Análisis clínicos en pediatría: la necesidad de minimizar las horas de ayuno / Clinical analysis in pediatrics: the need to minimize fasting hours

Los informes de laboratorio tienen impacto en las decisiones médicas. El ayuno es un factor preanalítico "controlable" que influye en los distintos parámetros bioquímicos. El objetivo del presente trabajo es poner en discusión la realización en pediatría de análisis clínicos con la indicación de un ayuno fisiológico , analizando resultados obtenidos por diferentes autores y evaluando las diferencias clínicas encontradas según los criterios de calidad establecidos por el laboratorio de Química Clínica. La mayoría de los individuos durante el día se encuentran en estado postprandial. Los resultados del perfil lipídico en ayunas no representan las concentraciones reales promedios de los lípidos plasmáticos de un paciente. El ayuno no sería crítico en la etapa de pesquisa , pero puede ser relevante para establecer un diagnóstico certero o inicio de tratamiento. En el caso de la glucemia si se indica en el control rutinario del paciente, y no hay sospecha de alteraciones en el metabolismo de los hidratos de carbono la glucemia sin ayuno puede ser solicitada comparando la misma con valores de corte adecuado. Las diferentes guías nacionales e internacionales recomiendan que la elección de la métrica para la evaluación, control y seguimiento de pacientes con diagnóstico de diabetes se realicen según el objetivo terapéutico. En los trabajos analizados, observamos que varios parámetros bioquímicos presentaron diferencias estadísticas, aunque las diferencias clínicas no fueron relevantes y permanecieron dentro de los intervalos de referencia. El factor limitante para evaluar parámetros bioquímicos sin ayuno es la falta de valores de referencia adecuados. Hay evidencia suficiente para que tanto el perfil lipídico, la glucemia como el resto de los parámetros bioquímicos del laboratorio de química clínica, sean solicitados con la indicación de un ayuno fisiológico de 2, 4 o 6 horas, dependiendo siempre del motivo de consulta y/o la edad del paciente. Es esencial extender la evaluación a otros analitos en población pediátrica, así como evaluar nuevos puntos de corte para parámetros bioquímicos sin ayuno (AU)

Laboratory reports have an impact on medical decision-making. Fasting is a "controllable" preanalytical factor that influences the different biochemical parameters. The aim of this study is to discuss the performance of clinical analyses in pediatrics with the indication of physiological fasting, analyzing results obtained in different disciplines, and evaluating the clinical differences found according to the quality criteria established by the clinical chemistry laboratory. During the day, most patients are in a postprandial state. Fasting lipid profile results do not represent the actual average plasma lipid concentrations of a patient. Fasting would not be critical in the screening stage, but it may be relevant to establish an accurate diagnosis or initiate treatment. Regarding glycemia, if it is indicated in the routine control of the patient and there is no suspicion of alterations in carbohydrate metabolism, non-fasting glycemia can be requested, comparing it with adequate cut-off values. Different national and international guidelines recommend that the choice of metrics for the evaluation, control, and follow-up of patients with diabetes should be made according to the therapeutic objective. In the studies analyzed, we found that several biochemical parameters presented statistical differences, although the clinical differences were not relevant and remained within the reference range. The limiting factor in the evaluation of biochemical parameters without fasting is the lack of adequate reference values. There is sufficient evidence that the lipid profile, glycemia, and the remaining biochemical parameters of the clinical chemistry laboratory should be requested with the indication of a physiological fast of 2, 4, or 6 hours, always depending on the reason for consultation and/or the patient's age. It is essential to extend the evaluation to other analytes in the pediatric population, as well as to evaluate new cut-off points for biochemical parameters without fasting (AU)

Comparación clínica y laboratorial de la fiebre amarilla severa versus dengue grave en Perú / Clinical and laboratory differences between severe yellow fever and severe dengue in emergency patients

En los centros de Emergencia con poco apoyo de laboratorio, es difícil diferenciar a los pacientes con dengue grave y fiebre amarilla severa. El objetivo fue comparar el perfil clínico y de laboratorio de los pacientes con dengue grave y fiebre amarilla severa en Urgencias. Se realizó un estudio observacional retrospectivo de pacientes con diagnóstico confirmado de dengue y fiebre amarilla en el período 2018 a 2020 atendidos en la Unidad de Emergencia del Hospital Carrión, Huancayo-Perú. Se evaluaron un total de 35 pacientes, 11 pacientes (31,4%) fueron diagnosticados con fiebre amarilla severa y 24 pacientes (68,5%) con dengue grave. La media de los resultados de laboratorio con fiebre amarilla severa fueron bilirrubina indirecta 4,7 ml/dL, aspartato transaminasa 4463 UI/L, transaminasa aminotransferasa 4329 UI/L, creatinina 4,9 mg/dl. En pacientes con dengue grave el hematocrito promedio fue 51,8, hemoglobina 17,6 g/dl, plaquetas 24 × 103/mm. En pacientes con síndrome ictérico-febril la presencia de bradicardia, bilirrubina indirecta elevada y transaminasas muy elevadas debe hacer sospechar de fiebre amarilla; mientras que los pacientes que acuden por ascitis, derrame pleural, aumento de hematocrito y deficiencia de plaquetas, se debe tratar como dengue grave sobre todo en Unidades de Emergencia con poco apoyo de laboratorio(AU)

In Emergency centers with little laboratory support, differentiating patients with dengue and yellow fever is difficult. The Aim was to compare the clinical and laboratory profile of patients with severe dengue and severe yellow fever in the Emergency unit. We conducted a retrospective observational study of patients with a confirmed diagnosis of dengue and yellow fever in the period 2018 to 2020 treated in the Emergency Unit of the Carrión hospital, Huancayo-Peru. A total of 35 patients were evaluated, 11 patients (31.4%) were diagnosed with severe yellow fever and 24 patients (68.5%) with severe dengue. The mean laboratory results in patients with severe yellow fever were indirect bilirubin 4.7 ml/dL, aspartate transaminase 4463 IU/L, transaminase aminotransferase 4329 IU/L, creatinine 4.9 mg / dl. In patients with severe dengue were hematocrit 51.8, hemoglobin 17.6 g / dl, platelets 24 × 103 / mm. In patients with syndrome jaundice and fever the presence of bradycardia, elevated indirect bilirubin, and very elevated transaminases should be suspicious for yellow fever; while in patients who come for ascites, pleural effusion, increased hematocrit and platelet deficiency, it should be treated as severe dengue especially in Emergency Units with little laboratory support(AU)

Validação de intervalos de referência de exames bioquímicos do laboratório de análises clínicas de um hospital universitário / Validation of reference intervals for biochemical tests at the clinical analysis laboratory of a university hospital

Introdução: Os intervalos de referência (IRs) disponibilizados em laudos de exames laboratoriais orientam a interpretação dos resultados, respaldando a avaliação clínica realizada por profissionais de saúde. Objetivo: Validar IRs de parâmetros bioquímicos, com base nas características da população local, bem como em informações disponíveis nas bulas dos reagentes e na literatura científica. Material e Métodos: Foi realizado um estudo observacional, descritivo e transversal para padronização de IRs de trinta e quatro parâmetros bioquímicos, executados pelo laboratório de análises clínicas de um hospital universitário. Participaram do estudo quarenta indivíduos adultos, pareados pelo sexo, que responderam um questionário sobre o estado geral de saúde. Uma amostra de sangue foi coletada de cada participante e analisada conforme os padrões do laboratório. Resultados: Os dados obtidos com os voluntários saudáveis permitiram a validação dos IRs de albumina, alanina aminotransferase, amilase, aspartato aminotransferase, bilirrubina direta, bilirrubina indireta, bilirrubina total, cálcio iônico, capacidade total e latente de fixação de ferro, creatinoquinase fração MB, cloro, ferro, fosfatase alcalina, fósforo, gama glutamiltransferase, glicose, lipoproteína de alta densidade, lactato, lactato desidrogenase, lipase, magnésio, potássio, proteínas totais, saturação da transferrina, sódio, triglicerídeos e ureia, de ambos os sexos. Ácido úrico foi validado apenas para o sexo masculino e creatinoquinase total (CK) foi validado apenas para o sexo feminino. Conclusão: Os IRs contidos nas bulas destes reagentes representam a população atendida pelo laboratório e podem continuar sendo utilizados. Em contrapartida, os IRs dos analitos colesterol total, lipoproteína de baixa densidade, cálcio, ácido úrico feminino e CK masculino não foram validados e necessitam de novos estudos para a validação dos intervalos de referência utilizados

Introduction: The reference intervals (RIs) provided in laboratory test reports orientate the interpretation of results, supporting the clinical evaluation performed by health professionals. Objective: Validate RIs of biochemical parameters, based on the characteristics of the local population, as well as on information available in the package inserts of the reagents and in the scientific literature. Material and Methods: An observational, descriptive, and cross-sectional study was carried out for the standardization of RIs of thirty-four biochemical parameters, performed by the Clinical Analysis laboratory of a university hospital. Forty adult individuals, matched by sex, participated in the study, who answered a questionnaire about their general health status. A blood sample was taken from each participant and analyzed according to laboratory standards. Results: Data obtained from healthy volunteers allowed the validation of the RIs of albumin, alanine aminotransferase, amylase, aspartate aminotransferase, direct bilirubin, indirect bilirubin, total bilirubin, ionic calcium, total and latent iron-binding capacity, creatine kinase MB fraction, chlorine, iron, alkaline phosphatase, phosphorus, gamma glutamyltransferase, glucose, high density lipoprotein, lactate, lactate dehydrogenase, lipase, magnesium, potassium, total proteins, transferrin saturation, sodium, triglycerides and urea, of both sexes. Uric acid has been validated for males only and total creatine kinase (CK) has been validated for females only. Conclusion: The RIs contained in the package inserts of these reagents represent the population assisted by laboratory and can continue to be used. The RIs of total cholesterol, low-density lipoprotein, calcium, female uric acid and male CK analytes were not validated and require further studies to validate the reference intervals used

The Togo national proficiency test pilot programme for basic clinical chemistry tests

Background: A national proficiency test (PT) programme is not currently implemented in most low-income countries. However, participation in such PT programmes assists improves test performance and result accuracy.Objective: This study assessed how well 11 government hospital laboratories performed 18 basic clinical chemistry tests and identified areas needing improvement.Methods: A cross-sectional study was carried out by the Division of Laboratories of the Ministry of Health of Togo from 01 July 2016 to 31 December 2016. The test performance was evaluated using panels provided by One World Accuracy, Canada (Vancouver). The Clinical Laboratory Improvement Amendments criteria were used in evaluating the laboratories, and their success rates were compared with the World Health Organization Regional Office for Africa's target of 80%.Results: The overall rate of acceptable results at the laboratories was over 80% for glucose, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, alkaline phosphatase and triglycerides tests. The laboratories using fully automated spectrophotometers had an acceptable results rate of 89% (p = 0.001). The overall performance of the laboratories by cycles varied from 71% to 82%.Conclusion: This national PT programme identified the tests, which laboratories must improve their performance (urea, creatinine, uric acid, bilirubin, cholesterol, total protein, calcium, magnesium, phosphorus). It demonstrated the need for the use of routine appropriate internal quality control in all laboratories. The proficiency test programme should be extended to all clinical laboratories and target all biology disciplines

The application of sigma metrics in the laboratory to assess quality control processes in South Africa

Objective: This study aimed to determine the sigma metrics of analytes when using different total allowable error guidelines.Methods: A retrospective analysis was performed on 19 general chemistry analytes at Charlotte Maxeke Johannesburg Academic Hospital in South Africa between January 2017 and December 2017. Sigma metrics were calculated on two identical analysers, using internal quality control data and total allowable error guidelines from the Ricos biological variation database and three alternative sources (the Royal College of Pathologists of Australasia, the Clinical Laboratory Improvements Amendment, and the European Federation of Clinical Chemistry and Laboratory Medicine). Results: The sigma performance was similar on both analysers but varied based on the guideline used, with the Clinical Laboratory Improvements Amendment guidelines resulting in the best sigma metrics (53% of analytes on one analyser and 46% on the other had acceptable sigma metrics) and the Royal College of Pathologists of Australia guidelines being the most stringent (21% and 23%). Sodium and chloride performed poorly across all guidelines (sigma < 3). There were also month-to-month variations that may result in acceptable sigma despite poor performance during certain months.Conclusion: The sigma varies greatly depending on the total allowable error, but could be a valuable tool to save time and decrease costs in high-volume laboratories. Sigma metrics calculations need to be standardised

Clinical Application of Overlapping Confidence Intervals for Monitoring Changes in Serial Clinical Chemistry Test Results

BACKGROUND: Interpretation of changes in serial laboratory results is necessary for both clinicians and laboratories; however, setting decision limits is not easy. Although the reference change value (RCV) has been widely used for auto-verification, it has limitations in clinical settings. We introduce the concept of overlapping confidence intervals (CIs) to determine whether the changes are statistically significant in clinical chemistry laboratory test results.METHODS: In total, 1,202,096 paired results for 33 analytes routinely tested in our clinical chemistry laboratory were analyzed. The distributions of delta% absolute values and cut-off values for certain percentiles were calculated. The CIs for each analyte were set based on biological variation, and data were analyzed at various confidence levels. Additionally, we analyzed the data using RCVs and compared their clinical utility.RESULTS: Most analytes had low indexes of individuality with large inter-individual variability. The 97.5th percentile cut-offs for each analyte were much larger than conventional RCVs. The percentages of results exceeding RCV(95%) and RCV(99%) corresponded to those with no overlap at the 83.4% and 93.2% confidence levels, respectively.CONCLUSIONS: The use of overlapping CIs in serial clinical chemistry test results can overcome the limitations of existing RCVs and replace them, especially for analytes with large intra-individual variation.

EQA-based evaluation of metrological traceability of clinical chemistry test results in Argentina / EQA-based evaluation of metrological traceability of clinical chemistry test results in Argentina

Equivalence of results among laboratories is a major mission for medical laboratories. In the Netherlands, medical laboratories only use homogenous, commercial for general chemistry analytes, whereas in Argentina heterogenous, home brew test applications are common. The effect of this practice difference on test accuracy is studied using key features of the accuracy-based EQA program of the Netherlands. Six frozen, human-based, commutable poolsera, covering the (patho) physiological measuring range for 17 general chemistry analytes, were assayed by ~75 Argentinian labs and ~200 Dutch laboratories in 2014. After removal of outliers, harmonization status among laboratories was evaluated by calculating overall mean interlaboratory coefficients of variation (CVs, %) per analyte and per country for all 6 levels. Evenso, standardization status was evaluated after removal of outliers by calculating overall mean recoveries (%) as compared to the assigned target values per analyte per country for all 6 levels. Absolute median biases were compared to (minimal/desirable) biases derived from biological variation criteria. For serum enzymes interlaboratory CVs in the Argentinian laboratories ranged between 10 and 22%, as compared to 3-6% in the Netherlands. For serum uric acid, creatinine, glucose and total protein, interlaboratory CVs varied between 4.3 and 13.1% in Argentinian labs, as compared to <3.5% in the Netherlands. For serum electrolytes, interlaboratory CVs ranged between 1.8 and 3.8% for Na+; 2.9-5.8% for Cl-; 3.8-7.5% for K+; 9.4-10.4% for Ca2+ and 16.2-22.3% for Mg2+ as compared to ≤2% (Na+, K+, Cl-, Ca2+) and ≤3% (Mg2+) in the Netherlands. Mean recoveries in Argentinian laboratories for e.g. serum creatinine, glucose, CK, Ca2+ and Na+ were 95-119%; 95-104%; 98-102%; 98-102% and 96-100% respectively, whereas min-max recovery ranges were 65-155%; 58-126%; 47-132%; 66-132% and 85-115%. In the Netherlands, absolute mean recoveries were overall 98.9% with a SD of 2.0%. Median biases in Argentinian laboratories ranged from -2.9 to 18.2%; -3.1 - 2.6%; -3.3 - 0.5%; -1.1 - 3.8% and -4.3-0% for serum creatinine, glucose, CK, Ca2+ and Na+. In the Netherlands overall mean/median biases were 1.1% (SD=2.0%). Exchange of commutable, value- assigned EQA-materials was helpful for studying the harmonization and standardization status of medical tests in Argentina, and for revealing the future harmonization and standardization potential. The results clearly demonstrate that metrological traceability of test results in Argentina is on average in line with what is expected; yet, the spreading among laboratories is far too high and should be improved.

La equivalencia de resultados entre laboratorios es una mision importante para los laboratorios medicos. En los Paises Bajos, los laboratorios medicos solo usan aplicaciones comerciales homogeneas, regulatoriamente aprobadas (CE-IVD) para analitos quimicos, mientras que en la Argentina son comunes las aplicaciones heterogeneas caseras. El efecto de esta diferencia practica en la precision de la prueba se estudia utilizando caracteristicas clave del programa EQA, basado en la precision, de los Paises Bajos. Se ensayaron seis pools de sueros, congelados, de origen humano, conmutables, que cubrian el rango de medidas (pato)fisiologicas para 17 analitos de quimica clinica. Estos analitos de quimica clinica fueron analizados por ~75 laboratorios argentinos y ~200 laboratorios holandeses en 2014. Despues de eliminar los valores atipicos, el estado de armonizacion entre los laboratorios fue evaluado calculando los coeficientes de variacion interlaboratorios medios globales (CV%) por analito y por pais para los 6 niveles. No obstante, el estado de estandarizacion se evaluo despues de la eliminacion de valores atipicos mediante el calculo de recuperaciones medias generales (%) en comparacion con los valores asignados por analito por pais para los 6 niveles. Los sesgos medios absolutos se compararon con los sesgos (minimos / deseables) derivados de los criterios de variacion biologica. Para enzimas sericas los CV interlaboratorio en los laboratorios argentinos oscilaron entre 10 y 22%, en comparacion con 3-6% en los Paises Bajos. Para el acido urico serico, creatinina, glucosa y proteinas totales, los CV entre laboratorios variaron entre 4,3 y 13,1% en los laboratorios argentinos, en comparacion con <3,5% en los Paises Bajos. Para los electrolitos sericos, los CV interlaboratorios oscilaron entre 1,8 y 3,8% para Na+; 2,9-5,8% para Cl-; 3,8-7,5% para K+; 9,4-10,4% para Ca2+ y 16,2-22,3% para Mg2+ en comparacion a ≤2% (Na+, K+, Cl-, Ca2+) y ≤3% (Mg2+) en los Paises Bajos. Las recuperaciones medias en laboratorios argentinos para, p.ej. la creatinina serica, glucosa, CK, Ca2+ y Na+ fueron 95-119%; 95-104%; 98-102%; 98-102% y 96-100% respectivamente, mientras que los rangos de recuperacion min-max fueron 65-155%; 58-126%; 47-132%; 66-132% y 85-115%. En los Paises Bajos, las recuperaciones medias absolutas fueron en general del 98,9% con una desviacion estandar (DE) del 2,0%. La mediana de los sesgos medios de los laboratorios argentinos oscilo entre -2,9 y 18,2%; -3,1 - 2,6%; -3,3 - 0,5%; -1,1 - 3,8% y -4,3-0% para creatinina serica, glucosa, CK, Ca2+ y Na+. En los Paises Bajos, las medias / medianas en general fueron de 1,1% (DE=2,0%). El intercambio de los valores asignados a los materiales EQA, conmutables fue de gran ayuda para la armonizacion y estandarizacion de los ensayos medicos en la Argentina y para revelar el potencial futuro de armonizacion y estandarizacion. Estos resultados claramente demuestran que la trazabilidad metrologica de los resultados de las pruebas en la Argentina esta, en promedio, de acuerdo con lo esperable; sin embargo, la dispersion entre laboratorios es muy grande y deberia ser mejorada.

A equivalencia de resultados entre laboratorios e uma missao importante para os laboratorios medicos. Nos Paises Baixos, os laboratorios medicos so utilizam aplicacoes comerciais homogeneas, aprovadas por regulacoes (CE-IVD) para analitos quimicos, ao passo que na Argentina sao comuns as aplicacoes heterogeneas caseiras. O efeito desta diferenca pratica na exatidao do teste e estudado utilizando caracteristicas essenciais do programa EQA, dos Paises Baixos, baseado na exatidao. Foram ensaiados seis pools de soros, congelados, de origem humana, comutaveis, que abrangiam a faixa de medidas (pato)fisiologicas para 17 analitos quimicos gerais. Esses analitos quimicos foram analisados por ~75 laboratorios argentinos e ~200 laboratorios holandeses em 2014. Apos eliminar os valores atipicos, o estado de harmonizacao entre os laboratorios foi avaliado atraves do calculo dos coeficientes de variacao interlaboratorio meios globais (CV%) por analito e por pais para os 6 niveis. Nao obstante, o estado de padronizacao foi avaliado depois da eliminacao de valores atipicos pelo calculo de recuperacoes medias gerais (%) se comparados com os valores atribuidos por analito por pais para os 6 niveis. Os vieses medios absolutos foram comparados com os vieses (minimos / desejaveis) decorrentes dos criterios de variacao biologica. Para enzimas sericas, os CV interlaboratorio nos laboratorios argentinos oscilaram entre 10 e 22%, em comparacao com 3-6% nos Paises Baixos. Para o acido urico serico, creatinina, glicose e proteinas totais, os CV entre laboratorios variaram entre 4,3 e 13,1% nos laboratorios argentinos, em comparacao com <3,5% nos Paises Baixos para os eletrolitos sericos, os CV interlaboratorios oscilaram entre 1,8 e 3,8% para Na+; 2,9-5,8% para Cl-; 3,8-7,5% para K+; 9,4-10,4% para Ca2+ e 16,2-22,3% para Mg2+ em comparacao com ≤2% (Na+, K+, Cl-, Ca2+) e ≤3% (Mg2+) nos Paises Baixos. As recuperacoes medias em laboratorios argentinos para, p.ex. a creatinina serica, glicose, CK, Ca2+ e Na+ foram 95-119%; 95-104%; 98-102%; 98-102% e 96-100% respectivamente, enquanto que os intervalos de recuperacao min-max. foram 65-155%; 58-126%; 47-132%; 66-132% e 85-115%. Nos Paises Baixos, as recuperacoes medias absolutas foram em geral de 98,9% com um desvio padrao (DE) de 2,0%. A mediana dos vieses medios dos laboratorios argentinos oscilou entre -2,9 e 18,2%; -3,1 - 2,6%; -3,3 - 0,5%; -1,1 - 3,8% e -4,3-0% para creatinina serica, glicose, CK, Ca2+ e Na+. Nos Paises Baixos, as medias / medianas em geral foram de 1,1% (DE=2,0%). O intercambio dos valores atribuidos aos materiais EQA, comutaveis, foi de grande ajuda para a harmonizacao e padronizacao dos ensaios medicos na Argentina e para revelar o potencial futuro de harmonizacao e padronizacao. Esses resultados demonstram as claras que a rastreabilidade metrologica dos resultados dos testes na Argentina esta de acordo com o esperavel; a dispersao entre laboratorios ainda e muito grande e deveria ser melhorada.

Comparison of Method Group Precision in Proficiency Testing of Clinical Chemistry Tests Before and After Two Major Changes: Reorganization of Proficiency Testing and Implementation of the Differential Benefit for the Quality of Laboratory Tests

No abstract available.

Quality Management of Clinical Chemistry Tests in Blood Center / 대한수혈학회지

The main goal of transfusion medicine is safe and appropriate blood transfusion in all situations. To accomplish this, it is essential to have a high level quality management system for the entire process from blood donation to transfusion. Regulations regarding blood management have been adopted and strictly managed in Korea since 2007. Blood center's blood management tasks should establish appropriate quality management systems to ensure the safe supply of blood, as well as the basic resources of personnel, facilities and equipment in accordance with laws and regulations governed by the Ministry of Health and Welfare in Korea. The purpose of this review is to examine the contents and processes for quality control of clinical chemistry tests in Korean blood centers.

The Advantage of Cyclosporine A and Methotrexate Rotational Therapy in Long-Term Systemic Treatment for Chronic Plaque Psoriasis in a Real World Practice

BACKGROUND: Psoriasis is a chronic inflammatory disease. In the treatment of psoriasis, cyclosporine is commonly prescribed systemic agents. However, long-term use of cyclosporine is not recommended because of side effects such as nephrotoxicity or hypertension. OBJECTIVE: To ascertain the improved safety of rotational therapy using cyclosporine and methotrexate, we investigated the frequency of abnormal results in laboratory test after long term rotational therapy using cyclosporine and methotrexate. METHODS: From January 2009 to June 2014, patients who were treated with cyclosporine or methotrexate were enrolled. The clinical data and usage of medications were reviewed. Laboratory tests were conducted before starting the treatment and regularly follow-up. The occurrences of any laboratory abnormalities during the treatments were investigated. RESULTS: A total of 21 psoriatic patients were enrolled. The mean of medication period and cumulative dose of cyclosporine and methotrexate were 497.81±512.06 days and 115.68±184.34 g in cyclosporine and 264.19±264.71 days and 448.71±448.63 mg in methotrexate. Laboratory abnormalities were found in total two patients after rotational therapy: two patients (9.5%) in aspartate aminotransferase/alanine aminotransferase and one patient (4.8%) in uric acid. No laboratory abnormalities were found in renal function test. CONCLUSION: We found that the rotational approaches using cyclosporine and methotrexate reduced the possibility of the development of nephrotoxicity. In addition to other advantage such as quick switching from one agent to another, the rotational therapy using cyclosporine and methotrexate can minimize the adverse events during the systemic treatment of chronic plaque psoriasis.

The Advantage of Cyclosporine A and Methotrexate Rotational Therapy in Long-Term Systemic Treatment for Chronic Plaque Psoriasis in a Real World Practice

BACKGROUND: Psoriasis is a chronic inflammatory disease. In the treatment of psoriasis, cyclosporine is commonly prescribed systemic agents. However, long-term use of cyclosporine is not recommended because of side effects such as nephrotoxicity or hypertension. OBJECTIVE: To ascertain the improved safety of rotational therapy using cyclosporine and methotrexate, we investigated the frequency of abnormal results in laboratory test after long term rotational therapy using cyclosporine and methotrexate. METHODS: From January 2009 to June 2014, patients who were treated with cyclosporine or methotrexate were enrolled. The clinical data and usage of medications were reviewed. Laboratory tests were conducted before starting the treatment and regularly follow-up. The occurrences of any laboratory abnormalities during the treatments were investigated. RESULTS: A total of 21 psoriatic patients were enrolled. The mean of medication period and cumulative dose of cyclosporine and methotrexate were 497.81±512.06 days and 115.68±184.34 g in cyclosporine and 264.19±264.71 days and 448.71±448.63 mg in methotrexate. Laboratory abnormalities were found in total two patients after rotational therapy: two patients (9.5%) in aspartate aminotransferase/alanine aminotransferase and one patient (4.8%) in uric acid. No laboratory abnormalities were found in renal function test. CONCLUSION: We found that the rotational approaches using cyclosporine and methotrexate reduced the possibility of the development of nephrotoxicity. In addition to other advantage such as quick switching from one agent to another, the rotational therapy using cyclosporine and methotrexate can minimize the adverse events during the systemic treatment of chronic plaque psoriasis.

Effect of Accreditation on Accuracy of Diagnostic Tests in Medical Laboratories

BACKGROUND: Medical laboratories play a central role in health care. Many laboratories are taking a more focused and stringent approach to quality system management. In Korea, laboratory standardization efforts undertaken by the Korean Laboratory Accreditation Program (KLAP) and the Korean External Quality Assessment Scheme (KEQAS) may have facilitated an improvement in laboratory performance, but there are no fundamental studies demonstrating that laboratory standardization is effective. We analyzed the results of the KEQAS to identify significant differences between laboratories with or without KLAP and to determine the impact of laboratory standardization on the accuracy of diagnostic tests. METHODS: We analyzed KEQAS participant data on clinical chemistry tests such as albumin, ALT, AST, and glucose from 2010 to 2013. As a statistical parameter to assess performance bias between laboratories, we compared 4-yr variance index score (VIS) between the two groups with or without KLAP. RESULTS: Compared with the group without KLAP, the group with KLAP exhibited significantly lower geometric means of 4-yr VIS for all clinical chemistry tests (P<0.0001); this difference justified a high level of confidence in standardized services provided by accredited laboratories. Confidence intervals for the mean of each test in the two groups (accredited and non-accredited) did not overlap, suggesting that the means of the groups are significantly different. CONCLUSIONS: These results confirmed that practice standardization is strongly associated with the accuracy of test results. Our study emphasizes the necessity of establishing a system for standardization of diagnostic testing.

Annual Report on the External Quality Assessment Scheme for Clinical Chemistry in Korea (2015)

The Clinical Chemistry Subcommittee of the Korean Association for External Quality Assessment Service conducted external quality assessments in 2015. This included general chemistry and blood gas measurements as part of a scheme of six trials, comprising three samples each. All control materials were included at the same time. The overall response rates were 94.4% for general chemistry and 92.2% for blood gas. The parameters tested included sodium, potassium, chloride, blood urea nitrogen, glucose, calcium, phosphorus, uric acid, creatinine, bilirubin, total protein, albumin, total cholesterol, triglyceride, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase, lactate dehydrogenase, gamma glutamyl transferase, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol for general chemistry, and pH, partial pressure of carbon dioxide (pCO₂), and partial pressure of oxygen (pO₂) for blood gas assessments. Two types of reports were generated: a method summary, including mean, standard deviation, and coefficient of variation for each test method; and a result summary of each participating laboratory, including mean, standard deviation, number of peer groups, and standard deviation index and variance index scores of each laboratory. The overall quality performance in 2015 was similar to that of previous years, and showed lower interlaboratory variation than that in 2014. The requisite continual improvement in clinical chemistry testing quality can be achieved through participation in similar proficiency testing programs.

Verification of the Comparability of Laboratory Results from Two Instruments within One Health Care System According to Clinical and Laboratory Standard Institute EP31-A-IR

BACKGROUND: For convenience, multiple instruments can be used to measure the same laboratory results within one health care system. However, the laboratory must verify the comparability of the results. In this study, we evaluated a method for verifying the comparability of patient results obtained from two instruments within one health care system, EP31-A-IR, proposed by the Clinical and Laboratory Standards Institute. METHODS: Using the range test proposed by the EP31-A-IR, we evaluated the comparability of 17 clinical chemistry test results from the HITACHII/MODULAR system (Roche Diagnostics, Switzerland) and the TOSHIBA/200FR system (Toshiba Medical Systems Co., Japan). The 0.33× biological variability, allowable total error, and standards of the Clinical Laboratory Improvement Amendments were used to determine the acceptance criteria. RESULTS: Among 16 test parameters, the differences of means between the two instruments were less than their range rejection limit in 15 tests, and so the comparability between the two instruments was considered acceptable. Creatinine was not evaluated using this protocol because its range rejection limit was not deducible from the EP31-A-IR statistics table. CONCLUSIONS: The EP31-A-IR guideline is useful for verifying the comparability of results between two instruments. However, not all parameters are covered by the guideline. With consideration of the characteristics of each test parameter, each laboratory should devise its own method for evaluating comparability.

Reference Intervals of Hematology and Clinical Chemistry Analytes for 1-Year-Old Korean Children

BACKGROUND: Reference intervals need to be established according to age. We established reference intervals of hematology and chemistry from community-based healthy 1-yr-old children and analyzed their iron status according to the feeding methods during the first six months after birth. METHODS: A total of 887 children who received a medical check-up between 2010 and 2014 at Boramae Hospital (Seoul, Korea) were enrolled. A total of 534 children (247 boys and 287 girls) were enrolled as reference individuals after the exclusion of data obtained from children with suspected iron deficiency. Hematology and clinical chemistry analytes were measured, and the reference value of each analyte was estimated by using parametric (mean±2 SD) or nonparametric methods (2.5-97.5th percentile). Iron, total iron-binding capacity, and ferritin were measured, and transferrin saturation was calculated. RESULTS: As there were no differences in the mean values between boys and girls, we established the reference intervals for 1-yr-old children regardless of sex. The analysis of serum iron status according to feeding methods during the first six months revealed higher iron, ferritin, and transferrin saturation levels in children exclusively or mainly fed formula than in children exclusively or mainly fed breast milk. CONCLUSIONS: We established reference intervals of hematology and clinical chemistry analytes from community-based healthy children at one year of age. These reference intervals will be useful for interpreting results of medical check-ups at one year of age.

Stability indicating RP-LC-PDA method for the quantitative analysis of saxagliptin in pharmaceutical dosage form / Estabilidade indicando o método de RP-LC-PDA para a análise quantitativa de saxagliptina em forma de dosagem farmacêutica

Saxagliptin is a potent and selective inhibitor of the enzyme dipeptidyl peptidase 4. It is effective in the treatment of type 2 diabetes mellitus because it stimulates the pancreas to produce insulin. In the present study, a liquid chromatography method was developed and validated to quantify the drug in tablets. This method was based on the isocratic elution of saxagliptin, using a mobile phase consisting of 0.1% phosphoric acid at pH 3.0 - methanol (70: 30, v/v) at a flow rate of 1 mL.min^-1 with UV detection at 225 nm. The chromatographic separation was achieved in 8 minutes on a Waters XBridge C18 column (250 mm x 4.6 mm, 5µm) maintained at ambient temperature. The proposed method proved to be specific and robust for the quality control of saxagliptin in pharmaceutical dosage forms, showing good linearity in the range of 15.0 - 100.0 µg.mL^-1 (r>0.999), precision (RSD<1.49%) and accuracy values between 99.42 and 101.59%. The method was found to be stability indicating and was successfully applied for the analysis of saxagliptin in tablets in a routine quality control laboratory...

A saxagliptina é uma inibidora potente e seletiva da enzima dipeptidil peptidase 4. É efetiva no tratamento do Diabete mellitus tipo 2, pois estimula a produção de insulina pelo pâncreas. No presente estudo, desenvolveu-se e validou-se método por cromatografia líquida de alta eficiência para quantificar o fármaco em comprimidos. O método foi baseado em eluição isocrática, utilizando fase móvel constituída por ácido fosfórico 0,1% pH 3,0-metanol (70 : 30, v/v), fluxo de 1,0 mL.min^-1, com detecção UV em 225 nm. A separação cromatográfica foi alcançada em 8 minutos em coluna Waters XBridge C18 (250 mm x 4,6 mm, 5 µm) mantida à temperatura ambiente. O método proposto mostrou-se específico e robusto para o controle de qualidade de saxagliptina em comprimidos, sendo linear na faixa de concentração de 15,0-100,0 µg.mL^-1 (r>0,999), preciso (RSD<1,49%) e exato, com resultados entre 99,42 e 101,59%. O método mostrou-se indicativo de estabilidade e foi aplicado com sucesso no controle de qualidade de saxagliptina em comprimidos...

Pharmacokinetic-pharmacodynamic correlation of imipenem in pediatric burn patients using a bioanalytical liquid chromatographic method / Correlação farmacocinética-farmacodinâmica de imipenem em pacientes queimados pediátricos utilizando um método bioanalítico de cromatografia líquida

A bioanalytical method was developed and applied to quantify the free imipenem concentrations for pharmacokinetics and PK/PD correlation studies of the dose adjustments required to maintain antimicrobial effectiveness in pediatric burn patients. A reverse-phase Supelcosil LC18 column (250 x 4.6 mm 5 micra), binary mobile phase consisting of 0.01 M, pH 7.0 phosphate buffer and acetonitrile (99:1, v/v), flow rate of 0.8 mL/min, was applied. The method showed good absolute recovery (above 90%), good linearity (0.25-100.0 µg/mL, r²=0.999), good sensitivity (LLOQ: 0.25 µg/mL; LLOD: 0.12 µg/mL) and acceptable stability. Inter/intraday precision values were 7.3/5.9%, and mean accuracy was 92.9%. A bioanalytical method was applied to quantify free drug concentrations in children with burns. Six pediatric burn patients (median 7.0 years old, 27.5 kg), normal renal function, and 33% total burn surface area were prospectively investigated; inhalation injuries were present in 4/6 (67%) of the patients. Plasma monitoring and PK assessments were performed using a serial blood sample collection for each set, totaling 10 sets. The PK/PD target attained (40%T>MIC) for each minimum inhibitory concentration (MIC: 0.5, 1.0, 2.0, 4.0 mg/L) occurred at a percentage higher than 80% of the sets investigated and 100% after dose adjustment. In conclusion, the purification of plasma samples using an ultrafiltration technique followed by quantification of imipenem plasma measurements using the LC method is quite simple, useful, and requires small volumes for blood sampling. In addition, a small amount of plasma (0.25 mL) is needed to guarantee drug effectiveness in pediatric burn patients. There is also a low risk of neurotoxicity, which is important because pharmacokinetics are unpredictable in these critical patients with severe hospital infection. Finally, the PK/PD target was attained for imipenem in the control of sepsis in pediatric patients...

Desenvolveu-se e aplicou-se método bioanalítico para quantificar concentrações de imipenem livre para estudos de farmacocinética (PK) e de correlação PK/PD dos ajustes de dose requeridos para manter a efetividade antimicrobiana em pacientes pediátricos queimados. Utilizou-se coluna Supelcosil LC18 (250 x 4,6 mm 5 micra), fase móvel binária, consistindo de tampão fosfato 0,01M pH 7,0 e acetonitrila (99:1, v/v) e fluxo de 0,8 mL/min. O método mostrou boa recuperação absoluta (acima de 90%), boa linearidade (0,25-100,0 µg/mL, r²=0.999), boa sensibilidade (LLOQ: 0,25 µg/mL; LLOD: 0,12 µg/mL) e estabilidade aceitável. Os valores de precisão inter/intradia foram 7,3/5,9% e a exatidão média foi de 92,9%. O método bioanalítico foi aplicado para quantificar concentrações de fármaco livre em crianças com queimaduras, Seis pacientes pediátricos queimados (idade média de 7,0 anos, 27,5 kg), com função renal normal e 33% da superfície total queimada foram investigados prospectivamente. Lesões por inalação estavam presentes em 4/6 (67%) dos pacientes. O monitoramento plasmático e a as avaliações de PK foram efetuadas utilizando coleção de amostras seriais de sangue para cada série, totalizando 10 conjuntos. O alvo PK/PD alcançado (40%T>MIC) para cada concentração inibitória mínima (MIC: 0,5, 1,0, 2,0, 4,0 mg/L) ocorreu em porcentagem maior do que 80% dos conjuntos investigados e 100% após o ajuste de dose. Em conclusão, a purificação das amostras do plasma usando técnica de ultrafiltração seguida de quantificação das medidas do imipenem no plasma usando método de cromatografia líquida é bastante simples, útil e necessita de pequenos volumes para as amostras de sangue. Além disso, pequena quantidade de plasma (0,25 mL) é necessário para garantir a efetividade do fármaco nos pacientes pediátricos queimados. Há, ainda, baixo risco de neurotoxicidade, o que é importante, visto que as farmacocinéticas são imprevisíveis nesses pacientes...

Differential pulse voltammetric determination of diclofenac in pharmaceutical preparations and human serum / Pulso diferencial determinação voltamétrica de diclofenaco em preparações farmacêuticas e em soro humano

This article describes a differential pulse voltammetric (DPV) method for the determination of diclofenac in pharmaceutical preparations and human serum. The proposed method was based on electro-oxidation of diclofenac at platinum electrode in 0.1 M TBAClO₄/acetonitrile solution. The well-defined two oxidation peaks were observed at 0.87 and 1.27 V, respectively. Calibration curves that obtained by using current values measured for second peak were linear over the concentration range of 1.5-17.5 μg mL^-1and 2-20 μg mL^-1 in supporting electrolyte and serum, respectively. Precision and accuracy were also checked in all media. Intra- and inter-day precision values for diclofenac were less than 3.87, and accuracy (relative error) was better than 4.12%. The method developed in this study is accurate, precise and can be easily applied to Diclomec, Dicloflam and Voltaren tablets as pharmaceutical preparation. In addition, the proposed technique was successfully applied to spiked human serum samples. No electro-active interferences from the endogenous substances were found in human serum...

Este artigo descreve um método de voltametria de pulso diferencial (VPD) para a determinação de diclofenaco em preparações farmacêuticas e em soro humano. O método proposto foi baseado em eletroxidação de diclofenaco no eléctrodo de platina em solução 0,1 M TBAClO₄/acetonitrila. Dois picos de oxidação bem definidos foram observados em 0,87 e 1,27 V, respectivamente. As curvas de calibração obtidas utilizando-se valores de corrente medidos por segundo pico foram lineares no intervalo de concentração de 1,5-17,5 μg mL^-1e 2-20 μg mL^-1em eletrólito suporte e soro, respectivamente. Precisão e exatidão também foram verificadas em todos os meios. Valores de precisão intra- e inter-dia para o diclofenaco foram inferiores a 3.87 e a precisão (erro relativo) foi melhor do que 4,12%. O método desenvolvido neste estudo é exato, preciso e pode ser facilmente aplicado a Diclomec, Dicloflam e comprimidos Voltaren, como preparação farmacêutica. Além disso, a técnica proposta foi aplicada com sucesso em amostras de soro humano. Não se observaram interferências das substâncias endógenas no soro humano...

Annual Report on the External Quality Assessment Scheme for Clinical Chemistry in Korea (2014)

The Clinical Chemistry subcommittee of The Korean Association of External Quality Assessment Service conducted external quality assessments in 2014. This included general chemistry and blood gas measurements as part of a scheme of six trials, comprising of three samples each. All control materials were sent at the same time. The overall response rates were 93.4% for general chemistry and 90.0% for blood gas. The parameters tested included sodium, potassium, chloride, blood urea nitrogen, glucose, calcium, phosphorus, uric acid, creatinine, bilirubin, total protein, albumin, total cholesterol, triglyceride, AST, ALT, alkaline phosphatase, lactate dehydrogenase, gamma glutamyl transferase, HDL cholesterol, and LDL cholesterol for general chemistry and pH, partial pressure of carbon dioxide, and partial pressure of oxygen for blood gas assessment. Two types of reports were generated, namely, a method summary report including mean, standard deviation, and coefficient of variation, for each test method, as well as a result summary report of each participating laboratory, including mean, standard deviation, number of peer groups, and standard deviation index and variance index scores of each laboratory. The overall quality performance in 2014 was similar to that of previous years and as compared to results from 2013, the inter-laboratory variation was lower. The requisite continual improvement in the quality of clinical chemistry testing can be achieved through participation in similar proficiency testing programs.

Evaluation of i-STAT CHEM8+ Point-of-Care Chemistry Analyzer

BACKGROUND: We evaluated the analytical performance of the Abbott i-STAT CHEM8+, a point-of-care testing system that measures 8 basic chemical analytes, namely, sodium, potassium, chloride, total carbon dioxide, BUN, creatinine, glucose, and ionized calcium. METHODS: The precision and linearity of 8 analytes were evaluated according to the CLSI guidelines EP15-A and EP6-A, respectively, using standard material provided by the manufacturer. i-STAT CHEM8+ and other primary methods (e.g. Hitachi Clinical Analyzer 7600 for 7 analytes, Nova CCX for ionized calcium) were also compared according to the CLSI guideline EP9-A2, using 113 patient samples. RESULTS: The standard deviation (SD) of within-run and total precision of 7 analytes except chloride was within the claimed SD or within the verification value. The coefficient of variation of total precision of 7 analytes except creatinine was within 2%. With regard to linearity, all 8 analytes showed first-order equation or at least no statistical difference with the first-order equation. We observed that the efficiency of i-STAT CHEM8+ was comparable to that of primary methods, and that this method has potential applications in the clinical laboratory. CONCLUSIONS: i-STAT CHEM8+ showed good precision and linearity, and an efficiency comparable to that shown by routine chemistry analyzers; thus, it has potential applications in the clinical laboratory. It can provide much faster results and relatively accurate value to clinicians in need of immediate results, such as in an emergency unit or in the intensive care unit.