Degrowth in the clinical laboratory: A key step towards integrating planetary health into the healthcare system.

Guidelines Committee: The preparation of this revised monograph was achieved with the expert input of the editors, members of the guidelines committee, experts who submitted manuscripts for each section and many expert reviewers, who are listed in Appendix A. The material in this monograph represents the opinions of the editors and does not represent the official position of the National Academy of Clinical Biochemistry or any of the co-sponsoring organizations. The National Academy of Clinical Biochemistry is the official academy of the American Association of Clinical Chemistry. Single copies for personal use may be printed from authorized Internet sources such as the NACB’ s Home Page (www.nacb.org), provided it is printed in its entirety, including this notice. Printing of selected portions of the document is also permitted for personal use provided the user also prints and attaches the title page and cover pages to the selected reprint or otherwise clearly identifies the reprint as having been produced by the NACB. Otherwise, this document may not be reproduced in whole or in part, stored in a retrieval system, translated into another language, or transmitted in any form without express written permission of the National Academy of Clinical Biochemistry (NACB, 2101 L Street, N.W., Washington, DC 20037-1526). Permission will ordinarily be granted provided the logo of the NACB and the following notice appear prominently at the front of the document: Reproduced (translated) with permission of the National Academy of Clinical Biochemistry, Washington, DC Single or multiple copies may also be purchased from the NACB at the address above or by ordering through the Home Page (http://www.nacb.org/ ). © 2002 by the National Academy of Clinical Biochemistry. We gratefully acknowledge the support of Abbott Laboratories for the publication of these guidelines and are indebted to the following individuals who contributed the original manuscripts upon which this monograph is based:

In laboratory medicine meaningful measurements are essential for diagnosis, risk assessment, treatment and monitoring of patients. Thus methods applied in diagnostic measurements must be accurate, precise, specific and comparable among laboratories. Inadequate or incorrect analytical performance has consequences for the patients, the clinicians, and the health care system. One key element of metrology is the traceability of a measurement result to the SI system ensuring comparable results. This principle is described in the ISO/TC 212/WG2 N65 prEN 17511 Standard. In addition to the principles of metrology, the clinical usefulness, the diagnostic needs, and the biological and disease associated variations in patients' specimens have to be considered when the analytical biases for diagnostic purposes are defined. It must be the general goal of diagnostic laboratories to produce results that are true and comparable worldwide. The recent European in vitro diagnostic (IVD) Directive 98/79 EC follows the above mentioned standard of the International Organization for Standardization (ISO) and the European Committee for Standardization (CEN) requesting its application for all IVD reagents used within the European Union. This new European legislation will have a worldwide impact on manufacturers and clinical laboratories and will be implemented in 2003. It states that "traceability of values assigned to calibrators and/or control materials must be assured through available reference measurement procedures and/or available reference materials of a higher order". Thus a worldwide reference system needs to be established by collaboration and mutual recognition between the United States National Institute of Standards and Technology (NIST), European Metrology Institutes (EUROMET), regulatory bodies (e.g. United States Food and Drug Administration, FDA) the IVD industry and professional organizations (e.g. International Federation of Clinical Chemistry and Laboratory Medicine, IFCC). In June 2002, in Paris, representatives of international and regional organizations and institutions decided to form the "Joint Committee on Traceability for Laboratory Medicine" (JCTLM), which will support industry in registration and licensing of the "CE" label to test systems conforming to the IVD Directive.

Minor hand procedures can often be completed in the office without any laboratory testing. Preoperative screening tests before minor hand procedures are unnecessary and considered low value because they can lead to preventable invasive confirmatory tests and/or procedures. Prior studies have shown that low-value testing before low-risk hand surgery is still common, yet little is known about their downstream effects and associated costs. Assessing these downstream events can elucidate the consequences of obtaining a low-value test and inform context-specific interventions to reduce their use. (1) Among healthy adults undergoing low-risk hand surgery, are patients who receive a preoperative low-value test more likely to have subsequent diagnostic tests and procedures than those who do not receive a low-value test? (2) What is the increased 90-day reimbursement associated with subsequent diagnostic tests and procedures in patients who received a low-value test compared with those who did not? In this retrospective, comparative study using a large national database, we queried a large health insurance provider's administrative claims data to identify adult patients undergoing low-risk hand surgery (carpal tunnel release, trigger finger release, Dupuytren fasciectomy, de Quervain release, thumb carpometacarpal arthroplasty, wrist ganglion cyst, or mass excision) between 2011 and 2017. This database was selected for its ability to track patient claims longitudinally with direct provision of reimbursement data in a large, geographically diverse patient population. Patients who received at least one preoperative low-value test, including complete blood count, basic metabolic panel, electrocardiogram, chest radiography, pulmonary function test, and urinalysis within the 30-day preoperative period, were matched with propensity scores to those who did not. Among the 73,112 patients who met our inclusion criteria (mean age 57 ± 14 years; 68% [49,847] were women), 27% (19,453) received at least one preoperative low-value test and were propensity score-matched to those who did not. Multivariable regression analyses were performed to assess the frequency and reimbursements of subsequent diagnostic tests and procedures in the 90 days after surgery while controlling for potentially confounding variables such as age, sex, comorbidities, and baseline healthcare use. When controlling for covariates such as age, sex, comorbidities, and baseline healthcare use, patients in the low-value test cohort had an adjusted odds ratio of 1.57 (95% confidence interval [CI] 1.50 to 1.64; p < 0.001) for a postoperative use event (a downstream diagnostic test or procedure) compared with those who did not have a low-value test. The median (IQR) per-patient reimbursements associated with downstream utilization events in patients who received a low-value test was USD 231.97 (64.37 to 1138.84), and those who did not receive a low-value test had a median of USD 191.52 (57.1 to 899.42) (adjusted difference when controlling for covariates: USD 217.27 per patient [95% CI 59.51 to 375.03]; p = 0.007). After adjusting for inflation, total additional reimbursements for patients in the low-value test cohort increased annually. Low-value tests generate downstream tests and procedures that are known to provide minimal benefit to healthy patients and may expose patients to potential harms associated with subsequent, unnecessary invasive tests and procedures in response to false positives. Nevertheless, low-value testing remains common and the rising trend in low-value test-associated spending demonstrates the need for multicomponent interventions that target change at both the payer and health system level. Such interventions should disincentivize the initial low-value test and the cascade that may follow. Future work to identify the barriers and facilitators to reduce low-value testing in hand surgery can inform the development and revision of deimplementation strategies. Level III, therapeutic study.

Expedited SARS-CoV-2 screening of donors and recipients supports continued solid organ transplantation.

On being a pathologist

In the era of precision medicine, liquid chromatography-mass spectrometry (LC-MS) will continue to have significant impact on laboratory medicine in spite of the inherent challenges posed by the technology. It seeks to explain what is clinical mass spectrometry , and describes its basic framework and life cycle. It concludeds the key points of clinical LC-MS through the practical experiences of CLSI guideline and Cleveland health care clinical mass spectrometry laboratory. It then illustrates the challenges of appropriately applying LC-MS to clinical diagnostics through comparisons with research based LC-MS utilizations. Furthermore, It attempts to elucidate the challenges and endeavors It has made toward implementing clinical LC-MS in China. Finally, It discusses the prospective future of LC-MS in clinical diagnostics.(Chin J Lab Med, 2017, 40: 737-734) Key words: Chromatography, liquid; Mass spectrometry; Clinical laboratory techniques

There is no doubting that healthcare professionals gave the initial impetus for establishing hospital and laboratory accreditation systems, the main purpose of which is to improve quality and patient safety, as highlighted by eminent physicians, such as Ernest Amory Codman and Avedis Donabedian [1]. After an initial pioneering stage, essentially based on the peer-review concept, some regulatory activities have inevitably gained a footing in accreditation programs. In recent decades laboratory medicine has become increasingly subject to legislation and regulation, so much so that the voluntary and educational aspects of accreditation seem to have been overlooked and displaced by an emphasis on inspection and compliance. In addition, the mounting relevance of models for quality management may shift the focus of the accreditation from its main goal – particularly in health care and in laboratory medicine – of competently providing specific services. The evolution of the accreditation of clinical laboratories in different countries was once based on distinct models, standards, and accreditation bodies, and this led to confusion and disenchantment in the laboratory community. In particular, two distinct lines of International Standard development were applied to the medical laboratory. One, ISO 9001:2000 (the latest version issued in 2008) [2], focused on the “requirements for quality management systems” applicable to any organization, and the other, ISO 17025:1999 (the latest version issued in 2005) [3], originally designed to assess the technical competence of laboratories, is a generic standard used in the accreditation of any type of testing or calibration laboratory [4]. In 2003, after a long journey, the Working Group 1 of the Technical Committee, ISO/TC 212 “Clinical laboratory testing and in vitro diagnostic systems” (established in 1995), issued the first edition of an International Standard, the ISO 15189 “Medical laboratories – Requirements for quality and competence”, specifically designed for the medical laboratory [5]. ISO 15189 brought together the quality system requirements of ISO 9001 and the competency requirements of ISO/IEC 17025, addressing the specific needs of medical laboratory professionals worldwide. In particular, it incorporated sector specific issues of crucial importance in the provision of medical laboratory services. For example, it emphasizes the quality of not only the measurement but also that of the total service (e.g., consultation, turnaround time and cost-effectiveness), highlights important features of pre-and post-examination issues, focuses on patient outcomes and addresses ethics and the information needs of the medical laboratory [6]. The ISO 15189, developed with a significant contribution from the European Communities Confederation of Clinical Chemistry – EC4 – (now merged with the Federation of European Societies of Clinical Chemistry – FESCC – in the European Federation of Clinical Chemistry and Laboratory Medicine – EFLM), has been recognized by both the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and the International Laboratory Accreditation Co-operation (ILAC). However, the standards are only one of the four elements of an accreditation system as both the accreditation body and assessors/inspectors play a relevant role. Moreover, the user laboratory represents the fourth element. It is important to bear in mind that accreditation according to the ISO 15189 International Standard was conceived as a voluntary process, as is clearly highlighted by the inclusion of a specific clause (8.4.3 in the latest revision of the International Standard) on “continual improvement”. The evidence that in some countries, such as France and, at least in part, Belgium, accreditation according to the ISO 15189 is mandatory is further proof of its value and may facilitate the efforts of clinical laboratories to comply with a series of consensually developed and harmonized requirements other than with some national or regional standards. Yet, despite its growing global recognition by the main scientific organizations in the field of laboratory medicine, in many countries only a small number of laboratories are currently accredited [7]. The reasons for the variations between countries include differences in experience, competence, the interests of national

Cholesteryl ester storage disease (CESD) is an autosomal recessive chronic liver disease caused by lysosomal acid lipase (LAL) deficiency. The gene is located on chromosome 10q23.2-q23.3, and the enzyme is essential for triglycerides and cholesteryl ester hydrolysis in lysosomes. CESD is characterized by hypercholesterolemia, hypertriglyceridemia, HDL deficiency, and abnormal lipid deposition in many organs. In the liver this results in hepatomegaly caused by hepatic steatosis and fibrosis that can lead to micronodular cirrhosis.1 Disease onset takes place during childhood or adolescence. Males and females are affected in about equal numbers. Patients rarely reach the age of 30. Biochemically, the disorder is recognized by largely reduced lysosomal acid lipase activity.2,3 Complete absence of LAL activity causes Wolman Disease, which is normally fatal within the first 6 months of life.1,4 Several groups have identified mutations in the LAL gene underlying CESD and Wolman disease.5–9 Mutations causing Wolman disease produce an enzyme with no residual activity or no enzyme at all, whereas CESD-causing mutations encode for LAL which retains some enzyme activity.4,10 A G-to-A transition at position −1 of the exon 8 splice donor (E8SJM, E xon 8 S plice J unction M utation) leads to an in-frame deletion of exon 8. The resulting protein is 24 amino acids shorter and has no residual LAL activity, however E8SJM does not cause Wolman Disease because 2% to 4% of normally spliced LAL is present in homozygote carriers.11,12 The vast majority of CESD …

The central role of laboratory medicine as the integrating element in healthcare services

When quality is referred to in clinical chemistry and laboratory medicine, the focus is mainly on the analytical process. But good professional quality starts with a sound education. In an attempt to describe the practice of clinical chemistry and laboratory medicine in the 15 member states of the "old" European Union, it was noticed that (sometimes) large differences existed in the way professionals are being trained (see: Sanders et al, Clin Chem Lab Med 2002; 40: 196-204). With that outcome, a survey of the Websites of the different Member Societies and Corporate Members of IFCC was conducted. It showed that less than one third of either two groups paid attention to, or offered, education. This led to a series of questions to a non-representative group of colleagues outside the former EU who were willing to give more insight in the educational system of their country. All colleagues were known to be involved actively in clinical chemistry and laboratory medicine. The outcome did not give a uniform pattern, since every country regulates health care in its own way, according to its own historical development, needs, social vision, etc. From that a number of conclusions have been drawn: a. Proper University Training is required to enter vocational training b. Regulated Vocational Training seems to be necessary (4 years) c. A clear Syllabus as an indicative guide to the vocational training is important d. Management training should be included since a clinical chemist will have organizational responsibilities as well e. Examinations may help in improving the quality of the education f. Official Register, recognized by Law, is essential, but not always existing h. Re-Registration can be seen as part of the Quality Cycle. Finally, some attention is being paid to the activities of the EMD. This Division of the IFCC provides the membership of IFCC and the health-care community with education which it considers relevant to Clinical Chemistry and Laboratory Medicine. It is the intention of EMD to improve the quality of the profession by educational activities in molecular biology, evidence based laboratory medicine, quality assurance, distance education, and laboratory management. Specific projects are a Master Course in Laboratory Science, a course in Flowcytometry, and the Visiting Lecturer Program which supports national societies in inviting lecturers on specific topics. More information can be found on the IFCC Web-site (www.ifcc.org). In the future, it is to be expected that emphasis on education in our profession will be on the clinical use of tests, modern media and e-learning, and specific courses in new technologies. EMD works continuously to improve the quality of clinical chemistry and laboratory medicine. The input from all National Societies is appreciated to discern topics most relevant to the membership of IFCC. .

Machine learning (ML) has been applied to an increasing number of predictive problems in laboratory medicine, and published work to date suggests that it has tremendous potential for clinical applications. However, a number of groups have noted the potential pitfalls associated with this work, particularly if certain details of the development and validation pipelines are not carefully controlled. To address these pitfalls and other specific challenges when applying machine learning in a laboratory medicine setting, a working group of the International Federation for Clinical Chemistry and Laboratory Medicine was convened to provide a guidance document for this domain. This manuscript represents consensus recommendations for best practices from that committee, with the goal of improving the quality of developed and published ML models designed for use in clinical laboratories. The committee believes that implementation of these best practices will improve the quality and reproducibility of machine learning utilized in laboratory medicine. We have provided our consensus assessment of a number of important practices that are required to ensure that valid, reproducible machine learning (ML) models can be applied to address operational and diagnostic questions in the clinical laboratory. These practices span all phases of model development, from problem formulation through predictive implementation. Although it is not possible to exhaustively discuss every potential pitfall in ML workflows, we believe that our current guidelines capture best practices for avoiding the most common and potentially dangerous errors in this important emerging field.

The 4th version of the guide to the Register for European Specialists in Laboratory Medicine (EuSpLM) established by the European Communities Confederation of Clinical Chemistry and Laboratory Medicine describes the transfer of the register to the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) in 2016, the extension in 2018 of the Register beyond the European Union to Europe and the benefits of membership of the EFLM Academy to which the Register transferred on the Academy's launch in 2019. The Academy offers EuSpLM registrants access to benefits that include reduced registration rates at selected conferences and free subscription to Clinical Chemistry and Laboratory Medicine. With effect from 2020 eligibility was extended to anyone with an interest in laboratory medicine. The updated guide describes the electronically driven processes for individual membership and block enrolment from national societies/organisations, and the stepping stones to recognition as anEuSpLM within the Academy. Whilst eligibility for recognition as an EuSpLM remains largely unchanged newexpectations across Europe in education, training, professional regulation and qualifications are reflected in updated criteria. The continuing driver for establishing the Academy and growing the EFLM Register reflects the federation's leadership role in the harmonisation of high quality education and training for those with an interest in laboratory medicine as well as ongoing initiatives to establish a Common Training Framework for Specialists in Laboratory Medicine under EU Directive 2013/55/EC (The Recognition of Professional Qualifications).

In 1997, the European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) set up a Register for European Specialists in Clinical Chemistry and Laboratory Medicine. The operation of the Register is undertaken by a Register Commission (EC4RC). During the last 12 years, more than 2200 specialists in Clinical Chemistry and Laboratory Medicine have joined the Register. In 2007, EC4 merged with the Forum of European Societies of Clinical Chemistry and Laboratory Medicine (FESCC) to form the European Federation of Clinical Chemistry and Laboratory Medicine (EFCC). Two previous Guides to the Register have been published, one in 1997 and another in 2003. The third version of the Guide is presented in this article and is based on the experience gained and development of the profession since the last revision. Registration is valid for 5 years and the procedure and criteria for re-registration are presented as an Appendix at the end of the article.

In 1997, the European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) set up a Register for European Specialists in Clinical Chemistry and Laboratory Medicine. The operation of the Register is undertaken by a Register Commission (EC4RC). During the last 10 years, more than 2000 specialists in Clinical Chemistry and Laboratory Medicine have joined the Register. In 2007, EC4 merged with the Federation of European Societies of Clinical Chemistry and Laboratory Medicine (FESCC) to form the European Federation of Clinical Chemistry and Laboratory Medicine (EFCC). A Code of Conduct was adopted in 2003 and a revised and updated version, taking account particularly of the guidelines of the Conseil Européen des Professions Libérales (CEPLIS) of which EFCC is a member, is presented in this article. The revised version was approved by the EC4 Register Commission and by the EFCC Executive Board in Paris on 6 November, 2008.

An alternative perspective on how laboratory medicine can contribute to solve the health care crisis: A model to save costs by acquiring excellence in diagnostic systems