What is an "ongoing" clinical trial? An analysis of different sources revealed heterogeneous definitions of when a clinical trial starts and ends: a meta-research study

ABSTRACT BACKGROUND: Although the concept of an "ongoing study" seems self-explanatory, it is difficult to determine whether a trial is underway. OBJECTIVE: To analyze the definitions of "ongoing clinical trial" across different clinical trial registries, methodological guidelines, and other sources. DESIGN AND SETTING: This meta-research study was conducted at the Universidade Federal de São Paulo (UNIFESP), Brazil. METHODS: We performed a cross-sectional analysis of relevant clinical trial registry databases, methodological guidelines for conducting systematic reviews, and other sources that would define or regulate clinical trials. RESULTS: We identified various heterogeneous definitions used by eligible sources at both the start and end of a clinical trial. The starting criteria used were as follows: when the team is planning the protocol, when permission is given to conduct the study, or when the first participant is enrolled. Some sources used the time at which the last outcome data was collected as a criterion to determine the end of the trial. The International Committee of Medical Journal Editors stated that a study is still "ongoing" during the analysis process. Several sources use a vague definition or present no clear criteria for defining the start or end of a study. CONCLUSION: The concept of "ongoing clinical trials" lacks a transparent and homogeneous definition across relevant sources. A consensus on this concept is important to facilitate the evaluation of available evidence and conduct research synthesis. Further efforts are necessary to determine the best definition for the start and end of a clinical trial.

El índice de fragilidad y sus características en ensayos clínicos aleatorizados de diabetes mellitus / The Fragility Index and its characteristics in randomized clinical trials of diabetes mellitus

Resumen Introducción: para valorar la robustez de los resultados se ha propuesto una herramienta llamada el Índice de Fragilidad (IF), esta se define como el mínimo número de pacientes que se tienen que cambiar de "No eventos" a "Eventos" en el grupo de intervención para que un resultado estadísticamente significativo pase a no significativo, evidenciando que entre menor sea el IF, los resultados serán más frágiles. Diferentes autores han encontrado que la significancia de los resultados de muchos Ensayos Clínicos Controlados (ECA) dependen de pocos eventos. El objetivo del estudio fue evaluar el IF de los ECA en diabetes mellitus de cinco de las revistas médicas de mayor impacto a nivel mundial. Metodología: se realizó búsqueda electrónica en PubMed, para identificar ECA en Annals of Internal Medicine, BMJ, The Lancet, The New England Journal of Medicine y JAMA. Se revisaron los ECA en pacientes con diabetes mellitus o prediabetes y se calculó el IF para cada desenlace según el método descrito por Walsh et al, usando tablas de contingencia 2x2. Se planeó usar el coeficiente de correlación de Spearman para evaluar la correlación entre el IF y el tamaño de la muestra, el número de eventos, el valor de p y el tiempo de seguimiento. Se evaluó la significancia de todos los resultados con un valor de p<0,05. Resultados: la mediana del IF fue 11, y en tres estudios (7,3%) se encontró que el resultado no era estadísticamente significativo después de recalcular la p con el test exacto de Fisher. Se encontró relación directa leve entre el número de eventos y el IF (Rho= 0,343, p= 0,02) y correlación moderada inversa entre el valor de p y el IF (Rho= -0,632, p= 0,000). No se encontró correlación estadísticamente significativa entre el tamaño de muestra, tiempo de seguimiento y pérdidas con el IF. Conclusiones: en los ECA sobre diabetes, los resultados estadísticamente significativos dependen de pocos eventos, evidenciado por un bajo valor en el IF, los valores de esta medición están relacionados de forma directa con el número de eventos, e inversa con el valor de p.

Abstract Introduction: to evaluate the robustness of the results, a tool called the Fragility Index (FI) has been proposed, which is defined as the minimum number of patients that have to be changed from "No events" to "Events" in the intervention group to change a statistically significant to nonsignificant result. Showing that among a lower Fragility Index, the results of the trial will be less robust or more fragile. Different authors have found that the significance of the results of many controlled clinical trials (RCTs) depend on very few events. The objective of the study is to evaluate the FI of controlled clinical trials in diabetes mellitus in five of the general medical journals with the greatest impact factor worldwide. Methods: an electronic search was conducted in PubMed to identify randomized clinical trials in The Annals of Internal Medicine, BMJ, The Lancet, The New England Journal of Medicine and JAMA. Clinical trials were reviewed with diabetic or prediabetic patients and the FI was then calculated for each outcome according to the method described by Walsh et al, using 2x2 contingency tables. A priori was planned to use the Spearman correlation coefficient to evaluate the direct correlation between the Fragility Index and sample size, number of events, p-value and follow-up time. The significance of all the results was evaluated with a value of p <0.05. Results: the median Fragility Index was 11, and in three studies (7.3%) the result were not statistically significant after recalculating the p value with Fisher's exact test. A slight direct relationship between the number of events and the Fragility Index (Rho = 0.343, p = 0.02) was found and a moderate inverse correlation was observed between the p value and the FI (Rho = -0.632, p = 0.000 ). No statistically significant correlation was found between sample size, follow-up time and losses with the FI. Conclusions: in controlled clinical trials on diabetes, we found that the statistically significant results depend on a few events, evidenced by a low value in the Fragility Index. The values of this measurement are related to the number of events and negatively to the p value.

Dietary n-3 polyunsaturated fatty acids improve endothelial markers in metabolic syndrome: A systematic review

ABSTRACT Metabolic syndrome (MS) is a global health problem. Dietary factors, especially fatty acids, may affect MS pathology. However, the associations between omega-3 polyunsaturated fatty acids (n-3 PUFAs) and MS risk demonstrate inconsistent results. To clarify the relationship between dietary n-3 PUFA and endothelial function on MS, we carried out a systematic review. An electronic literature search based on controlled clinical trials (CCTs) between 2004 and 2020 was conducted. A total of 28 articles were included in the systematic review. Studies were analyzed according intervention type: dietary interventions (12 CCTs), dietary supplementation interventions (9 CCTs) and mixed interventions (7 CCTs). Studies with dietary interventions characterized by n-3 PUFAs increased by food source, such as Mediterranean and Nordic-style diets, reported significant reduction in systolic and diastolic blood pressure, and also in inflammatory endothelial biomarkers. The same effect was also observed in mixed interventions and in CCTs with n-3 PUFAs supplementation. Dietary interventions with n-3 PUFAs contributes to improved endothelial and cardiovascular health in SM and associated risk factors.

RESUMEN El síndrome metabólico (SM) es un problema sanitario global. Los factores dietéticos, especialmente los ácidos grasos, pueden afectar la patología del SM. Sin embargo, las asociaciones entre los ácidos grasos poliinsaturados omega-3 (AGPI n-3) y el riesgo de SM pueden ser inconsistentes. Para aclarar esta relación entre AGPI n-3 dietarios y la función endotelial en el SM, realizamos una revisión sistemática. Se realizó una búsqueda bibliográfica en fuentes electrónicas de ensayos clínicos controlados (ECC) entre 2004 y 2020. Se incluyeron un total de 28 artículos en la revisión. Los estudios fueron analizados según intervención realizada: intervención dietaria (12 ECC), intervención con suplementación dietética (9 ECC) e intervenciones mixtas (7 ECC). Los estudios que utilizaron intervenciones dietéticas con aumento de AGPI n-3 a través de alimentos, como las dietas mediterráneas y nórdicas, reportaron una reducción significativa de la presión arterial sistólica (PAS), diastólica (PAD) y de biomarcadores endoteliales inflamatorios. El mismo efecto se observó en intervenciones mixtas y ECC con suplementación de AGPI n-3. Las intervenciones dietéticas con AGPI n-3 contribuyen a mejorar la salud endotelial y cardiovascular y sus factores de riesgo asociados.

Quality assessment of reporting items in randomized controlled trials of Chinese herbal medicine as an adjunctive therapy for advanced non-small cell lung cancer / 国际生物医学工程杂志

Objective To evaluate the reporting item quality of randomized controlled trials of Chinese herbal medicine as an adjunctive therapy for advanced non-small cell lung cancer. Methods The terms including Chinese medicine, Chinese herbal medicine, randomized controlled trials, and non-small cell lung cancer were searched in Chinese and English databases by computer systems to collect relevant literatures. Based on the CONSORT 2010 (consolidated standards of reporting trials 2010), the reporting item quality of the abstracts and main text in eligible papers was evaluated. Results Ninety-five eligible studies were identified from 692 potential eligible articles. None reported all of abstract and main text items in CONSORT 2010. Only 4.12％could be identified as the randomized trial in the title. More than 40％of reports showed the scientific background or rationale in the abstract but not in the main text. Three (3.16％) eligible reports defined the primary or secondary outcome measures. None reported complete information of subjects throughout the clinical trial process. Results A total of 95 eligible papers were collected, of which 0 papers reported complete abstracts and text entries according to the CONSORT. The titles of 4.12％papers were identified as randomized trials. More than 40％of the papers only reported the study purpose or hypothesis in the abstract. 3.16％of the papers reported primary and secondary efficacy index entries, and 0 papers reported complete information of subjects from enrollment to included data analysis sets. Conclusion There is a serious problem of items shortage in the literatures of randomized controlled clinical trials on Chinese herbal medicine as an adjunctive therapy for advanced non-small cell lung cancer. The randomized controlled clinical trials of Chinese herbal medicine as an adjunctive therapy for advanced non-small cell lung cancer should be reported based on the CONSORT to improve the quality of trials.

Changes in dental esthetic perceptions of patients subjected to inoffice tooth bleaching / Mudanças nas percepções estéticas odontológicas de pacientes submetidos a clareamento dental de consultório

Objective: This study evaluated changes in the esthetic perceptions of patients subjected to inoffice tooth bleaching. Material and Methods: Fifty participants included in a clinical trial evaluating the in-office tooth bleaching answered two questionnaires about their dental esthetic perceptions. The participants answered the Orofacial Esthetic Scale (OES) questionnaire and the Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) before and after treatment. The average scores observed at baseline were compared with those recorded after tooth bleaching using the paired t-test or the Wilcoxon signed rank test (α = 0.05). Results: Improvement in tooth color (reduction of 5.1 shade guide units) had a positive impact on patients' perceptions. According to PIDAQ, tooth bleaching significantly increased the psychological impact and dental selfconfidence; and reduced esthetic concerns. The OES demonstrated improvements in participants' satisfaction for all questions, except for the one on "facial appearance". However, higher effect size was observed for the question related to tooth color, as expected. Conclusion: Tooth bleaching was associated with an overall improvement in dental esthetic perception, even when only tooth color was affected. (AU)

Objetivo: Este estudo avaliou mudanças nas percepções estéticas de pacientes submetidos a clareamento dental de consultório. Material e Métodos: Cinquenta pacientes incluídos em um ensaio clínico avaliando clareamento dental de consultório responderam a dois questionários sobre suas percepções estética odontológicas. Os participantes responderam ao questionário de escala estética orofacial (EEO) e o questionário de impacto psicossocial da estética orofacial (PIDAQ) antes e após o tratamento. As médias dos escores no início do tratamento foram comparados com aqueles mensurados após o clareamento usando o teste-T pareado ou de Wilcoxon (α = 0,05). Resultados: Melhora na cor dental (redução de 5,1 unidades da escala de cor) teve um impacto positivo nas percepções dos pacientes. De acordo com PIDAQ, o clareamento dental significativamente aumentou o impacto psicossocial e autoconfiança dental, e reduziu as preocupações estéticas. O EEO demonstrou melhora na satisfação dos participantes para todas as questões, exceto para a de "aparência facial". Entretanto, maior efeito foi observado para a questão relacionada à cor dos dentes, como esperado. Conclusão: O clareamento dental foi associado com um aumento geral na percepção estética odontológica, mesmo que apenas a cor dos dentes foi afetada. (AU)

Endorsing and enhancing ophthalmological clinical research in China / 中华实验眼科杂志

Although there are numerous case resource,there still exist a relatively long distance in clinical research in China in comparison with developing countries because of inadequate recognition and funding,which has greatly affected the development of standardization of clinical medical in China for the past few decades.With the deepening of recognition and increasing of special support to clinical medical research in China,the development based on clinic research will face new opportunities.As a result,it is necessary for ophthalmologists to explore clinical issues,leverage from the mega trend of clinical research and deliver high-quality results.To achieve this goal,ophthalmologists will have to constantly update their knowledge base,standardize clinical practice and improve diagnosis methods.So far,challenges persist in clinical research in ophthalmology as follows:It is difficult to get funding for clinical research project;It is difficult to get ethnics approval for clinical research project;The research design for forward-looking projects is yet to be standardized;Cross-disciplinary collaboration needs to be enhanced.This review was expected to inspire more attention from clinical research specialists and consequently more highquality clinical studies.

Consentimiento informado en investigación clínica: un proceso dinámico / Informed consent in clinical research: a dynamic process / Consentimento informado em pesquisa clínica: um processo dinâmico

Resumen En investigación clínica, el consentimiento informado es un documento legal y un mecanismo para respetar la dignidad y proteger los derechos y el bienestar de los sujetos participantes; debe incluir información sobre el propósito de la investigación, la justificación, los riesgos y beneficios, que le permitan a un sujeto decidir voluntariamente su participación. Como es deber del investigador velar por la protección de la vida, la salud, la dignidad, la integridad, el derecho a la autodeterminación, la intimidad y la confidencialidad de los sujetos que enrole en un estudio, tiene que establecer un diálogo permanente con estos para valorar los riesgos y la seguridad de la participación; esta condición se convierte en un proceso dinámico que no comienza ni termina únicamente con la firma del documento, y que no solamente debe trascender la legalidad, sino acercarse a la ética y la legitimidad.

Abstract In clinical research, informed consent is both a legal document and mechanism for respecting the dignity of participating subjects and protecting their rights and wellbeing. It should include information on the purpose of the research, its justification, and the risks and the benefits involved, so as to enable a subject to decide to participate voluntarily. Because it is the researcher's duty to ensure protection of the life, health, dignity, integrity, right to self-determination, privacy and confidentiality of the subjects who take part in a study, the researcher must establish a permanent dialogue with them to assess the risks and safety inherent in their participation. This condition becomes a dynamic process that neither begins nor ends when informed consent is signed. It goes beyond legality and becomes a question of ethics and legitimacy.

Resumo Em pesquisa clínica, o consentimento informado é um documento legal e um mecanismo para respeitar a dignidade e proteger os direitos e o bem-estar dos sujeitos participantes; deve incluir informação sobre o propósito da pesquisa, a justificativa, os riscos e benefícios, que permitam a um sujeito decidir voluntariamente sua participação. Como é dever do pesquisador velar pela proteção da vida, da saúde, da dignidade, da integridade, do direito à autodeterminação, da intimidade e da confidencialidade dos sujeitos que se envolvam num estudo, tem que estabelecer um diálogo permanente com estes para valorizar os riscos e a segurança da participação; essa condição torna-se um processo dinâmico que não começa nem termina unicamente com a assinatura do documento, e que não somente deve transcender a legalidade, mas, sim, se aproximar à ética e à legitimidade.

Estudios experimentales 1 Parte: el ensayo clínico / Experimental studies 1st Part: clinical trial

Los estudios experimentales, se caracterizan por la valoración del efecto de una o más intervenciones, habitualmente de forma comparativa con otra intervención, o un placebo; y el carácter prospectivo, de la recolección de los datos y el seguimiento de los grupos en estudio. Bajo la denominación de estudios experimentales, existe una diversidad de diseños, desde los ensayos clínicos (EC) y sus variantes, hasta los estudios cuasi-experimentales y los experientos naturales. El objetivo de este manuscrito, es reportar los principios básicos, características y estructura de un EC.

Experimental studies are characterized by the assessment of effect of one or more interventions, usually comparatively with other intervention, or placebo; and the prospective nature of data collection and follow-up. Included in the term experimental studies, there are a variety of designs: Clinical trials (CT) and its variants, quasi-experimental studies and natural experiments. The aim of this manuscript is to report basic principles, characteristics and CT structure.

Standard Retention Enema ofQu-Yu Tong-Bi Decoction on Inflammatory Mediators and Hemorrheology among Chronic Prostatitis Cases / 世界科学技术-中医药现代化

Through observation on changes of inflammatory mediators and hemorrheology among chronic prostatitis patients before and after treatment, this study was aimed to compare the therapeutic differences between the applications of standard retention enema ofQu-Yu Tong-Bi (QYTB) decoction andα-blockers combined with quinolones. During the same period, 164 patients of the Henan Province of Traditional Chinese Medicine Hospital were randomly divided into the observation group and control group, with 62 cases in each group. Retention enema of QYTB decoction was given in the observation group; andα-blockers combined with quinolones were used in the control group. The treatment course was one month. And the differences were compared. The results showed that the total effective rate of the observation group was 79.03% (49 cases); and that of the control group was 61.29%(39 cases). There was statistical significance between two groups (P < 0.05). There was statistical significance on TNF-α, IFN-γ and NIH-CPSI score comparison before and after treatment of two groups (P < 0.05). Compared to the control group, the posttreatment TNF-α, IFN-γ and NIH-CPSI score in the observation group had significant difference (P < 0.01). There were no significant differences on the whole blood viscosity (high shear), plasma viscosity and erythrocyte deposited test value contrast between pretreatment and posttreatment in the control group. There were significant differences on the whole blood viscosity (high shear) and plasma viscosity between pretreatment and posttreatment in the observation group (P < 0.05). However, there was no significant differences on erythrocyte deposited test value contrast. It was concluded that both methods had certain therapeutic effect in the treatment of chronic prostatitis. However, the effect of retention enema of QYTB decoction was better than the treatment of quinolones combined withα-blockers.

Additive Beneficial Effects of Valsartan Combined with Rosuvastatin in the Treatment of Hypercholesterolemic Hypertensive Patients

BACKGROUND AND OBJECTIVES: We compared the efficacy and safety of valsartan and rosuvastatin combination therapy with each treatment alone in hypercholesterolemic hypertensive patients. SUBJECTS AND METHODS: Patients who met inclusion criteria were randomized to receive 1 of the following 2-month drug regimens: valsartan 160 mg plus rosuvastatin 20 mg, valsartan 160 mg plus placebo, or rosuvastatin 20 mg plus placebo. The primary efficacy variables were change in sitting diastolic blood pressure (sitDBP) and sitting systolic blood pressure (sitSBP), and percentage change in low-density lipoprotein-cholesterol (LDL-C) in the combination, valsartan, and rosuvastatin groups. Adverse events (AEs) during the study were analyzed. RESULTS: A total of 354 patients were screened and 123 of them were finally randomized. Changes of sitDBP by least squares mean (LSM) were -11.1, -7.2, and -3.6 mm Hg, respectively, and was greater in the combination, as compared to both valsartan (p=0.02) and rosuvastatin (p<0.001). Changes of sitSBP by LSM were -13.2, -10.8, and -4.9 mm Hg, and was greater in the combination, as compared to rosuvastatin (p=0.006) and not valsartan (p=0.42). Percentage changes of LDL-C by LSM were -52, -4, and -47% in each group, and was greater in the combination, as compared to valsartan (p<0.001), similar to rosuvastatin (p=0.16). Most AEs were mild and resolved by the end of the study. CONCLUSION: Combination treatment with valsartan and rosuvastatin exhibited an additive blood pressure-lowering effect with acceptable tolerability, as compared to valsartan monotherapy. Its lipid lowering effect was similar to rosuvatatin monotherapy.

El placebo y el efecto placebo / Placebo and placebo effect

Se denomina placebo a una intervención diseñada para simular una terapia médica, que no tiene efectos específicos para la condición que está siendo aplicada. El efecto placebo es la modificación, muchas veces fisiológicamente demostrable, que se produce en el organismo como resultado del estímulo psicológico inducido por la administración de una sustancia inerte, de un fármaco o de un tratamiento. En este trabajo se abordan las definiciones de placebo, el origen de este término, los factores y mecanismos que intervienen en el efecto placebo, así como el uso de los placebos en la práctica médica y en la investigación clínica...

Placebo is an intervention designed to simulate a medical therapy, which has no specific effects for the condition that is being applied. The placebo effect is the change, often physiologically provable, which is produced in the body as a result of a psychological stimulus induced by the administration of an inert substance, a drug or a treatment. We hereby include the definition of placebo, the origin of this word, the factors and mechanisms involved in the placebo effect, and the use of placebos in medical practice and clinical research...

A prospective clinical controlled study of retroperitoneal laparoscopic nephroureterectomy combined with transurethral electric coagulation for upper urinary tract urothelial carcinoma / 中华泌尿外科杂志

Objective To evaluate the clinical efficacy of retroperitoneal laparoscopic nephroureterectomy (RLNU) combined with transurethral electric coagulation on upper urinary tract urothelial carcinoma (UUTUC).Methods Sixty UUTUC patients were enrolled from Jun.2012 to Apr.2013.The prospective clinical controlled analysis method was adopted in this study.All patients were divided into test group and control group according to the order of admission.Thirty cases (test group) underwent RLNU combined with electric coagulation,and 30 cases (control group) underwent RLNU combined with electric resection.The differences in operation time,blood loss,hospital stay and tumor recurrence rate between the 2 groups were compared.Results All the 60 operations for UUTUC were successful without conversion to open surgery.No intraoperative complications such as great vessels or surrounding organs damage occurred.There were 2 cases loss to follow-up in test group and 3 cases in control group.There were no significant differences in operation time,blood loss,follow-up time,tumor stage and tumor grade between the 2 groups.The hospital stay in the test group was shorter (5.5±2.0 d versus 7.1±2.2 d),the tumor recurrence rate was lower [4％ (1/28) versus 30％ (8/27)],and the differences were significant (P＜0.05).Conclusion Compared with RLNU combined with transurethral electric resection,RLNU combined with electric coagulation has advantages of shorter hospital stay and lower tumor recurrence rate.

Breast approach the effect of cavity mirror thyroid surgery and traditional surgery / 中国基层医药

Objective To explore the superiority and clinical efficacy of endoscopic thyroidectomy via breast approach in treatment of thyroid diseases .At the same time evaluation of endoscopic application value in the treatment of the disease .Methods Retrospective analysis of menstrual breast approach endoscopic 20 patients with benign thy-roid tumor patient clinical data ,and with the same period in 20 cases of thyroid cancer patients underwent convention-al operation of undergraduate clinical comparativeanalysis .Results Cavity mirrors the operative time , intraoperative blood loss,postoperative flow,length of hospital stay,postoperative complications and beauty satisfaction respectively (97.2 ±15.6)min,(17.8 ±8.6)mL,(30.2 ±11.8)mL,(4.7 ±0.9)d,15%,90%;the traditional group respec-tively(70.3 ±19.0)min,(24.6 ±15.2)mL,(35.6 ±19.6)mL,(5.2 ±0.6)d,10%,30%.Two groups of postoper-ative hospital stay,led traffic,beauty satisfaction difference had statistical significance (t=-2.203,-2.427,χ2 =54.432,all P<0.05).Conclusion Laparoscopic operation for treatment of thyroid disease has the advantages of small operation wound ,fewer complications ,and without scar on the neck ,which is an ideal minimally invasive opera-tion treatment .

Efeitos da terapia miofuncional orofacial sobre o ronco e a qualidade de sono em pacientes com ronco primário e apneia obstrutiva do sono leve a moderada / Effects of orofacial myofuncional therapy on snoring of patients with primary snoring and mild to moderate OSA

O ronco é gerado pela obstrução parcial e vibração da faringe durante o sono. Apesar de causar graves problemas sociais e poder indicar presença de apneia obstrutiva do sono (AOS), o ronco não é medido de forma objetiva. O tratamento do ronco primário ou associado a formas leves de AOS é controverso. A Terapia Miofuncional Orofacial consiste em exercícios isotônicos e isométricos para língua e palato mole desenvolvidos para o tratamento da AOS moderada. No entanto, os efeitos da Terapia Miofuncional Orofacial sobre o ronco não foram medidos de forma objetiva. OBJETIVOS: Primário: determinar a eficiência da Terapia Miofuncional Orofacial em reduzir o ronco de pacientes com ronco primário, AOS leve e moderada. Secundários: desenvolver uma metodologia de quantificação objetiva do ronco; avaliar a relação das características do ronco com a gravidade da AOS; avaliar o efeito da terapia miofuncional orofacial sobre a percepção do ronco e sobre a qualidade de sono do parceiro de quarto. MÉTODOS: Foram incluídos pacientes de ambos os sexos, com idade entre 20 e 65 anos com diagnóstico polissonográfico de ronco primário, AOS leve ou AOS moderada. Os pacientes foram randomizados por 3 meses para tratamento com Terapia Miofuncional Orofacial ou Controle (uso de dilatador nasal e exercícios respiratórios). Os pacientes foram avaliados no início e final do estudo por questionários de grau de sonolência (Epworth), qualidade de sono (Pittsburgh), percepção do próprio ronco e avaliação de motricidade orofacial, bem como polissonografia completa com registro contínuo do ronco. Os parceiros de quarto avaliaram o ronco do parceiro incluído no estudo e a sua própria qualidade do sono (Pittsburgh). RESULTADOS: Foram incluídos 39 pacientes com idade (média ± desvio padrão) = 46 ± 13 anos e índice de massa corpórea (IMC) = 28,2 ± 3,1 Kg/m2, Índice de apneia e hipopneia (IAH) = 15,3 ± 9,3 eventos/hora, sendo 6 pacientes com ronco primário, 17 com AOS leve e 16 com AOS moderada...

Snoring is generated by pharyngeal obstruction and vibration during sleep. Snoring is extremely common and may cause severe social problems and may indicate obstructive sleep apnea (OSA). However, there are no standardized methods for measuring snoring and the treatment of primary snoring or snoring associated with mild forms of OSA is controversial. Orofacial Myofunctional Therapy consists of isometric and isotonic exercises directed to tongue and soft palate for the treatment of moderated OSA. However, the effects of Orofacial Myofunctional Therapy on snoring were not objectively measured. OBJECTIVES: Primary: to determine the efficiency of Orofacial Myofunctional Therapy in reducing snoring of patients with primary snoring, mild and moderated OSA. Secondary: to develop a methodology to objectively quantify snoring; to assess the relation of snoring characteristics with OSA severity; to assess the effect of Orofacial Myofunctional Therapy upon the perception of snoring and sleep quality of the bed partner. METHODS: We included patients of both genders aged between 20 to 65 years old with polissomnographyc diagnoses of primary snoring, mild or moderated OSA. Patients were randomized for treatment with Orofacial Myofunctional Therapy or Control (use of nasal dilator strips and respiratory exercises) for 3 months. All patients were evaluated at the beginning and end of the study by questionnaires (Epworth, Pittsburgh), orofacial motricity assessment and complete polysomnography with the register of snoring. Bed partners assessed snoring and their own sleep quality (Pittsburgh). RESULTS: Thirty nine patients aged (mean ± standard deviation) =46 ± 13 yeas old and body mass index (BMI) (mean ± standard deviation) = 28,2 ± 3,1 Kg/m2, apnea hypopnea index (AHI)= 15,3 ± 9,3 events/hour, being 6 patients with primary snoring, 17 with mild OSA and 16 with moderated OSA completed the study. No significant change occurred in the Control Group in all variables...

A Meta-Analysis Comparing Open-Label versus Placebo- Controlled Clinical Trials for Aripiprazole Augmentation in the Treatment of Major Depressive Disorder: Lessons and Promises

OBJECTIVE: The present study is to provide whether open-label studies (OLS) may properly foresee the efficacy of randomized, placebo-controlled trials (RCTs) using OLSs and RCTs data for aripiprazole in the treatment of MDD, with the use of meta-analysis approach. METHODS: A search of the studies used the key terms "depression and aripiprazole" from the databases of PubMed/PsychInfo from Jan 2005 through July 2013. The data were selected and verified for publication in English-based peer-reviewed journals based on rigorous inclusion criteria. Extracted data were delivered into and run by the Comprehensive Meta Analysis program v2. RESULTS: The pooled SMDs for the primary efficacy measure was statistically significant, pointing out the significant reduction of depressive symptoms after aripiprazole augmentation (AA) to current antidepressant treatment in OLSs (pooled SMD=-2.114, z=-9.625, p<0.001); similar results were also found in RCTs (pooled SMD=-2.202, z=-6.862, p<0.001). The meta-regression analysis revealed no influence of the study design for treatment outcome. CONCLUSION: There was no difference in the treatment effects of aripiprazole as an augmentation therapy in both OLSs and RCTs, indicating that open-label design may be a potentially useful predictor for treatment outcomes of controlled-clinical trials. The proper conduction of OLSs may provide informative, useful and preliminary clinical data and factors to be involved in controlled-clinical trials, by which we may have better understanding on the role of AA (e.g., dosing issues, proper duration of treatment, specific population for AA) implicated in the treatment of MDD in clinical practice.

Consideraciones metodológicas y éticas para la conducción de ensayos clínicos controlados aleatorizados (ECCA) sobre intervenciones para las adicciones / Methodological and ethical aspects in conducting randomized controlled clinical trials (RCT) for addictive disorder's interventions

According to epidemiologic reports, the harmful use of alcohol and illicit drugs has increased among the Mexican population. This use is associated to several risks and issues that affect public health and the public well-being of the country. In this article it is acknowledged the need for development of treatment models and interventions whose therapeutic value is demonstrated by scientific evidence, that respond to the attention needs of the population affected by substance use in our country and that can be generalized in community clinical practice. In clinical research, randomized controlled clinical trials (RCT's) are the "gold standard" to demonstrate the effect of a therapeutic intervention. A randomized controlled clinical trial is a prospective study in which the effect, value and safety of one or various experimental interventions are tested against a "control" intervention in human subjects. Acknowledging that in Mexico there is a lack of research on addiction treatment that is compliant with all the requirements to be considered as an RCT, this article presents some methodological and ethical considerations that are neccesary for their design and conduction. These considerations include from the establishment of a relevant research question and objectives, adequate study design, development of strategies for data management, statistical analysis, monitoring of interventions, safety monitoring and research quality assurance and protection of human subjects.

Según reportes epidemiológicos, el consumo nocivo de alcohol y drogas ilegales dentro de la población mexicana ha ido en aumento, lo que se asocia a varios riesgos o problemáticas que afectan la salud y bienestar públicos del país. Se reconoce la necesidad de desarrollar modelos de tratamiento e intervenciones cuyo valor terapéutico esté respaldado por la evidencia científica, que respondan a las necesidades de atención de la población afectada por el consumo de sustancias en nuestro país y que puedan generalizarse en la práctica clínica comunitaria. Dentro de la investigación clínica, el "estándar de oro" para demostrar el efecto de una intervención terapéutica son los ensayos clínicos controlados aleatorizados (ECCA). Un ECCA es un estudio prospectivo en el cual se prueba el efecto, valor y seguridad de una o varias intervenciones experimentales contra una intervención "control" en sujetos humanos. Reconociendo que en México hay una falta de investigaciones sobre tratamientos para las adicciones que cumplan con todos los requisitos para ser considerados ECCA, en este artículo se presentan distintas consideraciones metodológicas y éticas que deben tomarse en cuenta para su diseño y conducción en la materia; abarcando aspectos que parten desde el establecimiento de una pregunta y objetivos relevantes hasta el diseño adecuado del estudio y el desarrollo de estrategias para la administración de datos, análisis estadístico, monitoreo de las intervenciones, monitoreo de seguridad y aseguramiento de la calidad de la investigación y protección de los sujetos humanos que participan.

Outcomes of open and minimally invasive esophagectomy for esophageal cancer / 中华消化内镜杂志

Objective To compare the safety,feasibility,and long-term outcomes between combined thoracoscopic and laparoscopic esophagectomy (TLE) and open three-field esophagectomy (OE) for esophageal cancer.Methods The data of 183 patients with esophageal cancer who accepted TLE (n =94) or OE (n =89) from February 2009 to December 2011 were retrospectively collected and compared.Results Demographics,pathologic data in each cohort were almost identical.No significant differences were observed in operative time,the number of lymph node harvested,rates of anastomotic leak,thoracic abscess,chyle chest,re-operation,vocal cord paralysis,gastric emptying dysfunction and morbidity.A significant difference was observed in blood loss (86.6 ±38.3 ml in TLE group vs.217.4 ±87.2 ml in OE group,P=0.000),rate of transfusion (1.1％ vs.6.7％,P =0.045),hospital stay (13.9 ±7.5 d vs.17.1 ±10.2 d,P =0.017),rate of overall surgical complications (23.4％ vs.38.2％,P =0.030),rate of pulmonary complications (9.6％ vs.27.0％,P =0.002) and rate of arythmia (4.1％ vs.12.4％,P =0.046).Median follow-up time was 28.0 ±2.0 months (95％ CI:24.2-31.8).No difference between the two groups concerning survival was observed (P =0.954).Conclusion The TLE for esophageal cancer is safe and feasible.Although it cannot improve the survival of long-term,it is worth spreading in intraoperative and postoperative advantages compared with OE group.

Understanding noninferiority trials / 소아과

Noninferiority trials test whether a new experimental treatment is not unacceptably less efficacious than an active control treatment already in use. With continuous improvements in health technologies, standard care, and clinical outcomes, the incremental benefits of newly developed treatments may be only marginal over existing treatments. Sometimes assigning patients to a placebo is unethical. In such circumstances, there has been increasing emphasis on the use of noninferiority trial designs. Noninferiority trials are more complex to design, conduct, and interpret than typical superiority trials. This paper reviews the concept of noninferiority trials and discusses some important issues related to them.

Qingpeng ointment in the treatment of eczema: a multi-center, randomized, double-blind, placebo controlled study / 中华皮肤科杂志

Objective To evaluate the efficacy and safety of Qingpeng ointment in the treatment of eczema.Methods A multi-center,randomized,double-blind and placebo-controlled clinical trial was conducted.A total of 246 patients with eczema were randomly assigned with a ratio of 2∶1 to the treatment group and control group to topically apply Qingpeng ointment and placebo respectively twice daily for 3 weeks.Total symptom scores were calculated for the patients at the baseline,on week 1,2 and 3 during the treatment according to the individual scores for pruritus,lesions including erythema,papules,papulovesicles or vesicles,desquamation,crusting,infiltration and lichenification.The occurrence of adverse events was recorded.Results Totally,228 patients completed the trial,including 154 patients in the treatment group and 74 patients in the control group.After 3 weeks of treatment,a statistical difference was observed in the response rate (85.71％ vs.41.89％,Z=47.16,P＜ 0.01) and cure rate (31.82％ vs.12.16％,Z=12.30,P＜ 0.01) between the treatment and control group.There was no significant difference in the incidence of adverse events between the two groups (2.48％ vs.2.56％,x2 =0,P ＞ 0.05).Conclusion Qingpeng ointment displays a promising efficacy for the treatment of mild to moderate eczema with a rapid onset and high safety.

A multi-center, randomized, controlled, double blind and double dummy clinical trial of antofloxacin hydrochloride tablet versus levofloxacin tablet for the treatment of acute bacterial infections / 中华内科杂志

Objective To evaluate the clinical efficacy and safety of antofloxacin hydrochloride tablet for the treatment of acute bacterial infections. Methods A multi-center randomized control, double blind and double dummy clinical trial was conducted; levofloxacin tablet was chosed as controlled drug. The duration of treatment was 7-14 days in both groups. Results A total of 719 patients were enrolled in the study, in which 359 patients treated with antofloxacin and 360 patients treated with levofloxacin were included. Three hundred and thirty and 337 patients completed the study and met with all the criteria for perprotocol analysis, respectively. By the end of chemotherapy, the cured rates in per protocol set (PPS)population were 79.7% and 77.4%, the effective rates were 95.2% and 96. 7%, and the bacterial clearance were 96. 7% and 97. 5% for the treating and control group, respectively. The clinical and bacterial efficacy of antofloxacin and levofloxacin was comparable by the analysis of infectious sites. Three hundred and fifty-seven and 356 patients in antofloxacin and levofloxacin groups were evaluated the safety.The drug adverse events occurred both in 10. 1%, and drug adverse reactions accurred in 7. 8% and 7.9%patients in the two groups. The most common drug adverse reactions were mild gastroenteric symptoms. No QTc prologation was detected in all the patients. One patient in each group had mild blood glucose increase at the end of therapy, but the glucose returned to normal level without any intervention. No statistic significant difference between the two groups in clinical efficacy and safety was detected (P＞0.05).Conclusions Antofloxacin hydrochloride tablet was effective and safe for the treatment of acute bacterial infections.