Post-marketing sampling and testing programs for licensed medicinal products: a narrative review

Abstract The globalization of the pharmaceutical market has enabled access to a considerable number of new medicinal products. Consequently, the circulation of substandard medicinal products has also increased. To minimize this problem, post-marketing quality sampling and testing programs are performed to monitor and confirm that the medicinal products available in the market meet appropriate quality requirements. In this review, the post-approval sampling and testing procedures of six regulatory authorities were compared with the goal of strengthening these market surveillance systems. Similarities were observed between the procedures adopted by different regulatory authorities. However, the agencies were not always transparent about the results of these monitoring procedures. A probable mismatch between the registration procedures and the quality requirements listed in official compendiums was observed, which resulted in dissonance and contradiction between the specifications approved by the regulatory authorities and those required in the pharmacopeias. Therefore, strengthening harmonization projects related to these activities can help minimize such difficulties.

O Regulamento (UE) N°536/2014 relativo aos ensaios clínicos de medicamentos para uso humano: oportunidades de inovação e desafios éticos / Regulation (EU) Nº 536/2014 ofclinical trials on medicinal products for human use: opportunities for innovation and ethical challenges / Reglamento (UE) Nº 536/2014 sobre los ensayos clínicos de medicamentos de uso humano: oportunidades de innovación y desafíos éticos

Objetivo: identificar os principais aspetos inovadores do Regulamento relativo aos ensaios clínicos de medicamentos para uso humano, em termos de oportunidades para a investigação e desenvolvimento e refletir sobre os desafios éticos deste novo quadro legal. Metodologia: estudo documental, descritivo, comparativo, do Regulamento face à Diretiva 2001/20/CE, e leitura de bibliografia publicada no PubMed, usando termos de pesquisa combinados ou simples como clinical, trials, European, Regulation, Directive, opportunities, challenges e innovation. Resultados: os principais aspetos inovadores identificados foram o Portal da União Europeia para submissão do dossiê do ensaio clínico e avaliação conjunta entre os Estados-Membros envolvidos num ensaio clínico; disponibilização pública de informação, resultados dos ensaios e um sumário de resultados para leigos; foram criadas a figura do copromotor, categorias de ensaios em função do risco; estabelecidos novos procedimentos para obtenção de consentimento informado e requisitos para uma maior proteção para os indivíduos mais vulneráveis; e definido o quadro normativo para a realização de ensaios clínicos em situação de emergência. Discussão: estão previstos procedimentos que visam contrariar a perda de competitividade da Europa, promovendo a inovação, alguns dos quais não estão isentos de questionamento ético. Conclusão: a simplificação, harmonização e maior transparência em todo o processo de submissão e condução dos ensaios clínicos tem o potencial de promover a investigação, mas traz alguns aspetos inquietantes em matéria de proteção dos participantes nos ensaios clínicos.

Objective: to identify the main innovative aspects of the Regulation on clinical trials of medicines for human use, in terms of opportunities for research and development and to reflect on the ethical challenges of this new legal framework. Methods: documentary, descriptive, comparative study of the Regulation in regard with the Directive 2001/20/EC, reading bibliography published in PubMed, using combined or simple research terms such as clinical, trials, European, Regulation, Directive, opportunities, challengesand innovation. Results: the main innovative aspects identified were the Portal for submission of the clinical trial dossier and joint evaluation between the Member States involved in a clinical trial; public dissemination of clinical trial ́s information, results and lay summary. The idea of co-sponsor and new categories of trials depending on to the risks were created; new procedures for obtaining informed consent and requirements for the protection of the most vulnerable individuals, and the regulatory framework for conducting clinical trials in an emergency were established. Discussion:in order to counteract the loss of competitiveness in Europe, some procedures were implemented in order to promote innovation, some of which are not exempt from ethical questioning. Conclusion: simplification, harmonization and transparency for the submission and conduction of clinical trials have the potential to boost research, but brings some concerns regarding the protection of participants in clinical trials.

Objetivo: identificar los principales aspectos innovadores del Reglamento sobre ensayos clínicos de medicamentos de uso humano, en términos de oportunidades de investigación y desarrollo y reflexionar sobre los desafíos éticos de este nuevo marco legal. Metodología: estudio documental, descriptivo, comparativo del Reglamento en relación con la Directiva 2001/20/CE, y lectura de bibliografía publicada en PubMed, utilizando términos de investigación combinados o simples como clinical, trials, European, Regulation, Directive, opportunities, challengesy innovation. Resultados: los principales aspectos innovadores identificados fueron el Portal de presentación del expediente de ensayo clínico y evaluación conjunta entre los Estados miembros implicados en un ensayo clínico; disponibilidad pública de información, resultados de pruebas y un resumen de resultados para laicos; se creó la figura del co-promotor, categorías de pruebas según el riesgo; se han establecido nuevos procedimientos para obtener el consentimiento informado y requisitos para una mayor protección de las personas más vulnerables; y definió el marco regulatorio para la realización de ensayos clínicos en una situación de emergencia. Discusión:se prevén procedimientos para contrarrestar la pérdida de competitividad en Europa, promoviendo la innovación, algunas de las cuales no están exentas de cuestionamientos éticos. Conclusión: la simplificación, armonización y mayor transparencia en todo el proceso de envío y realización de ensayos clínicos tiene el potencial de promover la investigación, pero trae algunos aspectos inquietantes en términos de protección de los participantes en los ensayos clínicos.

Lifting facial não cirúrgico com fios de polidioxanona: revisão de literatura / Non-surgical facelift with polydiaxanone threads: literature review

O objetivo deste estudo foi realizar uma revisão de literatura acerca do lifting facial não cirúrgico com fios de PDO, abordando os diferentes tipos, suas indicações, a degradação no organismo, pla no de inserção, contraindicações, vantagens e possíveis complicações. As buscas foram realizadas nas bases de dados Pubmed, Bireme, Scielo, Sumários de Revistas Brasileiras e BVS, selecionan do-se artigos relevantes disponibilizados entre 2005 e 2020. Sendo os descritores utilizados em português e inglês para busca: "Harmonização Facial", "Fios de Sustentação", "Lifting Facial". Após aplicação dos critérios de inclusão e exclusão, dos 44 artigos encontrados, foram selecionados 16 para esse estudo. O uso dos fios de sustentação facial consiste em um método minimamente inva sivo, indolor, de caráter ambulatorial, anestesia local e efeito imediato. Diante dos possíveis riscos que acompanham o lifting cirúrgico, as pessoas estão buscando por alternativas menos invasivas, como os fios de sustentação. Apesar de não poderem ser considerados como alternativa a cirurgia reparadora convencional, os pacientes muitas vezes acabam optando pelo lifting com fios por se sentirem mais seguros, mesmo com resultados mais modestos. Observou-se que a utilização dos fios de PDO tem demostrado eficácia no rejuvenescimento facial quando bem indicados, apesar da possibilidade de ocorrência de efeitos adversos, normalmente pequenos e passageiros... (AU)

The aim of this study is to perform a literature review about non-surgical facial lifting with PDS threads, addressing its variety of types, indications, organism degradation, insertion plan, contrain dications, advantages and possible complications.The researches were conducted in the Pubmed, Bi reme, Scielo, Sumários de Revistas Brasileiras and BVS data bases, selecting relevant articles available between 2005 and 2020. After applying the inclusion and exclusion criteria, of the 44 articles found, 16 were selected for this study. Being used the following descriptors in Portuguese and English for research purposes: "Facial Harmonization", "Supporti Threads", "Face Lift". The use of facial support threads consists in a minimally invasive, painless, outpatient method, local anesthesia and imme diate effect. Faced with the possible risks that accompany the surgical facelift, people are looking for less invasive alternatives, such as the support wires. Although they cannot be considered as an alternative to conventional reparative surgery, patients often end up opting for a facelift because they feel safer, even with more modest results. It was observed that the use of PDO threads has been shown to be effective in facial rejuvenation when well indicated, despite the possibility of adverse effects, usually small and transient... (AU)

Armonización de la determinación de ANCA por inmunofluorescencia indirecta: primera reunión argentina / Harmonization of the determination of ANCA by indirect immunofluorescence: first argentine meeting / Harmonização da determinação de ANCA por imunofluorescência indireta: primeira reunião argentina

Resumen La determinación de anticuerpos anti-citoplasma de neutrófilos (ANCA) es utilizada en la clínica diaria como una herramienta diagnóstica en distintas formas de vasculitis de pequeños vasos (vasculitis asociadas a ANCA), incluyendo la granulomatosis con poliangeítis (antes: granulomatosis de Wegener), poliangeítis microscópica y granulomatosis eosinofílica con poliangeítis (antes: síndrome de Churg-Strauss), y como apoyo diagnóstico de colitis ulcerosa, colangitis esclerosante primaria y enfermedad de Crohn. Estos anticuerpos están dirigidos contra distintos epítopos antigénicos de diferentes proteínas presentes en el citoplasma del neutrófilo. La determinación de ANCA, habitualmente realizada por la técnica de inmunofluorescencia indirecta (IFI), presenta cierto grado de complejidad en la definición de las imágenes de los diferentes patrones, variabilidad en la forma de trabajo y expresión de resultados. El 24 de octubre de 2018 en el marco del X Congreso Argentino de la Calidad en el Laboratorio Clínico y VIII Jornadas Latinoamericanas de la Calidad en el Laboratorio Clínico, en la Ciudad de Buenos Aires, se realizó una reunión de Armonización de la Determinación de ANCA por IFI con el objeto de presentar, discutir y consensuar los distintos aspectos que se presentan en esta técnica. Las propuestas iniciales fueron discutidas arribándose a recomendaciones generales para proporcionar estándares de trabajo e interpretación de imágenes con el objeto de disminuir la variabilidad de resultados entre los laboratorios clínico-inmunológicos.

Abstract Anti-neutrophil cytoplasmic antibodies (ANCA) tests are widely used in daily clinical practice as a useful tool for the diagnosis of pathologies such as granulomatosis with polyangiitis, microscopic polyangiitis, pauci-immune necrotizing segmental glomerulonephritis and eosinophilic granulomatosis with polyangiitis, ulcerative colitis, primary sclerosing cholangitis, Crohn's disease, etc. These antibodies are directed against different antigenic epitopes of various proteins which are present in the neutrophil cytoplasm. ANCA testing is usually carried out by using indirect immunofluorescence (IIF) method. The determination of ANCA presents some difficulties in the definition of the images of the different patterns, work protocols and result reports uniformity. The "Harmonization Conference on the Determination of ANCA by IIF" was held within the framework of the X Argentine Congress on Quality in the Clinical Laboratory and VIII Latin American Conference on Quality in the Clinical Laboratory, in Buenos Aires, Argentina, on October 24, 2018, in order to present, discuss and agree on different aspects of this method. Some initial proposals were discussed, arriving at general recommendations to provide standards of work and an image interpretation, with the aim of reducing the variability of results among the clinical-immunological laboratories.

Resumo A determinação de anticorpos anti-citoplasma de neutrófilos (ANCA) é utilizada na prática clínica diária como um suporte diagnóstico para várias patologias, como granulomatose com poliangiite, poliangiite microscópica, glomerulonefrite segmentar necrotizante pauci-imune e granulomatose eosinofílica com poliangiite, poliarterite nodosa, colite ulcerosa, colangite esclerosante primária, doença de Crohn. Esses anticorpos são dirigidos contra diferentes epítopos antigênicos de diferentes proteínas presentes no citoplasma do neutrófilo. A determinação de ANCA, normalmente realizada pela técnica de imunofluorescência indireta IFI, apresenta certo grau de complexidade na definição das imagens dos diferentes padrões, variabilidade na forma de trabalho e expressão de resultados. Em 24 de outubro de 2018, no âmbito do X Congreso Argentino de la Calidad en el Laboratorio Clínico (X Congresso Argentino da Qualidade no Laboratório Clínico) e VIII Jornadas Latinoamericanas de la Calidad en el Laboratorio Clínico (VIII Jornadas Latino-americanas da Qualidade no Laboratório), na cidade de Buenos Aires, foi realizada uma Jornada de Harmonização da Determinação de ANCA pelo IFI a fim de apresentar, discutir e concordar sobre os diferentes aspectos que são apresentados nesta técnica. As propostas iniciais foram discutidas, chegando a recomendações gerais para fornecer padrões de trabalho e interpretação de imagens visando reduzir a variabilidade de resultados entre os laboratórios clínico-imunológicos.

Uso de láser de baja potencia como coadyuvante en tratamiento con terapias combinadas en paciente con parálisis facial periférica / Use of low level laser therapy as an adjunct in treatment with combined therapies in patients with peripheral facial palsy

La parálisis facial periférica es un trastorno neurológico que tiene consecuencias motoras y sensoriales y que afecta al nervio facial. Ocasiona alteraciones en la acción de los músculos del rostro, en la secreción de saliva, lágrimas y en el sentido del gusto.El objetivo de esta publicación es dar cuenta de un caso en el que se realizó un tratamiento con terapias combinadas mínimamente invasivas junto con el uso de láserterapia de baja potencia, en un paciente femenino, 52 años de edad, con antecedentes médicos relevantes, derivada para evaluación estética. La paciente presenta una parálisis facial moderada sin resolver. Fue sometida a láserterapia con longitud de onda (808 nm) y una energía de 3 Joules por sesión en el lado afectado, complementada con toxina botulinica Tipo A, en el lado sano.El tratamiento de parálisis facial periférica con terapias combinadas mínimamente invasivas ha mostrado ser una herramienta útil terapéutica de las secuelas faciales. A su vez, la terapia de fotobiomodulación con láser de baja potencia es prometedora como coadyuvante en el proceso de reparación nerviosa lo que permitiría la recuperación funcional del nervio facial a mediano y largo plazo.

Peripheral Facial Palsy is a neurological disorder that has motor and sensory consequences and affects the facial nerve. It causes alterations in the action of the muscles of the face, in the secretion of saliva, tears, and in the sense of taste.The objective of this publication is to report a case in which a treatment with minimally invasive combined therapies was performed together with the use of low-level laser therapy, in a 52-year-old female patient. With relevant medical history, referred for aesthetic evaluation and with unresolved moderate facial paralysis. She was subjected to laser therapy with wavelength (808 nm) and an energy of 3 Joules per session on the affected side, supplemented with Botulinum Toxin Type A, on the healthy side.The treatment of peripheral facial paralysis with minimally invasive combined therapies has proven to be a useful therapeutic tool for facial sequelae. In turn, low-level laser photobiomodulation therapy is promising as an adjunct in the nerve repair process, which would allow functional recovery of the facial nerve in the medium and long term.

The functional architecture of the stomatognathic system and orofacial aesthetic repositioning during the aging process

Introduction: Facial aging implies special care and personalized treatment. Thus,the new strand of Neomodern Dentistry seeks, through Orofacial Harmonization,the functional and aesthetic balance between the stomatognathic system and thefacial aspect. Objective: This article seeks to disclose, through a literature review, the aesthetical consequences of the stomatognatic system repositioning andorofacial aging. Data source: The present literature review consisted in researchesup to May 2019 using PubMed and Google Academic electronic databases. A 10-year publication limit was applied in the research. No language restriction wasapplied. Inclusion criteria were clinical investigations, books, dissertations, thesisor literature reviews that addressed the topics of interest. Data synthesis: A totalof 231 articles were retrieved from databases. After applying a 10-year publicationlimit, 111 remained and, based on the inclusion and exclusion criteria, 20 articleswere selected and included in this review. Conclusion: Considering the limitationsof the present study, it can be concluded that the aging process is natural andpredictable and can be changeable and malleable through procedures that restorethe support nutrients that were lost. The aesthetics can be achieved as a functionalconsequence of the stomatognathic system repositioning due to orofacial aging.

Introdução: O envelhecimento facial implica em cuidados especiais e um tratamento diferenciado. Desse modo, a nova vertente da Odontologia Neomoderna busca, por meio da Harmonização Orofacial, o equilíbrio funcional e estético entre o aparelho estomatognático e a face. Objetivo: Esse artigo busca compreender, por meio de uma revisão de literatura, as consequências estéticas do reposicionamento do aparelho estomatognático e envelhecimento orofacial. Fonte dos dados: A presente revisão de literatura consistiu em um viés qualitativo nas plataformas PubMed e Google Acadêmico, nos últimos 10 anos, sem restrição de idiomas. Os critérios de inclusão consistiram em estudos clínicos, livros, dissertações, teses ou revisões de literatura que abordavam os tópicos de interesse. Síntese dos dados: Foram recuperados nas bases de dados 231 artigos. Após a aplicação de um limite de publicação de 10 anos, 111 permaneceram e, com base nos critérios de inclusão e exclusão, 20 artigos foram selecionados e incluídos nesta revisão. Conclusão: Com as limitações do presente estudo, pode-se concluir que o processo de envelhecimento é natural e previsível e pode ser mutável e maleável por meio de procedimentos que restauram os nutrientes de suporte perdidos. A estética pode ser alcançada como uma consequência funcional do reposicionamento do sistema estomatognático e do envelhecimento orofacial.

Rp-Hplc Method Development And Validation For The Combination Of Imiquimod And Salicylic Acid

Objective: The present study was undertaken to develop and validate an RP-HPLC method for the combination of imiquimod and salicylic acid Methods: The method was carried out on Nucleodur C18 (250 mm × 4.6 mm I.D., 5 ????m) using low-pressure gradient elution mode. The mobile phase was used as 30M potassium dihydrogen phosphate and acetonitrile (45:55) pH 6.5 adjusted using ortho-phosphoric acid. The concentration of solvents was 1-20 µg/ml and the volume of injection was 20 mcl with the flow rate of 1.0 ml/min. The absorption maxima of salicylic acid and imiquimod were found 234 nm and 226 nm, respectively. Results: The method was validated and showed the linearity greater than 0.99% and with precision (RSD%<1). The limit of detection (LOD) and limit of quantification (LOQ) of salicylic acid was found to be 0.09756 µg/ml and 0.2956 µg/ml, respectively, and imiquimod was found to be 0.044031 µg/ml and 0.13334 µg/ml, respectively. Conclusion: The method developed in the present study was found to be sensitive, specific, and can be applied for the simultaneous estimation of imiquimod and salicylic acid.

Armonizacion del estudio de lipidos en el laboratorio clinico / Harmonization of the study of lipids in the clinical laboratory

Los profesionales que ejercen la bioquimica clinica son conscientes de la falta de resultados comparables entre laboratorios, independientemente de donde y cuando se realicen. Durante muchos anos el centro de la gestion de la calidad estuvo en la estandarizacion de los procedimientos de medida, la armonizacion va mas alla del metodo y los resultados analiticos e incluye todos los aspectos que hay que tener en cuenta durante el proceso total de la prueba. Los laboratorios de bioquimica clinica han logrado en las ultimas decadas importantes mejoras en la calidad de los procesos analiticos, pero es necesario un esfuerzo mayor dedicado a la vulnerabilidad de los procedimientos extra analiticos para asegurar la comparacion y la concordancia de los resultados obtenidos por diferentes laboratorios clinicos. Las iniciativas destinadas a mejorar la armonizacion de los resultados de laboratorio tienen una dimension etica y de gran importancia en el diagnostico de las dislipemias asociadas al desarrollo de aterosclerosis y la evaluacion del riesgo cardiovascular. Los estudios poblacionales aun muestran dificultades en la identificacion del mejor biomarcador que pueda evidenciar adecuadamente el riesgo cardiovascular en un individuo. La correlacion, discordancia y concordancia muestran que es necesario el diseno de un perfil de pruebas de laboratorio personalizado, con marcadores estandarizados y armonizados, que permita la prediccion del riesgo.

The health professionals who practice clinical biochemistry are aware of the lack of comparable results between laboratories, regardless of where and when they are performed. For many years, the objective of the quality management was the standardization of measurement procedures. The harmonization is beyond the methods and the analytical results, and it includes all the aspects to be taken into account during the whole process of the test. The clinical biochemistry laboratories have achieved important improvements in the quality of the analytical processes in the last decades, but greater effort is necessary for the vulnerability of the extra analytical procedures to ensure the comparison and the agreement of the results obtained by different clinical laboratories. The initiatives aimed to improve the harmonization of laboratory results have an ethical dimension and importance in the diagnosis of dyslipidemia associated with the development of atherosclerosis and the assessment of cardiovascular risk. The population studies still show difficulties in the identification of the best biomarker that can adequately show the cardiovascular risk in an individual. The correlation, discordance and concordance between biomarkers show that it is necessary to design a personalized laboratory test profile, and with standardized and harmonized markers that allow the prediction of risk.

Os profissionais que exercem a bioquímica clínica Clinical estão cientes da falta de resultados comparáveis entre laboratórios, independentemente de onde e quando forem realizados. Por muitos anos, o centro de gestão da qualidade esteve na padronização dos procedimentos de medição, a harmonização vai além do método analítico e dos resultados analíticos e inclui todos os aspectos a considerar durante o processo do teste. Laboratórios bioquímica clínica têm alcançado, nas últimas décadas grandes melhorias na qualidade dos processos analíticos, mas precisa de um esforço maior dedicado à vulnerabilidade dos procedimentos extra-analíticos, para garantir a comparação e concordancia dos resultados obtidos pelos diferentes laboratórios clínicos. Iniciativas para melhorar a harmonização dos resultados laboratoriais têm uma dimensão ética e de grande importȃncia no diagnóstico de dislipidemias associadas ao desenvolvimento de aterosclerose e à avaliação do risco cardiovascular. As pesquisas populacionais mostram ainda dificuldades em identificar o melhor biomarcador que possa demonstrar em forma adecuada o risco cardiovascular em um individuo, a correlação, discordância e concordância mostram que é necessário o desenho de um perfil de testes personalizado, com marcadores padronizados e harmonizada, que permite a previsão de risco.

Harmonization of epidemiological studies on dementia in Latin America why does it matter? / Harmonização de estudos epidemiológicos em demência na América Latina: qual a sua importância?

ABSTRACT Evidence on dementia in Latin America (LA) is limited and varies between and within countries, contributing to a delay in the establishment and implementation of dementia action plans by governments and services. The harmonization of standardised measurement outcomes and the use of unified databases that address the key issues affecting the LA population can help address this issue. This paper is based on a presentation delivered at a satellite Alzheimer's Association International Conference held in April 2019, in Brazil, and aims to discuss the challenges and benefits of harmonizing epidemiological studies on dementia in the region. First, we mention some of the characteristics of LA in relation to geography, population, socioeconomic and epidemiological conditions, which could potentially affect preventative measures and dementia diagnosis in the region. Second, we cite some studies to demonstrate how research on dementia in LA is limited and uses diverse methodology. We proceed by justifying the need for harmonization of epidemiological studies in LA and discuss what type of data could be harmonised. We conclude by briefly mentioning harmonization in relation to risk factors for dementia.

RESUMO As evidências científicas sobre demência na América Latina (AL) são limitadas e variam entre e dentro dos países, o que contribui para um atraso no estabelecimento e na implementação de planos de ação para demência por governos e serviços. A harmonização de medidas por instrumentos padronizados e o uso de bancos de dados unificados que abordam os principais problemas que afetam a população da AL podem ajudar a resolver esse problema. Este artigo é baseado em uma apresentação realizada durante a Alzheimer's Association International Conference que aconteceu em abril de 2019 no Brasil e tem como objetivo discutir os desafios e benefícios da harmonização de estudos epidemiológicos sobre demência nesta região. Primeiramente, mencionamos algumas das características da AL em relação à geografia, população, condições socioeconômicas e epidemiológicas, que podem potencialmente afetar ações de prevenção e diagnóstico de demência na região. Depois, citamos alguns estudos para demonstrar como os estudos sobre a demência na AL são limitados e utilizam metodologias diversas. Em seguida, argumentamos pela necessidade de harmonização dos estudos epidemiológicos sobre demência na AL e discutimos os tipos de dados podem ser harmonizados. Por fim, mencionamos brevemente a importância da harmonização em estudos envolvendo os fatores de risco para demência.

Professor experience in treatment of dysmenorrhea with "three-regulation and one-harmonization" therapy of acupuncture / 中国针灸

The clinical experience of professor in treatment of dysmenorrhea with "three-regulation and one-harmonization" therapy of acupuncture was introduced. Professor invented a needling technique for "three-regulation and one-harmonization", meaning regulation, blood regulation and regulation of meridian tendon region as well as the spirit () harmonization. In regulation, the extreme fine needles are used to regulate movement of the whole function with the coordination of respiration and the corresponding acupoint prescriptions. In blood regulation, the special small bleeding device is selected and the bloodletting theory is improved for bloodletting at the specific stagnant site. In the regulation of meridian tendon region, a special sterile injection needle is chosen to release the cord-like mass. The spirit harmonization is exerted in combination with regulation. During acupuncture, the spirit of both the clinical practitioner and the patient should be in a harmonized spirit condition, coordinated with respiration regulation. In the treatment with acupuncture therapy of "three-regulation and one-harmonization" for dysmenorrhea, bloodletting therapy is used firstly to remove stasis, secondly, the "releasing cord-like mass" technique is followed to regulate meridian tendon region, finally, the fine needling technique is adopted to regulate and harmonize spirit. The clinical effect is definite in clinical practice.

Application of codon optimization strategy in heterologous protein expression / 生物工程学报

Enzymes are widely used in medical and biopharmaceuticals. They can be used not only for various disease treatments, but also clinical diagnosis. The use of microorganisms to express heterologous proteins has become the easiest and fastest way to obtain enzymes. In order to obtain high concentration and high-quality heterologous proteins, a common method is codon optimization of gene sequences. The traditional codon optimization strategy is mainly based on codon bias and GC content, ignoring complex and varied factors such as translational dynamics and metabolic levels. We provide here comprehensive codon optimization strategy based on gene level, transcriptional level, translational level, post-translational level and metabolic level, mainly including codon bias, codon harmonization, codon sensitivity, adjustment of gene sequence structure and some other influencing factors. We also summarize the aspects of strategy content, theoretical support and application. Besides, the advantages and disadvantages of each strategy are also systematically compared, providing an all-round, multi-level and multi-selection optimization strategy for heterogeneous protein expression, and also providing references for the enzyme industry and biopharmaceuticals.

Differences in Perspectives of Medical Device Adverse Events: Observational Results in Training Program Using Virtual Cases

BACKGROUND: Medical device adverse event reporting is an essential activity for mitigating device-related risks. Reporting of adverse events can be done by anyone like healthcare workers, patients, and others. However, for an individual to determine the reporting, he or she should recognize the current situation as an adverse event. The objective of this report is to share observed individual differences in the perception of a medical device adverse event, which may affect the judgment and the reporting of adverse events. METHODS: We trained twenty-three participants from twelve Asia-Pacific Economic Cooperation (APEC) member economies about international guidelines for medical device vigilance. We developed and used six virtual cases and six questions. We divided participants into six groups and compared their opinions. We also surveyed the country's opinion to investigate the beginning point of ‘patient use’. The phases of ‘patient use’ are divided into: 1) inspecting, 2) preparing, and 3) applying medical device. RESULTS: As for the question on the beginning point of ‘patient use,’ 28.6%, 35.7%, and 35.7% of participants provided answers regarding the first, second, and third phases, respectively. In training for applying international guidelines to virtual cases, only one of the six questions reached a consensus between the two groups in all six virtual cases. For the other five questions, different judgments were given in at least two groups. CONCLUSION: From training courses using virtual cases, we found that there was no consensus on ‘patient use’ point of view of medical devices. There was a significant difference in applying definitions of adverse events written in guidelines regarding the medical device associated incidents. Our results point out that international harmonization effort is needed not only to harmonize differences in regulations between countries but also to overcome diversity in perspectives existing at the site of medical device use.

Characterization of different native american physalis species and evaluation of their processing potential as jelly in combination with brie-type cheese

Abstract Faced with the need for greater knowledge of the different physalis species, the aim of this study was to characterize different Native American physalis species (Physalis peruviana L., Physalis pubescens L., Physalis angulata L., Physalis mínimos L. and Physalis ixocarpa Brot) as to their physicochemical characteristics, bioactive compounds and antioxidant activity. Besides that, in order to increase their use and add even more value to this fruit, we also evaluate the influence of these different species on the physicochemical, rheological and sensory characteristics of physalis jelly. In addition, this study evaluated the sensory acceptance of the combination of physalis jellies obtained from different species with brie-type cheese. The Peruviana, Pubences and Angulata, are highlighted for being the nutritionally richest species, with the highest levels of phenolic compounds, vitamin C and antioxidant. Moreover, they stand out for originating the most widely sensory accepted jellies, either in pure form or in combination with brie-type cheese.

Data harmonization and sharing in study cohorts of respiratory diseases / 中华流行病学杂志

Objective Chronic obstructive pulmonary disease,asthma,interstitial lung disease and pulmonary thromboembolism are the most common and severe respiratory diseases,which seriously jeopardizing the health of the Chinese citizens.Large-scale prospective cohort studies are needed to explore the relationships between potential risk factors and respiratory disease outcomes and to observe disease prognoses through long-term follow-ups.We aimed to develop a common data model (CDM) for cohort studies on respiratory diseases,in order to harmonize and facilitate the exchange,pooling,sharing,and storing of data from multiple sources to serve the purpose of reusing or uniforming those follow-up data appeared in the cohorts.Methods The process of developing this CDM of respiratory diseases would follow the steps as:①Reviewing the international standards,including the Clinical Data Interchange Standards Consortium (CDISC),Clinical Data Acquisition Standards Harmonization (CDASH) and the Observational Medical Outcomes Partnership (OMOP) CDM;②Summarizing four cohort studies of respiratory diseases recruited in this research and assessing the data availability;③Developing a CDM related to respiratory diseases.Results Data on recruited cohorts shared a few similar domains but with various schema.The cohorts also shared homogeneous data collection purposes for future follow-up studies,making the harmonization of current and future data feasible.The derived CDM would include two parts:①thirteen common domains for all the four cohorts and derived variables from disparate questions with a common schema,②additional domains designed upon disease-specific research needs,as well as additional variables that were disease-specific but not initially included in the common domains.Conclusion Data harmonization appeared essential for sharing,comparing and pooled analyses,both retrospectively and prospectively.CDM was needed to convert heterogeneous data from multiple studies into one harmonized dataset.The use of a CDM in multicenter respiratory cohort studies would make the constant collection of uniformed data possible,so to guarantee the data exchange and sharing in the future.

Current Status and the Future of Occupational Safety and Health Legislation in Low- and Middle-Income Countries

This article addresses three key issues. First, the commonalities, differences, strengths, and limitations of existing occupational safety and health (OSH) legislation of low- and middle-income countries were determined. Second, required revisions were identified and discussed to strengthen the laws in accordance with the best international practice. Finally, proposals for additional OSH laws and interventions were suggested. A literature search of OSH laws of 10 selected low- and middle-income countries was carried out. The laws were subjected to uniform review criteria. Although the agricultural sector employs more than 70% of the population, most of the reviewed countries lack OSH legislation on the sector. Existing OSH laws are gender insensitive, fragmented among various government departments, insufficient, outdated, and nondeterrent to perpetrators and lack incentives for compliance. Conclusively, the legal frameworks require reformation and harmonization for the collective benefit to employees, employers, and regulatory authorities. New OSH legislation for the agricultural sector is required.

Harmonization of laboratory results by data adjustment in multicenter clinical trials

BACKGROUND/AIMS: In multicenter clinical trials, laboratory tests are performed in the laboratory of each center, mostly using different measuring methodologies. The purpose of this study was to evaluate coefficients of variation (CVs) of laboratory results produced by various measuring methods and to determine whether mathematical data adjustment could achieve harmonization between the methods. METHODS: We chose 10 clinical laboratories, including Green Cross Laboratories (GC Labs), the central laboratory, for the measurement of total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), serum triglycerides, creatinine, and glucose. The serum panels made with patient samples referred to GC Labs were sent to the other laboratories. Twenty serum samples for each analyte were prepared, sent frozen, and analyzed by each participating laboratory. RESULTS: All methods used by participating laboratories for the six analytes had traceability by reference materials and methods. When the results from the nine laboratories were compared with those from GC Labs, the mean CVs for total cholesterol, HDL-C, LDL-C, and glucose analyzed using the same method were 1.7%, 3.7%, 4.3%, and 1.7%, respectively; and those for triglycerides and creatinine analyzed using two different methods were 4.5% and 4.48%, respectively. After adjusting data using Deming regression, the mean CV were 0.7%, 1.4%, 1.8%, 1.4%, 1.6%, and 0.8% for total cholesterol, HDL-C, LDL-C, triglyceride, creatinine, and glucose, respectively. CONCLUSIONS: We found that more comparable results can be produced by laboratory data harmonization using commutable samples. Therefore, harmonization efforts should be undertaken in multicenter trials for accurate data analysis (CRIS number; KCT0001235).

Data harmonization and sharing in study cohorts of respiratory diseases / 中华流行病学杂志

Objective Chronic obstructive pulmonary disease,asthma,interstitial lung disease and pulmonary thromboembolism are the most common and severe respiratory diseases,which seriously jeopardizing the health of the Chinese citizens.Large-scale prospective cohort studies are needed to explore the relationships between potential risk factors and respiratory disease outcomes and to observe disease prognoses through long-term follow-ups.We aimed to develop a common data model (CDM) for cohort studies on respiratory diseases,in order to harmonize and facilitate the exchange,pooling,sharing,and storing of data from multiple sources to serve the purpose of reusing or uniforming those follow-up data appeared in the cohorts.Methods The process of developing this CDM of respiratory diseases would follow the steps as:①Reviewing the international standards,including the Clinical Data Interchange Standards Consortium (CDISC),Clinical Data Acquisition Standards Harmonization (CDASH) and the Observational Medical Outcomes Partnership (OMOP) CDM;②Summarizing four cohort studies of respiratory diseases recruited in this research and assessing the data availability;③Developing a CDM related to respiratory diseases.Results Data on recruited cohorts shared a few similar domains but with various schema.The cohorts also shared homogeneous data collection purposes for future follow-up studies,making the harmonization of current and future data feasible.The derived CDM would include two parts:①thirteen common domains for all the four cohorts and derived variables from disparate questions with a common schema,②additional domains designed upon disease-specific research needs,as well as additional variables that were disease-specific but not initially included in the common domains.Conclusion Data harmonization appeared essential for sharing,comparing and pooled analyses,both retrospectively and prospectively.CDM was needed to convert heterogeneous data from multiple studies into one harmonized dataset.The use of a CDM in multicenter respiratory cohort studies would make the constant collection of uniformed data possible,so to guarantee the data exchange and sharing in the future.

Necesidad de armonizar la etapa preanalítica de la orina de 24 horas: evidencias de una encuesta / Need to harmonize the pre-analytical phase of 24-hour urine: evidence from a survey / Necessidade de harmonizar a fase pré-analítica da urina de 24 horas: evidência de uma pesquisa

El objetivo del trabajo consistió en evaluar el estado de armonización de la etapa preanalítica de la orina de 24 horas (orina-24h). Se realizó una encuesta anónima sobre la etapa preanalítica de la orina-24h a bioquímicos de Argentina. Respondieron 92 profesionales. Del análisis de las respuestas surge que el 95% de los bioquímicos facilita a los pacientes instrucciones escritas para la recolección; 11% incluye instrucciones con información visual gráfica además de escrita; 37% registra hora de inicio y finalización de la recolección; 59% recomienda que durante la misma la muestra se mantenga refrigerada; 73% suministra al paciente el recipiente para la recolección; 47% proporciona el envase con conservante, si corresponde; 100% solicita al paciente llevar al laboratorio la totalidad de la orina juntada; 4% solicita al paciente medir y anotar la diuresis y entregar al laboratorio una alícuota de la orina-24h; 78% realiza una o más acciones para evaluar la correcta recolección. Los criterios de rechazo seleccionados en orden decreciente fueron: pérdida de micciones, incumplimiento del tiempo de recolección, según la diuresis, según la eliminación diaria de creatinina y recipiente no apto. Esta encuesta evidenció que existen aspectos de la etapa preanalítica de la orina- 24h que requieren de mejora y armonización entre los laboratorios.

The objective of the present work was to evaluate the harmonization state of the pre-analytical phase of 24-hour urine. To this aim, an anonymous survey on the pre-analytical phase of 24-hour urine (Moreno-Carbonell, et. al) was carried out by biochemists from Argentina. A total of 92 professionals responded to the the survey. As a result, 95% provide patients with written instructions for collection; 11% include visual graphic instructions; 37% record starting and finishing time of collection; 59% recommend sample refrigeration during collection time; 73% supply the container; 47% provide the container with a preservative, if necessary; 100% ask the patient to take the complete 24-hour volume to the laboratory; 4% indicate to measure and record sample volume and to take an aliquot of it; and 78% perform one or more actions to evaluate the proper collection procedure. The rejection criteria selected in decreasing order were: loss of micturition, non-compliance with collection time, according to the volume and daily creatinine excretion, and improper container. To conclude with, this survey showed that there are aspects of the pre-analytical phase of 24-h urine that need improvement and harmonization between laboratories.

O objetivo do trabalho foi avaliar o estado de harmonização da fase pré-analítica da urina de 24 horas (urina-24h). Foi realizado um levantamento anônimo sobre a fase pré-analítica da urina-24h a bioquímicos da Argentina. Responderam 92 profissionais. Da análise das respostas surge que 95% fornecem aos pacientes instruções escritas para a coleta; 11% inclui instruções com informação visual gráfica além de escrita; 37% registra hora de início e finalização da coleta; 59% recomenda que durante a coleta a urina seja mantida refrigerada; 73% fornece o recipiente para a coleta; 47% fornece o recipiente com um conservante, se necessário; 100% solicita ao paciente que leve o volume completo de 24 horas ao laboratório; 4% indica ao paciente medir e registrar a diurese e entregar ao laboratório uma alíquota da urina-24h; 78% realiza uma ou mais ações para avaliar o procedimento apropriado de coleta. Os critérios de rejeição selecionados em ordem decrescente foram: perda das micções, descumprimento do tempo de coleta, de acordo com a diurese, conforme a eliminação diária de creatinina, e recipiente inadequado. Esta pesquisa mostrou que há aspectos da fase pré-analítica da urina de 24h que precisam ser melhorados e harmonizados entre os laboratórios.

Validation protocol for multiple blood gas analyzers in accordance with laboratory accreditation programs / Protocolo de validação de múltiplos equipamentos para análise de gases sanguíneos em conformidade com os programas de acreditação laboratorial

ABSTRACTIntroduction:The results of blood gas analysis using different instrumentation can vary widely due to the methodological differences, the calibration procedures and the use of different configurations for each type of instrument.Objective:The objective of this study was to evaluate multiple analytical systems for measurement of blood gases, electrolytes and metabolites in accordance with the accreditation program (PALC) of Sociedade Brasileira de Patologia Clínica/Medicina Laboratorial (SBPC/ML).Materials and methods:20 samples were evaluated in three ABL800 Flex (Radiometer Medical ApS, Denmark) blood gas analyzers, and the results were compared with those of the device in use, which was considered the reference. The analysis of variance (Anova) was applied for statistical purposes, as well as the calculation of mean, standard deviation and coefficient of variation.Results:The p values obtained in the statistical analysis were: pH = 0.983, pO2 = 0.991, pCO2 = 0.353, lactate = 0.584, glucose = 0.995, ionized calcium = 0.983, sodium = 0.991, potassium = 0.926, chlorine = 0.029.Conclusion:The evaluation of multiple analytical systems is an essential procedure in the clinical laboratory for quality assurance and accuracy of the results.

RESUMOIntrodução:Os resultados da análise dos gases sanguíneos utilizando diferentes equipamentos podem apresentar grandes variações decorrentes das diferenças metodológicas, dos procedimentos de calibração e da aplicação de configurações distintas para cada tipo de instrumento.Objetivo:O objetivo deste trabalho foi avaliar múltiplos sistemas analíticos para teste de gases sanguíneos, eletrólitos e metabólitos, em conformidade com o Programa de Acreditação de Laboratórios Clínicos (PALC) da Sociedade Brasileira de Patologia Clínica/Medicina Laboratorial (SBPC/ML).Materiais e métodos:Foram avaliadas 20 amostras em três analisadores de gases sanguíneos ABL800 Flex (Radiometer Medical ApS, Dinamarca) em relação ao equipamento em uso, que foi considerado referência. A análise de variância (Anova) foi aplicada para fins de estudo estatístico dos resultados obtidos nos quatro equipamentos, bem como o cálculo da média, do desvio padrão e do coeficiente de variação.Resultados:Os valores de p obtidos na análise estatística foram: pH = 0,983, pO2 = 0,991, pCO2 = 0,353, lactato = 0,584, glicose = 0,995, cálcio ionizado = 0,983, sódio = 0,991, potássio = 0,926 e cloro = 0,029.Conclusão:A avaliação de múltiplos sistemas analíticos é procedimento essencial no laboratório clínico para garantia da qualidade e da exatidão dos resultados.

Improved RP-HPLC Method for Quantitation of Swertiamarin from Swertia Densifolia Leaves and Marketed Herbal Formulations.

Objective: Present study aims at developing and validating an improved RP-HPLC method for determination of Swertiamarin from extracts of Swertia densifolia (Griseb.) Kashyap leaves and marketed herbal formulations. Methods: Developed RP-HPLC method is validated and is used for determination of Swertiamarin from hydroalcoholic extracts of test plant material and marketed herbal formulations. The separation is carried out on C18 column. The mobile phase used is 10 mM Ammonium acetate: Acetonitrile: Formic acid in ratio 90:10:0.2% (v/v/v/). The wavelength selected is 237 nm using UV detector. Results and Discussion: A seven-point calibration curve over the concentration range of 50.00 –20000.00 ng/mL for Swertiamarin provides an optimum linear detector response (with r2>0.9970). The % R.S.D. (n = 6) for the low, middle and high quality control samples are within <6.44 and < 9.04 for inter-day and intra-day precision and accuracy respectively. Conclusion: A simple, sensitive and precise method is developed for quantitation of SWM. Method is validated as per International Conference on Harmonization (ICH) guidelines and its applicability is demonstrated by successful measurement of Swertiamarin from hydroalcoholic extracts of Swertia densifolia leaves and selected marketed herbal formulations.