Royal College Of Pathologists Of Australasia Quality Assurance Programs Research Articles

RCPAQAP audit of antimicrobial reporting in Australian and New Zealand laboratories: opportunities for laboratory contribution to antimicrobial stewardship.

A 2017 laboratory survey conducted by the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) asked participants which antimicrobials they would report for given organisms in either blood or urine cultures in order to identify opportunities for improvement of antimicrobial reporting. Over-reporting was defined as reporting of broad-spectrum antimicrobials on isolates susceptible to narrow-spectrum antimicrobials. Inappropriate reporting was defined as reporting antimicrobials not appropriate for the site of infection. For a fully susceptible Escherichia coli in blood culture, 65% of laboratories (55/84) over-reported at least one antimicrobial. Importantly, 15% (10/65) of laboratories that tested meropenem reported the result. A significant proportion of laboratories (12%, 10/84) reported antimicrobials generally considered inappropriate for treatment of bacteraemia on blood culture isolates. Overall, 82% (77/94) of laboratories either over-reported or inappropriately reported at least one antimicrobial. This survey identifies significant opportunities for improvement and standardization of 'cascade' or 'selective' reporting of antimicrobials and highlights ways in which microbiology laboratories can contribute to antimicrobial stewardship and judicious use of antimicrobials.

Informatics External Quality Assurance (IEQA) Down Under: evaluation of a pilot implementation

AbstractExternal quality assurance (EQA) provides ongoing evaluation to verify that laboratory medicine results conform to quality standards expected for patient care. While attention has focused predominantly on test accuracy, the diagnostic phases, consisting of pre- and post-laboratory phases of testing, have thus far lagged in the development of an appropriate diagnostic-phase EQA program. One of the challenges faced by Australian EQA has been a lack of standardisation or “harmonisation” resulting from variations in reporting between different laboratory medicine providers. This may introduce interpretation errors and misunderstanding of results by clinicians, resulting in a threat to patient safety. While initiatives such as the Australian Pathology Information, Terminology and Units Standardisation (PITUS) program have produced Standards for Pathology Informatics in Australia (SPIA), conformity to these requires regular monitoring to maintain integrity of data between sending (laboratory medicine providers) and receiving (physicians, MyHealth Record, registries) organisations’ systems. The PITUS 16 Informatics EQA (IEQA) Project together with the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) has created a system to perform quality assurance on the electronic laboratory message when the laboratory sends a result back to the EQA provider. The purpose of this study was to perform a small scale pilot implementation of an IEQA protocol, which was performed to test the suitability of the system to check compliance of existing Health Level-7 (HL7 v2.4) reporting standards localised and constrained by the RCPA SPIA. Here, we present key milestones from the implementation, including: (1) software development, (2) installation, and verification of the system and communication services, (3) implementation of the IEQA program and compliance testing of the received HL7 v2.4 report messages, (4) compilation of a draft Informatics Program Survey Report for each laboratory and (5) review consisting of presentation of a report showing the compliance checking tool to each participating laboratory.

Informatics External Quality Assurance (IEQA) Down Under: evaluation of a pilot implementation

External quality assurance (EQA) provides ongoing evaluation to verify that laboratory medicine results conform to quality standards expected for patient care. While attention has focused predominantly on test accuracy, the diagnostic phases, consisting of pre- and post-laboratory phases of testing, have thus far lagged in the development of an appropriate diagnostic-phase EQA program. One of the challenges faced by Australian EQA has been a lack of standardisation or “harmonisation” resulting from variations in reporting between different laboratory medicine providers. This may introduce interpretation errors and misunderstanding of results by clinicians, resulting in a threat to patient safety. While initiatives such as the Australian Pathology Information, Terminology and Units Standardisation (PITUS) program have produced Standards for Pathology Informatics in Australia (SPIA), conformity to these requires regular monitoring to maintain integrity of data between sending (laboratory medicine providers) and receiving (physicians, MyHealth Record, registries) organisations’ systems. The PITUS 16 Informatics EQA (IEQA) Project together with the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) has created a system to perform quality assurance on the electronic laboratory message when the laboratory sends a result back to the EQA provider. The purpose of this study was to perform a small scale pilot implementation of an IEQA protocol, which was performed to test the suitability of the system to check compliance of existing Health Level-7 (HL7 v2.4) reporting standards localised and constrained by the RCPA SPIA. Here, we present key milestones from the implementation, including: (1) software development, (2) installation, and verification of the system and communication services, (3) implementation of the IEQA program and compliance testing of the received HL7 v2.4 report messages, (4) compilation of a draft Informatics Program Survey Report for each laboratory and (5) review consisting of presentation of a report showing the compliance checking tool to each participating laboratory.

High rates of variation in HLA-DQ2/DQ8 testing for coeliac disease: results from an RCPAQAP pilot program

AimCoeliac disease(CD) is a highly prevalent, gluten-dependent, autoimmune enteropathy. While the diagnosis is based on serological and histological criteria, genotyping of the human leucocyte antigens (HLA) DQ2 and DQ8 has...

The RCPA Quality Assurance Program in Dermatopathology: A Retrospective Review.

To review the Royal College of Pathologists of Australasia (RCPA) Quality Assurance Program Dermatopathology module from 2005 to 2016 to assess diagnostic performance, changes over time, and areas of diagnostic difficulty. The computerized records of the RCPA Dermatopathology subspecialist module were reviewed. Cases were categorized into groups including nonneoplastic disorders, neoplasms, and cases with multiple diagnoses. The performance of participants over time in each of these categories and in more specific areas (including melanocytic and adnexal neoplasms) was assessed. Cases which showed high rates of discordant responses were specifically reviewed. One hundred sixteen cases circulated over 10 years were evaluated. The overall concordance rate was 77%, with a major discordance rate of 7%. There was a slightly higher concordance rate for neoplasms compared with nonneoplastic lesions (80% vs. 74%). Specific areas associated with lower concordance rates included classification of adnexal tumors and identification of multiple pathologies. A spindle cell nevus of Reed yielded a 40% discordance rate, with most misclassifications indicating melanoma. The RCPA quality assurance program module has circulated a wide range of common and uncommon cases to participants over the 12 years studied, highlighting a low but important rate of major discordant responses. Melanocytic lesions, hematolymphoid infiltrates, adnexal tumors, and identification of multiple pathologies are identified as areas worthy of particular attention in quality improvement activities.

RCPAQAP – Parasitology: Processing, finding and identifying

The Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) for parasitology supplies the QAP to 158 laboratories throughout the southern hemisphere. Modern technology has provided a molecular screening test for a limited range of parasites. Most laboratories still rely on the traditional methods for the diagnosis of gastrointestinal parasites. The traditional techniques rely on some means of concentration and microscopy.

Multi-drug resistant gram-negative bacteria: Results of RCPAQAP microbiology program pilot study

Background: Multi-antibiotic resistant (MDR) Gram-negative rods (GNRs), especially carbapenem-resistant Enterobacteriaceae (CREs), are a significant threat to public health globally. The Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) is developing an EQA module for detecting this type of organism.

The Royal College of Pathologists of Australasia Quality Assurance Program: Immunohistochemistry Breast Marker Audit Overview 2005-2015.

The Royal College of Pathologists of Australasia Quality Assurance Program (RCPAQAP) Anatomical Pathology provides a comprehensive External Quality Assurance (EQA) exercise to review the reporting of immunohistochemistry (IHC) and in-situ hybridization (ISH) breast markers through an audit of clinical results. The aim of this exercise was to provide information regarding the quality of breast marker testing within clinical laboratories from 2005 to 2015. This comprehensive audit included estrogen, progesterone, and HER2 marker reporting. This was an important quality assurance activity established in response to ongoing difficulties experienced in laboratories in this area of testing.

P1: INTER‐LABORATORY VARIATION IN THE MEASUREMENT OF SERUM TRYPTASE

Serum tryptase quantitation is used as a marker of mast cell activation. Levels are elevated in allergic (anaphylactic) reactions, but can also be chronically high in conditions such as mastocytosis and haematological neoplasms. Blood samples for measurement of tryptase levels in the assessment of allergic conditions are optimally obtained 15 min to 3 h after symptom onset. Serial measurement of tryptase levels and measurement of a baseline level after recovery are reported to be more useful than measurement at only one point in time in this assessment. In all routine clinical laboratories enrolled in the RCPAQAP Tryptase Program levels of serum tryptase are measured using the Thermo Fisher ImmunoCAP systems. Considering this, there should be limited methodological variation in results obtained across laboratories. A retrospective review of results from January 2014 to June 2017 from the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) tryptase module was undertaken. Average inter laboratory coefficient of variation (CV%) over a range of serum tryptase levels were reviewed. Twenty-eight samples were analysed, with 20–27 results submitted for each sample. Mean serum tryptase values ranged from 3.3 to 127 μg/L. The average CV% of all samples was 8% (range 4.4–12.7%). Good inter laboratory variation was seen at all levels. The inter laboratory CV% of serum tryptase as measured on the ImmunoCAP system shows good reproducibility across a range of levels.

Full Blood Count - Internal QC Protocol: a review by the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) Pty Ltd - Haematology.

The RCPAQAP (Royal College of Pathologists of Australasia Quality Assurance Program) Haematology has undertaken an exercise to review the internal quality control protocol for full blood count (FBC) instrumentation as well as review the action taken by laboratories when nonconforming results are evident in the RCPAQAP proficiency testing reports. A questionnaire was sent to laboratories enrolled in the RCPAQAP FBC module. Laboratories were asked to provide information with regard to the type of control measures used within their testing environment that would trigger alerts for nonconforming events. The questionnaire also reviewed the action taken by laboratories in response to nonconforming test results in their external QA reports. A total of 253 of the 850 laboratories enrolled in the FBC module returned a response to the questionnaire, which identified variation in the QC protocol used to identify nonconforming events on the FBC analyser, including the type of controls, control levels processed and the frequency of use. This questionnaire identified variation in the internal QC protocol used by laboratories, including the types of control measures used and the rules applied to identify nonconforming events. However, the majority of laboratories appear to follow the most favourable choice of actions supplied when reviewing results of external QA data.

Ebola Preparedness: Diagnosis Improvement Using Rapid Approaches for Proficiency Testing

The unprecedented 2015 Ebolavirus (EBOV) outbreak in West Africa was declared a public health emergency, making diagnosis and quality of testing a global issue. The accuracy of laboratory diagnostic capacity for EBOV was assessed in 2014 to 2016 using a proficiency testing (PT) strategy developed by the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) in Biosecurity. Following a literature search, EBOV-specific gene targets were ranked according to the frequency of their use in published methods. The most commonly used gene regions (nucleoprotein [NP], glycoprotein [GP], and RNA-dependent RNA polymerase [L]) were selected for the design of in vitro RNA transcripts to be included in the simulated EBOV specimens used for EBOV detection with PCR-based assays. Specimens were tested for stability and found to be stable on long-term storage (1 year) at -80°C and on shorter-term storage in lyophilized form (1 week at ambient temperature and a subsequent week at -80°C). These specimens were used in three EBOV PTs offered from April 2014 to March 2016. In the first and third PTs, all laboratories (3/3 and 9/9, respectively) correctly identified specimens containing EBOV RNA transcripts, while in the second PT, all but one laboratory (5/6) correctly confirmed the presence of EBOV. The EBOV PT panel was useful for ensuring the competency of laboratories in detecting EBOV in the absence of readily available clinical samples. The simulated EBOV specimen was safe, stable, and reliable and can be used in lyophilized form for future EBOV PT programs, allowing simplicity of transport.

The effect of the direct factor Xa inhibitors apixaban and rivaroxaban on haemostasis tests: a comprehensive assessment using in vitro and ex vivo samples

The direct oral anticoagulants (DOACs), now including dabigatran, apixaban and rivaroxaban, have given clinicians alternative options to low molecular weight heparins (LMWHs) and vitamin K antagonist therapy, including warfarin, for the treatment of atrial fibrillation and treatment and prevention of venous thromboembolic (VTE) disease. DOACs have been successfully marketed as not requiring monitoring; however, there will be situations where clinicians will request laboratory testing, including emergency department admissions for haemorrhage or thrombosis, or emergency surgical interventions. We report the results of several Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) surveys using apixaban and rivaroxaban spiked samples to either assess the suitability of certain potential screening or drug-quantifying assays, for assessment of drug presence or absence or measurement of levels, as well as assessing potential interference in a wide variety of haemostasis assays. We also include additional evaluations using exvivo samples from patients given apixaban and rivaroxaban for various therapeutic reasons. The prothrombin time (PT) and activated partial thromboplastin time (APTT) show better sensitivity with rivaroxaban than apixaban. Anti-Xa assays show good concordance and reproducibility with expected drug levels; however, availability of these assays may be limited to larger institutions. Interference of apixaban and rivaroxaban on haemostasis testing extends beyond routine coagulation assays to encompass a plethora of specialised assays, including factor assays, lupus inhibitor, and FVIII inhibitor estimation. In conclusion, this report highlights the influence of these drugs on most tests performed in haemostasis laboratories, and the potential for some tests to predict the presence, absence or level of these drugs in plasma.

A candidate reference method using ICP-MS for sweat chloride quantification

The aim of the study was to develop a method for sweat chloride (Cl) quantification using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) to present to the Joint Committee for Traceability in Laboratory Medicine (JCTLM) as a candidate reference method for the diagnosis of cystic fibrosis (CF). Calibration standards were prepared from sodium chloride (NaCl) to cover the expected range of sweat Cl values. Germanium (Ge) and scandium (Sc) were selected as on-line (instrument based) internal standards (IS) and gallium (Ga) as the off-line (sample based) IS. The method was validated through linearity, accuracy and imprecision studies as well as enrolment into the Royal College of Pathologists of Australasia Quality Assurance Program (RCPAQAP) for sweat electrolyte testing. Two variations of the ICP-MS method were developed, an on-line and off-line IS, and compared. Linearity was determined up to 225 mmol/L with a limit of quantitation of 7.4 mmol/L. The off-line IS demonstrated increased accuracy through the RCPAQAP performance assessment (CV of 1.9%, bias of 1.5 mmol/L) in comparison to the on-line IS (CV of 8.0%, bias of 3.8 mmol/L). Paired t-tests confirmed no significant differences between sample means of the two IS methods (p=0.53) or from each method against the RCPAQAP target values (p=0.08 and p=0.29). Both on and off-line IS methods generated highly reproducible results and excellent linear comparison to the RCPAQAP target results. ICP-MS is a highly accurate method with a low limit of quantitation for sweat Cl analysis and should be recognised as a candidate reference method for the monitoring and diagnosis of CF. Laboratories that currently practice sweat Cl analysis using ICP-MS should include an off-line IS to help negate any pre-analytical errors.

The effect of dabigatran on haemostasis tests: a comprehensive assessment using in vitro and ex vivo samples

The new direct oral anticoagulants (DOACS) dabigatran, rivaroxaban, apixaban and edoxaban provide alternatives to warfarin for treatment and prevention of atrial fibrillation and venous thromboembolic disease in various settings. These have been developed as not requiring laboratory monitoring; however, under certain clinical situations, including recent haemorrhage/thrombosis, emergency surgical procedures, testing may be indicated.The aim of this study was to assess findings of haemostasis laboratory tests for one of the DOACs, dabigatran (Pradaxa), tested across a wide range of laboratory assays.Laboratories (n = 72) enrolled in the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) Haematology program were sent set(s) of seven dabigatran spiked plasma samples covering the concentration 0-800 ng/mL. Also, 30 ex vivo patient samples under therapy with dabigatran were assessed.Prothrombin time and activated partial thromboplastin time assays showed some sensitivity to dabigatran; however, a normal result could not inform on drug exclusion. The thrombin time (TT) was very sensitive to dabigatran, and a normal TT could generally be used for drug exclusion. More specialised assays such as the Hemoclot, a direct thrombin inhibition assay, and in-house dilute TT methods, showed good reproducibility and concordance with expected drug levels assessed by mass spectrometry and were effective to quantify drug levels. Dabigatran also affected factor assays, lupus anticoagulant and factor inhibitor measurement, leading to potential misinterpretation of test results. Ex vivo sample testing provided similar and extended information.Dabigatran affects many haemostasis tests. Some can be used to predict the presence, absence or quantity of dabigatran in patient plasma. For others, interference may lead to false conclusions regarding patients' haemostatic status.

External Quality Assessment/Proficiency Testing and Internal Quality Control for the PFA-100 and PFA-200: An Update

Platelet function testing is an essential component of comprehensive hemostasis evaluation within the framework of bleeding and/or bruising investigations, and it may also be performed to evaluate antiplatelet medication effects. Globally, the platelet function analyzer (PFA)-100 (Siemens Healthcare, Marburg, Germany) is the most used primary hemostasis-screening instrument and has also been recently remodeled/upgraded to the PFA-200. The PFA-100 is sensitive to a wide range of associated disorders, including platelet function defects and von Willebrand disease (VWD), as well as to various antiplatelet medications. The PFA-100 is also useful in therapy monitoring, especially in VWD. External quality assessment (EQA) (or proficiency testing) and internal quality control (IQC) are critical to ensuring quality of test practice, inclusive of all hemostasis tests. However, both EQA and IQC for platelet function testing, including the PFA-100, is logistically challenging, given theoretical requirements for production, storage, and shipment of large volumes of "stabilized" normal and pathological blood/platelets covering both normal function plus a wide variety of potential defects. We accordingly describe the development and testing of novel feasible approaches to both EQA and IQC of PFA-100/PFA-200 instruments, whereby a range of formulated "platelet function antagonist" materials are utilized. For EQA purposes, these are distributed to participants, and citrated normal whole blood collected on site is then added locally, thereby creating test material that can be locally evaluated. Several exercises have been conducted by the Royal College of Pathologists of Australasia Quality Assurance Program (RCPAQAP) over the past 6 years. A total of 26 challenges, with most designed to mimic moderate to severe primary hemostasis defects, have been tested in 26 to 50 laboratories depending on the year of dispatch. Numerical results for PFA-100/PFA-200 closure times (CTs) and interpretive comments supplied by participants are analyzed by the RCPAQAP. During this period, reported CTs for each challenge were within limits of expectation and good reproducibility was evidenced by repeated challenges. Coefficients of variation (CVs) generated for challenges using the two major PFA-100/PFA-200 cartridge types (collagen/adenosine diphosphate and collagen/epinephrine) are always similar to those obtained using native whole blood, and in general range from 15 to 25%. Interpretations are also in general consistent with expectations and test data provided by laboratories. The EQA created material has also been assessed within the context of possible IQC material. In conclusion, EQA and IQC processes for the PFA-100/PFA-200 have been developed that include highly reproducible test challenge processes, not only supporting the concept that EQA/IQC is possible for platelet function testing but also providing a valuable mechanism for monitoring and improving laboratory performance in this area.

Performance monitoring and transfusion QAP performance levels

This presentation will endeavour to provide an understanding of Performance Monitoring in Quality Assurance of Transfusion as measured by a project undertaken by the Royal College of Pathologists of Australasia (RCPA) Quality Assurance Program (QAP) in 2012. In 2001 the Commonwealth Department of Health and Ageing (DoHA) sought proposals to undertake an evaluation of Australian pathology laboratory accreditation arrangements. Recommendations from the report were that (1) the DoHA and the Health Insurance Commission seek the cooperation of the RCPA QAP to establish explicit external quality assurance performance criteria and a mechanism for the RCPA QAP to identify relatively poorly performing laboratories; (2) RCPA QAP and other external quality assurance providers regularly submit to the National Association of Testing Authorities (NATA) reports identifying laboratories that are poorly performing according to these agreed performance criteria. The review process included establishment of a methodology/scoring system; a retrospective data analysis; establishment of criteria for acceptable performance based on the retrospective data analysis and reasonable expectations for completing a corrective action. Information and results from QAP surveys was used to assess individual participant data against established criteria to provide laboratories of an objective measure of their performance relative to their peers whilst meeting the needs of the performance review process.

Performance monitoring in anatomical pathology

In 2012, the Royal College of Pathologists of Australasia (RCPA) Anatomical Pathology Quality Assurance Program (QAP) will introduce a pilot for performance monitoring in the General and Breast Diagnostic Modules. The Anatomical Pathology Performance Review Committee has developed a set of criteria for Diagnostic Pathology assessment. If any of the following criteria apply, a participant will be considered to be outside criteria for satisfactory performance: <h3>Participation</h3> 1 x survey non-participation. <h3>Performance of test</h3> ≥ 3 x in the bottom 10% survey rank, over 3 years; thereafter, if in bottom 10% rank subsequently. Average survey rank ≤10%, over 3 years; thereafter, if average survey rank is < the average survey rank on the previous survey; thereafter reset scoring if > 10% 3 x consecutively. If average discordant sum is ≥1.50 AND number of surveys completed is ≥2 (in rolling 12 month period); thereafter, if ≥1.50 AND ≥2 surveys completed AND survey contains discordant result. ≥5 non-concordant results per survey. <h3>Notification</h3> RCPA QAP response to notifiable unsatisfactory performance will initially take the form of letter to participants; subsequent deviations from the outlined criteria may result in copies of notifications forwarded also to National Association of Testing Authorities (NATA).

RCPA QAP chemical pathology

The Chemical Pathology section of the Royal College of Pathologists of Australasia Quality Assurance Program (RCPA-QAP) continues to grow in number of participants, number of programs and number of analytes. Developments also continue in data analysis. The new analytes which were introduced in 2009 included red cell folate (from haematology), whole blood HbA1c, plasma metanephrines and point of care testing for urine albumin/creatinine ratio. New analytes for 2010 include bile acids vitamin C and on-site toxicology. Proposals for revision of the allowable limits of performance and calculations of standard deviation and coefficient of variation are also being prepared. These issues will be discussed in the session using the latest information available.

Frequency and reliability of oestrogen receptor, progesterone receptor and HER2 in breast carcinoma determined by immunohistochemistry in Australasia: results of the RCPA Quality Assurance Program

Background and Aims:Immunohistochemistry (IHC) has replaced radioligand binding assay for the determination of oestrogen receptor (ER) status in breast carcinoma. IHC is also used for assessment of progesterone receptor (PR)...