Result of a Pilot External Quality Assessment Scheme for Clinical Diagnosis of Inherited Metabolic Disorders in China.

BACKGROUND: We aimed to evaluate the diagnostic capabilities of Chinese laboratories for inherited metabolic disorders (IMDs) using gas chromatography-mass spectrometry (GC-MS) on urine samples. Meanwhile, based on the result of the pilot external quality assessment (EQA) scheme, we hope to establish a standardized and reliable procedure for future EQA practice. METHODS: We recruited laboratories that participated in the EQA of quantitative analysis of urinary organic acids with GC-MS before joining the surveys. In each survey, a set of five real urine samples was distributed to each participant. The participants should analyze the sample by GC-MS and report the "analytical result", "the most likely diagnosis", and "recommendation for further tests" to the NCCL before the deadline. RESULTS: A total of 21 laboratories participated in the scheme. The pass rates were 94.4% in 2020 and 89.5% in 2021. For all eight IMDs tested, the analytical proficiency rates ranged from 84.7% - 100%, and the interpretational performance rate ranged from 88.2% - 97.0%. The performance on hyperphenylalaninemia (HPA), 3-methylcrotonyl-CoA carboxylase deficiency (MCCD), and ethylmalonic encephalopathy (EE) samples were not satisfactory. CONCLUSIONS: In general, the participants of this pilot EQA scheme are equipped with the basic capability for qualitative organic acid analysis and interpretation of the results. Limited by the small size of laboratories and samples involved, this activity could not fully reflect the state of clinical practice of Chinese laboratories. NCCL will improve the EQA scheme and implement more EQA activities in the future.

Developing a competency assessment framework for medical laboratory technologists in primary healthcare settings in India.

Medical Laboratory Technologists play a significant role in delivering quality laboratory Services. The competency assessment of MLTs is a critical driver for enhancing primary healthcare performance. While several countries have developed competency frameworks for MLTs in primary care, such frameworks are lacking in the Indian context. This study aimed to create a competency assessment framework to assess the competencies of MLTs (Medical Laboratory Technologists) working in Indian public primary healthcare facilities. The research followed a five-step process, starting with a review of existing literature on MLTs' competencies in primary healthcare. Expert consultations were then conducted to establish a consensus on these competencies. Following this, assessment tools were developed based on the literature review and expert input. Another round of expert consultations was held to ensure agreement on the assessment tools. Finally, the developed tools were tested in a public primary healthcare facility. The literature review identified 86 competencies across 11 domains: safe work practices, data/ sample collection, specimen preparation equipment instruments and regiments, assessment and analysis, recording and reporting, infection control, quality management, critical thinking, communication and interaction, and professional practice. Expert consultations resulted in the consensus on ninety-five competencies in ten domains of MLTs in primary healthcare settings. Competencies for each domain were discussed and agreed upon. A competency assessment tool was finalized after unanimous agreement among experts. The competency assessment tool was later finalized after pre-testing on MLTs in a clinical laboratory part of a public primary health care facility. This study successfully developed a competency assessment framework for in-service MLTs in Indian public primary healthcare settings. The framework encompasses ninety-five competencies covering ten domains of MLT responsibilities. It provides a comprehensive tool for assessing MLT's competencies and identifying competency gaps. The framework can be used to capacitate MLTs, improve their performance in primary healthcare settings, and enhance the delivery of healthcare services in India. It bridges a critical gap in the existing literature and can aid as a valuable resource for policymakers, educators, and healthcare professionals involved in practicing medical laboratory Services in primary healthcare settings.

Quality assessment of malaria microscopic diagnosis at the Aristide Le Dantec University Hospital of Dakar, Senegal, in 2020.

BACKGROUND: Following WHO guidelines, microscopy is the gold standard for malaria diagnosis in endemic countries. The Parasitology-Mycology laboratory (LPM) is the National Reference Laboratory and is currently undergoing ISO 15189 accreditation. In this context, we assessed the performance of the laboratory by confirming the reliability and the accuracy of results obtained in accordance with the requirements of the ISO 15189 standards. This study aimed to verify the method of microscopic diagnosis of malaria at the LPM, in the Aristide Le Dantec hospital (HALD) in Dakar, Senegal. METHODS: This is a validation/verification study conducted from June to August 2020. Twenty (20) microscopic slides of thick/thin blood smear with known parasite densities (PD) selected from the Cheick Anta Diop University malaria slide bank in Dakar were used for this assessment. Six (6) were used to assess microscopists' ability to determine PD and fourteen (14) slides were used for detection (positive vs negative) and identification of parasites. Four (4) LPM-HALD microscopists read and recorded their results on prepared sheets. Data analysis was done with Microsoft Excel 2010 software. RESULTS: A minimum threshold of 50% concordance was used for comparison. Of the twenty (20) slides read, 100% concordance was obtained on eight (8) detection (positive vs negative) slides. Four (4) out of the six (6) parasite density evaluation slides obtained a concordance of less than 50%. Thirteen (13) out of the fourteen (14) identification slides obtained a concordance greater than 50%. Only one (1) identification slide obtained zero agreement from the microscopists. For species identification a concordance greater than 80% was noted and the microscopists obtained scores between 0.20 and 0.4 on a scale of 0 to 1 for parasite density reading. The microscopists obtained 100% precision, sensitivity, specificity and both negative and positive predictive values. CONCLUSION: This work demonstrated that the microscopic method of malaria diagnosis used in the LPM/HALD is in accordance with the requirements of WHO and ISO 15189. Further training of microscopists may be needed to maintain competency.

External quality assessment for molecular detection of Ureaplasma urealyticum in China.

BACKGROUND AND AIMS: A pilot external quality assessment (EQA) scheme for molecular detection of Ureaplasma urealyticum (UU) was conducted by the National Center for Clinical Laboratories (NCCL) to evaluate the testing capabilities of clinical laboratories and the actual performance of DNA-based nucleic acid amplification tests (NAAT) and RNA-based NAATs when applied in clinical settings. MATERIALS AND METHODS: The EQA panel contained twelve lyophilized samples, including positive samples containing inactivated cell culture supernatants of UU at different concentrations and sterile saline for negative samples. The positive samples were further divided into three groups of high, moderate and low concentrations. The panels were distributed to the participants and the datasets were analyzed according to the qualitative results. RESULTS: A total of 365 laboratories participated in the EQA scheme, and 360 results submitted by 338 laboratories were collected, of which 96.11 % (346/360) of the returned results and 95.86 % (324/338) of the laboratories were deemed competent. The positive percentage agreement (PPA) was ≥ 97.5 % for high and moderate concentration samples, but varied significantly for low concentration samples, decreasing from 86.94 % to 51.94 % as the sample concentration decreased. Additionally, for low concentration samples, RNA-based NAAT showed higher PPAs than DNA-based NAATs, but these results were specific to UU supernatants used in this study. CONCLUSION: Most of UU detection assays employed by the participants were generally consistent with their estimated limit of detection (LOD), and the majority of participants can reliably detect UU samples with high and moderate concentrations, while the poor analytical performance for low concentration samples requires further improvement and optimization.

Optimizing the Positioning of Detectors for Improved Counting Efficiencies Using Monte Carlo Simulations.

ABSTRACT: The Human Monitoring Laboratory (HML) at Health Canada updated its whole-body counter with four new electrically cooled HPGe detectors. To optimize the counting efficiency of the new system, Monte Carlo simulation was used to model the whole-body counter using a reference BOMAB male phantom. The resulting modeled counting efficiencies showed that the best position to install the four new detectors could be obtained without performing laborious real measurements, thereby reducing the cost of preparing the BOMAB phantoms and reconfiguring the detector arrays in multiple geometries, saving time and energy.

In-lab synthesized turn-off fluorescence sensor for estimation of Gemigliptin and Rosuvastatin polypill appraised by Spider diagram, AGREE and whiteness metrics.

Gemigliptin-Rosuvastatin single-pill combination is a promising therapeutic tool in the effective control of hyperglycemia and hypercholesterolemia. Organic sensors with high quantum yields have profoundly significant applications in the pharmaceutical industry, such as routine quality control of marketed formulations. Herein, the fluorescence sensor, 2-Morpholino-4,6-dimethyl nicotinonitrile 3, (λex; 226 nm, λem; 406 nm), was synthesized with a fluorescence quantum yield of 56.86% and fully characterized in our laboratory. This sensor showed high efficiency for the determination of Gemigliptin (GEM) and Rosuvastatin (RSV) traces through their stoichiometric interactions and simultaneously fractionated by selective solvation. The interaction between the stated analytes and sensor 3 was a quenching effect. Various experimental parameters and the turn-off mechanism were addressed. The adopted approach fulfilled the ICH validation criteria and showed linear satisfactory ranges, 0.2-2 and 0.1-1 µg/mL for GEM and RSV, respectively with nano-limits of detection less than 30 ng/mL for both analytes. The synthesized sensor has been successfully applied for GEM and RSV co-assessment in their synthetic polypill with excellent % recoveries of 98.83 ± 0.86 and 100.19 ± 0.64, respectively. No statistically significant difference between the results of the proposed and reported spectrophotometric methods in terms of the F- and t-tests. Ecological and whiteness appraisals of the proposed study were conducted via three novel approaches: the Greenness Index via Spider Diagram, the Analytical Greenness Metric, and the Red-Green-Blue 12 model. The aforementioned metrics proved the superiority of the adopted approach over the previously published one regarding eco-friendliness and sustainability. Our devised fluorimetric turn-off sensing method showed high sensitivity, selectivity, feasibility, and rapidity with minimal cost and environmental burden over other sophisticated techniques, making it reliable in quality control labs.

In-vitro assessment of a novel intraocular lens made of crosslinked polyisobutylene.

PURPOSE: To describe and analyse the particularities of the material and the optical quality of the first intraocular lens (IOL) (Eyedeal® lens) made of crosslinked polyisobutylene (xPIB). METHODS: We assessed the material quality using an accelerated ageing process (to provoke glistenings) and compared values with a control, AcrySof® lens. Using the sessile drop method, the contact angle of the new IOL was measured. Images of the lens surface were recorded by scanning electron microscopy (SEM). Optical quality was assessed by measuring the labeled power and modulation transfer function (MTF) using standard metrology equipment (OptiSpheric IOL PRO2). RESULTS: The Eyedeal® lens had an average glistening density result of 7.46 ± 3.78 MV/mm2 compared to the control AcrySof® whose glistenings number was 142.42 ± 72.47 MV/mm2. The contact angle was 97.2° whereas the angle of AcrySof material is between 73.3 ± 2.4° and 84.4 ± 0.1°. Using SEM, Eyedeal® lenses were examined and all appeared to be comparable to modern IOLs made of acrylic materials. The power and MTF values were normal and conformed to ISO standards. CONCLUSIONS: In the laboratory, the new Eyedeal® lens showed equivalence to current hydrophobic- or hydrophilic-acrylic lens models. It showed superiority in its glistening density result compared to the control lens.

An integrative approach to medical laboratory equipment risk management.

Medical Laboratory Equipment (MLE) is one of the most influential means for diagnosing a patient in healthcare facilities. The accuracy and dependability of clinical laboratory testing is essential for making disease diagnosis. A risk-reduction plan for managing MLE is presented in the study. The methodology was initially based on the Failure Mode and Effects Analysis (FMEA) method. Because of the drawbacks of standard FMEA implementation, a Technique for Ordering Preference by Similarity to the Ideal Solution (TOPSIS) was adopted in addition to the Simple Additive Weighting (SAW) method. Each piece of MLE under investigation was given a risk priority number (RPN), which in turn assigned its risk level. The equipment performance can be improved, and maintenance work can be prioritized using the generated RPN values. Moreover, five machine learning classifiers were employed to classify TOPSIS results for appropriate decision-making. The current study was conducted on 15 various hospitals in Egypt, utilizing a 150 MLE set of data from an actual laboratory, considering three different types of MLE. By applying the TOPSIS and SAW methods, new RPN values were obtained to rank the MLE risk. Because of its stability in ranking the MLE risk value compared to the conventional FMEA and SAW methods, the TOPSIS approach has been accepted. Thus, a prioritized list of MLEs was identified to make decisions related to appropriate incoming maintenance and scrapping strategies according to the guidance of machine learning classifiers.

FDA's proposed rule for the regulation of laboratory-developed tests.

In October 2023, the Food and Drug Administration (FDA) released a proposed rule that ends enforcement discretion for laboratory-developed tests (LDTs). The FDA's proposal outlines a five-stage implementation to begin regulating LDTs as they do for commercial in vitro diagnostics (IVDs), including modified FDA-approved/cleared tests. We outline here concerns from the clinical and public health microbiology laboratory perspective. It is our opinion that LDTs performed by individual Clinical Laboratory Improvement Amendments-certified diagnostic laboratories should not be regulated in the same way as commercial IVDs. This rule, if finalized, will negatively impact the diagnostic services currently offered by clinical and public health laboratories and, therefore, patients and the providers who care for them. Ending enforcement discretion will likely stifle diagnostic innovation and decrease access to diagnostic testing and health equity. Furthermore, the lack of infrastructure, including personnel and funding, at the FDA and diagnostic laboratories to support the required submissions for review is an obstacle. Like the FDA, diagnostic laboratories prioritize patient safety, accurate clinical diagnostics, and health equity. Since the scope of the LDT landscape is currently unknown, we are supportive of a registration process, along with non-burdensome adverse event reporting, to first understand the scope of clinical use of LDTs and any associated safety concerns. Any regulatory rule should be based on data that have been gathered systematically, not anecdotes or case reports. A rule must also balance the potential negative impact to patient care with realistic safety risks for infectious disease diagnostics.

Selecting an Ecological Momentary Assessment Platform: Tutorial for Researchers.

BACKGROUND: Although ecological momentary assessment (EMA) has been applied in psychological research for decades, delivery methods have evolved with the proliferation of digital technology. Technological advances have engendered opportunities for enhanced accessibility, convenience, measurement precision, and integration with wearable sensors. Notwithstanding, researchers must navigate novel complexities in EMA research design and implementation. OBJECTIVE: In this paper, we aimed to provide guidance on platform selection for clinical scientists launching EMA studies. METHODS: Our team includes diverse specialties in child and adolescent behavioral and mental health with varying expertise on EMA platforms (eg, users and developers). We (2 research sites) evaluated EMA platforms with the goal of identifying the platform or platforms with the best fit for our research. We created a list of extant EMA platforms; conducted a web-based review; considered institutional security, privacy, and data management requirements; met with developers; and evaluated each of the candidate EMA platforms for 1 week. RESULTS: We selected 2 different EMA platforms, rather than a single platform, for use at our 2 research sites. Our results underscore the importance of platform selection driven by individualized and prioritized laboratory needs; there is no single, ideal platform for EMA researchers. In addition, our project generated 11 considerations for researchers in selecting an EMA platform: (1) location; (2) developer involvement; (3) sample characteristics; (4) onboarding; (5) survey design features; (6) sampling scheme and scheduling; (7) viewing results; (8) dashboards; (9) security, privacy, and data management; (10) pricing and cost structure; and (11) future directions. Furthermore, our project yielded a suggested timeline for the EMA platform selection process. CONCLUSIONS: This study will guide scientists initiating studies using EMA, an in vivo, real-time research tool with tremendous promise for facilitating advances in psychological assessment and intervention.

Assessment of Developmental Neurotoxicity Using Semi-automatic Behavior Analysis System for Zebrafish.

Traditionally, morphological, conventional, and toxicological approaches have been used to demonstrate neurotoxicity; however, there has been a growing interest in animal behavioral methods for assessing neurotoxicity, both at the scientific and regulatory levels. Zebrafish (Danio rerio) is a small tropical freshwater fish currently recognized as a suitable model organism for investigating developmental neurotoxicity. There are many animal-tracking software programms used for behavioral analysis in biomedical research. Some of these software programms require a fee, which may exceed the laboratory budget and require detailed technical equipment. As a solution, freely available programs can be used. However, animal tracking may not be possible due to the glare from the aquatic environment of fish, and the small size of zebrafish embryos makes animal tracking difficult. In our laboratory, we developed a semi-automatic system to overcome these difficulties by using three different software available for free. This chapter explains the system for zebrafish embryos and adult zebrafish.

High quality of SARS-CoV-2 molecular diagnostics in a diverse laboratory landscape through supported benchmark testing and External Quality Assessment.

A two-step strategy combining assisted benchmark testing (entry controls) and External Quality Assessments (EQAs) with blinded simulated clinical specimens to enhance and maintain the quality of nucleic acid amplification testing was developed. This strategy was successfully applied to 71 diagnostic laboratories in The Netherlands when upscaling the national diagnostic capacity during the SARS-CoV-2 pandemic. The availability of benchmark testing in combination with advice for improvement substantially enhanced the quality of the laboratory testing procedures for SARS-CoV-2 detection. The three subsequent EQA rounds demonstrated high quality testing with regard to specificity (99.6% correctly identified) and sensitivity (93.3% correctly identified). Even with the implementation of novel assays, changing workflows using diverse equipment and a high degree of assay heterogeneity, the overall high quality was maintained using this two-step strategy. We show that in contrast to the limited value of Cq value for absolute proxies of viral load, these Cq values can, in combination with metadata on strategies and techniques, provide valuable information for laboratories to improve their procedures. In conclusion, our two-step strategy (preparation phase followed by a series of EQAs) is a rapid and flexible system capable of scaling, improving, and maintaining high quality diagnostics even in a rapidly evolving (e.g. pandemic) situation.

On-site evaluation as external quality assessment of microbiology laboratories involved in sentinel laboratory-based antimicrobial resistance surveillance network in Burkina Faso.

BACKGROUND: The laboratory-based surveillance of antimicrobial resistance (AMR) is a priority component of the multisectoral national action plan to combat AMR in Burkina Faso. This study aimed to assess the QMS of microbiology laboratories involved in the Sentinel laboratory-based antimicrobial resistance surveillance network in Burkina Faso. METHODS: A cross-sectional study was conducted from September 1st to November 30th, 2022. The external quality assessment (EQA) method used was on-site evaluation using a checklist that was developed and validated by a technical committee of experts. Teams of two, including an antimicrobial susceptibility test (AST) specialist and a QMS specialist, were trained on this checklist to conduct the assessment. Satisfactory performance was defined as any on-site evaluation score 80% and above with the aim of developing action plans to address gaps. RESULTS: All 18 laboratories were evaluated. The overall average performance score of the participating laboratories was 40%. The highest overall performance score was 58%, and the lowest overall performance score was 26%. The average overall scores were not significantly different between private and public laboratories (p value = 0.78). The only section of the checklist with the satisfactory performance concerned the "Analytical step of AST", with 76.5% (13/17) of the sentinel laboratories having a score ≥ 80%. CONCLUSION: The performance of the QMS of the sentinel laboratories in Burkina Faso for AMR surveillance was unsatisfactory, and a corrective action plan was proposed to support these laboratories in improving their QMS over the next 3 years.

Costs and consequences of over-investigation of minor transfusion reactions.

BACKGROUND: Adverse transfusion events create a direct cost burden on the healthcare system through increased morbidity, mortality, extra investigations for diagnosis, patient treatment and increased use of hospital resources. Understanding the costs and impact minor transfusion reactions have on the healthcare system presents an opportunity for potential cost savings and improved clinical practice. AIMS: To determine the cost associated with investigating minor transfusion reactions, to identify opportunities to improve the management of blood transfusion reactions and potential cost savings through the application of current national guidelines. METHODS: A retrospective review of all suspected transfusion reactions reported to the laboratory over a 6-year period was performed. Reports were assessed for appropriateness of clinical management and associated investigations. Cost of inappropriate investigations and associated blood product discard was calculated using current national tariffs. RESULTS: Of the 274 reports, febrile non-haemolytic transfusion reactions were the most common reactions, with 96 (35%) cases. One hundred forty-eight patients were unnecessarily investigated for suspected transfusion reactions totalling AU$ 32 427.00. The initial total value of partially discarded blood products was AU$ 55 656.00. CONCLUSION: The study demonstrated that unnecessary investigation of minor transfusion reactions adds a significant financial burden to the healthcare system.

Research on the interplay between green finance and manufacturing sustainability outcomes: insights for low-carbon economy in the post-COVID-19 era.

In the quest to strengthen resilient and sustainable recovery in the post-COVID-19 era, there is a huge requirement for manufacturing firms to adopt green finance which is dominated by green bond issuance. Nevertheless, published studies that provide insights on factors that influence the issuance of green bonds within manufacturing firms in the post-COVID-19 era and the impact on sustainable outcomes are currently non-existent. Therefore, this study analyzed the interrelationships that exist between the influencing factors of green bond issuance within manufacturing firms using decision-making trial and evaluation laboratory (DEMATEL) and data from Nigerian manufacturing firms. Then, a structural model of their importance levels was illustrated using interpretive structural modeling (ISM) while their impact on manufacturing sustainability outcomes was estimated with the aid of evaluation based on distance from average solution (EDAS). The study results highlight the key influencing factors of green bond issuance as environmental competencies, policy framing, low corruption, public awareness, and government support thereby signifying the criticality of strong institutions in facilitating green finance in the post-pandemic era. Besides, the study results demonstrate that green finance can significantly strengthen manufacturing sustainability in the post-COVID-19 era via green bonds by enhancing sustainable waste management, technological growth, and quality improvement as well as reducing carbon emissions. The study findings can provide a reference to decision-makers in manufacturing enterprises to predict scenarios and enact policies that facilitate the success of green finance in the post-COVID-19 era to further develop a low-carbon economy and increase competitive edge.

A small-scale external quality assessment for PCR detection of group B streptococcus in China.

BACKGROUND: Group B streptococcus (GBS) is considered a leading cause of maternal and infant morbidity and mortality. Molecular diagnosis is a routinely used approach for GBS screening to protect pregnant women and prevent early-onset GBS neonatal disease. The objective of this study was to identify issues and guarantee the dependability of GBS molecular diagnosis by an external quality assessment (EQA) scheme. METHODS: The EQA panel comprised eight samples spiked with 10-fold dilutions of GBS suspension (20-2,000,000 copies/mL), and 2 negative control samples. The panels were coded randomly and distributed to participating laboratories for GBS detection. RESULTS: In total, 44 participating laboratories submitted results with eight commercial GBS PCR assays and one in-house assay. Among them, 36 obtained an acceptable or higher performance score, while 8 required improvement. Among the 440 results returned, 62 (14.1 %) were incorrect, including 5 false positives and 57 false negatives. CONCLUSIONS: Our small-scale EQA showed that most participating laboratories have reliable diagnostic capacities for GBS PCR detection. Nonetheless, further improvements in the detection performance of some laboratories are required, particularly with low-concentration samples. Our survey also reinforces the use of EQA as an essential tool to evaluate the overall proficiency of clinical laboratories.

Evaluating Quality Management and Diagnostics Microbiology Performance Within an International External Quality Assessment (EQA) Program Serving National One Health Sector Reference Laboratories Across Asia: Experience Amid the Coronavirus Disease 2019 (COVID-19) Pandemic.

BACKGROUND: Strengthening external quality assessment (EQA) services across the One Health sector supports implementation of effective antimicrobial resistance (AMR) control strategies. Here we describe and compare 2 different approaches for conducting virtual laboratory follow-up assessments within an EQA program to evaluate quality management system (QMS) and procedures for pathogen identification and antimicrobial susceptibility testing (AST). METHODS: During the coronavirus disease 2019 (COVID-19) pandemic in 2021 and 2022, 2 laboratory assessment approaches were introduced: virtual-based and survey-based methodologies. The evaluation of 2 underperforming Animal Health laboratories through a virtual-based approach occurred between May and August 2021. This evaluation encompassed the utilization of 3 online meetings and document reviews, performed subsequent to the execution of EQA procedures. Within a distinct group of laboratories, the survey-based assessment was implemented from December 2021 to February 2022, also following EQA procedures. This phase encompassed the dissemination of an online survey to 31 participating laboratories, alongside a sole online consultation meeting involving 4 specific underperforming laboratories. RESULTS: The virtual-based assessment post-EQA aimed to identify gaps and areas for improvement in the laboratory's practices for pathogen identification and AST. This approach was, however, time-intensive, and, hence, only 2 laboratories were assessed. In addition, limited interactions in virtual platforms compromised the assessment quality. The survey-based post-EQA assessment enabled evaluation of 31 laboratories. Despite limitations for in-depth analysis of each procedure, gaps in QMS across multiple laboratories were identified and tailored laboratory-specific recommendations were provided. CONCLUSIONS: Reliable internet and plans for efficient time management, post-EQA virtual laboratory follow-up assessments are an effective alternative when conducting onsite evaluation is infeasible as observed during the COVID-19 pandemic, although the successful implementation of remediation plans will likely require in person assessments. We advocate application of hybrid approaches (both onsite and virtual) for targeted capacity building of AMR procedures with the ability to implement and oversee the process.