Effect of prosthetic design and restorative material on the stress distribution of implant-supported 3-unit fixed partial dentures: 3D-FEA / Efeito do desenho protético e do material restaurador na distribuição de tensão de próteses parciais fixas de 3 elementos suportada por implante: FEA 3D

Objective: Evaluate the effect of Implant prosthetic designs and restorative material on the stress concentration of 3-unit implant-supported restoration with two restorative materials. Material and Methods: Six different screw-retained prostheses models were virtually designed and divided according to design: fixed bridge (FB), cantilever bridge (CB), and separate crowns (SC). Then, each model was also divided into two subgroups according to the material: Ultra-translucent multi-layered zirconia (Kuraray Noritake Dental Inc., Japan); or a combination of PEEK (Polyetheretherketone) framework (BioHPP, Bredent, GmbH & Co., KG, Germany) and zirconia (ZR) crowns (ultra-translucent multi-layered zirconia, Kuraray Noritake Dental Inc., Japan). A vertical load of 100 N was applied statically perpendicular to the central fossa of each crown. The von-Mises stress was computed using Solidworks software (SolidWorks Corp, Massachusetts, USA), based on the physical parameters of the materials. Results: FB showed the lowest von Mises stress values out of all 3 design models. Moreover, the combination of PEEK and zirconia showed strain values smaller than full zirconia. The highest von Mises stress value was recorded in CB with the zirconia subgroup at (1098 MPa) while the lowest von Mises stress value was recorded in FB with combined PEEK and zirconia subgroup at (190 MPa). Conclusion: For three-unit implant supported restorations, the use of PEEK framework and zirconia crowns was found to be more favorable biomechanically regarding the prosthetic components, implant and bone stresses. (AU)

Objetivo: Avaliar o efeito do desenho da prótese sobre implantes e do material restaurador na concentração de tensão de próteses fixas de 3 elementos implantossuportada, com dois materiais restauradores. Material e Métodos: Seis diferentes modelos de próteses aparafusadas foram virtualmente projetados e divididos de acordo com o desenho: ponte fixa (PF), ponte cantilever (PC) e coroas individuais (CI). Em seguida, cada modelo também foi dividido em dois subgrupos de acordo com o material: Zircônia multicamada ultra translúcida (Kuraray Noritake Dental Inc., Japão); ou associada a uma estrutura de PEEK (Polyetheretherketone) (BioHPP, Bredent, GmbH & Co., KG, Alemanha) e coroas de zircônia (CZ) (zircônia multicamada ultra translúcida, Kuraray Noritake Dental Inc., Japão). Uma carga vertical estática de 100 N foi aplicada perpendicular à fossa central de cada coroa. A tensão de von-Mises foi calculada usando o software Solidworks (SolidWorks Corp, Massachusetts, EUA), com base nos parâmetros físicos dos materiais. Resultados:PF apresentou os menores valores de tensão de von Mises de todos os 3 modelos propostos. Além disso, a combinação de PEEK e zircônia apresentou valores de deformação menores do que a zircônia pura. O maior valor de tensão de von Mises foi registrado em PC com o subgrupo de zircônia em (1098 MPa), enquanto o menor valor de tensão de von Mises foi registrado em PF com PEEK combinado e subgrupo de zircônia em (190 MPa). Conclusão: Para ponte fixa de 3 elementos implantossuportadas, o uso de estrutura PEEK e coroas de zircônia mostrou-se mais favorável biomecanicamente em relação aos componentes protéticos, implante e tensão sobre o osso. (AU)

Application of optical illusion in stomatological aesthetics / 口腔疾病防治

@#Optical illusion refers to the phenomenon in which the scene observed by the human eye is not completely consistent with the objectively presented scene. Optical illusions in stomatology, as well as their clinical application, are demonstrated in this paper in terms of shade, shape and aesthetic design. Shade is not only affected by the optical illusions with which it is associated, such as color metamerism, color constancy and the Chevreul illusion, but also influenced by the surroundings. It is suggested that the surrounding lighting during veneering should be the same as that during color matching in the clinic. As indicated by the Poggendorf illusion and the Leaning Tower illusion, the practice should be conducted and checked from multiple perspectives to compensate for the limitation of human eyes, such as intraoral scanning. Other digital technologies, including digital facial scanning and cephalometric measurement, could be used to reduce the subjective influence of observation. In terms of esthetic design, the interaction of the part and the whole, suggested by Ebbinghaus illusion, should be considered: an individual harmony smile should be designed considering the characteristics of the personality and the features of the face, lips, teeth and gingiva of the patient. Furthermore, personal information, such as gender and age, should be taken into consideration in beautification presentation. Further research should be focused on the influence of optical illusions in stomatology in more details. More communication among doctors, technicians and patients is needed. Clinicians should be aware of the impact of optical illusions to reduce subjective bias in clinical standardized operations and further take advantage of optical illusions to create beautification presentations of dental restorations and smiles.

Gather wisdom to overcome barriers: Well-designed nano-drug delivery systems for treating gliomas

Due to the special physiological and pathological characteristics of gliomas, most therapeutic drugs are prevented from entering the brain. To improve the poor prognosis of existing therapies, researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy. Although these strategies can be used clinically to overcome the blood‒brain barrier (BBB), the accurate delivery of drugs to the glioma lesions cannot be ensured. Nano-drug delivery systems (NDDS) have been widely used for precise drug delivery. In recent years, researchers have gathered their wisdom to overcome barriers, so many well-designed NDDS have performed prominently in preclinical studies. These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions, drug release in response to the glioma microenvironment, biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein, and carriers created according to the active ingredients of traditional Chinese medicines. We reviewed these well-designed NDDS in detail. Furthermore, we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy, and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.

Media development and process parameter optimization using statistical experimental designs for the production of nonribosomal peptides in Escherichia coli

BACKGROUND: Nonribosomal peptide synthases (NRPS) can synthesize functionally diverse bioactive peptides by incorporating nonproteinogenic amino acids, offering a rich source of new drug leads. The bacterium Escherichia coli is a well-characterized production host and a promising candidate for the synthesis of nonribosomal peptides, but only limited bioprocess engineering has been reported for such molecules. We therefore developed a medium and optimized process parameters using the design of experiments (DoE) approach. RESULTS: We found that glycerol is not suitable as a carbon source for rhabdopeptide production, at least for the NRPS used for this study. Alternative carbon sources from the tricarboxylic acid cycle achieved much higher yields. DoE was used to optimize the pH and temperature in a stirred-tank reactor, revealing that optimal growth and optimal production required substantially different conditions. CONCLUSIONS: We developed a chemically defined adapted M9 medium matching the performance of complex medium (lysogeny broth) in terms of product concentration. The maximum yield in the reactor under optimized conditions was 126 mg L-1, representing a 31-fold increase compared to the first shaking-flask experiments with M9 medium and glycerol as the carbon source. Conditions that promoted cell growth tended to inhibit NRPS productivity. The challenge was therefore to find a compromise between these factors as the basis for further process development.

Ensaio clínico randomizado: padrão ouro de desenhos experimentais - importância, vantagens, desvantagens e preconceitos / Randomized clinical trial: gold standard of experimental designs - importance, advantages, disadvantages and prejudice

Ensaios clínicos randomizados (ECR) são o padrão ouro para desenho experimental de estudo ou ensaio clínico. Apenas por meio de uma investigação do tipo ECR é possível avaliar e demonstrar a relação de causa-e-efeito entre um conjunto de variáveis independentes e dependentes. O ECR adicionou vantagens em relação aos outros modelos experimentais, principalmente devido à presença de um grupo controle. Existem várias críticas à validade interna das pesquisas em saúde, incluindo preconceitos e desvantagens que são apontadas para seu descrédito. OBJETIVO: O objetivo do presente estudo é informar características, vantagens, desvantagens e desvios deste método científico. MATERIAL E MÉTODOS: Análise crítica de método científico com base em revisão narrativa da literatura. Foi consultada a base de dados Medline por meio dos portais PubMed e Scopus, sem data de início e até julho de 2020, para extração das informações relativas aos ECR. Apenas artigos de língua inglesa foram incluídos, usando as palavras-chave "estudo randomizado controlado", "ensaio clínico randomizado", "projeto experimental" e "estudo experimental", intercaladas pelos operadores booleanos "AND ," "OR" e "NOT". Anais de conferências e resumos não foram considerados para a análise dos dados. RESULTADOS: Dos ECR selecionados, foram extraídas características, vantagens, desvantagens, importância e vantagens dos controles em pesquisa, o princípio de equilíbrio, ensaios clínicos randomizados na população pediátrica, ECR na população geriátrica, ameaças à validade interna e medidas para minimização de viéses e preconceitos em ECR. CONCLUSÃO: Tópicos relevantes dos ECR foram explicados nesta revisão que devem guiar pesquisadores clínicos.

Randomized controlled trial (RCT) is the gold standard of experimental design or clinical trial design. Only by RCT in research, the cause-and-effect relationship between a set of independent and dependent variables could be demonstrated. RCT has added advantages over other experimental designs due to the presence of the control group. The importance of control in health research trials and its advantages to be elaborated. Though various threats to internal validity in health research trials could be minimized by RCT, various biases in RCT and disadvantages add to its discredit. OBJECTIVE: The aim of the present narrative review is to brief the characteristics, advantages, disadvantages, and various biases in RCT. METHODS: This review does not follow the PRISMA statement, as it was a narrative review. Two databases, namely, Medline through PubMed and Scopus, were searched from inception to July 2020 for the information pertaining to RCTs and included in this narrative review. Only English language articles were searched with the keywords, "Randomized controlled trial," "Randomized clinical trial," "experimental design," and "experimental study." These keywords are linked together by the Boolean words, "AND," "OR" and "NOT." Conference proceedings and only abstracts were not considered for the review. RESULTS: RCTs were explained under characteristics, advantages, disadvantages, importance, and advantages of controls in research, the principle of equipoise, RCTs in the pediatric population, RCTs in the geriatric population, threats to internal validity and steps to minimize them and various biases in RCTs. CONCLUSION: The narrative presentation of RCTs under various important topics have been explained in this review.

Formulation And Evaluation Of Chlorothalidone Loaded Mouth Dissolving Film-A Bioavailability Enhancement Approach Using Multilevel Categoric Design

Objective: The intension of the present study includes fabrication and optimization of mouth dissolving film loaded with Chlorothalidone by solvent evaporation techniques using two components and their three levels as multilevel Categoric design. Methods: Major problem associated with the development of film loaded with BCS class II drug is to increase its solubility. Here the Chlorothalidone solubility achieved by co-solvents, such as methanol. After dissolving the drug in co-solvent, this drug solution is poured into an aqueous dispersion of Hydroxypropyl Methylcellulose E5 (HPMC E5) and Polyethylene glycol 400 (PEG 400). The two independent variables selected are factor A (concentration of HPMC E5) and factor B (concentration of PEG 400) was selected on the basis of preliminary trials. The percentage drug release (R1), Disintegration time in sec (R2) and folding endurance (R3) were selected as dependent variables. Here HPMC E5 used as a film former, PEG 400 as plasticizer, mannitol as bulking agent, Sodium starch glycolate as a disintegrating agent, tween 80 as the surfactant, tartaric acid as saliva stimulating agent, sodium saccharin as a sweetener and orange flavour etc. These fabricated films were evaluated for physicochemical properties, disintegration time and In vitro drug release study. Results: The formulation F6 has more favorable responses as per multilevel categoric design is % drug release about 98.95 %, average disintegration time about 24.33 second and folding endurance is 117. Thus formulation F6 was preferred as an optimized formulation. Conclusion: The present formulation delivers medicament accurately with good therapeutic efficiency by oral administration, this mouth dissolving films having a rapid onset of action than conventional tablet formulations.

Load to failure of three different monolithic zirconia inlay- retained fixed dental prosthesis designs with three surface treatments / Carga até falha de três diferentes desenhos de inlays de zircônia monolítica com três tratamentos de superfície

Objective: The purpose of the study was to evaluate the effect of different preparation designs and different surface treatments on the fracture resistance of monolithic zirconia inlay-retained fixed dental prosthesis [IRFDP]. Material and methods: Forty-five translucent zirconia IRFDPs were divided into three groups according to preparation designs (n = 15); group I: proximal box, group II: inlay-box and group III: butterfly wing (modified inlay). Each group was further subdivided into three subgroups according to the surface treatments utilized (n = 5); sandblasting, tribochemical silica coating (Cojet system) and erbium, chromium: Yttrium, scandium, gallium, garnet (Er, Cr: YSGG) laser irradiation. All zirconia IRFDPs were cemented to their respective resin models using selfadhesive resin cement. All cemented IRFDPs were subjected to fracture resistance test using universal testing machine. The initial fracture site was determined by using a stereomicroscope (x6.7magnification). Two-way analysis of variance (ANOVA) was used to evaluate the effect of different designs, different surface treatments and their interaction on the mean fracture resistance. Bonferroni's post-hoc test was used when ANOVA is significant (P ≤ 0.05). Results: Butterfly wings design showed the highest fracture resistance values followed by inlay and box designs respectively (P ≤ 0.05). Sandblasting and Cojet showed significantly the highest mean fracture resistance values than Laser with no significance difference between them. Conclusion: The butterfly wing design increased the fracture resistance of the zirconia IRFDPs. Sandblasting and tribochemical silica coating of zirconia surfaces had a greater effect than Er, Cr: YSGG laser to gain higher fracture resistance of zirconia IRRDPs (AU)

Objetivo: O objetivo do estudo foi avaliar o efeito de diferentes modelos de preparações e diferentes tratamentos de superfície na resistência à fratura de inlays de zircônia monolítica. Material e métodos: Quarenta e cinco inlays translúcidos de zircônia foram divididos em três grupos de acordo com os desenhos de preparação (n = 15); grupo I: caixa proximal, grupo II: inlay convencional e grupo III: asa de borboleta (inlay modificado). Cada grupo foi subdividido em três subgrupos de acordo com os tratamentos de superfície utilizados (n = 5); jateamento de areia, revestimento triboquímico de sílica (sistema Cojet) e érbio, cromo: ítrio, escândio, gálio, granada (Er, Cr: YSGG) irradiação a laser. Todos os inlays de zircônia foram cimentados em seus respectivos modelos de resina usando cimento de resina auto-adesivo. Todos os inlays cimentados foram submetidos a teste de resistência à fratura usando máquina de teste universal. O local inicial da fratura foi determinado usando um estereomicroscópio (ampliação de 6,7x). A análise de variância (ANOVA) de dois fatores foi usada para avaliar o efeito de diferentes desenhos, diferentes tratamentos de superfície e sua interação na resistência média à fratura. O teste post-hoc de Bonferroni foi usado quando a ANOVA foi significativa (P ≤ 0,05). Resultados: O design das asas de borboleta apresentou os maiores valores de resistência à fratura, seguidos pelos designs de inlay convencional e caixa, respectivamente (P ≤ 0,05). O jateamento de areia e o Cojet apresentaram significativamente os maiores valores médios de resistência à fratura do que o Laser, sem diferença de significânc=ia entre eles. Conclusão: O design da asa de borboleta aumentou a resistência à fratura dos inlays de zircônia. O revestimento por jato de areia e triboquímica de sílica das superfícies de zircônia teve um efeito maior que o laser Er, Cr: YSGG para obter maior resistência à fratura dos inlays de zircônia. (AU)

Summary of clinical trial design and evaluation of Chinese materia medica for treatment of children with influenza / 中草药

Influenza is a common infective respiratory system disease in pediatric clinical. Based on the guidelines for diagnosis and treatment of influenza in children at home and abroad, guidelines for clinical trials of influenza drugs, and related registrations or published clinical trials combined with clinical experiences, the key technical points and characteristics of clinical trial design and evaluation of Chinese medicine for this disease was mainly elaborated, in order to enrich the methodological content of traditional Chinese medicine clinical evaluation of pediatric diseases.

Effects of Class II division 1 malocclusion treatment with three types of fixed functional appliances

ABSTRACT Objective: This study aimed at comparing the dentoskeletal changes in patients with Class II division 1 malocclusion, treated with three types of fixed functional appliances. Methods: A sample comprising 95 patients with the same malocclusion, retrospectively selected, and divided into four groups, was used: G1 consisted of 25 patients (mean age 12.77 ± 1.24 years) treated with Jasper Jumper appliance; G2, with 25 patients (mean age 12.58 ± 1.65 years) treated with the Herbst appliance; G3, with 23 patients (mean age 12.37 ± 1.72 years) treated with the Mandibular Protraction Appliance (MPA); and a Control Group (CG) comprised of 22 untreated subjects (mean age 12.66 ± 1.12 years). Intergroup comparison was performed with ANOVA, followed by Tukey test. Results: The Jasper Jumper and the Herbst group showed significantly greater maxillary anterior displacement restriction. The Jasper Jumper demonstrated significantly greater increase in the mandibular plane angle, as compared to the control group. The MPA group demonstrated significantly greater palatal inclination of the maxillary incisors. Vertical development of the maxillary molars was significantly greater in the Herbst group. Conclusions: Despite some intergroup differences in the amount of dentoskeletal changes, the appliances were effective in correcting the main features of Class II malocclusions.

RESUMO Objetivo: o objetivo do presente estudo foi comparar as alterações dentoesqueléticas em pacientes com má oclusão de Classe II, divisão 1, tratados com três tipos de aparelhos funcionais fixos. Métodos: a amostra compreendeu 95 pacientes, selecionados retrospectivamente e divididos em quatro grupos: G1, composto por 25 pacientes (idade média de 12,77 ± 1,24 anos), tratados com aparelho Jasper Jumper; G2, com 25 pacientes (idade média de 12,58 ± 1,65 anos), tratados com aparelho Herbst; G3, com 23 pacientes (idade média de 12,37 ± 1,72 anos), tratados com o Aparelho de Protração Mandibular (APM); e um Grupo Controle (GC), composto por 22 sujeitos não tratados (idade média de 12,66 ± 1,12 anos) que apresentavam a mesma má oclusão. A comparação intergrupos foi realizada com ANOVA, seguida do teste Tukey. Resultados: os grupos Jasper Jumper e Herbst apresentaram significativamente maior restrição de deslocamento anterior da maxila. O Jasper Jumper demonstrou aumento significativamente maior no ângulo do plano mandibular, em comparação ao grupo controle. O grupo APM demonstrou inclinação palatina significativamente maior dos incisivos superiores. O desenvolvimento vertical dos molares superiores foi significativamente maior no grupo Herbst. Conclusões: apesar de algumas diferenças intergrupos na quantidade de alterações dentoesqueléticas, os aparelhos foram eficazes na correção das principais características das más oclusões de Classe II.

De vuelta a la clínica. Métodos I. Diseños de investigación. Mayor calidad de información, mayor certeza a la respuesta / Back to the clinic. Methods I. Research designs. Higher quality of information, greater certainty to the answer

Resumen Los diseños de investigación se refieren a la forma como se obtiene la información y están limitados por viabilidad ética, económica y temporal. Son estrategias estandarizadas para disminuir los sesgos que en el modelo arquitectónico de la investigación se identifican en el estado basal, maniobra y desenlace; de ahí que no hay diseños específicos para cada pregunta. El diseño con menor probabilidad de sesgos es el ensayo clínico, seguido de la cohorte, el estudio de casos y controles y, finalmente, la encuesta transversal. Entre las principales características que dan mérito a los diseños están las siguientes: la pesquisa de la población, que se refiere a la ubicación de la población en relación con el curso clínico o historia natural de la enfermedad; la maniobra, o acción que se espera modifique la condición basal, que puede ser observacional o experimental; el seguimiento, o monitoreo documentado que se le da a cada sujeto, que puede ser longitudinal o transversal; y la direccionalidad, prolectiva o retrolectiva, que alude al tiempo de recopilación de la información con fines de investigación. Siempre será mejor tener una pregunta valiosa, incluso cuando se responda con un diseño con mayor riesgo de sesgos, que una pregunta irrelevante o sin aplicabilidad.

Abstract Research designs refer to the way information is obtained and are limited by ethical, economic and temporal viability. Research designs are standardized strategies to reduce biases, which in the architectural model of research are identified in the baseline state, the maneuver and the outcome; hence, there are no specific designs for each question. The design with the lowest probability of bias is the clinical trial, followed by cohort and case-control studies and, finally, by cross-sectional surveys. Among the main characteristics that give merit to research designs are the following: population inquiry, which refers to the situation of the population in relation to the clinical course/natural history of the disease; the maneuver, or action that is expected to modify the baseline state, which can be observational or experimental; follow-up, or documented monitoring that is given to each subject, which can be longitudinal or cross-sectional; and directionality, which can prolective or retrolective and refers to the timing of data collection for research purposes. It will always be better having a valuable question, even when answered with a design with higher risk of bias, than a question that is irrelevant or has no applicability.

Métodos actuales para asegurar la validez de los estudios de causalidad en Medicina / Current methods to assure the validity of the causality studies in Medicine

RESUMEN Fundamento: Los estudios de causalidad deben aportar resultados certeros, lo cual depende de la adecuación de los mismos, de ahí la necesidad de conocer los métodos que aseguren la validez de estas investigaciones. Objetivo: Sistematizar los métodos actuales para el estudio de causalidad en Medicina que incluye el diseño, los requerimientos que aseguran su validez y los métodos para el cumplimiento de estos requerimientos. Desarrollo: Se realizó una revisión bibliográfica en bases de datos biomédicas, se seleccionó la literatura de mayor actualidad, integralidad y cientificidad con la cual se organizó una síntesis crítica, a la que se le agregó la experiencia de las autoras. Se presentan técnicas para la detección y tratamiento de la confusión y la interacción y para garantizar la comparabilidad entre grupos. Entre las técnicas se destacan la aleatorización mendeliana, el puntaje de susceptibilidad, los G-métodos, los modelos estructurales marginales y anidados, la lógica difusa y el análisis estadístico implicativo. Conclusiones: A pesar del avance en los métodos estadísticos es el investigador el encargado de garantizar la no confusión residual y discernir entre lo estadísticamente significativo y lo clínicamente aceptable.

ABSTRACT Background: Causality studies must provide accurate results, which depends on their adequacy, therefore the need of knowing the methods that ensure the validity of these investigations. Objective: To systematize the current methods for the study of causality in Medicine that includes the design, the requirements that ensure its validity and the methods for complying with these requirements. Development: It was carried out a bibliographic review in biomedical databases and selected the most current, comprehensive, scientific literature, with this, a critical synthesis was organized, with the experience of the authors. Techniques for the detection and treatment of confusion and interaction were presented, also to ensure comparability between groups. Among the techniques, Mendelian randomization, susceptibility score, G-methods, marginal and nested structural models, fuzzy logic and implicative statistical analysis stand out. Conclusions: Despite the progress in statistical methods, the researcher is responsible for guaranteeing residual non-confusion and distinguishing between statistically significant and clinically acceptable.

Bioestatística e epidemiologia: perguntas que você sempre quis fazer, mas nunca teve coragem / Biostatistics and epidemiology: questions you always wanted to ask but never had the courage to

Dando continuidade aos artigos da série "Perguntas que você sempre quis fazer, mas nunca teve coragem", que tem como objetivo responder e sugerir referências para o melhor entendimento das principais dúvidas estatísticas levantadas por pesquisadores da área da saúde, este terceiro artigo aborda o contexto epidemiológico. Neste contexto, foram diferenciadas as principais medidas como prevalência, incidência, Odds Ratio (OR), Risco Relativo (RR), Razão de Prevalência (RP) e Hazard Ratio (HR), foi esclarecido o uso de análises por intenção de tratar e análise por protocolo, e também discutidos alguns dos termos comumente utilizados e pouco compreendidos como tipo de amostra, nível de evidência, relevância clínica e estatística, entre outros. (AU)

Continuing the series of articles "Questions you always wanted to ask but never had the courage to," which aims to answer key statistical questions raised by health researchers and suggest references for a better understanding, this third article addresses the epidemiological context. In this context, important measures such as prevalence, incidence, odds ratio (OR), relative risk (RR), prevalence ratio (PR) and hazard ratio (HR) were differentiated; the use of intention-to-treat analysis and per-protocol analysis was clarified; and some terms commonly used and poorly understood were discussed, such as type of sample, level of evidence, clinical and statistical relevance, among others. (AU)

Introduction on 'assessing the risk of bias of individual studies' in systematic review of healthcare intervention programs revised by the Agency for Healthcare Research and Quality / 中华流行病学杂志

This paper summarizes the Risk of Bias of Individual Studies in Systematic Reviews of Health Care Interventions revised by the Agency for Healthcare Research and Quality (AHRQ) and introduces how to use Revman software make risk of bias graph or risk of bias summary.AHRQ tool can be used to evaluate following study designs:RCTs,cohort study,case-control study (including nested case-control),case series study and cross-sectional study.The tool evaluates the risk of bias of individual studies from selection bias,performance bias,attrition bias,detection bias and reporting bias.Each of the bias domains contains different items,and each item is available for the assessment of one or more study designs.It is worth noting that the appropriate items should be selected for evaluation different study designs instead of using all items to directly assess the risk of bias.AHRQ tool can be used to evaluate risk of bias individual studies when systematic reviews of health care interventions is including different study designs.Moreover,the tool items are relatively easy to understand and the assessment process is not complicated.AHRQ recommends the use of high,medium and low risk classification methods to assess the overall risk of bias of individual studies.However,AHRQ gives no recommendations on how to determine the overall bias grade.It is expected that future research will give corresponding recommendations.

Introduction on 'assessing the risk of bias of individual studies' in systematic review of healthcare intervention programs revised by the Agency for Healthcare Research and Quality / 中华流行病学杂志

This paper summarizes the Risk of Bias of Individual Studies in Systematic Reviews of Health Care Interventions revised by the Agency for Healthcare Research and Quality (AHRQ) and introduces how to use Revman software make risk of bias graph or risk of bias summary.AHRQ tool can be used to evaluate following study designs:RCTs,cohort study,case-control study (including nested case-control),case series study and cross-sectional study.The tool evaluates the risk of bias of individual studies from selection bias,performance bias,attrition bias,detection bias and reporting bias.Each of the bias domains contains different items,and each item is available for the assessment of one or more study designs.It is worth noting that the appropriate items should be selected for evaluation different study designs instead of using all items to directly assess the risk of bias.AHRQ tool can be used to evaluate risk of bias individual studies when systematic reviews of health care interventions is including different study designs.Moreover,the tool items are relatively easy to understand and the assessment process is not complicated.AHRQ recommends the use of high,medium and low risk classification methods to assess the overall risk of bias of individual studies.However,AHRQ gives no recommendations on how to determine the overall bias grade.It is expected that future research will give corresponding recommendations.

Statistics applied to plant micropropagation: a critical review of inadequate use / Estatísticas aplicadas a micropropagação de plantas: uma revisão crítica sobre usos inadequados

Statistical analyses are an essential part of scientific research. Several choices, including the setup of the experiment, influence the selection of statistical procedures. Thus, successful planning implies accurate analysis. We used a 95% confidence interval and a 7% error margin to sample and characterize the statistical techniques used in studies on micropropagation and to discuss the effects of misusing these techniques. We quantified the following: sample size, number of replications, design, scheme (factorial or not factorial) and number of treatments, whether data transformation was used, transformation type and criteria for selection; variable type (quantitative or qualitative); statistical test and regression types. Although statistics were consistently used in these micropropagation experiments, there were several limitations such as small plot sizes, low replication numbers, employing data transformation while neglecting to inform the criteria used or even using the wrong criteria. Although statistical approaches were applied homogeneously, neglecting to use blocking can lead to errors. Blocking is recommended to increase sample size. For example, the times of an experiment or the number of people needed to set up an experiment can be used as blocks. Micropropagation studies typically employ factorial experiments to identify plant regulator types and application rates. Thus, these experiments have numerous treatments. The Tukey test is used for qualitative data while regression models (linear and quadratic) are more frequently used for quantitative data.

As análises estatísticas são uma parte essencial da pesquisa científica. Vários procedimentos desde a elaboração do experimento têm impacto nos procedimentos estatísticos finais adotados, assim um correto planejamento implica em uma análise precisa. Por meio de uma amostragem utilizando intervalo de confiança a 95% e margem de erro de 7% objetivou caracterizar as estatísticas utilizadas pelos pesquisadores da área de cultura de tecidos vegetais, e com base nos resultados discutir os principais impactos do mau uso. Foram quantificadas as informações referentes ao tamanho da amostra; número de repetições; delineamento; esquema adotado (fatorial ou não) e número de tratamentos; uso ou não de transformação, critério para adoção e tipo de transformação; tipo da variável (quantitativo ou qualitativo), teste e tipos de regressão. Mesmo com uso consistente da estatística nos experimentos de micropropagação alguns gargalos permanecem, como o tamanho das parcelas e o número reduzido de repetições. Soma-se a isto, a transformação de dados na qual não são informados os critérios para a adoção, ou usam-se critérios equivocados. Mesmo considerando as condições homogêneas, o não uso da blocagem nos experimentos pode configurar em um erro. Recomenda-se a blocagem para aumentar o tamanho da amostra, tendo como bloco o tempo e, ou, o fator humano envolvido na instalação do experimento. Como característica da área tem-se o uso de experimentos fatoriais, visando definir doses e reguladores vegetais, assim os experimentos apresentam grande número de tratamentos. Para comparação dos dados qualitativos utiliza-se o teste de Tukey e no quantitativo as regressões preferidas são as lineares e quadráticas.

Design of Experiments (DoE) applied to Pharmaceutical and Analytical Quality by Design (QbD)

According to Quality by Design (QbD) concept, quality should be built into product/method during pharmaceutical/analytical development. Usually, there are many input factors that may affect quality of product and methods. Recently, Design of Experiments (DoE) have been widely used to understand the effects of multidimensional and interactions of input factors on the output responses of pharmaceutical products and analytical methods. This paper provides theoretical and practical considerations for implementation of Design of Experiments (DoE) in pharmaceutical and/or analytical Quality by Design (QbD). This review illustrates the principles and applications of the most common screening designs, such as two-level full factorial, fractionate factorial, and Plackett-Burman designs; and optimization designs, such as three-level full factorial, central composite designs (CCD), and Box-Behnken designs. In addition, the main aspects related to multiple regression model adjustment were discussed, including the analysis of variance (ANOVA), regression significance, residuals analysis, determination coefficients (R2, R2-adj, and R2-pred), and lack-of-fit of regression model. Therefore, DoE was presented in detail since it is the main component of pharmaceutical and analytical QbD.

A structural classification of strategies for confounding control in research design / 中华流行病学杂志

Confounding affects the causal relation among the population.Depending on whether the confounders are known,measurable or measured,they can be divided into four categories.Based on Directed Acyclic Graphs,the strategies for confounding control can be classified as (1) the broken-confounding-path method,which can be further divided into single and dual broken paths,corresponding to exposure complete intervention,restriction and stratification,(2) and the reserved-confounding-path method,which can be further divided into incomplete exposure intervention (in instrumental variable design and non-perfect random control test),mediator method and matching method.Among them,random control test,instrumental variable design or Mendelian randomized design,mediator method can meet the requirements for controlling all four types of confounders,while the restriction,stratification and matching methods are only applicable to known,measurable and measured confounders.Identifying the mechanisms of confounding control is a prerequisite for obtaining correct causal effect estimates,which will be helpful in research design.

A structural classification of strategies for confounding control in research design / 中华流行病学杂志

Confounding affects the causal relation among the population.Depending on whether the confounders are known,measurable or measured,they can be divided into four categories.Based on Directed Acyclic Graphs,the strategies for confounding control can be classified as (1) the broken-confounding-path method,which can be further divided into single and dual broken paths,corresponding to exposure complete intervention,restriction and stratification,(2) and the reserved-confounding-path method,which can be further divided into incomplete exposure intervention (in instrumental variable design and non-perfect random control test),mediator method and matching method.Among them,random control test,instrumental variable design or Mendelian randomized design,mediator method can meet the requirements for controlling all four types of confounders,while the restriction,stratification and matching methods are only applicable to known,measurable and measured confounders.Identifying the mechanisms of confounding control is a prerequisite for obtaining correct causal effect estimates,which will be helpful in research design.

Formulation optimization of rutaecarpine lipid liquid crystalline nanoparticles by Box-Behnken design-response surface methodology / 中草药

Objective To optimize the formulation of rutaecarpine lipid liquid crystalline nanoparticles (Rut-LLCN) by Box-Behnken design-response surface methodology. Methods Rut-LLCN were prepared by precursor injection-high pressure homogenization method. A three factor and three-level Box-Behnken design was employed with the glyceryl monoolein quality, percentage of poloxamer in glyceryl monoolein and the rutaecarpine quality as independent variables, the entrapment efficiency, drug loading, mean particle size and polydispersity index as the dependent variables to sereen the optimal formaula. Results Optimized prescription was GMO 450 mg, F127-GMO 12%, and Rut 20 mg. All items of optimized prescription were similar to target values. According to the optimized prescription, the entrapment efficiency, drug loading, average particle size, and PDI of Rut-LLCN were (84.02 ± 7.99)%, (3.24 ± 0.30)%, (186.90 ± 13.50) nm, and 0.313 ± 0.020, respectively. Conclusion The prescription optimization model of Rut-LLCN was optimized by Box-Behnken designs-response surface methodology, and entrapment efficiency, drug loading, mean particle size, and PDI of Rut-LLCN are measured to investigate the model.

Key technologies of clinical study of traditional Chinese medicine on pediatric functional abdominal pain / 药物评价研究

Functional abdominal pain is one of the most common problems in functional gastrointestinal disorders,and it's also one of the diseases benefit most from traditional Chinese medicine (TCM) treatment.This paper illustrates some key considerations on the study design of traditional Chinese medicine intended for the treatment of FAP based on the latest treatment and evaluation guidelines,technical guidance,professional authority works as well as the latest clinical studies,and combined with experience of clinical trial design.It hopes to offer helps for research designers in this genera.