Methods for development of a core outcome set for clinical trials integrating traditional Chinese medicine and Western medicine / 中西医结合学报

Clinical trial outcome reporting differs between studies integrating traditional Chinese medicine (TCM) and Western medicine, so that some clinical trials are not eligible for inclusion in a systematic review. The excluded studies are therefore less widely disseminated, and even valid studies are less likely to yield impact. This problem may be addressed by developing core outcome sets (COSs) for integrative medicine in specific healthcare areas. The first stage of development is to define the scope of the COS for integrative medicine, the second stage is to establish the need for such a COS, and the third stage is to develop a protocol and register the COS. The final stage involves three steps: (i) development of a comprehensive list of outcomes (including efficacy outcomes and safety outcomes and TCM syndromes) using systematic review, qualitative or cross-sectional research, and reviews of package inserts and medical records; (ii) merging and grouping of outcomes within domains; (iii) conducting two rounds of Delphi survey and consensus meetings with a range of stakeholders. The final COS will include a general COS and core TCM syndrome- set. Development of COSs for clinical trials of integrative medicine may help to standardize outcome reporting and reduce publication bias in the future.

Study on endpoint determination method of tablet coating based on 3σ criteria and logic regression / 中国中药杂志

This paper explores the statistical distribution characteristics of coating film thickness, so as to present a new method for determining coating endpoint based on 3σ criterion and logic regression. Firstly, the spectrum and thickness of 4 batch samples were collected. Secondly, the spectral range of normal products was obtained by 3σ criterion, with the spectral feature NI as the number of test spectrum in the above range. Then, the model based on 3σ criterion and logic regression was built according to the best condition in K-fold cross-validation and the determined threshold of qualified rate in the coating endpoint. Finally, the qualified rate of test set samples at different time points was calculated by the above model, and the above change trend and the threshold value were combined to determine the coating endpoint. The results of KS analysis showed the distribution of thickness of the qualified products followed the normal distribution(P=0.081>0.05). The accuracy of the coating endpoint determination was as high as 100% by the model based on 3σ criterion and logic regression when the determined threshold of qualified rate was 90%. Therefore, the 3σ criterion was feasible to the research of coating eligibility. This paper reveals certain random phenomena in the coating process, and the method features a high accuracy, quick analysis and a good interpretability, which provides a reference for online detection and qualify evaluation in future.

Analysis of RCT outcome indicators of traditional Chinese medicine for essential hypertension in recent two years / 中国中药杂志

To find the status of outcome indicators reported in published randomized controlled trial(RCT) of traditional Chinese medicine(TCM) for essential hypertension in the past two years, we searched for relevant information from four Chinese databases, three English databases and two clinical trial registries in this study, from January 2018 to September 2019. The outcome indicators of RCT were extracted and categorized from trials and the risk of bias was assessed by ROB tools from the Cochrane Collaboration. A total of 125 RCTs and 15 RCT protocols were finally included after study screening. The results showed that the RCT outcomes mainly included efficacy and safety outcomes. Efficacy indicators mainly included blood pressure measurement, quality of life assessment, blood biochemical indicators, urine analysis, arterial ultrasound, vascular endothelial function indicators, hematocrit, hemorheology indicators and other indicators. The safety indicators mainly included general physical examination items, heart, liver and kidney function tests, blood, urine, and stool routine examinations as well as adverse drug reactions/events. The current RCTs cannot distinguish primary and secondary outcomes, and the RCT protocols didn't report efficacy criteria clearly. They both didn't report health economic indicators and the methodological qualities were relatively low. In view of the current status on outcome indicators reported in TCM RCTs, constructing a core outcome set of TCM for essential hypertension and improving the methodology quality of RCTs will help to accurately reflect the actual efficacy of TCM intervention.

The TyG index cutoff point and its association with body adiposity and lifestyle in children / Ponto de corte do índice TyG e sua associação com a adiposidade corporal e estilo de vida em crianças

Abstract Objective: To investigate the factors associated with insulin resistance in children aged 4-7 years, and to identify the cutoff point of the triglyceride-glucose index for the prediction of insulin resistance in this population. Methods: A cross-sectional study was conducted with 403 children from a retrospective cohort. Insulin resistance was also evaluated in a sub-sample using the HOMA index. Four indicators of body adiposity were assessed: body mass index, waist-to-height ratio, and the percentages of total and central body fat. Food habits were evaluated by the identification of dietary patterns, using principal component analysis. Information was also collected on lifestyle, socioeconomic status, and breastfeeding time. Results: The median index observed in the sample was 7.77, which did not differ between the genders. The shorter the time spent in active activities, the higher the triglyceride-glucose value; and increase in the values of body adiposity indicators was positively associated with triglyceride-glucose. The cutoff point with the best balance between sensitivity and specificity values was 7.88 (AUC = 0.63, 95% CI: 0.51-0.74). Conclusion: The present study identified that total and central body adiposity and shorter time spent in lively activities was positively associated with insulin resistance, evaluated through the triglyceride-glucose index. The cutoff point of 7.88 may be used in this population for insulin resistance risk screening, but caution is required when using it in other populations.

Resumo Objetivo: Investigar os fatores associados à resistência à insulina em crianças de 4 a 7 anos, e identificar o ponto de corte do índice triglicerídeos-glicemia (TyG) para predição da RI nessa população. Métodos: Estudo transversal, com 403 crianças pertencentes a uma coorte retrospectiva. A resistência à insulina foi avaliada pelo índice triglicerídeos-glicemia e também pelo índice HOMA, este em uma subamostra. Avaliou-se quatro indicadores de adiposidade corporal: o índice de massa corporal, a relação cintura-estatura e os percentuais de gordura corporal total e central. O hábito alimentar foi avaliado pela identificação dos padrões alimentares, utilizando-se a análise de componentes principais. Foram coletadas também informações sobre estilo de vida, condição socioeconômica e tempo de aleitamento materno. Resultados: A mediana observada do índice triglicerídeos-glicemia na amostra foi de 7,77 e não diferiu entre os sexos. Quanto menor o tempo diário em atividades ativas, maior o valor de triglicerídeos-glicemia; e o aumento nos valores dos indicadores de adiposidade corporal associou-se positivamente com o triglicerídeos-glicemia. O ponto de corte com melhor equilíbrio entre os valores de sensibilidade e especificidade foi o de 7,88 (AUC = 0,63; IC 95% 0,51 - 0,74). Conclusão: O presente estudo identificou que a adiposidade corporal total e central e o menor tempo diário em atividades ativas associou-se positivamente com a resistência à insulina, avaliada pelo índice triglicerídeos-glicemia. O ponto de corte de 7,88 pode ser utilizado nessa população para triagem do risco de resistência à insulina, mas é necessário cautela na sua utilização em outras populações.

Efectividad del programa de control de tuberculosis en las entidades estatales. Departamento de Córdoba, Colombia 2015 / Effectiveness of the tuberculosis control program in state entities. Department of Cordoba, Colombia 2015

Objetivo. Medir la efectividad del Programa de Control de Tuberculosis en las diferentes entidades estatales del departamento de Córdoba. Materiales y métodos.Estudio descriptivo, retrospectivo, utilizando datos de las fuentes secundarias relacionados con aspectos sociales y demográficos, epidemiológicos, clínicos, de laboratorio, tratamiento y evolución y diagnostico final, analizando el comportamiento de la atención y el grado de adherencia terapéutica de la Tuberculosis. Resultados. En 2015 la prevalencia de Tuberculosis fue de 17 casos por 100000 habitantes; en cuatro de las seis zonas geográficas sujetos de este estudio las prevalencias superaban la media nacional. Las regiones con prevalencias más altas corresponden al Alto Sinú y Alto San Jorge y las más bajas las zonas costaneras y de sabanas. El 79.2% de los casos fueron incidentes, 18.8% recaídas y 2.1% abandono del tratamiento. En 68.7% de las historias revisadas no se encontró evidencia de actividades realizadas a contactos. Los pacientes acuden a la consulta inicial tras un periodo entre 31 a 60 días de síntomas; 12.5% fueron diagnosticados después de 15 días de la consulta inicial, en 14.6% de los casos el tratamiento se inició después de 16 días de la consulta inicial. 41.7% culminaron con baciloscopia negativa, a 37.5% de quienes terminaron su tratamiento no se les realizó Baciloscopia al final, 2.1% de los casos fracasó y 14.6% falleció. Conclusiones. Existen factores de gestión del programa que se manifiestan en demoras para identificar los casos probables e iniciar tratamiento oportunamente

Objective. To measure the effectiveness of the Tuberculosis Control Program in the different entities of the department of Córdoba. Materials and methods. This is a descriptive and retrospective study. The researchers used data from the secondary sources relating to social, demographic, epidemiological, clinical, laboratory, treatment, final evolution, and diagnosis to analyze the behavior of the attention and the degree of therapeutic adherence to tuberculosis. Results. In 2015, the prevalence of disease was 17 cases per 1000 inhabitants. In four of the six geographic target areas, the prevalence exceeded the national average. The regions with the highest incidence were the Alto Sinú and Alto San Jorge. The lowest was the coastal and savanna areas. 79.2% of the cases were incidents, 18.8%, relapses, and 2.1%, treatment withdrawal. In 68.7% of the reviewed histories of the cases attended in the public network, no institutional evidence of activities performed to contacts was found. Patients go for the initial consultation after a period between 31 to 60 days of symptoms. 12.5% of the cases were diagnosed after 15 days of the initial consultation. In 14.6% of the cases, the tuberculosis treatment started after 16 days of the patient's initial meeting. In 41.7%, negative sputum smear microscopy was achieved. 37.5% of those who completed their treatment but did not undergo BK at the end. 2.1% of the cases failed, and 14.6% died. The process ended with positive bacilloscopy. Conclusions. There are program management factors that delay in identifying the probable instances and initiate treatment promptly.

Guideline Recommendation for Endpoints Used in Clinical Trials for Functional Dyspepsia / 대한소화기학회지

Functional dyspepsia is a disease, in which there is no organic lesion but chronic and repetitive postprandial fullness, early satiation, epigastric pain, and epigastric burning. Functional dyspepsia is not life-threatening but its symptoms are relapsing and remitting and persist over a lifetime, limiting the social life and reducing the quality of life. Therefore, the treatment for acute relapsing period may help improve the short-term symptoms. Continuous medication may be needed to improve the long-term symptoms. Research designs to demonstrate the short-term efficacy of therapeutic agents may differ from clinical trials to demonstrate long-term efficacy. There are many difficulties in clinical trial design, implementation, and screening because there are no international standards of clinical trials for functional dyspepsia. The purpose of this guideline recommendation is to develop a standard for clinical trials, such as clinical trial subjects and evaluation methods, in the development of therapeutic agents for functional dyspepsia. The ultimate aim is to enhance the safety and efficacy of therapeutic agents for functional dyspepsia and promote the development of new therapeutic agents.

Comparison of Aspirin and Naoxintong Capsule () with Adjusted-Dose Warfarin in Elderly Patients with High-Risk of Non-Valvular Atrial Fibrillation and Genetic Variants of Vitamin K Epoxide Reductase / 中国结合医学杂志

<p><b>OBJECTIVE</b>To compared the therapeutic effect of a Chinese patent medicine Naoxintong Capsule (, NXT) and aspirin with adjusted-dose warfarin in Chinese elderly patients (over 65 years) with nonvalvular atrial fibrillation (NVAF) and genetic variants of vitamin K epoxide reductase (VKORC1), who are at high-risk of thromboembolism.</p><p><b>METHODS</b>A total of 151 patients, with NVAF and AA genotype of VKORC1-1639 (a sensitive genotype to warfarin) and a CHADS-VASc clinical risk score of 2 or above, were chosen for this study. Patients were randomized into two groups and orally treated with a combination of aspirin (100 mg/day) and NXT (1.6 g thrice a day) or adjusted-dose warfarin [international normalized ratio 2.0-3.0). The primary end points including ischemic stroke and death as well as the secondary end points including hemorrhage events were followed up for at least 1 year.</p><p><b>RESULTS</b>Baseline clinical data and the rates of primary end points were similar between groups. However, the rate of serious bleeding (secondary event) in the combination therapy group was lower than that in the adjusted-dose warfarin group (0% vs. 7.9%, odds ratio: 0.921, 95% confidence interval: 0.862-0.984, P=0.028).</p><p><b>CONCLUSIONS</b>Aspirin combined with NXT and warfarin displayed comparable rates of primary end point including ischemic stroke and all-cause death during the 1-year follow-up. However, as compared with warfarin, the combination therapy reduced the rate of serious bleeding. Therefore, aspirin combined with NXT might provide an alternative pharmacotherapy in preventing ischemic stroke for elderly patients with NAVF who cannot tolerate warfarin. (No. ChiCTR-TRC-13003596).</p>

Is There a Sex-Related Difference in the Obesity Paradox in Systolic Heart Failure? Sex-Related Difference in the Obesity Paradox

PURPOSE: Obesity is often associated with better clinical outcomes in heart failure (HF). This so-called obesity paradox remains controversial. The aim of present study was to investigate the prognostic value of obesity in patients hospitalized for systolic HF. MATERIALS AND METHODS: We performed a pooled analysis of data from two multicenter, observational HF studies. Patients hospitalized for systolic HF were eligible for the present study. We divided the subjects into two groups, a normal body mass index (BMI) group and a high BMI group. Study endpoints included all-cause mortality and any re-hospitalization within 1 year. RESULTS: We enrolled 3145 patients (male, 1824; female, 1321). The high BMI group was significantly associated with lower 1-year mortality rate [odds ratio (OR), 0.543; 95% confidence interval (CI), 0.355−0.832] after adjusting for age, hypertension, diabetes, ischemic HF, previous myocardial infarction, serum creatinine level, anemia, and ejection fraction in men. After adjustment for clinical characteristics, high BMI was not significantly associated with 1-year mortality (OR, 0.739; 95% CI, 0.450−1.216) or 1-year re-hospitalization (OR, 0.958; 95% CI, 0.696−1.319) in women. CONCLUSION: In pooled analysis of data from two Korean HF registries, the high BMI group was independently associated with lower 1-year mortality rate from systolic HF, especially in men.

A fatal and metabolic experimental hemorrhagic shock in immature swine

Abstract Purpose: To use blood lactate (BL) as an end-point metabolic marker for the begin resuscitation of volume replacement in experimental hemorrhagic shock. Methods: Group I (n=7) was not bled (Control). Animals in Group II (n=7) were bled to a MAP of 30mmHg in thirty minutes. Hemodynamic and metabolic data were recorded at Baseline, at 30, 60 and 120 minutes after Baseline. The animals were intubated in spontaneous breathing (FIO2=0.21) with halothane. Results: Group I all survived. In Group II all died; no mortality occurred before a BL<10mM/L. Beyond the end-point all animals exhibited severe acidemia, hyperventilation and clinical signs of shock. Without treatment all animals died within 70.43±24.51 min of hypotension shortly after reaching an average level of BL 17.01±3.20mM/L. Conclusions: Swine's breathing room air spontaneously in hemorrhagic shock not treated a blood lactate over 10mM/L results fatal. The predictable outcome of this shock model is expected to produce consistent information based on possible different metabolic and hemodynamic patterns as far as the type of fluid and the timing of resuscitation in near fatal hemorrhagic shock.

Evaluation of the potential inhibitory activity of a combination of L. acidophilus, L. rhamnosus and L. sporogenes on Helicobacter pylori: A randomized double-blind placebo-controlled clinical trial / 中国结合医学杂志

<p><b>OBJECTIVES</b>To investigate whether three strains of probiotics, L. acidophilus, L. rhamnosus, and L. sporogenes, had signifificant inhibitive effects on Helicobacter pylori (H. pylori).</p><p><b>METHODS</b>This is a 4-week, randomly assigned, parallel-group, doubled-blind, and placebo-controlled study. Fifty patients with a positive H. pylori infection urea breath test (△UBT) result > 10% and without ulcer symptoms were randomized into a treatment group and a placebo group by a computer generated allocation sheet with 1:1. These subjects took one capsule of probiotics or placebo twice daily. The primary measurement was the change in △UBT values.</p><p><b>RESULTS</b>The △UBT values during the 4-week treatment period and the 2-week follow-up period were not signifificantly different between the treatment group and the placebo group, indicating that the inhibitive effects on H. pylori were comparable between both groups. The monocyte count (%) was 5.77±1.11 in the treatment group versus 5.09±1.12 in the placebo group (P=0.044), and the basophile count was 0.55±0.32 in the treatment group versus 0.36±0.23 in the placebo group (P=0.024) at week 2 of the treatment period, both of which reached statistical signifificance. The monocyte count was 5.75±1.26 in the treatment group and 4.72±0.99 in the placebo group at the end of the follow-up period (P=0.003).</p><p><b>CONCLUSION</b>There was no signifificant inhibitive effects of the three probiotic strains (L. acidophilus, L. rhamnosus, and L. sporogenes) on H. pylori. Probiotics can not play the same role as antibiotics in the eradication of H. pylori, the role of probiotics is likely to be important as adjuvant to the triple or quadruple therapy for H. pylori, especially in resistance cases.</p>

Acute Heart Failure Registry: Risk Assessment Model in Decompensated Heart Failure / Registro de Insuficiência Cardíaca Aguda: Modelo de Avaliação de Risco na Insuficiência Cardíaca Descompensada

Abstract Background: Heart failure (HF) is a highly prevalent syndrome. Although the long-term prognostic factors have been identified in chronic HF, this information is scarcer with respect to patients with acute HF. despite available data in the literature on long-term prognostic factors in chronic HF, data on acute HF patients are more scarce. Objectives: To develop a predictor of unfavorable prognostic events in patients hospitalized for acute HF syndromes, and to characterize a group at higher risk regarding their clinical characteristics, treatment and outcomes. Methods: cohort study of 600 patients admitted for acute HF, defined according to the European Society of Cardiology criteria. Primary endpoint for score derivation was defined as all-cause mortality and / or rehospitalization for HF at 12 months. For score validation, the following endpoints were used: all-cause mortality and / or readmission for HF at 6, 12 and 24 months. The exclusion criteria were: high output HF; patients with acute myocardial infraction, acute myocarditis, infectious endocarditis, pulmonary infection, pulmonary artery hypertension and severe mitral stenosis. Results: 505 patients were included, and prognostic predicting factors at 12 months were identified. One or two points were assigned according to the odds ratio (OR) obtained (p < 0.05). After the total score value was determined, a 4-point cut-off was determined for each ROC curve at 12 months. Two groups were formed according to the number of points, group A < 4 points, and group B = 4 points. Group B was composed of older patients, with higher number of comorbidities and predictors of the combined endpoint at 6, 12 and 24 months, as linearly represented in the survival curves (Log rank). Conclusions: This risk score enabled the identification of a group with worse prognosis at 12 months.

Resumo Fundamento: A insuficiência cardíaca (IC) é uma síndrome de elevada prevalência. Apesar de existir na literatura informação relativa aos fatores prognósticos a longo prazo na IC crônica, esta é mais escassa no que diz respeito aos pacientes com IC aguda. Objetivos: Desenvolver um score preditor de eventos prognósticos desfavoráveis em doentes admitidos com síndromes de IC aguda e caracterizar um grupo de maior risco quanto às suas características clínicas, terapêutica e resultados. Métodos: Estudo de coorte de 600 doentes internados com IC aguda, definida de acordo com os critérios da Sociedade Europeia de Cardiologia. O endpoint primário para a derivação do score foi definido como mortalidade de qualquer causa e/ou reinternação por IC aos 12 meses. Para a validação do score, foram utilizados como endpoints: mortalidade de qualquer causa e/ou reinternação por IC aos 6, 12 e 24 meses. Os critérios de exclusão foram: IC de alto débito, pacientes com infarto agudo do miocárdio, miocardite aguda, endocardite infeciosa, infeção pulmonar, hipertensão arterial pulmonar e estenose mitral grave. Resultados: Foram incluídos 505 doentes e identificados preditores prognósticos aos 12 meses. Atribuíram-se 1 ou 2 pontos (p.) de acordo com os odds ratio (OR) obtidos (p < 0,05). Após a determinação do valor de score total, foi estabelecido um cut-off de 4 pontos por curva ROC. Constituíram-se 2 grupos de acordo com a pontuação, grupo A < 4 p. versus grupo B = 4 p. O grupo B era constituído por idosos, com maior número de comorbidades e preditor de endpoint combinado aos 6, 12 e 24 meses traduzido linearmente nas curvas de sobrevida (Log rank). Conclusões: Este score de risco permitiu identificar um grupo com pior prognóstico aos 12 meses.

A prospective, randomized, blinded-endpoint, controlled study - continuous epidural infusion versus programmed intermittent epidural bolus in labor analgesia / Estudo prospectivo, randômico, controlado e de avaliação cega do desfecho - infusão peridural contínua versus bolus epidural intermitente programado em analgesia de parto

Abstract Background: There is evidence that administration of a programmed intermittent epidural bolus (PIEB) compared to continuous epidural infusion (CEI) leads to greater analgesia efficacy and maternal satisfaction with decreased anesthetic interventions. Methods: In this study, 166 women with viable pregnancies were included. After an epidural loading dose of 10 mL with Ropivacaine 0.16% plus Sufentanil 10 µg, parturient were randomly assigned to one of three regimens: A - Ropivacaine 0.15% plus Sufentanil 0.2 µg/mL solution as continuous epidural infusion (5 mL/h, beginning immediately after the initial bolus); B - Ropivacaine 0.1% plus Sufentanil 0.2 µg/mL as programmed intermittent epidural bolus and C - Same solution as group A as programmed intermittent epidural bolus. PIEB regimens were programmed as 10 mL/h starting 60 min after the initial bolus. Rescue boluses of 5 mL of the same solution were administered, with the infusion pump. We evaluated maternal satisfaction using a verbal numeric scale from 0 to 10. We also evaluated adverse, maternal and neonatal outcomes. Results: We analyzed 130 pregnants (A = 60; B = 33; C = 37). The median verbal numeric scale for maternal satisfaction was 8.8 in group A; 8.6 in group B and 8.6 in group C (p = 0.83). We found a higher caesarean delivery rate in group A (56.7%; p = 0.02). No differences in motor block, instrumental delivery rate and neonatal outcomes were observed. Conclusions: Maintenance of epidural analgesia with programmed intermittent epidural bolus is associated with a reduced incidence of caesarean delivery with equally high maternal satisfaction and no adverse outcomes.

Resumo Justificativa: Há evidências de que a administração de um bolus epidural intermitente programado (BEIP) comparada com a infusão epidural contínua (IEC) resulta em maior eficácia da analgesia e da satisfação materna, com redução das intervenções anestésicas. Métodos: Neste estudo, 166 mulheres com gravidezes viáveis foram incluídas. Após uma dose epidural de 10 mL de ropivacaína a 0,16% e adição de 10 µg de sufentanil, as parturientes foram aleatoriamente designadas para um dos três regimes: A - ropivacaína a 0,15% mais solução de sufentanil (0,2 µg/mL) como infusão peridural contínua (5 mL/h, imediatamente após o bolus inicial); B - ropivacaína a 0,1% mais sufentanil (0,2 µg/mL) como bolus epidural intermitente programado; C - solução idêntica à do Grupo A com bolus epidural intermitente programado. Os regimes BEIP foram programados como 10 mL por hora, começaram 60 minutos após o bolus inicial. Bolus de resgate de 5 mL da mesma solução foi administrado com bomba de infusão. A satisfação materna foi avaliada com uma escala numérica verbal de 0 a 10. Também avaliamos os resultados adversos maternais e neonatais. Resultados: Foram avaliadas 130 gestantes (A = 60, B = 33; C = 37). A mediana na escala numérica verbal para a satisfação materna foi de 8,8 no grupo A; 8,6 no grupo B e 8,6 no grupo C (p = 0,83). Encontramos uma taxa mais elevada para parto cesário no grupo A (56,7%; p = 0,02). Não observamos diferenças no bloqueio motor, taxa de parto instrumental e resultados neonatais. Conclusões: A manutenção da analgesia peridural com bolus epidural intermitente programado está associada a uma redução da incidência de parto cesariano com satisfação materna igualmente elevada e sem resultados adversos.

Outcomes of allogeneic stem cell transplantation among patients with acute myeloid leukemia presenting active disease: Experience of a single European Comprehensive Cancer Center / Resultados do transplante alogênico de células-tronco em doentes com leucemia mieloide aguda com doença ativa: experiência de um único Centro Oncológico Europeu

Summary Introduction: Allogeneic hematopoietic stem cell transplantation (ASCT) representes a potentially curative approach for patients with relapsed or refractory acute myeloid leukemia (AML). We report the outcome of relapsed/refractory AML patients treated with ASCT. Method: A retrospective cohort from 1994 to 2013 that included 61 patients with diagnosis of relapsed/refractory AML. Outcomes of interest were transplant-related mortality (TRM), incidence of acute and chronic graft-versus-host disease (GVHD), relapse incidence, progression-free survival (PFS) and overall survival (OS). Statistical significance was set at p<0.05. Results: The median age was 61 years (range 1 to 65). The cumulative incidence of 90 days, 1 year, and 3 years TRM were 60%, 26.7%, and 13.3%, respectively (p<0.001). The incidence of relapse was 21.7% at 1 year, 13% at 3 years, and 8.7% at 5 years. Median OS was estimated to be 8 months (95CI 3.266-12.734) and median PFS, 3 months (95CI 1.835-4.165). Conclusion: In our cohort, TRM in first years after ASCT remains considerable, but ASCT in this setting seems to be a good choice for AML patients with active disease. However, novel approaches are needed to reduce TRM and relapse in this set of patients.

Resumo Introdução: o transplante alogênico de células-tronco hematopoiéticas (TCTH-alo) representa uma abordagem potencialmente curativa para pacientes com leucemia mieloide aguda (LMA) recorrente ou refratária. Nosso trabalho apresenta o resultado de pacientes com recaída ou doença refratária tratados com TCTH-alo. Método: coorte retrospectiva incluindo 61 pacientes de 1994 a 2013 com diagnóstico de recidiva/LMA refratária. Os desfechos de interesse foram mortalidade relacionada ao transplante (MRT), incidência da doença aguda e crônica do enxerto contra hospedeiro (DECH), incidência de recaídas, sobrevida livre de progressão (PFS - progression-free survival) e sobrevida global (SG). A significância estatística foi considerada para p<0,05. Resultados: a média de idade foi de 61 anos (variação de 1 a 65). A incidência cumulativa de 90 dias, 1 ano e 3 anos de MRT foram de 60%, 26,7% e 13,3%, respectivamente (p<0,001). A incidência de recaída foi de 21,7% em 1 ano, 13% em 3 anos e 8,7% em 5 anos. A SG mediana foi estimada em 8 meses (IC 95% 3,266-12,734) e a mediana de PFS, em 3 meses (IC 95% 1,835-4,165). Conclusão: em nossa coorte, MRT no primeiro ano após o transplante permanece considerável, mas TCTH-alo nesse cenário parece ser uma boa opção para pacientes com LMA ativa. No entanto, novas abordagens são necessárias para reduzir MRT e recaída nesse conjunto de pacientes.

Colchicine to Reduce Atrial Fibrillation in the Postoperative Period of Myocardial Revascularization / Colchicina para Redução de Fibrilação Atrial em Pós-Operatório de Revascularização Miocárdica

Abstract Background: The high prevalence of atrial fibrillation (AF) in the postoperative period of myocardial revascularization surgery increases morbidity and mortality. Objective: To assess the efficacy of colchicine to prevent AF in the postoperative period of myocardial revascularization surgery, the impact of AF on hospital length of stay and death, and to identify its risk factors. Methods: Between May 2012 and November 2013, 140 patients submitted to myocardial revascularization surgery were randomized, 69 to the control group and 71 to the colchicine group. Colchicine was used at the dose of 1 mg orally, twice daily, preoperatively, and of 0.5 mg, twice daily, until hospital discharge. A single dose of 1 mg was administered to those admitted 12 hours or less before surgery. Results: The primary endpoint was AF rate in the postoperative period of myocardial revascularization surgery. Colchicine group patients showed no reduction in AF incidence as compared to control group patients (7.04% versus 13.04%, respectively; p = 0.271). There was no statistically significant difference between the groups regarding death from any cause rate (5.6% versus 10.1%; p = 0,363) and hospital length of stay (14.5 ± 11.5 versus 13.3 ± 9.4 days; p = 0.490). However, colchicine group patients had a higher infection rate (26.8% versus 8.7%; p = 0.007). Conclusion: The use of colchicine to prevent AF after myocardial revascularization surgery was not effective in the present study. Brazilian Registry of Clinical Trials number RBR-556dhr.

Resumo Fundamento: A alta prevalência de fibrilação atrial (FA) no pós-operatório de cirurgia de revascularização miocárdica ocasiona maior morbidade e mortalidade. Objetivos: Avaliar a eficácia da colchicina como profilaxia para FA no pós-operatório de cirurgia de revascularização miocárdica, o impacto da FA sobre o tempo de internação hospitalar e óbito e identificar fatores de risco para o seu aparecimento. Métodos: Entre maio de 2012 e novembro de 2013, 140 pacientes submetidos à cirurgia de revascularização miocárdica foram randomizados, 69 no grupo controle e 71 no grupo colchicina. A colchicina foi utilizada na dose de 1 mg via oral, duas vezes ao dia, no pré-operatório, e 0,5 mg, duas vezes ao dia, até a alta hospitalar. Dose única de 1 mg foi administrada aos internados 12 horas ou menos antes da cirurgia. Resultados: O desfecho primário foi a taxa de FA no pós-operatório de cirurgia de revascularização miocárdica. Os pacientes do grupo colchicina não apresentaram redução na incidência de FA em comparação aos do grupo controle (7,0% versus 13,0%, respectivamente; p = 0,271). Não houve diferença estatisticamente significativa entre os grupos em relação à taxa de óbito por qualquer causa (5,6% versus 10,1%; p = 0,363) e ao tempo de internação (14,5 ± 11,5 versus 13,3 ± 9,4 dias; p = 0,490). Porém, o grupo colchicina apresentou maior taxa de infecção (26,8% versus 8,7%; p = 0,007). Conclusões: O uso da colchicina para profilaxia da FA no pós-operatório de revascularização miocárdica não se mostrou eficaz neste estudo. Registro Brasileiro de Ensaios Clínicos número RBR-556dhr.

Is radioactive iodine- 131 treatment related to the occurrence of non-synchronous second primary malignancy in patients with differentiated thyroid cancer?

Objective Much controversy relates to the risk of non-synchronous second primary malignancies (NSSPM) after radioactive iodine treatment (RAI-131) in differentiated thyroid cancer (DTC) patients. This study evaluated the relationship between RAI-131 and NSSPM in DTC survivors with long-term follow-up. Materials and methods Retrospective analysis of 413 DTC cases was performed; 252 received RAI-131 and 161 were treated with thyroidectomy alone. Exclusion criteria were: prior or synchronous non-thyroidal malignancies (within the first year), familial syndromes associated to multiple neoplasms, ionizing radiation exposure or second tumors with unknown histopathology. Results During a mean follow-up of 11.0 ± 7.5 years, 17 (4.1%) patients developed solid NSSPM. Patients with NSSPM were older than those without (p = 0.02). RAI-131 and I-131 cumulative activity were similar in patients with and without NSSPM (p = 0.18 and p = 0.78, respectively). Incidence of NSSPM was 5.2% in patients with RAI-131 treatment and 2.5% in those without RAI-131 (p = 0.18). Using multivariate analysis, RAI-131 was not significantly associated with NSSPM occurrence (p = 0.35); age was the only independent predictor (p = 0.04). Under log rank statistical analysis, after 10 years of follow-up, it was observed a tendency of lower NSSPM-free survival among patients that received RAI-131 treatment (0.96 vs . 0.87; p = 0.06), what was not affected by age at DTC diagnosis. Conclusion In our cohort of DTC survivors, with a long-term follow-up period, RAI-131 treatment and I-131 cumulative dose were not significantly associated with NSSPM occurrence. A tendency of premature NSSPM occurrence among patients treated with RAI-131 was observed, suggesting an anticipating oncogenic effect by interaction with other risk factors.

Activating blood circulation to remove stasis treatment of hypertensive intracerebral hemorrhage: A multi-center prospective randomized open-label blinded-endpoint trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of the Chinese herbal therapeutic regimen of activating blood circulation (TRABC) in treatment of hypertensive intracerebral hemorrhage (HICH).</p><p><b>METHODS</b>This was a multi-center prospective randomized open-label blinded-endpoint (PROBE) trial with HICH admitted to 12 hospitals. Totally 240 participants were randomized to the treatment group treated with TRABC in addition to conventional Western treatment or the control group with conventional Western treatment equally for 3 months. Primary outcome was degree of disability as measured by modified Rankin Scale (mRS). Secondary outcomes were the absorption of hematoma and edema, National Institutes of Health Stroke Scale (NIHSS) scores and patient-reported outcome measures for stroke and Barthel activities of daily living index. Adverse events and mortality were also recorded.</p><p><b>RESULTS</b>After 3 months of treatment, the rate of mRS 0-1 and mRS 0-2 in the treatment group was 72.5% and 80.4%, respectively, and in the control group 48.1% and 63.9%, respectively, with a significant difference between groups (P<0.01). Hematoma volume decreased significantly at day 7 of treatment in the treatment group than the control group (P=0.038). Average Barthel scores in the treatment group after treatment was 89.11±19.93, and in the control group 82.18±24.02 (P=0.003). NIHSS scores of the two groups after treatment decreased significantly compared with before treatment (P=0.001). Patient-reported outcomes in the treatment group were lower than the control group at day 21 and 3 months of treatment (P<0.05). There were 4 deaths, 2 in each group, and 11 adverse events, 6 in the treatment group and 5 in the control group.</p><p><b>CONCLUSION</b>The integrative therapy combined TRABC with conventional Western treatment for HICH could promote hematoma absorption thus minimize neurologic impairment, without increasing intracerebral hematoma expansion and re-bleeding.</p>

Serum bilirubin value predicts hospital admission in carbon monoxide-poisoned patients. Active player or simple bystander?

OBJECTIVES:Although carbon monoxide poisoning is a major medical emergency, the armamentarium of recognized prognostic biomarkers displays unsatisfactory diagnostic performance for predicting cumulative endpoints.METHODS:We performed a retrospective and observational study to identify all patients admitted for carbon monoxide poisoning during a 2-year period. Complete demographical and clinical information, along with the laboratory data regarding arterial carboxyhemoglobin, hemoglobin, blood lactate and total serum bilirubin, was retrieved.RESULTS:The study population consisted of 38 poisoned patients (23 females and 15 males; mean age 39±21 years). Compared with discharged subjects, hospitalized patients displayed significantly higher values for blood lactate and total serum bilirubin, whereas arterial carboxyhemoglobin and hemoglobin did not differ. In a univariate analysis, hospitalization was significantly associated with blood lactate and total serum bilirubin, but not with age, sex, hemoglobin or carboxyhemoglobin. The diagnostic performance obtained after combining the blood lactate and total serum bilirubin results (area under the curve, 0.90; 95% CI, 0.81-0.99; p<0.001) was better than that obtained for either parameter alone.CONCLUSION:Although it remains unclear whether total serum bilirubin acts as an active player or a bystander, we conclude that the systematic assessment of bilirubin may, alongside lactate levels, provide useful information for clinical decision making regarding carbon monoxide poisoning.

Minimally access versus conventional hydrocelectomy: a randomized trial

ABSTRACTObjective:To compare our previously published new minimally access hydrocelectomy versus Jaboulay's procedure regarding operative outcome and patient's satisfaction.Materials and Methods:A total of 124 adult patients were divided into two groups: A and B. Group A patients were subjected to conventional surgical hydrocelectomy (Jaboulay's procedure) and group B patients were subjected to the new minimal access hydrocelectomy. The primary endpoint of the study was recurrence defined as a clinically detectable characteristic swelling in the scrotum and diagnosed by the two surgeons and confirmed by ultrasound imaging study. The secondary endpoints were postoperative hematoma, wound sepsis and persistent edema and hardening.Results:The mean operative time in group B was 15.1±4.24 minutes and in group A was 32.5±4.76 minutes (P≤0.02). The mean time to return to work was 8.5±2.1 (7–10) days in group B while in group A was 12.5±3.53 (10–15) days (P=0.0001). The overall complication rate in group B was 12.88% and in group A was 37%. The parameters of the study were postoperative hematoma, degree of scrotal edema, wound infection, patients’ satisfaction and recurrence.Conclusion:Hydrocelectomy is considered the gold standard technique for the treatment of hydrocele and the minimally access maneuvers provide the best operative outcomes regarding scrotal edema and hardening and patient's satisfaction when compared to conventional eversion-excision hydrocelectomies.

Assessment of Myocardial Infarction by Cardiac Magnetic Resonance Imaging and Long-Term Mortality / Avaliação do Infarto do Miocárdio pela Ressonância Magnética Cardíaca e Mortalidade em Longo Prazo

Background: Cardiac magnetic resonance imaging provides detailed anatomical information on infarction. However, few studies have investigated the association of these data with mortality after acute myocardial infarction. Objective: To study the association between data regarding infarct size and anatomy, as obtained from cardiac magnetic resonance imaging after acute myocardial infarction, and long-term mortality. Methods: A total of 1959 reports of “infarct size” were identified in 7119 cardiac magnetic resonance imaging studies, of which 420 had clinical and laboratory confirmation of previous myocardial infarction. The variables studied were the classic risk factors – left ventricular ejection fraction, categorized ventricular function, and location of acute myocardial infarction. Infarct size and acute myocardial infarction extent and transmurality were analyzed alone and together, using the variable named “MET-AMI”. The statistical analysis was carried out using the elastic net regularization, with the Cox model and survival trees. Results: The mean age was 62.3 ± 12 years, and 77.3% were males. During the mean follow-up of 6.4 ± 2.9 years, there were 76 deaths (18.1%). Serum creatinine, diabetes mellitus and previous myocardial infarction were independently associated with mortality. Age was the main explanatory factor. The cardiac magnetic resonance imaging variables independently associated with mortality were transmurality of acute myocardial infarction (p = 0.047), ventricular dysfunction (p = 0.0005) and infarcted size (p = 0.0005); the latter was the main explanatory variable for ischemic heart disease death. The MET-AMI variable was the most strongly associated with risk of ischemic heart disease death (HR: 16.04; 95%CI: 2.64-97.5; p = 0.003). Conclusion: The anatomical data of infarction, obtained from cardiac magnetic resonance imaging after acute myocardial infarction, were independently ...

Fundamento: A ressonância magnética cardíaca fornece informações anatômicas detalhadas do infarto, porém poucos estudos investigaram a associação desses dados com mortalidade pós-infarto agudo do miocárdio. Objetivo: Verificar a associação entre os dados de anatomia e magnitude do infarto, obtidos da ressonância magnética cardíaca pós-infarto agudo do miocárdio, e mortalidade em longo prazo. Métodos: Foram identificados 1.959 laudos com “massa infartada” em 7.119 exames de ressonância magnética cardíaca, dos quais 420 possuíam documentação clínica e laboratorial de infarto agudo do miocárdio prévio. As variáveis estudadas foram os fatores de risco clássicos, fração de ejeção do ventrículo esquerdo, função ventricular categorizada e localização do infarto agudo do miocárdio. Massa infartada, extensão e transmuralidade do infarto agudo do miocárdio foram analisadas de maneira isolada e conjuntamente, pela variável denominada “MET-IAM”. A análise estatística foi feita pelo elastic net regularization, pelo modelo de Cox e por árvores de sobrevida. Resultados: A idade média foi 62,3 ± 12 anos, sendo 77,3% de homens. Durante o seguimento de 6,4 ± 2,9 anos, foram identificados 76 óbitos (18,1%). Creatinina sérica, diabetes melito e infarto agudo do miocárdio prévio demonstraram associação independente com mortalidade. A idade foi o principal fator explicativo. As variáveis da ressonância magnética cardíaca que se associaram de forma independente com a mortalidade foram: transmuralidade do infarto agudo do miocárdio (p = 0,047), disfunção ventricular (p = 0,0005) e massa infartada (p = 0,0005) − sendo essa última a principal variável explicativa para morte por doença isquêmica cardíaca. A variável MET-IAM exibiu a maior associação de risco para morte por doença isquêmica cardíaca (HR: 16,04; IC95%: 2,64-97,5; p = 0,003). Conclusão: Os dados anatômicos do infarto obtidos da ressonância magnética cardíaca pós-infarto ...

Role of patient-reported outcomes and other efficacy endpoints in the drug approval process in Europe [2008-2012]

The present study aimed at systematically reviewing the role and extent of patient-reported outcomes [PROs] usage within the package of scientific evidence considered for marketing authorization [MA]. All regulatory information published by the European Medicines Agency [EMA] for products authorized between January 2008 and December 2012 and appearing in the European Public Assessment Report [EPAR] database was examined for efficacy endpoints. The endpoints here considered included: PROs, clinician reported outcomes [CROs], and laboratory reported outcomes [LROs]. LROs were the most frequently reported endpoints. Out of the 180 products here selected, 99 [55%], 67 [37%], and 30 [17%], respectively, used LROs, CROs and PROs as primary endpoints [PEs]. PROs as any endpoints were used in 82 [46%] products. Out of these, PROs were documented as PE in 30 [37%], with 27 [33%] products having used PROs both as primary and non-PEs. PRO usage was most frequently identified with nervous system and antineoplastic agents. During the study period, the use of all the three types of endpoints appeared to be static. Both the regulatory bodies and the industry should ensure complete and clear reporting of all endpoints used, including PROs, to improve transparency