Allowable bias derived from the NOBIDA reference values.

Figures of allowable bias are used to make rational choices of quality control rules, to judge the validity of published reference values, and to determine the stability of sample materials. Usually, allowable bias is parametrically defined as 0.25 times the total biological standard deviation, because that is half the width of the 90% confidence interval of parametrically estimated reference limits from 120 reference values. The published figures are mostly derived from very small populations, less than 120. We estimated allowable bias non-parametrically as the least of 4 percentile differences in distributions of reference values from the large Nordic reference interval project biobank and database (NOBIDA). The percentile differences are equivalent to 0.25 times the total biological standard deviation in Gaussian distributions. We also estimated allowable bias from the distributions of non-parametrically estimated reference limits after resampling 120 reference values from the same datasets. Clearly larger allowable bias was derived from the resampling method than from the percentile difference method, showing that non-parametric estimation of reference limits from 120 reference values implies a larger allowable bias than 0.25 times the normal biological standard deviation. With some exceptions, the figures of allowable bias using the percentile difference method were in the same order of magnitude as parametrically derived figures in other studies, and lend some support to the results from those smaller studies. Whether such bias specifications, if met, guarantee measurements of sufficient clinical quality is unknown.

Innovative Practice, Clinical Research, and the Ethical Advancement of Medicine.

Innovative practice occurs when a clinician provides something new, untested, or nonstandard to a patient in the course of clinical care, rather than as part of a research study. Commentators have noted that patients engaged in innovative practice are at significant risk of suffering harm, exploitation, or autonomy violations. By creating a pathway for harmful or nonbeneficial interventions to spread within medical practice without being subjected to rigorous scientific evaluation, innovative practice poses similar risks to the wider community of patients and society as a whole. Given these concerns, how should we control and oversee innovative practice, and in particular, how should we coordinate innovative practice and clinical research? In this article, I argue that an ethical approach overseeing innovative practice must encourage the early transition to rigorous clinical research without delaying or deferring the development of beneficial innovations or violating the autonomy rights of clinicians and their patients.

[I. A. Petrovsky and Implementation of Qualitative Approach into Clinical Medicine].

The article covers the life and the work of Ivan A. Petrovsky, doctor of medicine. His contribution into propaganda in the Russian Empire of the idea of French physician Pierre-Charles-Alexandre Louis (1787-1872) concerning necessity of applying the statistical method in the clinical medicine. At that, the new facts of the biography of P.-Ch.-A. Louis were established. So, it is established that in Russia he was family doctor in the family of Armand-Charles-Emmanuel de Guignard, Comte de Saint-Priest (1782-1863). This discovery permitted to specify the circumstances of life of P.-Ch.-A. Louis in the Russian Empire. The study is also based on the archive materials founded in the Russian State Military History Archive. They are introduced into the scientific circulation for the first time.

Identifying MSM-competent physicians in China: a national online cross-sectional survey among physicians who see male HIV/STI patients.

BACKGROUND: Men who have sex with men (MSM) are at high risk of human immunodeficiency virus (HIV) infection and sexually transmitted infection (STI) in China. Inadequate clinical services and poor clinical competency among physicians are major barriers to improving the sexual health of MSM. This study aims to understand physician clinical competency in providing MSM health services in China. METHODS: We conducted an online cross-sectional survey among Chinese physicians who have seen male patients for STI complaints in the past year. We obtained information on individual demographics, clinical practice, attitudes toward MSM, and interest in contributing to MSM clinical services. We defined an MSM-competent physician as one who asked male patients about sexual orientation, sexual practices, and recommended HIV/ STI testing during a clinic visit. We conducted multivariable logistic regression to identify factors associated with MSM competency. RESULTS: In total, 501 physicians completed the survey. The most common subspecialties were dermatovenereology (33.1%), urology (30.1%), and general medicine (14.4%). Roughly half (n = 267, 53.3%) reported seeing MSM in the past 12 months. Among physicians who saw MSM in the past 12 months, 60.3% (n = 161) met criteria as MSM-competent physicians, and most (n = 234, 87.6%) MSM-competent physicians reported positive or neutral attitudes towards MSM. Over 60% of all physicians were willing to participate in activities for improving MSM services, such as training and being on a list of physicians willing to serve MSM. MSM-competent physicians showed no sociodemographic differences compared with non MSM-competent physicians. MSM-competent physicians were more willing to have their medical institution named on a public clinic list capable of serving MSM (aOR: 1.70, 95%CI: 1.01-2.86) and being on a public physician list capable of serving MSM (aOR: 1.77, 95%CI: 1.03-3.03). CONCLUSIONS: MSM-competent physicians included a broad range of individuals that practiced in diverse clinical settings. Most physicians were interested in improving and expanding MSM clinical services, despite having neutral attitudes toward same-sex behavior. Future interventions should focus on developing MSM clinical competency and expanding services that meet the needs of MSM.

Strategies to define performance specifications in laboratory medicine: 3 years on from the Milan Strategic Conference.

Measurements in clinical laboratories produce results needed in the diagnosis and monitoring of patients. These results are always characterized by some uncertainty. What quality is needed and what measurement errors can be tolerated without jeopardizing patient safety should therefore be defined and specified for each analyte having clinical use. When these specifications are defined, the total examination process will be "fit for purpose" and the laboratory professionals should then set up rules to control the measuring systems to ensure they perform within specifications. The laboratory community has used different models to set performance specifications (PS). Recently, it was felt that there was a need to revisit different models and, at the same time, to emphasize the presuppositions for using the different models. Therefore, in 2014 the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) organized a Strategic Conference in Milan. It was felt that there was a need for more detailed discussions on, for instance, PS for EQAS, which measurands should use which models to set PS and how to set PS for the extra-analytical phases. There was also a need to critically evaluate the quality of data on biological variation studies and further discussing the use of the total error (TE) concept. Consequently, EFLM established five Task Finish Groups (TFGs) to address each of these topics. The TFGs are finishing their activity on 2017 and the content of this paper includes deliverables from these groups.

Osmotic Pressure in Clinical Medicine with an Emphasis on Dialysis.

Since the beginning of life of the first multicellular organisms, the preservation of a physiologic milieu for every cell in the organism has been a critical requirement. A particular range of osmolality of the body fluids is essential for the maintenance of cell volume. In humans the stability of electrolyte concentrations and their resulting osmolality in the body fluids is the consequence of complex interactions between cell membrane functions, hormonal control, thirst, and controlled kidney excretion of fluid and solutes. Knowledge of these mechanisms, of the biochemical principles of osmolality, and of the relevant situations occurring in disease is of importance to every physician. This comprehensive review summarizes the major facts on osmolality, its relation to electrolytes and other solutes, and its relevance in physiology and in disease states with a focus on dialysis-related considerations.

Medicine and management: looking inside the box of changing hospital governance.

BACKGROUND: Health policy has strengthened the demand for coordination between clinicians and managers and introduced new medical manager roles in hospitals to better connect medicine and management. These developments have created a scholarly debate of concepts and an increasing 'hybridization' of tasks and roles, yet the organizational effects are not well researched. This research introduces a multi-level governance approach and aims to explore the organizational needs of doctors using Sweden as a case study. METHODS: We apply an assessment framework focusing on macro-meso levels and managerial-professional modes of hospital governance (using document analysis, secondary sources, and expert information) and expand the analysis towards the micro-level. Qualitative explorative empirical material gathered in two different studies in Swedish hospitals serves to pilot research into actor-centred perceptions of clinical management from the viewpoint of the 'managed' and the 'managing' doctors in an organization. RESULTS: Sweden has developed a model of integrated hospital governance with complex structural coordination between medicine and management on the level of the organization. In terms of formal requirements, the professional background is less relevant for many management positions but in everyday work, medical managers are perceived primarily as colleagues and not as experts advising on managerial problems. The managers themselves seem to rely more on personal strength and medical knowledge than on management tools. Bringing doctors into management may hybridize formal roles and concepts, but it does not necessarily change the perceptions of doctors and improve managerial-professional coordination at the micro-level of the organization. CONCLUSION: This study brings gaps in hospital governance into view that may create organizational weaknesses and unmet management needs, thereby constraining more coordinated and integrated medical management.

[DOMESTIC CLINICISM AND ITS APPLICATION].

Domestic clinicism is a methodology implying the maximum use of diagnostic and therapeutic potential of the physician in combination with the optimal application of laboratory and instrumental techniques for the choice of personified means of pharmaceutical and non-pharmaceutical treatment and prophylaxis of various diseases. It can not be applied under routine working conditions of a district doctor who has only 10-15 min to handle each patient. The currently adopted principle of organization of primary medical care: "the more patients the better", negatively affects the patients' health and emotionally discourage doctors.

Ultrasound-guided synovial biopsy: a systematic review according to the OMERACT filter and recommendations for minimal reporting standards in clinical studies.

OBJECTIVES: To describe existing techniques of US-guided synovial biopsy (USG-SB) and critically appraise the literature on this technology through the OMERACT filter. METHODS: USG-SB techniques are described and compared. A systematic literature search of PubMed and Embase was performed for original research reports including US and SB. The subjects, procedure protocols and reported results were analysed. A future research agenda is proposed. RESULTS: USG-SB can be performed using a portal-and-forceps or a dedicated semi-automatic guillotine-type biopsy needle approach. Of 50 reports identified, 7 were included in the review. Large, intermediate and small joints were all amenable to USG-SB. We found great heterogeneity with regard to indications for and definition of a successful procedure and of synovitis. Adverse events were assessed in most papers with an overall major complication rate of 0.4%. However, there was a lack of construct validity using a histological comparator. Relatively few papers reported details on the technique used, tissue processing, synovitis scoring and blinding for tissue analysis. CONCLUSION: USG-SB can be regarded as a valuable tool for large-scale synovial tissue sampling. Standardization of the techniques of USG-SB and tissue processing is needed. Future research should focus on the reliability, responsiveness and feasibility of this procedure in prospective studies.

Flexible scope for ISO 15189 accreditation: a guidance prepared by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group Accreditation and ISO/CEN standards (WG-A/ISO).

The recent revision of ISO15189 has further strengthened its position as the standard for accreditation for medical laboratories. Both for laboratories and their customers it is important that the scope of such accreditation is clear. Therefore the European co-operation for accreditation (EA) demands that the national bodies responsible for accreditation describe the scope of every laboratory accreditation in a way that leaves no room for doubt about the range of competence of the particular laboratories. According to EA recommendations scopes may be fixed, mentioning every single test that is part of the accreditation, or flexible, mentioning all combinations of medical field, examination type and materials for which the laboratory is competent. Up to now national accreditation bodies perpetuate use of fixed scopes, partly by inertia, partly out of fear that a too flexible scope may lead to over-valuation of the competence of laboratories, most countries only use fixed scopes. The EA however promotes use of flexible scopes, since this allows for more readily innovation, which contributes to quality in laboratory medicine. In this position paper, the Working Group Accreditation and ISO/CEN Standards belonging to the Quality and Regulation Committee of the EFLM recommends using an approach that has led to successful introduction of the flexible scope for ISO15189 accreditation as intended in EA-4/17 in The Netherlands. The approach is risk-based, discipline and competence-based, and focuses on defining a uniform terminology transferable across the borders of scientific disciplines, laboratories and countries.

Permissible limits for uncertainty of measurement in laboratory medicine.

The international standard ISO 15189 requires that medical laboratories estimate the uncertainty of their quantitative test results obtained from patients' specimens. The standard does not provide details how and within which limits the measurement uncertainty should be determined. The most common concept for establishing permissible uncertainty limits is to relate them on biological variation defining the rate of false positive results or to base the limits on the state-of-the-art. The state-of-the-art is usually derived from data provided by a group of selected medical laboratories. The approach on biological variation should be preferred because of its transparency and scientific base. Hitherto, all recommendations were based on a linear relationship between biological and analytical variation leading to limits which are sometimes too stringent or too permissive for routine testing in laboratory medicine. In contrast, the present proposal is based on a non-linear relationship between biological and analytical variation leading to more realistic limits. The proposed algorithms can be applied to all measurands and consider any quantity to be assured. The suggested approach tries to provide the above mentioned details and is a compromise between the biological variation concept, the GUM uncertainty model and the technical state-of-the-art.

Harmonization of quality indicators in laboratory medicine. A preliminary consensus.

Quality indicators (QIs) are fundamental tools for enabling users to quantify the quality of all operational processes by comparing it against a defined criterion. QIs data should be collected over time to identify, correct, and continuously monitor defects and improve performance and patient safety by identifying and implementing effective interventions. According to the international standard for medical laboratories accreditation, the laboratory shall establish and periodically review QIs to monitor and evaluate performance throughout critical aspects of pre-, intra-, and post-analytical processes. However, while some interesting programs on indicators in the total testing process have been developed in some countries, there is no consensus for the production of joint recommendations focusing on the adoption of universal QIs and common terminology in the total testing process. A preliminary agreement has been achieved in a Consensus Conference organized in Padua in 2013, after revising the model of quality indicators (MQI) developed by the Working Group on "Laboratory Errors and Patient Safety" of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The consensually accepted list of QIs, which takes into consideration both their importance and applicability, should be tested by all potentially interested clinical laboratories to identify further steps in the harmonization project.

Non-communicable diseases and implications for medical practice in Australia: a framework for analysis.

Non-communicable diseases (NCDs) have become leading causes of mortality and morbidity as part of historical epidemiological, demographic and nutritional transitions. There has been considerable historical analysis of the immediate and underlying causes of this change in the impacts of communicable diseases and NCDs, but far less historical analysis of how this transition has shaped medical practice. We lay out a framework for future historical analysis by proposing four domains of inquiry into key areas of change: changes in the concept of disease; evolution of medical technology; changes in workforce, including variation in roles and emerging areas of specialisation; and changes in health care structures including models of care, government responses and transitioning health systems. Our aim is to encourage analysis that takes into account key features in each of the four domains, thus enabling a more complete understanding of why, how and under what circumstances NCDs have had an effect on medical practice.

[Rationalization in 20th-century Czechoslovak pharmacy practice - commission for rationalization and standardization in medicine, veterinary medicine and pharmacy - part 1]. / Racionalizace v ceskoslovenském lékárenství ve 20. století - farmaceutická sekce Komise pro racionalisaci a normalisaci v lékarství, zverolékarství a lékárnictví - 1. cást.

UNLABELLED: In the 1920s Czechoslovakia, an increased attention was paid to the new ideas of scientific management (Taylorism), work rationalization and standardization. This was reflected in the foundation of the Masaryk Academy of Work in 1920. An effort to implement the new principles into health care led to the establishment of the Commission for Rationalization and Standardization in Medicine, Veterinary Medicine and Pharmacy (RANOK) within the Department of Natural Science and Medicine of the Academy. Within RANOK, the group for pharmacy worked between 1928-1932. The first part of the paper describes the scientific management and standardization movement in interwar Czechoslovakia, and the establishment of Masaryk Academy of Work and RANOK, including the group for pharmacy. The paper discusses the work objectives of the commission and presents concise biographies of the group for pharmacy members, too. The second part will be focused on the work results, relative failure and role of the group. KEYWORDS: Masaryk Academy of Work Comission for Rationalization and Standardization in Medicine Veterinary Medicine and Pharmacy (RANOK) work rationalization standardization pharmacy practice.

[Rationalization in 20th-century czechoslovak pharmacy practice - commission for rationalization and standardization in medicine, veterinary medicine and pharmacy - part 2*]. / Racionalizace v ceskoslovenském lékárenství ve 20. století - farmaceutická sekce Komise pro racionalisaci a normalisaci v lékarství, zverolékarství a lékárnictví - 2. cást*

In interwar Czechoslovakia health care, an increased attention paid to the new ideas of scientific management (Taylorism), work rationalization and standardization led to the establishment of the Commission for Rationalization and Standardization in Medicine, Veterinary Medicine and Pharmacy (RANOK) within the Department of Natural Science and Medicine of the Masaryk Academy of Work. Within RANOK, the group for pharmacy worked between 1928 and 1932. The first part of the paper described the scientific management and standardization movement in interwar Czechoslovakia, the establishment of Masaryk Academy of Work and RANOK, and work objectives of RANOK and its group for pharmacy. The second part deals with the work results, relative failure and importance of the group for pharmacy.

The DSM-5: Hyperbole, Hope or Hypothesis?

The furore preceding the release of the new edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) is in contrast to the incremental changes to several diagnostic categories, which are derived from new research since its predecessor's birth in 1990. While many of these changes are indeed controversial, they do reflect the intrinsic ambiguity of the extant literature. Additionally, this may be a mirror of the frustration of the field's limited progress, especially given the false hopes at the dawn of the "decade of the brain". In the absence of a coherent pathophysiology, the DSM remains no more than a set of consensus based operationalized adjectives, albeit with some degree of reliability. It does not cleave nature at its joints, nor does it aim to, but neither does alternate systems. The largest problem with the DSM system is how it's used; sometimes too loosely by clinicians, and too rigidly by regulators, insurers, lawyers and at times researchers, who afford it reference and deference disproportionate to its overt acknowledged limitations.

Informing DSM-5: biological boundaries between bipolar I disorder, schizoaffective disorder, and schizophrenia.

BACKGROUND: The fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) opted to retain existing diagnostic boundaries between bipolar I disorder, schizoaffective disorder, and schizophrenia. The debate preceding this decision focused on understanding the biologic basis of these major mental illnesses. Evidence from genetics, neuroscience, and pharmacotherapeutics informed the DSM-5 development process. The following discussion will emphasize some of the key factors at the forefront of the debate. DISCUSSION: Family studies suggest a clear genetic link between bipolar I disorder, schizoaffective disorder, and schizophrenia. However, large-scale genome-wide association studies have not been successful in identifying susceptibility genes that make substantial etiological contributions. Boundaries between psychotic disorders are not further clarified by looking at brain morphology. The fact that symptoms of bipolar I disorder, but not schizophrenia, are often responsive to medications such as lithium and other anticonvulsants must be interpreted within a larger framework of biological research. SUMMARY: For DSM-5, existing nosological boundaries between bipolar I disorder and schizophrenia were retained and schizoaffective disorder preserved as an independent diagnosis since the biological data are not yet compelling enough to justify a move to a more neurodevelopmentally continuous model of psychosis.

Accuracy and applicability of the revised WHO classification (2009) of dengue in children seen at a tertiary healthcare facility in northern India.

BACKGROUND: Revised case definitions of dengue into dengue with/without warning signs (DWS/D) and severe dengue (SD) was proposed by the World Health Organization (WHO)/Tropical Disease Research (TDR) in 2009. To date, there has been no Indian study that has applied this classification. AIMS AND OBJECTIVES: To assess the accuracy and applicability of the revised WHO classification (2009) of dengue in children seen at a tertiary healthcare facility in India. MATERIALS AND METHODS: Over a period of 1 year children from the pediatric ward and Out Patient Department (OPD) of the King George Medical University Hospital, Lucknow were enrolled in the study according to predefined criteria and tested for dengue. Each dengue-positive patient was classified according to both the older system [dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS)] and the new system (D, DWS, and SD). The severity of dengue was compared to the level of treatment received. RESULTS: A total of 56 patients tested positive for dengue--51 from the pediatric ward and five from the OPD. According to the older WHO classification, 42 (75 %) patients were classified as DF and 13 (23.2 %) as DHF/DSS; one patient was unclassifiable. Five patients (8.9 %) received level 1 treatment, ten (17.8 %) received level 2 treatment, and 41 (73.2 %) received level 3 treatment. According to the new WHO/TDR classification, 46 (82.1 %) patients were classified as SD, nine (16 %) as DWS, and only one (1.7 %) as D. Many of the severe manifestations (encephalopathy, shock, mucosal bleed, platelet count <20,000, respiratory distress, liver enzymes >1,000 U/L) were seen in patients who were classified as DF according to old classification, whereas these patients were mostly classified as SD by the new classification. Sensitivity of the older and new classifications was 24.8 and 98 %, respectively. CONCLUSIONS: The revised WHO/TDR (2009) classification has very high sensitivity for identifying severe dengue and is easy to apply.

Metrological traceability - a concept for standardization in laboratory medicine.

The concept of measurement traceability provides the most important strategy in achieving standardization in laboratory medicine aimed at equivalent measurement results regardless of the principle of measurement, the method, the actual measurement procedure (test kit) and the laboratory where analyses are carried out.