Comparative analysis of the etanercept efficacy in children with juvenile idiopathic arthritis under the age of 4 years and children of older age groups using the propensity score matching method.

Objective: The aim of this study was to analyze the efficacy and safety of etanercept (ETA) in children with juvenile idiopathic arthritis (JIA) under the age of 4 years and to compare the data with those for older age groups. Methods: Three groups comprising 34 patients each (total of 102 patients) were selected using the propensity score matching (PSM) method. The study group (patients under the age of 4 years; the Junior group (JNR)) was compared with patients of the older age groups, adjusted for criteria such as gender, JIA category, JIA severity, and either age at disease onset (the Reference by Age of disease Onset (RAO) group) or disease duration (the Reference by Disease Duration (RDD) group). Results: All three groups showed a good response to ETA therapy. During the follow-up period, only 4 (3.9%) patients failed to reach American College of Rheumatology (ACR) Pediatric criteria improvement at ACR50 level. In the JNR group, 82.4% of patients achieved ACR90 within a median time of 3 months (IQR, 3-6 months), which was a better result compared to the other two groups: 61.8% (RAO group) and 58.8% (RDD group) of patients achieved ACR90 within 6 (Interquartile Range (IQR), 3-9) months (p = .028). Three (9%) patients in the JNR group and none of the RDD and RAO groups discontinued treatment because of clinical remission (p = .045). Conclusion: An analysis of the ETA efficacy in different age groups comparable in terms of the diagnosis and disease severity demonstrated a higher efficacy of earlier ETA therapy in children of the same age at disease onset. In children at the early stage of arthritis (≤ 2.5 years long), ETA was more efficient in those with an earlier disease onset.

Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial.

BACKGROUND: Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. METHODS: A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. RESULTS: By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/-IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14-32) and 32 (24-40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients. CONCLUSIONS: Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.

Predictors of Unfavorable Outcomes in Patients with Atrial Fibrillation and Concomitant Heart Failure with Different Ejection Fractions: RIF-CHF Register One-Year Follow-Up.

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) are tightly interrelated. The concurrence of these pathologies can aggravate the pathological process. The geographic and ethnic characteristics of patients may significantly affect the efficacy of different types of therapy and patients' compliance. The objective of this study was to analyze how the features of the course of the diseases and management of HF + AF influence the clinical outcomes. METHODS: The data of 1,003 patients from the first Russian register of patients with chronic heart failure and atrial fibrillation (RIF-CHF) were analyzed. The endpoints included hospitalization due to HF worsening, mortality, thromboembolic events, and hemorrhage. Predictors of unfavorable outcomes were analyzed separately for patients with HF and preserved ejection fraction (AF + HFpEF), midrange ejection fraction (AF + HFmrEF), and reduced ejection fraction (AF + HFrEF). Prevalence of HF + AF and compliance with long-term treatment of this pathology during one year were evaluated for each patient. RESULTS: The study involved 39% AF + HFpEF patients, 15% AF + HFmrEF patients, and 46% AF + HFrEF patients. AF + HFpEF patients were significantly older than patients in two other groups (40.6% of patients were older than ≥75 years vs. 24.8%, respectively, p < 0.001) and had the lowest rate of prior myocardial infarctions (25.3% vs. 46.1%, p < 0.001) and the lowest adherence to rational therapy of HF (27.4% vs. 47.1%, p < 0.001). AF + HFmrEF patients had the highest percentage of cases of HF onset after AF (61.3% vs. 49.2% in other patient groups, p=0.021). Among patients with AF + HFrEF, there was the highest percentage of males (74.2% vs. 41% in other patient groups, p < 0.001) and the highest percentage of ever-smokers (51.9% vs. 29.4% in other patient groups, p < 0.001). A total of 57.2% of patients were rehospitalized for decompensation of chronic heart failure within one year; the risk was the highest for AF + HFmrEF patients (66%, p=0.017). Reduced ejection fraction was associated with the increased risk of cardiovascular mortality (15.5% vs. 5.4% in other patient groups, p < 0.001) rather than ischemic stroke (2.4% vs. 3%, p=0.776). Patients with AF + HFpEF had lower risk to achieve the combination point (stroke + IM + CV death) as compared to patients with AF + HFmrEF and AF + HFrEF (12.7% vs. 22% and 25.5%, p < 0.001). Regression logistic analysis revealed that factors such as demographic characteristics, disease severity, and administered treatment had different effects on the risk of unfavorable outcomes depending on ejection fraction group. The clinical features and symptoms were found to be significant risk factors of cardiovascular mortality in AF + HFmrEF, while therapy characteristics were not associated with it. CONCLUSIONS: Each group of patients with different ejection fractions is characterized by its own pattern of factors associated with the development of unfavorable outcomes. The demographic and clinical characteristics of patients with midrange ejection fraction demonstrate that these patients need to be studied as a separate cohort.

Dynamics of concomitant therapy in children with juvenile idiopathic arthritis treated with etanercept and methotrexate.

BACKGROUND: Both the steroid- and NSAID-sparing effects of biologics in juvenile idiopathic arthritis (JIA) treatment are key aspects of the dynamics of patient's condition. The proper selection of biologics enables maximum treatment effectiveness and reduction of the dosage of concomitant therapy. Our aim was to study the dynamics of concomitant therapy during etanercept (ETA) and methotrexate (MTX) treatment in patients with JIA. METHODS: This analysis included 215 JIA patients (63.3% females) showing sufficient response to main therapy. One hundred patients received MTX as main therapy, 24 received ETA monotherapy, and 91 received ETA þ MTX combination therapy. The dynamics of concomitant therapy were analyzed after 1 month, every 3 months during the first year, and every 6 months during the long-term follow-up (up to 5 years). RESULTS: At the baseline, 24 (11.2%) patients received concomitant oral glucocorticoids (orGCs) and NSAIDs; the remaining 191 (88.8%) patients were treated with concomitant NSAIDs only. Within 1-year treatment, NSAIDs were discontinued in 162 (75.3%) patients. There were no significant differences in the dynamics of withdrawal of NSAIDs in patients who received and did not receive concomitant MTX. However, the percentage of treatment discontinuation in the MTX group was significantly lower compared to the other two groups (p < 0.001). Oral GCs were discontinued completely in 4 children (16.7%), and the dose of oral GCs was reduced in another 4 patients (16.7%). By the end of the follow-up period, 44 of 115 patients (38.3%) treated with ETA in combination with any concomitant therapy could switch to ETA monotherapy. CONCLUSION: Therapy with ETA makes it possible to reduce the dosage or completely discontinue most concomitant medications (orGCs, NSAIDs, MTX) in a significant percentage of patients. This reduces the risk of development of NSAID- and GC-induced pathological conditions, while the effectiveness of therapy of the underlying condition remains high.

Flow diversion versus parent artery occlusion with bypass in the treatment of complex intracranial aneurysms: Immediate and short-term outcomes of the randomized trial.

OBJECTIVE: We performed prospective randomized comparison of clinical and surgical outcomes of flow diversion versus PVO and bypass in patients with complex anterior circulation aneurysms. PATIENTS AND METHODS: Open, prospective, randomized, parallel group, multicenter study of complex intracranial aneurysms treatment was conducted. Patients with complex intracranial aneurysms of anterior circulation with neck is more than 4 mm wide, dome/neck ratio is equal or less than 2:1, which is suitable for flow diversion and occlusion with bypass were included in the study. A total of 111 potential participants were enrolled since March 2015. Additional propensity score matching was performed with 40 patients in each group selected for analysis. RESULTS: 39 out of 40 patients (97.5%) from matched FD group reached good clinical outcome. In the matched bypass group acceptable outcome was achieved in 32 (80%) out of 40 patients (difference between groups p = 0.029). The morbidity and mortality rates were 15% and 5%, respectively. Difference in the rates of favorable outcomes, compared by χ2 met statistical significance (p = 0.014). The rate of complete aneurysm occlusion at 6 months was 42.5% in the FD group and 95% in surgical group (p < 0.0001). The rate of complete occlusion at 12 months was 65% in the FD group and 97.5% in surgical group. The difference between groups was still significant (p = 0.001). There were no significant differences between groups by occurrence of ischemic (p = 0.108) and hemorrhagic (p = 0.615) complications. CONCLUSION: The study demonstrated superior clinical outcomes for endovascular flow diversion in comparison with bypass surgery in treatment of complex aneurysms. Though, both techniques grant similar percentage of major neurologic complications and comparable cure rate for cranial neuropathy. Nevertheless, flow diversion is associated with significantly lower early obliteration rate, thus possesses patient for risks of prolonged dual antiplatelet regimen and delayed rupture. Hence, it's important to stratify patient by the natural risk of aneurysm rupture prior to treatment selection.

Aspects of the use of propensity score matching methods in neurosurgery / Aspectos do uso dos métodos de pareamento de escore de propensão em neurocirurgia / Aspectos del uso de los métodos de emparejamiento de puntaje de propensión en neurocirugía

ABSTRACT Objective Observational studies and register data provide researchers with ample opportunities to obtain answers to questions that randomized controlled trials cannot answer for organizational or ethical reasons. One of the most common tools for solving this problem is the use of propensity score matching (PSM) methods. The purposes of our study were to compare various models and algorithms for selecting PSM parameters, using retrospective clinical data, and to compare the results obtained using the PSM method with those of prospective studies. Methods The results of two studies (randomized prospective and retrospective) conducted at the Novosibirsk Research Institute of Traumatology and Orthopedics were used for comparative analysis. The trials aimed to study the effectiveness and safety of surgical treatment of degenerative dystrophic lesions in the lumbar spine. We compared the results using the recommended PSM parameters (caliper=0.2 and 0.6) the propensity score is the probability of assignment to one treatment conditional on a subject's measured baseline covariates. Propensity-score matching is increasingly being used to estimate the effects of exposures using observational data. In the most common implementation of propensity-score matching, pairs of treated and untreated subjects are formed whose propensity scores differ by at most a pre-specified amount (the caliper widthand the caliper values often used in real-life studies (0.05, 0.1, 0.25, 0.5, and 0.8) with the those obtained in a similar prospective study. Results After eliminating systematic selection bias, the results of the retrospective and randomized prospective studies were qualitatively comparable. Conclusion The results of this study provide recommendations for the use of PSM: when evaluating efficacy scores in neurosurgical studies (with a sample size < 150 patients), we recommend matching on the logit of the propensity score using calipers of width equal to 0.6 of the standard deviation of the logit of the propensity score. Level of evidence V; Type of study is expert opinion.

RESUMO Objetivos Estudos observacionais e dados de registro fornecem aos pesquisadores amplas oportunidades de obter respostas às perguntas que os estudos clínicos randomizados não podem responder por razões institucionais ou éticas. Uma das ferramentas mais comuns para resolver esse problema é o uso dos métodos de Propensity Score Matching (PSM, pareamento de escore de propensão). O objetivo do nosso estudo foi comparar vários modelos e algoritmos para a seleção de parâmetros de PSM, usando os dados clínicos retrospectivos e comparar os resultados obtidos com esse método com os de estudos prospectivos. Métodos Os resultados de dois estudos (randomizado prospectivo e retrospectivo), realizados no Instituto de Pesquisa de Traumatologia e Ortopedia de Novosibirsk, foram utilizados para análise comparativa. Os estudos visaram estudar a eficácia e a segurança do tratamento cirúrgico de lesões distróficas degenerativas na coluna lombar. Comparamos os resultados usando os parâmetros recomendados pelo PSM, isto é calibração (caliper) de 0,2 e 0,6 e os valores de calibração usados com frequência em estudos da vida real (0,05, 0,1, 0,25, 0,5 e 0,8) com os obtidos em um estudo prospectivo semelhante. Resultados Depois de eliminar o viés sistemático de seleção, os resultados de estudos randomizados prospectivos e retrospectivos foram qualitativamente comparáveis. Conclusões Os resultados deste estudo fornecem recomendações para o uso do PSM: ao avaliar os escores de eficácia em estudos neurocirúrgicos (com tamanho de amostra < 150 pacientes), recomendamos a correspondência do logit do escore de propensão com calibração de largura de 0,6 do desvio padrão do logit do escore de propensão. Nível de evidência V; Opinião do especialista.

RESUMEN Objetivos Los estudios de observación y los datos de registro brindan a los investigadores amplias oportunidades para obtener respuestas a preguntas que los estudios clínicos aleatorizados no pueden responder por razones institucionales o éticas. Una de las herramientas más comunes para resolver este problema es el uso de los métodos de Propensity Score Matching (PSM, emparejamiento de puntaje de propensión). El objetivo de nuestro estudio fue comparar varios modelos y algoritmos para la selección de parámetros de PSM, utilizando los datos clínicos retrospectivos y comparar los resultados obtenidos con ese método con los de estudios prospectivos. Métodos Los resultados de dos estudios (prospectivo aleatorizado y retrospectivo) realizados en el Instituto de Investigación de Traumatología y Ortopedia de Novosibirsk se utilizaron para el análisis comparativo. Los estudios tuvieron como objetivo estudiar la eficacia y seguridad del tratamiento quirúrgico de las lesiones distróficas degenerativas en la columna lumbar. Comparamos los resultados usando los parámetros recomendados por el PSM, esto es, calibración (caliper) de 0,2 y 0,6 y los valores de calibración usados con frecuencia en estudios de la vida real (0,05, 0,1, 0,25, 0,5 y 0,8) con los obtenidos en un estudio prospectivo semejante. Resultados Después de eliminar el sesgo sistemático de selección, los resultados de estudios prospectivos aleatorizados y retrospectivos fueron cualitativamente comparables. Conclusiones Los resultados de este estudio proporcionan recomendaciones para el uso del PSM: al evaluar los puntajes de eficacia en estudios neuroquirúrgicos (con tamaño de muestra <150 pacientes), recomendamos la correspondencia del logit del puntaje de propensión con calibración de ancho de 0.6 de la desviación estándar del logit de puntaje de propensión. Nivel de evidencia V; Opinión del especialista.