodysplastic Syndromes ◽

Peripheral Blood ◽

Myeloid Leukemia ◽

Diagnostic Yield ◽

Panel Testing ◽

Acute Myeloid

Download Full-text

Comprehensive germline panel testing across cancer types: Diagnostic yield and clinical utility in 100,000 patient dataset.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e13013 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e13013-e13013

Author(s):

Shan Yang ◽

Scott T. Michalski ◽

Daniel Esteban Pineda Alvarez ◽

Stephen E Lincoln ◽

Pat W. Whitworth ◽

...

Keyword(s):

Pancreatic Cancer ◽

Genetic Testing ◽

Cancer Risk ◽

Sequence Data ◽

Diagnostic Yield ◽

Gene Panel ◽

Cancer Type ◽

Risk Genes ◽

Panel Testing ◽

Multigene Panel

e13013 Background: Over 608,000 patients with ovarian, breast, pancreatic, prostate and colorectal cancer are diagnosed each year. NCCN guidelines recommend offering germline genetic testing to all patients with ovarian and pancreatic cancer, and patients with prostate and breast cancer who meet specific criteria. We present data from ~113,000 patients who were tested on a comprehensive multigene panel and compare the diagnostic yield and clinical actionability with that of a limited gene panel strategy. Methods: We analyzed de-identified sequence data for 83 cancer-risk genes in patients with breast, ovarian, prostate and pancreatic cancer referred for germline genetic testing. Positive rates for a minimal gene panel for the respective indication were computed and compared to the positive rates when the comprehensive 83 gene panel was analyzed. Results: Four percent of 103,428 patients with breast, ovarian, pancreatic and prostate cancer harbored a BRCA1 or BRCA2 germline mutation including: breast 3.7%, ovarian 8.2%, prostate 5.2% and pancreatic 4.2%. When the comprehensive panel is applied, the overall diagnostic yield for all 113,107 patients increased to 16%. Excluding mono-allelic P/LP variants in recessive cancer-risk genes (e.g. MUTYH) reduces the diagnostic yield to 13%. Stratified by cancer type, and removing mono-allelic recessives, positive yield was: breast 11.8%, ovarian 18%, prostate 15%, and pancreatic 16%. Conclusions: These data show that comprehensive panel testing in patients with a broad range of cancers more than doubles the diagnostic yield, providing actionable results for an additional 9,737 per 113,107 patients tested. Potential germline-based clinical actionability for these patients includes: 1) pan-cancer eligibility for PARP inhibitor clinical trials, 2) FDA approved PD1 blockade for advanced cancer of ANY type and a molecular diagnosis of Lynch syndrome, 3) cascade family variant testing.This study suggests that genetic testing guidelines should be expanded to include recommendations supporting multigene panel testing in patients with cancer to improve the care of patients and their family members.

Download Full-text