Test Request Form Research Articles

Non-conformities in the Pre-analytical Phase at the Parasitology-Mycology Laboratory of the Mohammed VI University Hospital in Oujda.

The Parasitology-Mycology Laboratory's analytical process involves three stages: pre-analytical, analytical, and post-analytical. Our focus is on the pre-analytical phase (PAP). This study addresses managing PAP non-conformities at Mohammed VI University Hospital in Oujda, aligning with quality standards like ISO 15189 and GBEAand aiming to detect and resolve deviations. This 84-month retrospective study analyzed specimens at the Parasitology-Mycology lab in the Mohammed VI University Hospital in Oujda. Examination requests were made through the hospital's IT system (HOSIX), and samples were transported pneumatically. After administrative and technical checks, samples were rejected, processed, or retained for correction based on findings. Reports of non-conformities were sent to prescribers via the IT system. Data were analyzed and flowcharts were created using Microsoft Excel (Redmond, USA). During the study period, prescription errors were the most common non-conformities (65.88%; n=56), followed by sample nature errors (29.41%; n=25) and sample packaging errors (4.70%; n=4). Prescription discrepancies, mycological exams for patients on antifungal treatment or carrying Henna, and missing clinical information were the main causes. Outpatient samples accounted for 29.41% of non-conformities, while inpatient samples accounted for 70.59%. The majority of inpatient non-conformities came from the dermatology department (n=42; 49.41%). The pre-analytical phase in Parasitology-Mycology is crucial for ensuring accurate results, involving the coordination of various stages such as staff training, documentation, and non-conformity management. Prescription errors were predominant among non-conformities, followed by sample nature and packaging errors. Outpatient samples had fewer non-conformities compared to inpatient ones, possibly due to supervision by a biologist. Non-conformities lead to therapeutic, prognostic, and economic issues, underscoring the need for their reduction. Corrective actions are crucial, along with establishing policies for error detection and control. Potential causes of non-conformities can be analyzed using methods like the 5M approach. Suggestions for improvement include distributing a validated sampling manual, creating electronic test request forms, staff training, ongoing training programs, and regular meetings for information exchange. The pre-analytical phase in Parasitology-Mycology is crucial, demanding a quality-focused approach for strict adherence to procedures and traceability. Mastery of this phase ensures result reliability.

Abstract 6474: Real-world assessment of turn-around time for actionable variant testing in NSCLC in the community setting

Abstract Introduction: Rapid turnaround times (TAT) is a key parameter when evaluating the performance of cell free (cf) nucleic acid testing in clinical oncology practice. The purpose of this study was to evaluate the impact of the real-world factors on TAT for actionable variants in NSCLC, detected using commercially available molecular diagnostic tests. These test services are run in a single, centralized laboratory site and utilized primarily by practices in the community across the United States. Methods: In this study, de-identified reference data was reviewed for a ddPCR test that evaluates hotspot mutations including Single Nucleotide Variants (SNV), Insertions and Deletions (INDEL), and gene fusions. The NGS panel additionally tests for Copy Number Amplification (CNA) mutations. Specimen processing was initiated when the specimen was entered into the Laboratory Information System (LIS) and ended when the test result was ready for release. The turnaround time evaluation excluded holidays, and weekends unless the start or end-point occurred on a non-business day. Results: In total, 35,441 specimen results were analyzed. Specimens were typically received in the laboratory within 24 hours of being shipped (88% in 24 hours). Tests by ddPCR included 30,490 (86%) results, while NGS testing accounted for 4,951 (14%) of results. The average analytic lab processing TAT for the ddPCR and NGS test ranged between 2 and 3 days (ddPCR median = 24.5 hours; NGS panel median = 69.7 hours). When no information was missing on the specimen test request form, the turn-around time for the ddPCR tests averaged 30.2 hours and NGS panel averaged 66.2 hours. The percentage of missing or inaccurate information was similar when test requests were initially received. The largest impact factor impacting initiation of specimen processing was information related annotation of the stage of cancer, followed by demographic information related to patient and specimen identifiers. Conclusion: The focus on rapid turnaround times from specimen collection to results released is critical in oncology. Site and patient information, shipping methods, technologies and workflows used in the laboratory are all part of the test process and impact the release of potentially actionable results. Our study has highlighted that rapid turnaround of results is highly feasible for molecular tests being sent out from community practices across the US to a centralized reference laboratory. Specifically, actionable variant results related to NSCLC were successfully detected in the laboratory and were ready for delivery in 2 to 3 days. Automated methods for parsing the information necessary for test requests and delivery will continue to be important in maintaining rapid test result turnaround times. Citation Format: Brittany D'Alessio, Adam Stephen, Colin Cochran, Cole Hager, Zachariah Velasco, Amanda Weaver, Leisa Jackson, Janice Riley, Alisa Tubbs, Gary A. Pestano. Real-world assessment of turn-around time for actionable variant testing in NSCLC in the community setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6474.

Process improvement in automated blood cultures: Our road to better patient care

BackgroundBlood cultures (BC) are a complex multistep process susceptible to errors at multiple levels. Our study was conducted to monitor the compliance to standard operating procedures, design an intervention plan for improvement and monitor the impact of the intervention. The study design focuses on the intervention. MethodsA hospital-based prospective interventional study was carried out, monitoring various pre-analytical, analytical, and post-analytical factors in two phases. Our interventions focused on communication and training for the deficiencies noted in completeness of test request form, contamination rates, and sample loading interval. ResultsComparison between both phases showed a statistically significant improvement (p < 0.05, Chi square test) following our interventions in the completeness of test request form, contamination rates and sample loading interval. There was an improvement in the intimation of critical Gram stain from positive flagged bottles, which was not statistically significant. ConclusionOur study highlights how educational interventions can influence quality of BC. Continuous monitoring and interventions are key for quality improvement in BC processes.

A-188 Managing a Fully-automated Paperless Laboratory During a Cyber-attack

Abstract Background On 23rd Nov, 2022 a tertiary care apex medical institute in India was subject to cyberattack which disrupted the Hospital Information system (HIS) and the Laboratory Information system (LIS) servers. The services from the SmartLab, an end-to-end integrated total-lab-automation system, designed to run on paperless mode got disrupted. This is the main service laboratory with an average daily sample load of approx. 5000 including hematology, coagulation, clinical chemistry, immunoassays and serology services. Methods All lab operations were immediately shifted to manual mode. Standard operating protocols (SOPs) were designed for manual processing and circulated to OPD and IPD staff through WhatsApp. Instructions were issued to use previously used paper test-request-forms (TRFs) for sending samples. Previous stock of TRFs were retrieved from Stores and distributed to the IPD and OPDs. Staff from other areas of the hospital were mobilized.In OPD sample collection area, patients’ registrations were done by writing Patient-Id, Name, Age, Sex, Sample-Id, Treating department and Test requests in registers. A small sticker was introduced and pasted on the blood collection tubes capturing minimal relevant patient details, treating department codes and sample Id. Duplicates were pasted on OPD cards of respective patients. Traceability of patient Ids and sample Ids were maintained through data entry in registers. In the lab, the LIS were shut down on a precautionary note. Test requests corresponding to each sample Id were programmed directly on the analyzers. When done, print-outs of test results were obtained from the analyzers and hand-written results were entered by data entry operators on the TRFs. Reports were then segregated as per the treating department codes and dispatched to respective places. This continued till partial restoration of HIS services on and from 12th December, 2023. Results Despite best efforts, turn-around-time (TAT) for reports got compromised. IPD reports were prioritized and about 60% of the same could be dispatched by 9 PM same day, rest being delivered by 9 AM, next morning. TAT for OPD reports stretched up to 36 h. Inspite of introducing separate numbering systems with codes for different OPDs and IPDs, about 40% reports could not be traced to the respective OPDs. These reports were collected by the patients’ attendants from the lab itself. Manual report retrieval counters were set up outside the lab. At least 20% reports of the approx. 3000 reports generated per day remained unclaimed even after 30 days. The utilization of lab services also came down by 20%–25% during this period. About 5% reports had to be repeated with fresh samples due to inability to retrieve previous reports. The data generated during this 20-days period could not be stored electronically and hence are not available in our database now. Conclusion Cyberattacks may happen to any institution. Having a strict cyber-security protocol is a must for all institutions. However, having a back-up plan for handling such a crisis should be also in place in case of any eventuality. Sharing our experience is an endeavour to create awareness regarding the prerequisites of such a plan.

A Comparative Study on Determination of Erythrocyte Sedimentation Rate by Two Automated Erythrocyte Sedimentation Rate Analysis Techniques-Ves Matic Cube 30 and Mixrate X20 in Comparison to Modified Manual Westergren Method

BACKGROUND: Erythrocyte sedimentation rate (ESR) is a widely used simple and cost-efficient lab test for the diagnosis and follow-up of many diseases. Even though the Westergren method is considered as gold standard, it has many drawbacks such as long test time duration, infection risk to technician, and need of citrated blood sample and to overcome these limitations, automated ESR analysis techniques have been introduced. This study aimed to compare and assess the agreement as well as to analyze the correlation between the ESR values obtained by two automated ESR analysis techniques– Ves Matic Cube 30 and Mixrate-X20 against the gold standard–Modified Manual Westergren method. MATERIALS AND METHODS: Four milliliter blood samples were collected from 1174 patients who came to the Central laboratory with complete blood count and ESR test request forms, after taking informed consent. Each of these samples was subjected to ESR test in both Mixrate X20 and Ves Matic Cube 30, followed by ESR analysis through the modified manual Westergren method. All values obtained were recorded and analyzed using SPSS software. Mean, standard deviation, Bland–Altman agreement analysis, Linear regression, and Pearson's correlation coefficient analysis was done. RESULTS: Of 1174 study samples, 588 were male and 586 were female and major proportion of the study sample was in the age group of 50–59 years. Bland–Altman agreement analysis of manual ESR Vs Ves Matic cube 30, showed a mean difference of −2.44 ± 13.01 with 95% limit of agreement (LOA) between −27.93 and 23.05 whereas it was 0.05 ± 1.68 with 95% LOA between −3.24 and 3.34 for manual ESR vs Mixrate X20. Pearson's correlation coefficient for manual ESR Vs Ves Matic Cube 30 was r = 0.891 whereas r = 0.998 for manual ESR Vs Mixrate X20, indicating a strong positive correlation between ESR values obtained through manual method and both automated ESR analyzers. CONCLUSION: ESR results from both automated analyzers are agreeable to the reference method with no proportional bias statistically. However, the results from Mixrate X20 ESR analyzer correlate very well with the manual ESR, with close readings that do not affect the clinical interpretation and so can be used in clinical laboratories to optimize workflow and use of human resources.

Clinicians’ Perspectives on Glucose Tolerance Test Practices at a Tertiary Care Hospital in Coimbatore, Tamil Nadu, India

Introduction: The overuse of laboratory investigations is prevalent in hospital settings, with a major contributing factor being ignorance of test characteristics. The utilisation of laboratory tests depends on clinicians' perspectives. Aim: Present study aimed to assess clinicians' perspectives on Glucose Tolerance Test (GTT) practices in a tertiary care hospital in Coimbatore and identify any process deviations. Materials and Methods: A descriptive study was conducted in the Department of Biochemistry at PSG IMSR, Coimbatore, Tamil Nadu, India, involving 27 clinicians. Structured interviews were conducted in March 2019, covering indications for GTT, preferred glucose loads, fasting duration, blood sample collection time intervals, cut-off levels for glucose values at different time intervals (0, 1, 2, 3, 4 hours), and reference criteria used for interpretation {World Health Organisation (WHO), American Diabetes Association (ADA), The International Association of Diabetes and Pregnancy Study Groups (IADPSG)} . Test Request Forms (TRFs) for GTT over a one-month period were also analysed. Quantitative data was expressed as mean±SD, and qualitative data was expressed as frequency and percentage. Results: The structured interviews were conducted with 27 clinicians, predominantly from the Department of Obstetrics and Gynaecology. GTT usage was rare in other departments. A total of 217 TRFs were received for the one-month duration, with 94.9% indicating a glucose load of 75 grams (g). Conclusion: GTT is influenced by various factors throughout the testing process, that can have an impact on results and patient care. This study revealed differences between end- users' requirements and the laboratory's procedures. By revising the TRF and sample collection manual according to clinicians' needs, better optimisation between the laboratory and end-users of the test can be achieved.

Streamline of the gene line: Implementation of reflex homologous recombination deficiency (HRD) tumor testing in newly diagnosed ovarian cancer patients (593)

Streamline of the gene line: Implementation of reflex homologous recombination deficiency (HRD) tumor testing in newly diagnosed ovarian cancer patients (593)

Study of pre-analytical errors in clinical biochemistry laboratory in Dhiraj General hospital, Piparia

Introduction: Pre-analytical errors is the major source of mistakes in laboratory diagnostics. It includes from order of test by physician to sample is ready for analysis. Preanalytical errors are upto 70 % of errors of total diagnostic process. Objectives: 1. To evaluate the pre-analytical errors during pre-analytical testing process; 2. To formulate the possible corrective measures to be taken to minimise such errors. Materials and Methods: A prospective study was done for a period of 2 months from January 2022 to February 2022 in clinical biochemistry laboratory, central laboratory, Dhiraj general hospital, Piparia. All types of preanalytical errors were recorded. Total 15189 specimens were received during this period. Out of which 569 were sorted with pre analytical errors. Results: They were categorised as follows: Improper test request forms (n-91), Improper labelling (n-118), Insufficient sample (n-121), invalid samples (n-127), sample mix ups (n-18), Delay in sample transportation (n-32), Wrong timing for Collection (n-37), sample not received (SNR) (n-17), Sample from IV running area (n-08). Conclusion: The overall percentage of rejection found is 3.75 %. Hemolysis was the most common cause for sample rejection in clinical laboratory.

Mutations in viral nucleocapsid protein and endoRNase are discovered to associate with COVID19 hospitalization risk

SARS-CoV-2 is spreading worldwide with continuously evolving variants, some of which occur in the Spike protein and appear to increase viral transmissibility. However, variants that cause severe COVID-19 or lead to other breakthroughs have not been well characterized. To discover such viral variants, we assembled a cohort of 683 COVID-19 patients; 388 inpatients (“cases”) and 295 outpatients (“controls”) from April to August 2020 using electronically captured COVID test request forms and sequenced their viral genomes. To improve the analytical power, we accessed 7137 viral sequences in Washington State to filter out viral single nucleotide variants (SNVs) that did not have significant expansions over the collection period. Applying this filter led to the identification of 53 SNVs that were statistically significant, of which 13 SNVs each had 3 or more variant copies in the discovery cohort. Correlating these selected SNVs with case/control status, eight SNVs were found to significantly associate with inpatient status (q-values < 0.01). Using temporal synchrony, we identified a four SNV-haplotype (t19839-g28881-g28882-g28883) that was significantly associated with case/control status (Fisher’s exact p = 2.84 × 10–11). This haplotype appeared in April 2020, peaked in June, and persisted into January 2021. The association was replicated (OR = 5.46, p-value = 4.71 × 10−12) in an independent cohort of 964 COVID-19 patients (June 1, 2020 to March 31, 2021). The haplotype included a synonymous change N73N in endoRNase, and three non-synonymous changes coding residues R203K, R203S and G204R in the nucleocapsid protein. This discovery points to the potential functional role of the nucleocapsid protein in triggering “cytokine storms” and severe COVID-19 that led to hospitalization. The study further emphasizes a need for tracking and analyzing viral sequences in correlations with clinical status.

Assessment of laboratory test request forms for completeness

Background: Laboratory test request forms usually accompany patient’s samples to the laboratory, providing biodata and clinical details of the patient. This information is for purposes of identification and guiding pathologists to accurately interpret patient’s result. Clinicians however do not usually provide all the required information, thus making interpretation difficult. The frequency of such incompleteness is assessed in this study.Methods: Laboratory request forms received at the Chemical Pathology laboratory between July and September 2020 were assessed for completeness of all the required parameters. Parameters analyzed in this study included age, gender, hospital number, location, clinical information, name of requesting physician and the date of request. Frequency of missing parameters were expressed as proportions (%) of the total omissions.Results: There were 1906 request forms received during the course of this study and 789 (41.4%) of them had at least one missing parameter. Apart from patients’ names, nature of sample and the requested investigation, all other parameters were omitted at one time or the other making a total of 1117 omissions. Age (287; 25.7%) hospital number (264; 23.6%) and clinical information (246; 22%) were the most commonly omitted parameters. Majority of the omissions (69%) were from the outpatient clinics, 20% were from the wards while 10% of the forms had no ward or clinic indicated.Conclusion: Incomplete filling of laboratory test request forms is a regular occurrence among clinicians. Effort must be made to continually sensitize them of the importance of each of the required parameters to ensure a visible improvement. Â

Evaluation of pre-analytical phase performance of emergency laboratory by harmonized quality indicators and six sigma

Background: Pre-analytical errors account for up to 70% of all the errors made in laboratory diagnostics which are mostly not directly under laboratory control. Laboratories across the world have been using different Quality indicators (QIs) for identifying and quantification of pre-analytical errors. Objective of the present study is to identify the different pre-analytical errors with their frequency and to assess the pre-analytical phase performance of emergency laboratory by using harmonized Quality Indicators and six sigma metrics. Methods and material: A prospective observational study was conducted from January 2019 to December 2019 to monitor the inappropriateness of samples and test request forms. We have quantified the performance of pre-analytical phase of our emergency laboratory based on the harmonized QIs proposed by The International Federation of Clinical Chemistry Working Group on Laboratory Errors and Patient Safety (IFCC- WGLEPS) and six sigma metrics. Results: Emergency laboratory received a total of 55431 samples during Jan- 2019 to Dec- 2019. Number of pre-analytical errors were 1089 which accounted for 1.96% of total samples received. Haemolysed samples, clotted samples and samples with insufficient volume were contributed to 37%, 26% and 15% of the total pre-analytical errors respectively. Conclusions: Pre-analytical phase performance of our emergency laboratory complies with the quality specifications laid by the International Federation of Clinical Chemistry Working Group on Laboratory Errors and Patient Safety (IFCC-WGLEPS). Implementation of harmonised QIs assures the comparability of laboratory findings with different laboratories across the world.

Multigene assessment of genetic risk for women for two or more breast cancers.

The prevalence, penetrance, and spectrum of pathogenic variants that predispose women to two or more breast cancers is largely unknown. We queried clinical and genetic data from women with one or more breast cancer diagnosis who received multigene panel testing between 2013 and 2018. Clinical data were obtained from provider-completed test request forms. For each gene on the panel, a multivariable logistic regression model was constructed to test for association with risk of multiple breast cancer diagnoses. Models accounted for age of diagnosis, personal and family cancer history, and ancestry. Results are reported as odds ratios (ORs) with 95% confidence intervals (CIs). This study included 98,979 patients: 88,759 (89.7%) with a single breast cancer and 10,220 (10.3%) with ≥ 2 breast cancers. Of women with two or more breast cancers, 13.2% had a pathogenic variant in a cancer predisposition gene compared to 9.4% with a single breast cancer. BRCA1, BRCA2, CDH1, CHEK2, MSH6, PALB2, PTEN, and TP53 were significantly associated with two or more breast cancers, with ORs ranging from 1.35 for CHEK2 to 3.80 for PTEN. Overall, pathogenic variants in all breast cancer risk genes combined were associated with both metachronous (OR 1.65, 95% CI 1.53-1.79, p = 7.2 × 10-33) and synchronous (OR 1.33, 95% CI 1.19-1.50, p = 2.4 × 10-6) breast cancers. This study demonstrated that several high and moderate penetrance breast cancer susceptibility genes are associated with ≥ 2 breast cancers, affirming the association of two or more breast cancers with diverse genetic etiologies.

Immune Checkpoint Inhibitors in Urothelial Carcinoma: Recommendations for Practical Approaches to PD-L1 and Other Potential Predictive Biomarker Testing

Simple SummaryThe predominant histologic type of bladder cancer is urothelial carcinoma (UC). Programmed cell death-ligand 1 (PD-L1) expression levels in UC tumors help clinicians determine which patients are more likely to respond to immuno-oncology (IO) therapies; as such, the harmonization of PD-L1 testing in evaluating patients is increasingly important. A series of international workshops, involving renowned pathologists and oncologists, were held to develop best practice approaches to PD-L1 testing in UC. It was agreed that robust control of analytical standards is required to obtain quality PD-L1 results and that interpretation and reporting of PD-L1 require clear inter-clinician communication. Recommendations for the best practices for PD-L1 testing in UC are provided. A PD-L1 test request form for pathology laboratories was also developed and included here, encouraging communication between clinicians and pathologists, and ensuring fast and high-quality test results. Novel biomarkers being evaluated for immuno-oncology agents in UC are also briefly discussed.Immuno-oncology (IO) agents (anti–programmed cell death 1 (PD-1) and anti–programmed cell death-ligand 1 (PD-L1)) are approved as first- and second-line treatments for metastatic UC. PD-L1 expression levels in UC tumors help clinicians determine which patients are more likely to respond to IO therapies. Assays for approved IO agents use different antibodies, immunohistochemical protocols, cutoffs (defining “high” vs. “low” PD-L1 expression), and scoring algorithms. The robust control of pre-analytical and analytical standards is needed to obtain high-quality PD-L1 results. To better understand the status and perspectives of biomarker-guided patient selection for anti–PD-1 and anti–PD-L1 agents in UC, three workshops were held from December 2018 to December 2019 in Italy, Malaysia, and Spain. The primary goal was to develop recommendations for best practice approaches to PD-L1 testing in UC. Recommendations pertaining to the interpretation and reporting of the results of PD-L1 assays from experienced pathologists and oncologists from around the globe are included. A test request form for pathology laboratories was developed as a critical first step for oncologists/urologists to encourage communication between clinicians and pathologists, ensuring fast and high-quality test results. In this era of personalized medicine, we briefly discuss novel biomarkers being evaluated for IO agents in UC.

Effectiveness of computerized ordering of test using unique hospital identification number to reduce pre analytical errors - a cross sectional study in a tertiary care hospital of south India

Introduction: Laboratory test request forms are important communication device between the clinician and lab personnel. Studies have confirmed that most laboratory errors occur in the preanalytical phase clinicians are ordering investigations in paper request forms which are incomplete with regard to patient information and clinical details. Ordering the request through hospital computers using UHID number of the patient can reduce preanalytical errors. Materials and Methods: Our study evaluated 806 Biochemistry lab report forms, by systematic sampling that reached Central Biochemistry lab from August to October 2016 and the same patients report forms retrieved from hospital computer using UHID number are compared for specific variables. Results: Analysis of the study shows that information regarding sample collection time, sample receiving time in lab, reference range of the analyte, and name of the doctor are 100% entered in hospital computer but 0% entry in the paper request forms. General information of the patient 100% entry in hospital computer, in paper report form it is 98%. But clinical notes, drug history and diagnosis not mentioned in both the hospital computer and the paper request forms. Conclusion: Computerized entry and ordering of investigations by health care persons will reduce preanalytical errors. Keywords: Preanalytical errors, Computerised ordering, Biochemistry lab reports, UHID Number.

The impact of physician education regarding the importance of providing complete clinical information on the request forms of thrombophilia-screen tests atTygerberg hospital in South Africa.

BackgroundThrombophilia-screen tests are specialised haemostasis tests that are affected by numerous unique patient variables including the presence of acute thrombosis, the concomitant use of medication and patient demographics. Complete information on the request form is therefore crucial for the haematological pathologist to make patient-specific interpretation of patients’ results.ObjectivesTo assess the completeness of thrombophilia-screen test request forms and determine the impact of provision of incomplete information, on the interpretive comments generated by reporting haematological pathologists. To assess the impact of an educational session given to clinicians on the importance of providing all the relevant information on the request forms.MethodTwo retrospective audits, each covering 3 months, were performed to evaluate the completeness of demographic and clinical information on thrombophilia-screen request forms and its impact on the quality of the interpretive comments before and after an educational intervention.ResultsOne hundred and seventy-one request forms were included in the first audit and 146 in the second audit. The first audit revealed that all 171 thrombophilia-screen request forms had complete patient demographic information but none had clinical information. Haematological pathologists only made generic comments which could not be applied to a specific patient. The second audit, conducted after a physician educational session, did not reveal any improvement in the clinical information provision by the test-ordering physicians. This was reportedly due to the lack of space on the request form. The interpretive comments therefore remained generic and not patient-specific.ConclusionPhysicians’ failure to provide relevant clinical information made it impossible for pathologists to make patient-specific interpretation of the results. A single physician education session did not change the practice, reportedly due to the inappropriate design of the test request form. Further studies are required to investigate the impact of an improved request form and the planned electronic test requesting.

The Cascade of Care From Routine Point-of-Care HIV Testing at Birth: Results From an 18-Months Pilot Program in Eswatini.

Background:HIV testing at birth may improve early treatment, but concerns remain about feasibility and retention of infants in care. In 2017, point-of-care (POC) HIV birth testing was introduced into routine care at 3 high-volume maternity health facilities in Eswatini.Methods:POC birth testing was offered to HIV-exposed infants (HEI) born at, or presenting to, 3 maternities within 3 days of birth. Data were collected from a project-specific EID test request form and routine registers on all tests conducted from August 1, 2017 to November 30, 2018, including retesting at 6–8 weeks for infants testing negative at birth and six-month retention in HIV care and viral load suppression among infants testing HIV-positive at birth.Results:Of 4322 eligible HEI, 3311 (76.6%) were tested. Twenty-six HIV-infected infants were identified (positivity rate 0.8%) and 25 initiated on antiretroviral therapy (ART) (96.1%). The median time from sample collection to ART initiation was 20.50 days (IQR 14–45). Twenty-one (84%) ART-initiated infants were on ART at 6 months after initiation. Nineteen infants (90.5%) had viral load test information at 6 months and 16 (84.2%) were virally suppressed. Of 3126 HEI testing negative at birth, 3004 (96.1%) were linked to laboratory databases and 2744 (91.3%) were retested at 6–8 weeks, with 9 (0.3%) additional infants testing HIV-positive.Conclusions:Uptake of POC birth testing was high in Eswatini with low HIV positivity. Almost all infants identified HIV-positive at birth were initiated on ART, with high retention in care and viral suppression. Birth testing did not seem to significantly reduce subsequent 6–8-week testing.

Cancer risks associated with the HOXB13 c.251G&gt; A variant in men and women referred for hereditary cancer genetic testing.

e13653 Background: The HOXB13 c.251G &gt; A (p.G84E) variant is associated with increased prostate cancer risk, possibly at younger ages. Studies on this variant have focused primarily on men, although genetic testing for hereditary cancer risk is most often performed in women. There remains a need to assess whether male and female carriers of this variant have increased risk for other cancers. Methods: We identified male and female carriers of the HOXB13 c.251G &gt; A (p.G84E) variant among individuals referred for hereditary cancer panel genetic testing from October 2018 – December 2019. Non-carriers had no pathogenic variants in any gene or variants of uncertain significance in HOXB13. Personal and family (1st- and 2nd-degree relative) cancer histories were obtained from provider-completed test request forms. Multivariable logistic regression (MLR) models were conducted separately for males and females to estimate cancer risks for the variant as odds ratios (ORs), and 95% Wald confidence intervals (CIs) adjusted for age, ancestry and personal/family cancer history. Results: The analysis included 197,978 patients: 4.5% (8,998/197,978) male and 95.5% (188,980/197,978) female. The HOXB13 variant was present in 0.44% (40/8,998) of tested males, 45% (18/40) of whom had a diagnosis of prostate cancer. The variant was present in 0.32% (621/188,980) of tested females. Male carriers with prostate cancer were diagnosed at younger ages (median, 56; Interquartile ratio [IQR], 52, 62) than non-carriers (median, 63; IQR, 57,70), but this difference was not statistically significant. The MLR model calculated a 3.30 OR for prostate cancer in male carriers of c.251C &gt; A ( P = 0.01; 95% CI 1.30-8.39). In an analysis combining males and females, carriers were significantly more likely to report prostate cancer in a family member than non-carriers ( P = 3.5 x 10−7; OR 1.61, 95% CI 1.34-1.93). There was no apparent association with increased risk for other cancers among carriers versus non-carriers, or among relatives of carriers compared with relatives of non-carriers. Conclusions: The HOXB13 c.251G &gt; A (p.G84E) variant was associated with significantly increased risk of prostate cancer, confirming previously published studies. We found no evidence of association with other cancers. For unaffected male carriers, who may frequently be identified through testing of a female relative, identification of this HOXB13 variant provides an opportunity for more precise prostate cancer risk stratification and screening.

Abstract P5-01-06: Cell-free DNA (cfDNA) analysis of ESR1-mutant advanced breast cancer (aBC): Impact of subsequent therapy on mutation persistence

Abstract Background: Acquired ESR1 mutations (ESR1MUT) are common resistance mechanisms in estrogen receptor positive (ER+) aBC following aromatase inhibitor (AI) therapy. ESR1MUT can be identified using plasma-based cfDNA testing in patients with progressive aBC and may be cleared (i.e. become undetectable) following response to effective therapeutic interventions. Optimal treatment for ESR1MUTaBC has not been established. We retrospectively examined the impact of various treatments on ESR1MUT detection among patients with aBC undergoing serial cfDNA testing. Methods: The deidentified Guardant Health database was queried for patients with aBC (stage IIIB/IV) with multiple cfDNA samples, at least one of which had an ESR1MUT detected (patients tested between March 2014-March 2019 using a 54-73 gene cfDNA next-generation sequencing panel, Guardant360™). Consecutive sample pairs were identified in which the first sample had ≥1 ESR1MUT and subsequent treatment could be determined from the test request form. For patients receiving combination therapy, each therapy was counted individually (e.g. a patient receiving a CDK4/6 inhibitor and an AI would be counted once for each). Each sample pair was classified as to whether any ESR1MUT persisted in the subsequent cfDNA sample. Additionally, the change in ESR1 variant allele fraction (αVAF) between the first and subsequent sample was calculated for each ESR1MUT identified. We considered ESR1MUT that had lower VAF on the subsequent sample (e.g. a negative αVAF) as evidence of a therapeutic response against ESR1MUT for the purpose of this study. The proportion of sample pairs in which the ESR1MUT was cleared, as well as the proportion of any ESR1MUT with decreased VAF was compared by treatment type using Fisher’s exact test. Results: A total of 262 ESR1 mutations were found in 167 unique sample pairs from 124 aBC patients. The median time between sample collection for each pair was 17 weeks (range: 0.7 - 133 weeks). ESR1MUT were cleared in a minority (30/167, 18%) of sample pairs with an overall minimal change in observed VAF (median αVAF of -0.01). A negative ESR1MUT VAF was observed for more than half of all ESR1MUT in patients receiving certain endocrine therapies, including fulvestrant, tamoxifen, and goserelin, and non-endocrine therapies, including chemotherapy, anti-HER2, and CDK4/6 inhibitors, suggesting these agents may still have some efficacy against ESR1MUT (Table 1). The proportion of sample pairs with ESR1MUT clearance was not significantly different for those on endocrine therapy versus those not on endocrine therapy (16% vs 19%). Similarly, there was no significant difference between these groups when examining the proportion of ESR1MUT with decreased VAF (50% vs 50%). Conclusions: In this exploratory analysis of serial cfDNA testing of ESR1MUTin aBC, some variation was observed in the efficacy of commonly used therapies as measured by the proportion of sample pairs with clearance of ESR1MUT and by the proportion of all ESR1MUT with a decreased VAF. We believe these data may be useful in guiding future analysis into optimal therapy for patients with ESR1MUTaBC. Notably, none of the therapies stood out as having promising efficacy against a large proportion of ESR1MUT subclones suggesting that additional therapeutic options may be needed to effectively target and provide long-term disease control of ESR1MUT aBC. Table 1. Temporal changes in ESR1MUT in cfDNA by therapy in aBCTreatmentNo. Sample PairsESR1MUT ClearedNo. ESR1MUTESR1MUT with VAF DecreaseMedian αVAFAI2520%3842%0.09SERD (Fulvestrant)3312%4553%-0.03Estrogen Receptor Agonist (Tamoxifen)30%667%-0.18GnRH Agonist (Goserelin)813%1464%-0.09Chemotherapy8319%13052%-0.09Anti-HER2229%2752%-0.02Everolimus2512%3749%0.05CDK4/6 Inhibitor3119%4953%-0.05Immune Checkpoint520%838%0.02Any Endocrine Therapy6316%9250%-0.01No Endocrine Therapy10419%17050%-0.01OVERALL16718%26250%-0.01 Citation Format: Caroline M. Weipert, Thereasa A. Rich, Rebecca J. Nagy, Sarah Croessmann, Ben H. Park, Joyce O'Shaughnessy, Mohammad Nezami, Massimo Cristofanilli, Aditya Bardia, Richard B. Lanman. Cell-free DNA (cfDNA) analysis of ESR1-mutant advanced breast cancer (aBC): Impact of subsequent therapy on mutation persistence [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 P5-01-06.

Inadequate clinical data on Pap test request form: Where are we headed in the era of precision medicine?

The request form accompanying any sample to a clinical laboratory constitutes an important communication tool between the clinician and the laboratory personnel. Much has been written about the inadequacy of pertinent clinical data on the request slips for hematology and biochemistry tests and its impact on the subsequent test interpretation and error liability. Although the cytology laboratories, including those performing cervical cytology, have to deal with a similar problem of lack of clinical information critical to the proper interpretation of cytomorphologic features, the issue has not been attended to or reported adequately in the literature. This article attempts to explore this topic of inadequate clinical data on Pap test request form from multiple perspectives and suggest possible ways to circumvent this age-old problem. These recommendations may be tailor-made and adopted as per the individual laboratory’s logistics.

Task shifting for point-of-care early infant diagnosis: a comparison of the quality of testing between nurses and laboratory personnel in Zimbabwe

BackgroundTo decentralize point-of-care early infant diagnosis (POC EID), task shifting to cadres such as nurses is important. However, this should not compromise quality of testing through generating high rates of internal quality control (IQC) failures and long result turnaround times. We used data from a POC EID project in Zimbabwe to compare IQC rates and result return to caregivers for samples run on a POC EID technology (Alere q HIV 1/2 Detect) between nurses and laboratory-trained personnel to assess effects of task shifting on quality of testing.MethodsThis cross-sectional retrospective study used data from all 46 sites (10 hub and 36 spoke sites in Zimbabwe that piloted POC EID for routine clinical use from December 2016 to June 2017). IQC failure rates were downloaded from each POC EID platform and exported to excel to analyze IQC failure rates by type of operator. Turnaround time (TAT) from sample collection to issuing of results to caregiver was extracted from the EID test request form and uploaded into a project specific Excel-based database for analysis.ResultsA total of 1847 tests were conducted by 45 testers (12 laboratory-trained and 33 non-laboratory-trained personnel), including 165 errors. There were no significant differences in IQC failure rates between non-laboratory testers (137 [9.2%] of 14830 tests) and specialized laboratory-trained (28 [7.7%] of 364 tests; p = 0.354). Over time, IQC failure rates for both non-laboratory (χ2 = 18.5, p < 0.000) and specialized laboratory-trained testers (χ2 = 8.7, p < 0.003) decreased significantly. There were similar proportions of clients who were issued with results between samples processed by non-laboratory testers (1283 [98.9%] of 1297 tests) and samples processed by specialized laboratory-trained testers (315 [98.7%] of 319 tests; p = 0.790). The overall median turnaround time from sample collection to receipt of results by caregiver for samples run by laboratory-specialized testers was not statistically different from samples run by non-laboratory-specialized testers (1 day [IQR 0–3] versus 0 days [IQR 0–2]; p = 0.583).ConclusionsSimilar IQC failure rates and TATs between non-laboratory and specialized laboratory-trained operators suggest that non-specialized laboratory-trained personnel can perform POC EID equally well as specialized laboratory personnel.