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.

Assessment of the new World Health Organization's dengue classification for predicting severity of illness and level of healthcare required.

The objective of this study was to assess the validity of the new dengue classification proposed by the World Health Organization (WHO) in 2009 and to develop pragmatic guidelines for case triage and management. This retrospective study involved 357 laboratory-confirmed cases of dengue infection diagnosed at King Abdulaziz University Hospital, Jeddah, Saudi Arabia over a 4-year period from 2014 to 2017. The sensitivity of the new classification for identifying severe cases was limited (65%) but higher than the old one (30%). It had a higher sensitivity for identifying patients who needed advanced healthcare compared to the old one (72% versus 32%, respectively). We propose adding decompensation of chronic diseases and thrombocytopenia-related bleeding to the category of severe dengue in the new classification. This modification improves sensitivity from 72% to 98% for identifying patients who need advanced healthcare without altering specificity (97%). It also improves sensitivity in predicting severe outcomes from 32% to 88%. In conclusion, the new classification had a low sensitivity for identifying patients needing advanced care and for predicting morbidity and mortality. We propose to include decompensation of chronic diseases and thrombocytopenia-related bleeding to the category of severe dengue in the new classification to improve the sensitivity of predicting cases requiring advanced care.

Post-analytical laboratory work: national recommendations from the Working Group for Post-analytics on behalf of the Croatian Society of Medical Biochemistry and Laboratory Medicine.

The post-analytical phase is the final phase of the total testing process and involves evaluation of laboratory test results; release of test results in a timely manner to appropriate individuals, particularly critical results; and modification, annotation or revocation of results as necessary to support clinical decision-making. Here we present a series of recommendations for post-analytical best practices, tailored to medical biochemistry laboratories in Croatia, which are intended to ensure alignment with national and international norms and guidelines. Implementation of the national recommendations is illustrated through several examples.

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.

Analyses of clinical and laboratory characteristics of dengue adults at their hospital presentations based on the World Health Organization clinical-phase framework: Emphasizing risk of severe dengue in the elderly.

BACKGROUND/PURPOSE: Dengue clinically dynamically changes over time; the World Health Organization (WHO) dengue classification framework proposed 3 dengue clinical phases-febrile (days 1-3), critical (days 4-6) and recovery (days ≥7) phases. This study aimed to better understand clinical and laboratory characteristics in adults (≥18 years) suffering dengue in different clinical phases at their hospital presentations. METHODS: A retrospective analysis of adults suffering dengue between 2008 and 2014. RESULTS: Of the 669 included dengue adults, 146 (21.8%) were elderly (≥65 years), and 27 (4%) suffered severe dengue. When compared with those in febrile phase, significantly higher incidence of ascites, mucosal bleeding, and/or gastrointestinal bleeding; lower white blood cell (WBC) and platelet counts; higher hematocrit, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values were found in critical phase. When compared with their younger counterparts, elderly at febrile phase had significantly lower frequencies of bone pain, myalgia, headache and rash; higher frequencies of vomiting, pleural effusion and mucosal bleeding; higher WBC count, AST and ALT levels, and lower platelet count; in critical phase, elderly had significantly higher frequencies of pleural effusion, mucosal bleeding and gum bleeding. Four (0.6%) patients experienced severe dengue in recovery phase. Significantly higher proportions of elderly developed severe dengue in both febrile and critical phases as compared with younger adults. CONCLUSIONS: Elderly had lower frequency of classical dengue symptoms, yet were at higher risk of development of severe dengue during their early dengue course. A small number of patients developed severe dengue at the WHO-proposed recovery phase.

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.

[Standard Operating Procedures in Clinical Medicine]. / Standards in der klinischen Medizin.

Standard operating procedures (SOP) in hospital care have the potential to improve treatment quality and transparency. However, after arriving at the decision to generate a SOP for the own hospital or ward, the upcoming question is often, how to start?The present article tries to give some interdisciplinary guidance about reasonable structures and contents of SOPs that could be understood as a basic matrix for individual work.

Saúde é colocar-se em risco: normatividade vital em Georges Canguilhem / Health is putting oneself at risk: vital normativity in Georges Canguilhem

Resumo Este artigo objetiva apresentar uma crítica ao modelo biomédico de saúde predominante nas ciências médicas, a partir do conceito de normatividade vital, proposto por Georges Canguilhem. Na introdução apresentamos, a partir de um breve histórico do conceito de saúde, a normalização como o primado fundamental do modelo biomédico. Na primeira parte, discutimos o problema da determinação do normal e do patológico, da saúde e da doença, no pensamento de Canguilhem, buscando situar esses conceitos em função de valores individuais, questionando a existência de um processo normativo em biologia. Na segunda parte, pretende-se demonstrar que a normatividade vital defendida por Canguilhem é uma ferramenta conceitual fundamental para o entendimento da lógica de produção biológica. Esta lógica de produção não toma a norma como critério de valoração das formas de vida possíveis. Não são as individualidades biológicas que se adéquam ou se afastam das normas, mas, ao contrário, é a individualidade biológica enquanto potência de criação de novas formas que produz o processo de sua normatividade. Por fim, destacamos o impacto crítico do conceito de saúde entendido como uma abertura ao risco, enfatizando essa dimensão da saúde como a capacidade de enfrentar novas situações de vida.

Abstract This article aims to criticize the biomedical health model prevalent in medical sciences, based on the concept of vital normativity proposed by Georges Canguilhem. In the introduction we present, from a brief history of the health concept, normalization as the fundamental primacy of the biomedical model. In the first part, we discuss the problem of determining normal and pathological, health and illness in Canguilhem's thought, seeking to situate these concepts in function of individual values, questioning the existence of a normative process in Biology. In the second part, it aims to demonstrate that the vital normativity advocated by Canguilhem is a fundamental conceptual tool for the understanding of organic production logic. This production logic in Biology does not take the norm as criterion for valuing possible forms of life. Biological individuals do not fit or deviate from the rules, but biological individuality, as a power of generating new ways, produces the normativity process. Finally, we highlight the critical impact of the concept of health understood as an openness to risk, emphasizing this dimension of health as capacity to face new situations of life.

Sound understanding of environmental, health and safety, clinical, and market aspects is imperative to clinical translation of nanomedicines.

Nanotechnology has transformed materials engineering. However, despite much excitement in the scientific community, translation of nanotechnology-based developments has suffered from significant translational gaps, particularly in the field of biomedicine. Of the many concepts investigated, very few have entered routine clinical application. Safety concerns and associated socioeconomic uncertainties, together with the lack of incentives for technology transfer, are undoubtedly imposing significant hurdles to effective clinical translation of potentially game-changing developments. Commercialisation aspects are only rarely considered in the early stages and in many cases, the market is not identified early on in the process, hence precluding market-oriented development. However, methodologies and in-depth understanding of mechanistic processes existing in the environmental, health and safety (EHS) community could be leveraged to accelerate translation. Here, we discuss the most important stepping stones for (nano)medicine development along with a number of suggestions to facilitate future translation.

Humanities in Medicine: a road to reflect on clinical practice / Las humanidades en la medicina: un camino para reflexionar acerca de la práctica clínica

La medicina de hoy produce insatisfacción en los pacientes y en los profesionales. La queja fundamental es la dificultad del encuentro. Este escenario no permite abarcar la experiencia de los pacientes, de los familiares e incluso de los propios médicos que deben enfrentar la frustración y el agotamiento. La subcomisión de Humanidades de la Sociedad Argentina de Pediatría nace como consecuencia de esta preocupación y toma este tema desde una perspectiva humanística. El espíritu de este grupo es el de generar un espacio institucional para la producción de contenidos, apuntando a promover la sensibilización e incorporación de recursos que prioricen la calidad humana en la práctica profesional. Este artículo busca reflejar la primera actividad realizada en el 37 Congreso Nacional de Pediatría de 2015: el sustento teórico, el desarrollo de sus objetivos y la participación activa de la audiencia.

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.