HPV testing for cervical cancer screening in Croatia

Opportunistic screening based on the Pap smear has been undertaken in Croatia since 1953. However, cervical cancer remains an important health problem in Croatia when compared to European countries with organised screening programmes. In Croatia, in addition to screening based on well established cytology, Human papillomavirus (HPV) testing is widely used as secondary test as a triage to borderline cytology and as a follow-up after treatment of severe cervical lesions. Many different approaches for HPV testing arose in Croatia over the last decade depending on the needs of each medical institution involved. Presently, there is an urgent need for better networking between the laboratories, the implementation of quality assessment and the adaptation of a uniform system of referring to and reporting of HPV testing. In conclusion, the best possible organisation for HPV testing would be essential for implementation of HPV testing as primary screening test in Croatia, an thus ultimately and hopefully, the more successful cervical cancer control.     

National registry of cervical cytologic diagnoses in The Netherlands

The national cervical cytology registry being developed in the Netherlands is described. A large-scale screening program for cervical cancer has been in effect since 1975 in the region of the cities of Nijmegen, Utrecht and Rotterdam. At the start of the pilot projects, laboratories agreed upon a uniform protocol for reporting cytologic findings and recommendations for follow-up examinations in cases of abnormalities. Based on the results of the three pilot projects, in 1985 the Dutch government decided to organize a nationwide screening program for cervical cancer. All pathology laboratories involved in this national screening program are using the same screening protocol and the same coding system for cytologic and histologic diagnoses. By the end of 1989, all pathology laboratories will be linked to a central pathology diagnosis data base (PALGA). Linkage of screening results to previous and follow-up cytologic and histologic findings will enable epidemiologic studies on a regional or national level. Each physician who has submitted specimens will, next to the cytology reports, periodically receive reviews of the number of smears submitted, the cellular composition (quality) of those smears and the follow-up findings. The execution of requests for follow-up examination will be supervised by the participating pathology laboratories. The national cervical cytology registry will enable registration of all relevant cytologic and histologic diagnoses in a uniform way, but will also establish a unique high-quality national data bank, which will be of great value in the analysis of the effectiveness of the national screening program for cervical cancer. It will enable measurement of the impact of various screening protocols and give insight into the behavior of cervical cancer and the progressive or regressive character of its early stages. It will also offer the opportunity to initiate and evaluate quality control protocols.     

Implementing findings of research.

There are unacceptable delays in the implementation of many findings of research. This results in suboptimal care for patients. A number of approaches may be effective in speeding up implementation, including evidence based guidelines, the influence of opinion leaders, and computer based decision support systems. An integrated approach to speeding up this process by means of a number of mechanisms is likely to be most effective. The results of systematic reviews of the research literature should be incorporated into programmes of continuing medical education and clinical audit. Professional associations have an important role to play in ensuring that research based information is included in educational activities and clinical guidelines. Purchasers of health care could promote the uptake of research findings during contract negotiations. Improved methods of informing health care users and the public about evidence of effectiveness could also have an impact. Policy makers should take more account of the results of research when formulating recommendations. Methods of improving the implementation of research findings require further investigation and greater resources devoted to them.     

Electronic Laboratory Medicine ordering with evidence-based Order sets in primary care (ELMO study): protocol for a cluster randomised trial

Background

Laboratory testing is an important clinical act with a valuable role in screening, diagnosis, management and monitoring of diseases or therapies. However, inappropriate laboratory test ordering is frequent, burdening health care spending and negatively influencing quality of care. Inappropriate tests may also result in false-positive results and potentially cause excessive downstream activities. Clinical decision support systems (CDSSs) have shown promising results to influence the test-ordering behaviour of physicians and to improve appropriateness. Order sets, a form of CDSS where a limited set of evidence-based tests are proposed for a series of indications, integrated in a computerised physician order entry (CPOE) have been shown to be effective in reducing the volume of ordered laboratory tests but convincing evidence that they influence appropriateness is lacking. The aim of this study is to evaluate the effect of order sets on the quality and quantity of laboratory test orders by physicians. We also aim to evaluate the effect of order sets on diagnostic error and explore the effect on downstream or cascade activities.

Methods

We will conduct a cluster randomised controlled trial in Belgian primary care practices. The study is powered to measure two outcomes. We will primarily measure the influence of our CDSS on the appropriateness of laboratory test ordering. Additionally, we will also measure the influence on diagnostic error. We will also explore the effects of our intervention on cascade activities due to altered results of inappropriate tests.

Discussion

We have designed a study that should be able to demonstrate whether the CDSS aimed at diagnostic testing is not only able to influence appropriateness but also safe with respect to diagnostic error. These findings will influence a lager, nationwide implementation of this CDSS.

Trial registration

ClinicalTrials.gov, NCT02950142.

     

The impact of work organisation on the work life of people on pasture-based dairy farms

The seasonal workload combined with increased dairy herd sizes and a declining workforce have created social sustainability challenges for pasture-based dairy farms. Effective work organisation can build productive capacity that may have a positive impact on this scenario. Our objective was to develop a framework to characterise and examine the effect of work organisation on the working situations of the people involved in a sample of 55 pasture-based dairy farms in Ireland. We conceptualised that effective work organisation on a dairy farm could be considered as a system that is efficient from a labour input perspective, resulting in a profitable farming system with outcomes of good operator well-being, health and safety, and quality of life. A literature review established efficiency & productivity, flexibility and standardisation as our three characteristics of work organisation. Using data from an existing labour time-use study completed from the 1st February to 30th June 2019, we aimed to test the veracity of these work organisation characteristics in the Irish pasture-based dairy system. Two proxy indicators were selected to represent each of the three work organisation characteristics, and each of the 55 farms were categorised into quartiles based on their ranking for these six indicators (1 = most effective quartile to 4 = least effective quartile). The most and least effective quartiles of farms for work organisation showed similar levels of farm labour input and labour efficiency. Farmers in the most effective work organisation quartile were working 51.2 h/week from February to June compared with 70.0 h/week for farmers in the least effective quartile, which was attributed to later start times, earlier finish times, and more time at non-farm activity. Farms achieving effective work organisation had a labour-efficient system with relatively low farmer working hours. Extension of the work organisation concept to other farms could improve their labour situation and aid in alleviating some of the key quality of life challenges faced by dairy farmers.     

A pragmatic cluster randomised trial evaluating three implementation interventions

ABSTRACT: BACKGROUND: Implementation research is concerned with bridging the gap between evidence and practice through the study of methods to promote the uptake of research into routine practice. Good quality evidence has been summarised into guideline recommendations to show that peri-operative fasting times could be considerably shorter than patients currently experience. The objective of this trial was to evaluate the effectiveness of three strategies for the implementation of recommendations about peri-operative fasting. METHODS: A pragmatic cluster randomised trial underpinned by the PARIHS framework was conducted during 2006 to 2009 with a national sample of UK hospitals using time series with mixed methods process evaluation and cost analysis. Hospitals were randomised to one of three interventions: standard dissemination (SD) of a guideline package, SD plus a web-based resource championed by an opinion leader, and SD plus plan-do-study-act (PDSA). The primary outcome was duration of fluid fast prior to induction of anaesthesia. Secondary outcomes included duration of food fast, patients' experiences, and stakeholders' experiences of implementation, including influences. ANOVA was used to test differences over time and interventions. RESULTS: Nineteen acute NHS hospitals participated. Across timepoints, 3,505 duration of fasting observations were recorded. No significant effect of the interventions was observed for either fluid or food fasting times. The effect size was 0.33 for the web-based intervention compared to SD alone for the change in fluid fasting and was 0.12 for PDSA compared to SD alone. The process evaluation showed different types of impact, including changes to practices, policies, and attitudes. A rich picture of the implementation challenges emerged, including inter-professional tensions and a lack of clarity for decision-making authority and responsibility. CONCLUSIONS: This was a large, complex study and one of the first national randomised controlled trials conducted within acute care in implementation research. The evidence base for fasting practice was accepted by those participating in this study and the messages from it simple; however, implementation and practical challenges influenced the interventions' impact. A set of conditions for implementation emerges from the findings of this study, which are presented as theoretically transferable propositions that have international relevance. Trial registration ISRCTN18046709 - Peri-operative Implementation Study Evaluation (POISE).     

A matrix for a LIMS with a strategic focus

This article focuses on the impact that a laboratory information management system (LIMS) should make on both a laboratory and an organisation but rarely does. To be effective a system should deliver benefit to both the laboratory environment and the organisation. But how should this be designed? To overcome this problem a matrix is proposed, which will allow any LIMS to be developed with a strategic focus. The matrix can be used either as an aid to system implementation and deciding which applications the LIMS should interface with. Alternatively, the matrix can be a means of evaluating the effectiveness of existing applications and to chart their further development. The aim is to give analytical chemists, managers and computer scientists a tool to enable any LIMS to reach its true potential.     

Investigation of the effect of Interleukin-1 receptor antagonist (IL-1ra) on markers of inflammation in non-ST elevation acute coronary syndromes (The MRC-ILA-HEART Study)

Background

Point of care testing (PoCT) may be a useful adjunct in the management of chronic conditions in general practice (GP). The provision of pathology test results at the time of the consultation could lead to enhanced clinical management, better health outcomes, greater convenience and satisfaction for patients and general practitioners (GPs), and savings in costs and time. It could also result in inappropriate testing, increased consultations and poor health outcomes resulting from inaccurate results. Currently there are very few randomised controlled trials (RCTs) in GP that have investigated these aspects of PoCT.

Design/Methods

The Point of Care Testing in General Practice Trial (PoCT Trial) was an Australian Government funded multi-centre, cluster randomised controlled trial to determine the safety, clinical effectiveness, cost effectiveness and satisfaction of PoCT in a GP setting. The PoCT Trial covered an 18 month period with the intervention consisting of the use of PoCT for seven tests used in the management of patients with diabetes, hyperlipidaemia and patients on anticoagulant therapy. The primary outcome measure was the proportion of patients within target range, a measure of therapeutic control. In addition, the PoCT Trial investigated the safety of PoCT, impact of PoCT on patient compliance to medication, stakeholder satisfaction, cost effectiveness of PoCT versus laboratory testing, and influence of geographic location.

Discussion

The paper provides an overview of the Trial Design, the rationale for the research methodology chosen and how the Trial was implemented in a GP environment. The evaluation protocol and data collection processes took into account the large number of patients, the broad range of practice types distributed over a large geographic area, and the inclusion of pathology test results from multiple pathology laboratories. The evaluation protocol developed reflects the complexity of the Trial setting, the Trial Design and the approach taken within the funding provided. The PoCT Trial is regarded as a pragmatic RCT, evaluating the effectiveness of implementing PoCT in GP and every effort was made to ensure that, in these circumstances, internal and external validity was maintained.

Trial Registration

12612605000272695     

Standardisation of reference intervals: an Australasian view

The development of regional databases and doctors’ desktop programs that accept pathology results from different laboratories should improve patient care by allowing easy assessment of cumulative data. This has the potential to be unnecessarily confusing unless laboratories contributing to the databases provide standardised results and common reference intervals, where this is valid. The analytical methods that produce significantly different results need to be reported in a manner that avoids inappropriate interpretation.

The process of setting reference intervals requires an organisational structure which enables appropriate intervals to be set taking all relevant factors into account, including the opinions of expert clinicians. There must also be criteria for analytical agreement between the laboratories involved based on comparison studies using patient samples.

A network of QA groups across Australasia, with leadership from the AACB and RCPA, should be formed to share the ongoing work of defining reference intervals (RIs) for common tests, and reviewing them as the testing environment changes with the introduction of new techniques and instruments.

     

Tailoring an intervention to the context and system redesign related to the intervention: A case study of implementing shared medical appointments for diabetes

Background

Health care organizations exert significant influence on the manner in which clinicians practice and the processes and outcomes of care that patients experience. A greater understanding of the organizational milieu into which innovations will be introduced, as well as the organizational factors that are likely to foster or hinder the adoption and use of new technologies, care arrangements and quality improvement (QI) strategies are central to the effective implementation of research into practice. Unfortunately, much implementation research seems to not recognize or adequately address the influence and importance of organizations. Using examples from the U.S. Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI), we describe the role of organizational research in advancing the implementation of evidence-based practice into routine care settings.

Methods

Using the six-step QUERI process as a foundation, we present an organizational research framework designed to improve and accelerate the implementation of evidence-based practice into routine care. Specific QUERI-related organizational research applications are reviewed, with discussion of the measures and methods used to apply them. We describe these applications in the context of a continuum of organizational research activities to be conducted before, during and after implementation.

Results

Since QUERI's inception, various approaches to organizational research have been employed to foster progress through QUERI's six-step process. We report on how explicit integration of the evaluation of organizational factors into QUERI planning has informed the design of more effective care delivery system interventions and enabled their improved "fit" to individual VA facilities or practices. We examine the value and challenges in conducting organizational research, and briefly describe the contributions of organizational theory and environmental context to the research framework.

Conclusion

Understanding the organizational context of delivering evidence-based practice is a critical adjunct to efforts to systematically improve quality. Given the size and diversity of VA practices, coupled with unique organizational data sources, QUERI is well-positioned to make valuable contributions to the field of implementation science. More explicit accommodation of organizational inquiry into implementation research agendas has helped QUERI researchers to better frame and extend their work as they move toward regional and national spread activities.     

Improving Diabetes Care in Rural Areas: A Systematic Review and Meta-Analysis of Quality Improvement Interventions in OECD Countries

Background and Aims

Despite well documented disparities in health and healthcare in rural communities, evidence in relation to quality improvement (QI) interventions in those settings is still lacking. The main goals of this work were to assess the effectiveness of QI strategies designed to improve diabetes care in rural areas, and identify characteristics associated with greater success.

Methods

We conducted a systematic review and meta-analysis. Systematic electronic searches were conducted in MEDLINE, EMBASE, CINAHL, and 12 additional bibliographic sources. Experimental studies carried out in the OECD member countries assessing the effectiveness of QI interventions aiming to improve diabetes care in rural areas were included. The effect of the interventions and their impact on glycated hemoglobin was pooled using a random-effects meta-analysis.

Results

Twenty-six studies assessing the effectiveness of twenty QI interventions were included. Interventions targeted patients (45%), clinicians (5%), the health system (15%), or several targets (35%), and consisted of the implementation of one or multiple QI strategies. Most of the interventions produced a positive impact on processes of care or diabetes self-management, but a lower effect on health outcomes was observed. Interventions with multiple strategies and targeting the health system and/or clinicians were more likely to be effective. Six QI interventions were included in the meta-analysis (1,496 patients), which showed a significant reduction in overall glycated hemoglobin of 0.41 points from baseline in those patients receiving the interventions (95% CI -0.75% to -0.07%).

Conclusions

This work identified several characteristics associated with successful interventions to improve the quality of diabetes care in rural areas. Efforts to improve diabetes care in rural communities should focus on interventions with multiple strategies targeted at clinicians and/or the health system, rather than on traditional patient-oriented interventions.     

From Evidence to Best Practice in Laboratory Medicine

Laboratory tests offer value if they provide benefit to patients at acceptable costs. Laboratory testing is one of the most widely used diagnostic interventions supporting medical decisions, yet evidence demonstrating its value and impact on health outcomes is limited. This contributes to wide variations in test utilisation including underdiagnosis, overdiagnosis and misdiagnosis, which may impact the quality and the clinical- and cost-effectiveness of care and patient safety. Therefore implementing evidence into the care of patients is a moral and social imperative to laboratory professionals and all health care staff.This review investigates the reasons research does not get into practice, or only does with a very long delay. Apart from reviewing the common barriers to implementation, it also discusses the drivers of inappropriate test utilisation. By reviewing the theoretical and practical aspects of implementation science, recommendations are made for approaches that are thought to be most effective and that can be adopted to close the gap between evidence and practice, and to facilitate evidence-based laboratory medicine. Passive dissemination of the evidence and educational interventions are insufficient and do not offer sustainable solutions. A multifaceted and individualised implementation strategy, including individually tailored academic detailing, reminder systems, clinical decision support systems, feedback on performance, and participation of doctors and laboratory professionals in quality improvement activities addressing test selection and interpretation and in clinical audits, has greater potential for success. Examples of these initiatives at the laboratory and clinical interface are provided with links to valuable resources.

‘Knowing is not enough; we must apply.Willing is not enough; we must do.’JW von Goethe

     

Effects of a Computerized Order Set on the Inpatient Management of Hyperglycemia: A Cluster-Randomized Controlled Trial

ObjectiveTo determine the effects of a computerized order set on the inpatient management of diabetes and hyperglycemia.MethodsWe conducted a cluster-randomized controlled trial on the general medical service of an academic medical center staffed by residents and hospitalists. Consecutively enrolled patients with diabetes mellitus or inpatient hyperglycemia were randomized on the basis of their medical team to usual care (control group) or an admission order set built into the hospital’s computer provider order entry (CPOE) system (intervention group). All teams received a detailed subcutaneous insulin protocol and case-based education. The primary outcome was the mean percent of glucose readings per patient between 60 and 180 mg/dL.ResultsBetween April 5 and June 22, 2006, we identified 179 eligible study subjects. The mean percent of glucose readings per patient between 60 and 180 mg/dL was 75% in the intervention group and 71% in the usual care group (adjusted relative risk, 1.36; 95% confidence interval, 1.03 to 1.80). In comparison with usual care, the intervention group also had a lower patient-day weighted mean glucose (148 mg/dL versus 158 mg/dL, P = .04), less use of sliding-scale insulin by itself (25% versus 58%, P = .01), and no significant difference in the rate of severe hypoglycemia (glucose < 40 mg/dL; 0.5% versus 0.3% of patient-days, P = .58).ConclusionThe use of an order set built into a hospital’s CPOE system led to improvements in glycemic control and insulin ordering without causing a significant increase in hypoglycemia. Other institutions with CPOE should consider adopting similar order sets as part of a comprehensive inpatient glycemic management program. (Endocr Pract. 2010;16:209-218)     

The PSIP project for Adverse Drug Events prevention

The objective of Clinical Decision Support (CDSS) systems coupled with Computerised Physician Order Entry (CPOE) systems is to improve patient safety. However, there are still issues to be considered to improve the quality of CDSS, especially the difficulty to share the knowledge developed by institutions or healthcare organisations and to exploit it for other medical application. The aim of the Patient Safety through Intelligent Procedures (PSIP) project is to propose innovative tools to generate and provide relevant knowledge to healthcare professionals and patients for Adverse Drug Events (ADE) prevention. The particularity of the PSIP project is to consider the share of knowledge and the interoperability of medical applications via the elaboration of a Global Knowledge Platform (GKP). In this paper, we present the different components of the PSIP GKP and we show its implementation through three medical applications: a web application, an Electronic Health Record (EHR) and a CPOE.     

Collaborative Interventions for Circulation and Depression (COINCIDE): study protocol for a cluster randomized controlled trial of collaborative care for depression in people with diabetes and/or coronary heart disease

ABSTRACT: BACKGROUND: Depression is up to two to three times as common in people with long-term conditions. It negatively affects medical management of disease and self-care behaviors, and leads to poorer quality of life and high costs in primary care. Screening and treatment of depression is increasingly prioritized, but despite initiatives to improve access and quality of care, depression remains under-detected and under-treated, especially in people with long-term conditions. Collaborative care is known to positively affect the process and outcome of care for people with depression and long-term conditions, but its effectiveness outside the USA is still relatively unknown. Furthermore, collaborative care has yet to be tested in settings that resemble more naturalistic settings that include patient choice and the usual care providers. The aim of this study was to test the effectiveness of a collaborative-care intervention, for people with depression and diabetes/coronary heart disease in National Health Service (NHS) primary care, in which low-intensity psychological treatment services are delivered by the usual care provider - Increasing Access to Psychological Therapies (IAPT) services.s. The study also aimed to evaluate the cost-effectiveness of the intervention over 6 months of collaborative care, and to assess qualitatively the extent to which collaborative care was implemented in the intervention general practices. METHODS: This is a cluster randomized controlled trial of 30 general practices allocated to either collaborative care or usual care. Fifteen patients per practice will be recruited after a screening exercise to detect patients with recognized depression (greater than or equal to 10 on the nine-symptom Patient Health Questionnaire; PHQ-9). Patients in the collaborative-care arm with recognized depression will be offered a choice of evidence-based low-intensity psychological treatments based on cognitive and behavioral approaches. Patients will be case managed by psychological well-being practitioners employed by IAPT in partnership with a practice nurse and/or general practitioner. The primary outcome will be change in depressive symptoms at 6 months on the 90-item Symptoms Checklist (SCL-90). Secondary outcomes include change in health status, self-care behaviors, and self-efficacy. A qualitative process evaluation will be undertaken with patients and health practitioners to gauge the extent to which the collaborative-care model is implemented, and to explore sustainability beyond the clinical trial. DISCUSSION: COINCIDE will assess whether collaborative care can improve patient-centered outcomes, and evaluate access to and quality of care of co-morbid depression of varying intensity in people with diabetes/coronary heart disease. Additionally, by working with usual care providers such as IAPT, and by identifying and evaluating interventions that are effective and appropriate for routine use in the NHS, the COINCIDE trial offers opportunities to address translational gaps between research and implementation.Trial Registration NumberISRCTN80309252Trial StatusOpen.     

The tissue bank at the Instituto Nacional de Investigaciones Nucleares: ISO 9001:2000 certification of its quality management system

Tissue banking is a complex operation concerned with the organisation and coordination of all the steps, that is, from donor selection up to storage and distribution of the final products for therapeutic, diagnostic, instruction and research purposes. An appropriate quality framework should be established in order to cover all the specific methodology as well as the general aspects of quality management, such as research and development, design, instruction and training, specific documentation, traceability, corrective action, client satisfaction, and the like. Such a framework can be obtained by developing a quality management system (QMS) in accordance with a suitable international standard: ISO 9001:2000. This paper presents the implementation process of the tissue bank QMS at the Instituto Nacional de Investigaciones Nucleares in Mexico. Objective: The objective of the paper is to share the experience gained by the tissue bank personnel [radiosterilised tissue bank (BTR)] at the Instituto Nacional de Investigaciones Nucleares (ININ, National Institute of Nuclear Research), during implementation of the ISO 9001:2000 certification process. At present, the quality management system (QMS) of ININ also complies with the Mexican standard NMX-CC-9001:2000. The scope of this QMS is Research, Development and Processing of Biological Tissues Sterilised by Gamma Radiation, among others.     

Regulating whole exome sequencing as a diagnostic test

In the last decade, there has been a flood of new technology in the sequencing arena. The onset of next-generation sequencing (NGS) technology has resulted in the vast increase in genetic diagnostic testing available to the ordering physician. Whole exome sequencing (WES) has become available as a diagnostic test performed in certified clinical laboratories. This has led to increased presence in the diagnostic marketplace, increased consumer awareness, and the question has been raised by various stakeholders to whether there is sufficient stringent regulation of WES and other NGS-based tests. We discuss the various WES services currently available in the marketplace, current regulation of WES as a laboratory developed test, the proposed FDA involvement in its oversight as well as the response of various laboratory groups that provide these diagnostic services. Overall, a rigorous process oversight and assessment of inter-lab reproducibility is strongly warranted for WES as it is used as a diagnostic test, but regulation should be mindful of the excessive administrative burden on academic and smaller diagnostic laboratories.     

An update on the validation of whole slide imaging systems following FDA approval of a system for a routine pathology diagnostic service in the United States

Pathologists have used light microscopes and glass slides to interpret the histologic appearance of normal and diseased tissues for more than 150 years. The quality of both microtomes used to cut tissue sections and microscopes has improved significantly during the past few decades, but the process of rendering diagnoses has changed little. By contrast, major advances in digital technology have occurred since the introduction of hand held electronic devices, including the development of whole slide imaging (WSI) systems with software packages that can convert microscope images into virtual (digital) slides that can be viewed on computer monitors and via the internet. To date, however, these technological developments have had minimal impact on the way pathologists perform their daily work, with the exception of using computers to access electronic medical records and scholarly web sites for pertinent information to assist interpretation of cases. Traditional practice is likely to change significantly during the next decade, especially since the Federal Drug Administration in the USA has approved the first WSI system for routine diagnostic practice. I review here the development and slow acceptance of WSI by pathology departments. I focus on recent advances in validation of WSI systems that is required for routine diagnostic reporting of pathology cases using this technology.     

Assurance de Qualité et GBEA: Généralités et quelques applications à l’analyse en biologie de la reproduction

Definitions of Quality, Quality insurance and Quality controls are given. The applicability of general principles of Quality assurance to the analysis concerning the Biology of the Reproduction is underlined. The necessity of an overall organisation taking into account the different participants and services is stressed. The model with preanalytical, analytical and postanalytical steps is described. Good coordination between the different actors along the chain of interdependent steps is crucial. Documentation is an essential part of a quality system. All these elements and recommandations are indicated in the “Guide de Bonne Exécution des Analyses” or GBEA which was published in december 1994 and which is the french reference for the implementation of a quality system in the laboratories.