Gestión de calidad en equipos de gases en sangre POCT. Expandiendo las fronteras del laboratorio / Quality management in POCT blood gas equipment. Expanding the frontiers of the laboratory

La realización de pruebas de laboratorio en el lugar de atención del paciente (POCT) de equipos de gases en sangre representa un desafío continuo tanto para los usuarios como para el laboratorio. La vulnerabilidad al error y la amenaza del riesgo que rodea esta forma de trabajo obliga a establecer un sistema de trabajo robusto para la obtención de un "resultado confiable" cerca del paciente crítico. La formación de un grupo interdisciplinario, la capacitación de usuarios externos al laboratorio, el aseguramiento de la calidad analítica y la conectividad, son los cuatro pilares sobre los cuales se sostiene el éxito de esta nueva era de laboratorio clínico. Además es necesaria la reinvención de la imagen bioquímica, asumiendo un rol de líder, comunicador, asesor e integrado al sistema de salud (AU)

Point of care laboratory testing (POCT) with blood gas equipment is an ongoing challenge for both the users and the laboratory. The vulnerability to error and the threat of risk that surrounds this way of working necessitates the establishment of a robust working system to obtain "reliable results" for the critically ill patient. The creation of an interdisciplinary group, the training of external users, analytical quality assurance, and connectivity are the four pillars on which the success of this new era of clinical laboratories is based. It is also necessary to reinvent the biochemical image, assuming the role of leader, communicator, and advisor integrated into the health system (AU)

Inherited Proteoglycan Biosynthesis Defects-Current Laboratory Tools and Bikunin as a Promising Blood Biomarker.

Proteoglycans consist of proteins linked to sulfated glycosaminoglycan chains. They constitute a family of macromolecules mainly involved in the architecture of organs and tissues as major components of extracellular matrices. Some proteoglycans also act as signaling molecules involved in inflammatory response as well as cell proliferation, adhesion, and differentiation. Inborn errors of proteoglycan metabolism are a group of orphan diseases with severe and irreversible skeletal abnormalities associated with multiorgan impairments. Identifying the gene variants that cause these pathologies proves to be difficult because of unspecific clinical symptoms, hardly accessible functional laboratory tests, and a lack of convenient blood biomarkers. In this review, we summarize the molecular pathways of proteoglycan biosynthesis, the associated inherited syndromes, and the related biochemical screening techniques, and we focus especially on a circulating proteoglycan called bikunin and on its potential as a new biomarker of these diseases.

Pooled Testing for Expanding COVID-19 Mass Surveillance.

Diagnostic testing to identify patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a key role to control the coronavirus disease (COVID-19) pandemic. While several countries have implemented the use of diagnostic testing in a massive scale as a cornerstone for infection control and surveillance, other countries affected by the pandemic are hampered by its limited testing capacity. Pooled testing was first introduced in the 1940s and is now used for screening in blood banks. Testing is done by pooling multiple individual samples together. Only in the case of a positive pool test would individual samples of the pool be tested, thus substantially reducing the number of tests needed. Several studies regarding their use for SARS CoV-2 have been done in the United States, Israel, and Germany. Studies have shown that an individual positive sample can still be detected in pools of up to 32 samples, and possibly even 64 samples, provided that additional polymerase chain reaction (PCR) amplification cycles are conducted with a sensitivity of 96%. Simulation studies to determine optimal pool size and pooling techniques have also been conducted. Based on these studies, pooled testing is shown to be able to detect positive samples with sufficient accuracy and can easily be used with existing equipment and personnel for population-wide screening.

The Research on the Outpatient Cost Adjustment Framework of the Urban Workers in a Southern China City During 2013 to 2015.

Based on a large amount of data, the study aimed to analyze all expenses of outpatients in a southern China city from 2013 to 2015. It draws a conclusion that the total cost of outpatient has increased in the past 3 years, and various cost indexes either increased or decreased in different ways. Drug costs and treatment fees are the main influencing factors for the change in total outpatient cost. The structural change from 2013 to 2015 was 70.15%. Drug costs, laboratory fees, and inspection fees are the main indexes that account for the increasing total outpatient costs. This study puts emphasis on the cost of human resources, which eliminates the phenomenon of "Yi Yao Yang Yi" (support medical cost with medicine) and "Yi Xie Yang Yi" (support medical cost with medical device). This study also focuses on the balance of outpatient cost, as well as the compensation function of medical insurance, which encourages multiple participation and coordinated adjustment.

"On Vivo" and Wearable Clinical Laboratory Testing Devices for Emergency and Critical Care Laboratory Testing.

BACKGROUND: Point-of-care testing (POCT) devices are designed for clinical laboratory testing at the bedside or near the patient and can significantly reduce the turnaround time for laboratory test results. The next generation for clinical laboratory testing may be devices that are worn or attached to the patient. CONTENT: POCT devices that are designed where samples are tested directly on the patient include bilirubinometers, pulse oximeters, breathalyzers (for alcohol and, more recently, cannabinoid detection), transcutaneous blood gas analyses, and novel testing applications such as glucose and tumor signatures following surgical excision. The utility of these devices with special reference for use within the intensive care unit and the emergency department is reviewed. SUMMARY: It is likely that wearable POCT devices will be developed in the future that can meet current and emerging clinical needs. Advancements in biomedical engineering and information technology will be needed in the creation of next-generation devices.

[Could the publication of new european guidelines change practices in France?] / La publication au JO de nouveaux règlements européens sur les dispositifs médicaux pourrait-elle changer la pratique du diagnostic oncogénétique en France ?

The use of predictive biomarkers in the diagnosis and prediction of the efficacy of targeted therapies for the individualized management of patients is generally based on the use of in vitro medical diagnosis devices that are now covered by the guidelines 90/385/EEC, 93/42/EEC and 98/42/EEC. On 25 May 2017, the European Parliament and Council Regulations 2017/745 and 2017/746 of 5 April 2017, related to medical devices and in vitro medical diagnosis devices, respectively, were published, disrupting years of practices based on European directives. They tend to bring the in vitro diagnosis in Europe closer to the American regulation in order to improve the use of safety diagnosis tests, while the United States have been changing their practices in the face of biomedical, technological and digital evolutions. We will describe the different regulations of diagnostic tests and discuss their applications in the field of oncology.

Prostate cancer screening: guidelines review and laboratory issues.

Background Prostate-specific antigen (PSA) remains as the most used biomarker in the detection of early prostate cancer (PCa). Clinical practice guidelines (CPGs) are produced to facilitate incorporation of evidence into clinical practice. This is particularly useful when PCa screening remains controversial and guidelines diverge among different medical institutions, although opportunistic screening is not recommended. Methods We performed a systematic review of guidelines about PCa screening using PSA. Guidelines published since 2008 were included in this study. The most updated version of these CPGs was used for the evaluation. Results Twenty-two guidelines were selected for review. In 59% of these guidelines, recommendations were graded according to level of evidence (n = 13), but only 18% of the guidelines provided clear algorithms (n = 4). Each CPG was assessed using a checklist of laboratory issues, including pre-analytical, analytical, and post-analytical factors. We found that laboratory medicine specialists participate in 9% of the guidelines reviewed (n = 2) and laboratory issues were frequently omitted. We remarked that information concerning the consequences of World Health Organization (WHO) standard in PSA testing was considered by only two of 22 CPGs evaluated in this study. Conclusions We concluded that the quality of PCa early detection guidelines could be improved properly considering the laboratory issues in their development.

Continual improvement of the pre-analytical process in a public health laboratory with quality indicators-based risk management.

Background Quality indicators (QIs) and risk management are important tools for a quality management system designed to reduce errors in a laboratory. This study aimed to show the effectiveness of QI-based risk management for the continual improvement of pre-analytical processes in the Kayseri Public Health Laboratory (KPHL) which serves family physicians and collects samples from peripheral sampling units. Methods QIs of pre-analytical process were used for risk assessment with the failure modes and effects analysis (FMEA) method. Percentages and risk priority numbers (RPNs) of QIs were quantified. QI percentages were compared to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) performance specifications and RPNs were compared to risk level scale, and corrective actions planned if needed. The effectiveness of risk treatment actions was re-evaluated with the new percentages and with RPNs of predefined QIs. Results RPNs related to four QIs required corrective action according to the risk evaluation scale. After risk treatment, the continual improvement was achieved for performance and risk level of "transcription errors", for risk levels of "misidentified samples" and "not properly stored samples" and for the performance of "hemolyzed samples". "Not properly stored samples" had the highest risk score because of sample storage and centrifugation problems of peripheral sampling units which are not under the responsibility of the KPHL. Conclusions Public health laboratories may have different risk priorities for pre-analytical process. Risk management based on predefined QIs can decrease the risk levels and increase QI performance as evidence-based examples for continual improvement of the pre-analytical process.

Use of fertility preservation services in female reproductive-aged cancer patients.

OBJECTIVE: The objective of the study was to determine the rates and predictors of fertility preservation services among reproductive-aged women with common cancers in the United States. STUDY DESIGN: We used the MarketScan database to identify women 18-45 years of age with lung, breast, colorectal, or cervical cancer who underwent surgery and chemotherapy from 2009 through 2016. Services from 3 months before to 3 months after chemotherapy for evaluation for fertility preservation, laboratory testing for fertility evaluation, and fertility-preserving procedures were captured. Multivariable models were used to assess the factors associated with the use of fertility-preservation services. RESULTS: A total of 18,781 women, including 386 cervical, 1372 colorectal, 246 lung, and 16,777 with breast cancer, were identified. In women 18-35 years old, 11.7% underwent evaluation for fertility preservation, 13.7% underwent laboratory testing, and 6.3% pursued fertility-preserving procedures. The rates of office evaluation, laboratory testing, and performance of procedure were 3.3%, 7.5%, and 1.9 % in women aged 36-40 years and 0.5%, 7.2%, and 0.3% in those aged 41-45 years, respectively. The rate of fertility preservation evaluation rose from 1.0% in 2009 to 5.5% in 2016 (risk ratio, 4.66, 95% confidence interval, 2.38-9.11) while use of fertility-preserving procedures increased from 1.0% to 4.6% (risk ratio, 3.84, 95% confidence interval, 1.94-7.59) during the same time period. In a multivariable model, use of any fertility-preserving interventions were more common in patients with breast cancer (adjusted risk ratio, 2.30, 95% confidence interval, 1.30-4.06), those in the Northeast (adjusted risk ratio, 1.24, 95% confidence interval, 1.10-1.40), and in younger women (18-35 years) (adjusted risk ratio, 2.59, 95% confidence interval, 2.32-2.89). CONCLUSION: Although limited by lack of information regarding cancer stage and desire for future fertility, only a small fraction of reproductive-aged female cancer patients receiving chemotherapy are evaluated in a nationwide sample for fertility preservation or undergo fertility-preserving procedures.

Messages from the third International Conference on Clinical Metagenomics (ICCMg3).

Clinical metagenomics (CMg), referring to as the application of metagenomic sequencing of clinical samples in order to recover clinically-relevant information, has been rapidly evolving these last years. Following this trend, we held the third International Conference on Clinical Metagenomics (ICCMg3) in Geneva in October 2018. During the two days of the conference, several aspects of CMg were addressed, which we propose to summarize in the present manuscript. During this ICCMg3, we kept on following the progresses achieved worldwide on clinical metagenomics, but also this year in clinical genomics. Besides, the use of metagenomics in cancer diagnostic and management was addressed. Some new challenges have also been raised such as the way to report clinical (meta)genomics output to clinicians and the pivotal place of ethics in this expanding field.

Assessing the utility of yearly pre-season laboratory screening for athletes on a major professional sports team.

OBJECTIVES: Professional athletes undergo annual pre-season laboratory screening, although clinical evidence supporting the practice is limited and no uniform set of guidelines on pre-season laboratory screening exists. The aim of this study was to assess the clinical value of annual pre-season laboratory screening tests for a major professional sports team over multiple years. DESIGN: Retrospective chart review. METHODS: A retrospective analysis was performed of all laboratory results as well as screening ECGs for a single major professional sports team over a 9-year timeframe (2009-2017). RESULTS: The data show that 10.01% of initial screening test results were abnormal and 40.32% of abnormal tests resulted in additional testing. Overall, only 0.35% of initial tests resulted in a clinically significant outcome. Non-US born players showed a significantly higher average rate of abnormal tests/year compared to US-born players (p-value 0.006), but there was no difference in clinically significant outcomes. There was no relationship between athlete age and laboratory screening outcomes. CONCLUSIONS: In our study population, yearly pre-season laboratory screening of professional athletes did not yield substantial clinically significant outcomes and would not be warranted under normal clinical standards. Future best practice guidelines should combine research concerning effects of family medical history, race, gender, country of origin, and type of sport on athlete health when creating recommendations for which pre-season laboratory screenings may be pertinent even with evidence of little utility.

The role of the laboratory in the expanding field of neuroimmunology: Autoantibodies to neural targets.

Accelerated identification of autoantibodies associated with previously idiopathic neurological disease has provided insights into disease mechanisms, enhanced understanding of neurological function, and opportunities for improved therapeutic interventions. The role of the laboratory in the expanding field of neuroimmunology is critical as specific autoantibody identification provides guidance to clinicians in diagnosis, prognosis, tumor search strategies, and therapeutic interventions. The number of specific autoantibodies identified continues to increase and newer testing strategies increase efficiencies in the laboratory and availability to clinicians. The need for broadly targeted efficient testing is underscored by the variability in clinical presentation and tumor associations attributable to a specific autoantibody, and conversely the various autoantibody specificities that can be the cause of a given clinical presentation. While many of the antineural antibodies were first recognized in the setting of neoplastic disease, idiopathic autoimmune neurological disease in the absence of underlying tumor is increasingly recognized. Appropriation of therapeutic modalities used to treat autoimmune disease to treat these autoantibody mediated neurological diseases has improved patient outcomes. Interaction between clinicians and laboratorians is critical to our understanding of these diseases and optimization of the clinical benefits of our increasing knowledge in neuroimmunology.

Avaliação comparativa entre os novos métodos e os métodos tradicionais de diagnósticos laboratoriais para as hemofilias: revisão integrativa / Comparative evaluation between the new methods and the current methods of laboratory diagnosis for hemophilia: integrative literature review

A hemofilia é uma coagulopatia hereditária ligada ao cromossomo X, causada pela deficiên- cia dos fatores VIII (hemofilia A) e IX (hemofilia B). Essa doença acomete cerca de 1:10.000 nascidos vivos do sexo masculino na hemofilia A e de 1:40.000 na hemofilia B no mundo. Este estudo buscou avaliar os métodos atuais e os novos métodos de diagnóstico laboratoriais em fase de testes para detecção e acompanhamento dos pacientes com hemofilia. Reali- zou-se um estudo de revisão integrativa da literatura mediante busca de artigos indexados, utilizando as plataformas de dados PubMed e SciELO. A partir da pesquisa realizada foram selecionados oito artigos, categorizados em: Técnica Inovadora; Diagnóstico molecular; Método modificado e Potencialização de sensibilidade. Com essas novas técnicas será possível, com maior especificidade, a quantificação do fator VIII, identificação e diferencia- ção de anticorpos inibidores de anticorpos não inibidores; análise dos genes FVIII, FIX e outros genes da hemostasia, por técnicas de Citometria de Fluxo e o Biossensor de Resso- nância de Plasmon de Superfície; detecção de deleções, inserções e mutações conhecidas ou novas através do Sequenciamento de Nova Geração, podendo esses resultados serem correlacionados com outros testes para melhor definição dos fenótipos clínicos da doença.

Characteristics, properties, and potential applications of circulating cell-free dna in clinical diagnostics: a focus on transplantation.

The initial discovery of cell-free DNA (cfDNA) in 1948 by Mandel and Metais has led to numerous investigations evaluating the role of cfDNA in various disease states. cfDNA has been characterized in various patient populations with similar results. cfDNA are typically 150 bp of double-stranded DNA that are thought to be released from nucleosomes during apoptosis and necrosis. They are found in circulation as monomers, dimers, and trimers. Different specimen types yield significantly different amounts cfDNA. While serum yields the highest amount of cfDNA, it contains the most genomic DNA contamination compared to Streck and plasma specimen types. The utility of cfDNA as a biomarker was advanced by the completion of the Human Genome Project and enabled interrogation of tumor markers in cancer patients. While tumor genetics may have been the initial application of cfDNA, the most successful application of cfDNA as a clinical biomarker is noninvasive prenatal testing (NIPT). CfDNA has become the gold-standard for NIPT testing, allowing for high sensitivity while maintaining specificity for aneuploidy. Because prenatal testing is essentially mixed genome analysis, application of cfDNA analysis to solid organ transplantation is a clear diagnostic target. There have been several studies examining the role of cfDNA in solid organ transplantation. These studies identified cfDNA as a surrogate marker for rejection with a high level of concordance with biopsies. While the data thus far are promising, there is still a need for more prospective studies to determine the clinical utility of cfDNA in solid organ transplant rejection.

Transfusion-Transmitted Infections: an Update on Product Screening, Diagnostic Techniques, and the Path Ahead.

The mandated testing of blood components for infectious diseases, to prevent transfusion-transmitted infections (TTIs), began in the 1950s. Since then, changes in predonation questionnaires and advances in testing techniques have afforded more sensitive and specific tests for pathogens, in addition to allowing earlier detection. Given that these approaches have very low but detectable failure rates, the recent development and implementation of proactive pathogen reduction approaches is the new forefront of TTI prevention strategies. With globalization and the ability of pathogens to evolve rapidly, continuous redefining of testing standards and laboratory techniques is paramount for maintaining a safe blood supply.

Team-Based Learning Is Effective in Teaching Appropriate Utilization of Hemostasis Laboratory Tests Using Storyline Case-Authoring Software.

Introduction: Team-based learning (TBL) is an effective way to teach medical students a challenging topic: coagulation. This TBL requires students to discuss a differential diagnosis, order and analyze laboratory tests, and decide upon appropriate treatment. Methods: The coagulation TBL was utilized in a hematology/oncology system-based medical course. The TBL began with Individual and Group Readiness Assurance Tests (IRAT and GRAT, respectively) consisting of the same 10 multiple-choice questions. Next came a team application activity with the goal of evaluating a bleeding patient. Each team was given the clinical case and a whiteboard. Each team recorded a differential diagnosis and chose relevant laboratory tests from 20 hematology/coagulation assays placed in case-authoring software. Next, teams recorded the laboratory results, final diagnosis, and treatment on the whiteboards. Teams then voted for the best whiteboard. After discussing the highly voted whiteboard, instructors provided case discussion and elaboration about all 20 laboratory tests and their interpretation. Results: The IRAT average score was 77.0% compared to the GRAT group average of 99.5% for the year 2016-2017. Instructors noted great enthusiasm and teamwork. Institutional module evaluation feedback results showed that students were pleased and felt competent analyzing laboratory tests in a bleeding patient. Discussion: TBL provides a powerful way of teaching students the clinical reasoning approach to a bleeding patient and the appropriate use of laboratory test ordering and analysis. It is enjoyable and interactive and teaches students how to narrow their differential diagnosis by effective laboratory utilization.

The effects of an educational meeting and subsequent computer reminders on the ordering of laboratory tests by rheumatologists: an interrupted time series analysis.

OBJECTIVES: To examine the effects of an educational meeting and subsequent computer reminders on the number of ordered laboratory tests. METHODS: Using interrupted time series analysis we assessed whether trends in the number of laboratory tests ordered by rheumatologists between September 2012 and September 2015 at the Sint Maartenskliniek (the Netherlands) changed following an educational meeting (September 2013) and the introduction of computer reminders into the Computerised Physician Order Entry System (July 2014). The analyses were done for the set of tests on which both interventions had focussed (intervention tests; complement, cryoglobulins, immunoglobins, myeloma protein) and a set of control tests unrelated to the interventions (alanine transferase, anti-cyclic citrullinated peptide, C-reactive protein, creatine, haemoglobin, leukocytes, mean corpuscular volume, rheumatoid factor and thrombocytes). RESULTS: At the start of the study, 101 intervention tests and 7660 control tests were ordered per month by the rheumatologists. After the educational meeting, both the level and trend of ordered intervention and control tests did not change significantly. After implementation of the reminders, the level of ordered intervention tests decreased by 85.0 tests (95%-CI -133.3 to -36.8, p<0.01), the level of control tests did not change following the introduction of reminders. CONCLUSIONS: In summary, an educational meeting alone was not effective in decreasing the number of ordered intervention tests, but the combination with computer reminders did result in a large decrease of those tests. Therefore, we recommend using computer reminders in addition to education if reduction of inappropriate test use is aimed for.