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1.
Eur Rev Med Pharmacol Sci ; 24(9): 4697-4709, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32432733

RESUMO

OBJECTIVE: Studies have demonstrated that long non-coding RNAs (lncRNAs) are important in the development and prognosis of prostate cancer. The aim of this study was to investigate the functions and mechanism of lnc-SNHG14 in prostate cancer. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) or Western blot (WB) were performed to detect mRNA expressions of SNHG14 and miR-5590-3p, and the protein levels of Yin Yang-1 (YY1) in prostate cancer tissues, adjacent tissues, and cancer cell lines. The correlation analysis was used to analyze the correlations between SNHG14, miR-5590-3p, and YY1. Kaplan-Meier survival analysis was used to analyze the overall survival for prostate cancer patients. Cell Counting Kit-8 (CCK-8) assay was performed to measure cell proliferation ability and flow cytometry assay was used to detect cell apoptotic rate. Besides, transwell assay was used to measure cell invasion ability. In addition, WB was performed to measure protein expressions in prostate cancer cell lines. Finally, Luciferase reporter assay was performed to verify the binding sites between SNHG14 and miR-5590-3p, miR-5590-3p, and YY1. RESULTS: The results showed that SNHG14 was significantly increased in prostate cancer tissues and prostate cancer cell lines, which were related with advanced stage and poor diagnosis for prostate cancer patients. MiR-5590-3p was reduced in prostate cancer tissues and cell lines, which were negatively correlated with SNHG14. YY1 was found to be increased in prostate cancer tissues, which was negatively correlated with miR-5590-3p and positively correlated with SNHG14. Furthermore, SNHG14 knockdown inhibited cell proliferation, invasion, and promoted cell apoptosis in DU145 cells. In addition, protein expressions of Cyclin D1, Bcl-2, and N-cadherin were repressed, and the levels of Bax, Cleaved Caspase-3, and E-cadherin were increased. Besides, miR-5590-3p inhibition promoted cell proliferation and invasion, and inhibited apoptosis in DU145 cells. Importantly, Luciferase reporter assay proved that SNHG14 could directly sponge with miR-5590-3p, which could bind with YY1 and regulate the functions of cancer cell. Finally, we proved that SNHG14 regulated cell proliferation, cell apoptosis, and invasion via miR-5590-3p/ YY1 axis in prostate cancer. CONCLUSIONS: Above all, we found that SNHG14 was increased in prostate cancer patients, which was related with future diagnosis for prostate cancer patients. Of note, we discovered that SNHG14 could promote cell proliferation, invasion, and repress cell apoptosis via miR-5590-3p/YY1 axis in prostate cancer, which might provide a new target for treating prostate cancer.

2.
Zhonghua Yi Xue Za Zhi ; 99(32): 2532-2535, 2019 Aug 27.
Artigo em Chinês | MEDLINE | ID: mdl-31484282

RESUMO

Objective: Percutaneous renal biopsycurrently is the most important and widely used method of renal biopsy. However, there still are some patients in whom a percutaneous approach may be considered a major risk. In these patients, renal biopsy under direct vision is a reliable alternative. We described our personal technique and experience in a series of Chinese patients who underwent retroperitoneal laparoscopic renal biopsy. Methods: We retrospectively reviewed the patients who had performed retroperitoneal laparoscopic renal biopsy over a 4-year period (Jan 2013 to Jan 2017).Forty-three patients with renal dysfunction were involved inour center.Especially some patients showed atrophic kidney and poor visualization on ultrasonography. The patients' abnormal conditions includeddialysis (10 cases), morbid obesity (5 cases), deaf-mutes (2 cases) and uncontrolled severe hypertension. The kidney was approached via alaparoscopic retroperitoneal route using athree-ports technique. Then biopsies were performed bya 16-gaugebiopsy needle, and hemostasis was achieved by compression.In less cases, a topical spray hemostatic gel was required. Results: Biopsy was performed successfully in all cases and adequate renal tissue was acquired.Mean operative time was 59.4 minutes, mean blood loss was 36.5 ml.Under general anesthesia, no anesthetic accidents and related complications were recorded. Forty-onepatients were discharged within 24 h after operation. Onepatient occurred disseminated intravascular coagulationduring operation. Red blood cell transfusion and fresh-frozen plasma infusion were performed. Injury at hilum of kidney was detected in another patient. And extrapyelogenic repair surgery was performed. Conclusions: The retroperitoneallaparoscopic renal biopsy is a safe, reliable, minimallyinvasive alternative renal biopsy method with better haemostasis, fewer complications and a rapid recovery. As the helpful supplement of percutaneous renal biopsy, this technique may have to be used more often in the future.


Assuntos
Rim , Laparoscopia , Biópsia , Humanos , Espaço Retroperitoneal , Estudos Retrospectivos
3.
Eur Rev Med Pharmacol Sci ; 23(14): 6079-6090, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31364109

RESUMO

OBJECTIVE: Whether lymph node dissection (LND) should be performed concomitantly with radical nephrectomy (RN) for non-metastatic renal carcinoma has still been controversial recently. We conducted a meta-analysis assessing oncologic outcomes of radical nephrectomy with lymph node dissection (LND) and without lymph node dissection (non-LND) in non-metastatic renal cell carcinoma (NMRCC). PATIENTS AND METHODS: A systematic review was performed until April 2018 using a comprehensive search in PubMed, EMBASE, and Cochrane Library databases to identify eligible comparative studies. A formal meta-analysis was performed for studies comparing radical nephrectomy with LND and radical nephrectomy with non-LND for cT1-T4NxM0 tumors. Furthermore, a subgroup analysis for locally advanced renal cell carcinoma (cT3-T4NxM0) was conducted. RESULTS: Thirteen studies on patients with LND and non- LND were identified and included in the analysis. LND group did not have a significantly better survival than non-LND group for cT1-T4NxM0 tumors (HR 0.93, 95% CI 0.78-1.11, p=0.45), However, in the subgroup of locally advanced renal cell carcinoma (cT3-T4NxM0), it showed a significantly better OS rate in patients who had undergone LND compared to those without LND (HR 0.73, 95% CI 0.60-0.90; p=0.003). CONCLUSIONS: LND offers better cancer control and better long-term survival in locally advanced renal cell carcinomas (cT3-T4NxM0). This conclusion should be confirmed by a prospective randomized clinical trial.

4.
Artigo em Chinês | MEDLINE | ID: mdl-31189240

RESUMO

Objective: To analyze the situation of new occupational diseases in Hengyang City from 2006 to 2017, and put forward prevention and control strategies. Methods: The data of the new occupational disease report of Hengyang city in the Occupational Disease and Occupational Health Information Monitoring System from January 1, 2006 to December 31, 2017 was collected, and the age, working years, and the region and industry of the new occupational disease patients were analyzed. Results: From 2006 to 2017, there were 7 categories, 30 kinds and 2 110 cases of new occupational diseases in Hengyang City, including 1 117 cases of pneumoconiosis, 951 cases of chronic occupational poisoning, 15 cases of acute occupational poisoning, 12 cases of occupational otolaryngological and stomatological diseases, 7 cases of occupational skin diseases, 6 cases of occupational diseases caused by physical factors, and 1 case of occupational eye diseases(cataracts), 1 case of occupational tumor (lung cancer and skin cancer caused by arsenic and its compounds). New occupational diseases were mainly concentrated in Changning and Leiyang County-level city (87.82%, 1 853/2110), among which occupational poisoning had the most incidence in Changning County-level city (97.83%, 945/966), and pneumoconiosis had the most incidence in Leiyang County-level city (67.05%, 749/1 117). New occupational diseases were mainly concentrated in the manufacturing and mining industries (95.59%, 2 017/2 110). Pneumoconiosis (63.74%, 712/1 117) and acute occupational poisoning (60.00%, 9/15) were mainly caused by small businesses. Chronic occupational poisoning (61.62%, 586/951) and occupational otolaryngological and stomatological diseases (75.00%, 9/12) were mainly caused by large enterprises. Conclusion: The new occupational diseases in Hengyang city are mostly pneumoconiosis and chronic occupational poisoning, and we should focus on strengthening the prevention and control of occupational diseases in the mining industry and manufacturing industry.


Assuntos
Indústria Manufatureira , Doenças Profissionais , Pneumoconiose , China/epidemiologia , Humanos , Incidência , Indústrias , Doenças Profissionais/epidemiologia , Pneumoconiose/epidemiologia
5.
BMC Public Health ; 19(1): 841, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253112

RESUMO

BACKGROUND: Our objective was to determine the influence of the HealtheSteps™ lifestyle prescription program on physical activity and modifiable risk factors for chronic disease in individuals at risk. METHODS: One hundred eighteen participants were recruited from 5 sites in Southwestern Ontario, Canada and randomized to either the intervention (HealtheSteps™ program, n = 59) or a wait-list control group (n = 59). The study comprised three phases: an Active Phase (0 to 6 months) consisted of bi-monthly in-person lifestyle coaching with access to a suite of eHealth technology supports (Heathesteps app, telephone coaching and a private HealtheSteps™ social network) followed by a Minimally-Supported Phase I (6 to 12 months), in which in-person coaching was removed, but participants still had access to the full suite of eHealth technology supports. In the final stage, Minimally-Supported Phase II (12 to 18 months), access to the eHealth technology supports was restricted to the HealtheSteps™ app. Assessments were conducted at baseline, 6, 12 and 18 months. The study primary outcome was the 6-month change in average number of steps per day. Secondary outcomes included: self-reported physical activity and sedentary time; self-reported eating habits; weight and body composition measures; blood pressure and health-related quality of life. Data from all participants were analyzed using an intent-to-treat approach. We applied mixed effects models for repeated measurements and adjusted for age, sex, and site in the statistical analyses. RESULTS: Participants in HealtheSteps™ increased step counts (between-group [95% confidence interval]: 3132 [1969 to 4294], p < 0.001), decreased their sitting time (- 0.08 [- 0.16 to - 0.006], p = 0.03), and improved their overall healthful eating (- 1.5 [- 2.42 to - 0.58], p = 0.002) to a greater extent compared to control at 6 months. Furthermore, exploratory results showed that these individuals maintained these outcomes 12 months later, after a minimally-supported phase; and retained improvements in sedentary time and improved healthful eating after 18 months. No differences in self-reported physical activity, health-related quality of life, weight, waist circumference or blood pressure were observed between groups at 6 months. CONCLUSIONS: Our findings suggest that HealtheSteps™ is effective at increasing physical activity (i.e., step counts per day), decreasing weekday sitting time, and improving healthful eating in adults at increased risk for chronic disease after 6 months; however, we did not see change in other risk factors. Nonetheless, the maintenance of these behaviours with minimal support after 12 and even 18 months indicates the promise of HealtheSteps™ for long-term sustainability. TRIAL REGISTRATION: The trial was registered on April 6, 2015 with ClinicalTrials.gov (identifier: NCT02413385 ).


Assuntos
Doença Crônica/prevenção & controle , Exercício Físico/psicologia , Promoção da Saúde/métodos , Estilo de Vida Saudável , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ontário , Avaliação de Programas e Projetos de Saúde , Fatores de Risco , Autorrelato
6.
J Intern Med ; 286(6): 644-650, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31077464

RESUMO

BACKGROUND: Severe hypertriglyceridemia (serum triglyceride >10 mmol L-1 ) is implicated in ~9% of acute pancreatitis cases. Certain guidelines list severe hypertriglyceridemia as an indication for plasmapheresis. OBJECTIVE: We assembled the natural trajectory of triglyceride levels in patients with acute pancreatitis due to severe hypertriglyceridemia who were managed conservatively without plasmapheresis to evaluate the effectiveness of this approach. METHODS: A retrospective chart review was performed on 22 hospital admissions for acute pancreatitis episodes considered to be caused by severe hypertriglyceridemia. Patients were managed supportively, with cessation of oral intake (NPO) and intravenous hydration. Insulin infusion was used in 12 patients to manage concurrent hyperglycaemia. RESULTS: Triglyceride levels for the group were evaluated using a mixed-effects model. The average triglyceride level fell from 45.4 mmol L-1 on presentation to 13.3 mmol L-1 within 48 h, corresponding to a mean 69.8% decrease. Regression analysis showed a triglyceride half-life of 30.6 h. Findings were similar for NPO-only and insulin infusion subgroups. CONCLUSION: Patients with severe hypertriglyceridemia and acute pancreatitis can be conservatively managed safely and effectively without plasmapheresis.

7.
Eur Rev Med Pharmacol Sci ; 23(6): 2469-2475, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30964173

RESUMO

OBJECTIVE: Our study aimed to investigate the expression of microRNA-216a-5p (miR-216a-5p) in breast cancer (BC) and its effect on the proliferation and metastasis of BC cells by regulating the expression of p21-activated protein kinase 2 (PAK2) gene. PATIENTS AND METHODS: A total of 50 cases of cancer tissue specimens and corresponding para-carcinoma normal tissue specimens were collected from the breast surgery department of our hospital from July 2016 to December 2017. BC MCF-7 cell line and normal breast epithelial MCF-10A cells were cultured. MiR-NC (negative control), LV-p21-activated protein kinase 2 (PAK2) and/or miR-216a-5p mimics were synthesized and transfected. The protein and mRNA expression level in BC tissues and cells were detected by Western blot and quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay, respectively. Additionally, the Luciferase Reporter Assays, cell proliferation detection, clone formation assays and transwell migration and invasion assay were performed to determine the functional alteration of BC cells, respectively. RESULTS: The results of qRT-PCR demonstrated that miR-216a-5p was decreased in both BC tissues and cells compared with that in normal controls. Online target gene prediction software and Dual-Luciferase reporter assay were used for target identification, and PAK2 was identified as a functional target of miR-216a-5p in BC cells. The results were further clarified with the Western blot (WB) experiment. In vitro, cell functions were detected by Cell Counting Kit-8 (CCK-8), crystal violet staining and transwell experiment, respectively. The results indicated that decreased expression of PAK2 resulting from the up-regulation of miR-216a-5p could restrain the proliferation, clone formation, invasion and migration abilities of BC cells. CONCLUSIONS: We showed that miR-216a-5p played a role as antioncogene in BC, which provides a new therapeutic target for the treatment of BC.

8.
BMC Neurol ; 19(1): 20, 2019 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-30738426

RESUMO

BACKGROUND: Currently there are no disease-modifying treatments for Parkinson's disease dementia (PDD), a condition linked to aggregation of the protein α-synuclein in subcortical and cortical brain areas. One of the leading genetic risk factors for Parkinson's disease is being a carrier in the gene for ß-Glucocerebrosidase (GCase; gene name GBA1). Studies in cell culture and animal models have shown that raising the levels of GCase can decrease levels of α-synuclein. Ambroxol is a pharmacological chaperone for GCase and is able to raise the levels of GCase and could therefore be a disease-modifying treatment for PDD. The aims of this trial are to determine if Ambroxol is safe and well-tolerated by individuals with PDD and if Ambroxol affects cognitive, biochemical, and neuroimaging measures. METHODS: This is a phase II, single-centre, double-blind, randomized placebo-controlled trial involving 75 individuals with mild to moderate PDD. Participants will be randomized into Ambroxol high-dose (1050 mg/day), low-dose (525 mg/day), or placebo treatment arms. Assessments will be undertaken at baseline, 6-months, and 12-months follow up times. Primary outcome measures will be the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-Cog) and the ADCS Clinician's Global Impression of Change (CGIC). Secondary measures will include the Parkinson's disease Cognitive Rating Scale, Clinical Dementia Rating, Trail Making Test, Stroop Test, Unified Parkinson's disease Rating Scale, Purdue Pegboard, Timed Up and Go, and gait kinematics. Markers of neurodegeneration will include MRI and CSF measures. Pharmacokinetics and pharmacodynamics of Ambroxol will be examined through plasma levels during dose titration phase and evaluation of GCase activity in lymphocytes. DISCUSSION: If found effective and safe, Ambroxol will be one of the first disease-modifying treatments for PDD. TRIAL REGISTRATION: ClinicalTrials.gov NCT02914366, 26 Sep 2016/retrospectively registered.


Assuntos
Ambroxol/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Projetos de Pesquisa , Idoso , Encéfalo/efeitos dos fármacos , Demência/etiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/psicologia
9.
Eur Rev Med Pharmacol Sci ; 23(3): 1279-1290, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30779097

RESUMO

OBJECTIVE: To investigate the inhibitory effect of thymosin-ß4 (Tß4) on the activation of the human hepatic stellate cell line (HSC-LX2) induced by interleukin (IL)-1ß. MATERIALS AND METHODS: There were 5 groups in this study, i.e., blank control group, negative control group (SI-NC, empty plasmid), model group (20 ng/ml of IL-1ß), siRNA-Tß4 knockdown group (IL-1ß and si-Tß4) and Tß4 treatment group (IL-1ß and 1000 ng/ml of Tß4). Cell proliferation rate was measured using the Cell Counting Kit-8 (CCK-8) method. The cell cycle change and percentage of apoptotic cells were determined by Propidium Iodide (PI) DNA staining and Annexin V-fluorescein isothiocyanate (FITC) double staining. Cellular nucleic acid levels of p-IKB and nuclear factor-kappa B (NF-κB)/p65 proteins were measured by fluorescent quantitative Real Time-Polymerase Chain Reaction (RT-PCR). Double immunofluorescence staining and Western blot were used to detect nuclear translocation of NF-κB and p65 and levels of cytoplasmic p-IKB protein and nuclear p65 protein. RESULTS: Due to the G0/G1 phase arrest, the number of cells in the Tß4 treatment group increased, compared with the model group and the siRNA-Tß4 knockdown group (p<0.01). In the same between-group comparison, apoptotic rate in the Tß4 treatment group increased significantly (p<0.05). The cellular nucleic acid levels of p-IKB and NF-κB/p65 were markedly higher in the model group and the siRNA-Tß4 knockdown group than in the blank control group (p<0.01). The cellular nucleic acid levels of p-IKB and NF-κB/p65 were remarkably lower in the Tß4 treatment group than in the siRNA-Tß4 knockdown group (p<0.01). The expression levels of NF-κB/p65 and NF-κB/p50 were significantly lower in the Tß4 treatment group. The expression levels of cytoplasmic p-IKB and nuclear NF-κB/p65 were lower in the Tß4 treatment group than in the model group (p<0.01). CONCLUSIONS: Tß4 significantly inhibited IL-1ß-induced HSC-LX2 cell proliferation. The mechanism may involve decreased activation of the NF-κB pathway, decreased expression of p-IKB and nuclear translocation of p65. Therefore, Tß4 had the effect of reversing liver fibrosis.

10.
Eur J Neurol ; 26(4): 651-659, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30565793

RESUMO

BACKGROUND AND PURPOSE: Cognitive enhancers are commonly prescribed to people with Alzheimer's disease and related dementias to improve cognition and function. However, their effectiveness for individuals in the pre-stages of dementia, particularly in functional motor outcomes, remains unknown. We aimed to determine the efficacy of donepezil, a cognitive enhancer that improves cholinergic neurotransmission, on gait performance in mild cognitive impairment (MCI). METHODS: This was a double-blind, placebo-controlled trial including 60 older adults with MCI, randomized to receive donepezil (10 mg/daily, maximal dose) or placebo. Primary outcome was gait speed (cm/s) under single and three dual-task conditions (counting backwards by 1 or 7 and naming animals) measured using an electronic walkway. Dual-task gait cost (DTC), a valid measure of motor-cognitive interaction, was calculated as the percentage change between single (S) and dual-task (D) gait speeds: [(S - D)/S] × 100. Secondary outcomes included attention, executive function, balance and falls. RESULTS: After 6 months, the donepezil group experienced an improvement in dual-task gait speed (range 4-11 cm/s), although this was not statistically significant. The donepezil group showed a significant reduction in DTC (improvement) by counting backwards by 1 and 7 compared with placebo (10.25% vs. 1.75%, P = 0.048; 21.38% vs. 14.64%, P = 0.037, intention-to-treat analysis). Per-protocol analyses showed that all three DTCs improved in the donepezil group, along with a non-significant reduction of rate of falls. CONCLUSIONS: Donepezil treatment improved dual-task gait speed and DTC in elderly patients with MCI. Our results support the concept of reducing falls in MCI by targeting the motor-cognitive interface.

11.
Zhonghua Fu Chan Ke Za Zhi ; 53(9): 590-594, 2018 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-30293293

RESUMO

Objective: To evaluate the safety and perinatal outcomes of thoracoamniotic shunting in the treatment of fetuses with severe primary hydrothorax. Methods: 22 cases of suspected severe primary fetal hydrothorax which underwent thoraco-amniotic shunting in Shanghai First Maternity and Infant Hospital, Fetal Medicine Unit and Prenatal Diagnosis Center from January 2012 to December 2017 were analyzed retrospectively. Hydrothorax associated with structural or chromosomal abnormalities, infections and immune fetal hydrops were excluded. Results: Totally, 28 shunts were placed in 22 fetuses. The median gestational age at TAS was 31.3 weeks. Preterm membrane rupture within 7 days after the procedure occurred in 9.1% (2/22) cases. Catheter displacement occurred in 18% (4/22) cases. The interval from shunting to delivery was 26.0 days. One fetus ended in induced abortion; 21 (95%, 21/22) babies were born alive, and their median gestational age at delivery was 34.4 weeks. 62% (13/21) newborns required ventilator supports; 4 neonatal deaths were attributed to pulmonary hypoplasia. The overall perinatal survival rate was 81% (17/21) . The perinatal survival rate with hydrops and without hydrops were 10/13 and 7/8 respectively. Conclusion: Thoraco-amniotic shunting is a safe procedure for intrauterine therapy and could improve the perinatal outcomes of severe primary fetal hydrothorax.


Assuntos
Hidropisia Fetal/cirurgia , Hidrotórax/cirurgia , Âmnio , China , Drenagem/métodos , Feminino , Doenças Fetais/cirurgia , Idade Gestacional , Humanos , Recém-Nascido , Gravidez , Cuidado Pré-Natal , Diagnóstico Pré-Natal , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
12.
Zhonghua Yi Xue Za Zhi ; 98(36): 2910-2913, 2018 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-30293348

RESUMO

Objective: To investigate the clinicopathologic features of lipoprotein glomerulopathy (LPG). Methods: A total of 6 cases (5 males and 1 female, with a mean age of 27.5 years and age range of 11-53 years) of lipoprotein glomerulopathy with complete clinicopathologic data were enrolled. Except for light microscope, immunofluorescence and electron microscopic examination, renal biopsy tissues were checked by oil red O staining. The gene map of apolipoprotein E (ApoE) of 2 cases were analyzed. Results: All 6 cases presented with heavy proteinuria or nephrotic syndrome, and high level of low-density lipoprotein (LDL), very low-density lipoprotein (vLDL), ApoE. Family history of LPG was found in 3 cases, and 2 patients progressed to uremia, or even to death. Pathologic features showed that lipoprotein deposited in glomerulus capillary lumen and renal tubular epithelial cells. Gene analysis demonstrated that 2 cases expressed abnormal ApoE gene (162G>C and 455G>C). Conclusions: Lipoprotein glomerulopathy is autosomal-recessive disease with mutation of ApoE. Common clinical manifestations of LPG are heavy proteinuria or nephrotic syndrome, with a poor prognosis. Renal biopsy pathologic diagnosis can confirm this kidney disease. Emboli of lipoprotein being observed in glomerulus capillary lumen is the pathological feature of LPG.


Assuntos
Nefropatias , Glomérulos Renais , Adolescente , Adulto , Apolipoproteínas E , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica , Proteinúria , Adulto Jovem
13.
Gastroenterology ; 155(3): 687-695.e10, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29857091

RESUMO

BACKGROUND & AIMS: As more treatment options for inflammatory bowel diseases become available, it is important to identify patients most likely to respond to different therapies. We created and validated a scoring system to identify patients with Crohn's disease (CD) who respond to vedolizumab. METHODS: We collected data from the GEMINI 2 phase 3 trial of patients with active CD treated with vedolizumab for 26 weeks (n = 814) and performed logistic regression analysis to identify factors associated with clinical, steroid-free, and durable remission (derivation set). We used these data to develop a clinical decision support tool, which we validated using data from 366 participants in a separate clinical practice observational cohort of patients with active CD treated with vedolizumab for 26 weeks (the VICTORY cohort). We evaluated the ability of this tool to identify patients in clinical remission or corticosteroid-free remission, or those with mucosal healing (MH), clinical remission with MH, or corticosteroid-free remission with MH after vedolizumab therapy using receiver operating characteristic area under the curve (AUC) analyses. The primary outcome was to develop and validate a list of factors associated with achieving remission by vedolizumab in patients with active CD. RESULTS: In the derivation analysis, we identified absence of previous treatment with a tumor necrosis factor antagonist (+3 points), absence of prior bowel surgery (+2 points), absence of prior fistulizing disease (+2 points), baseline level of albumin (+0.4 points per g/L), and baseline concentration of C-reactive protein (reduction of 0.5 points for values between 3.0 and 10.0 mg/L and 3.0 points for values >10.0 mg/L) as factors associated with remission. In the validation set, our model identified patients in clinical remission with an AUC of 0.67, patients in corticosteroid-free remission with an AUC of 0.66, patients with MH with an AUC of 0.72, patients in clinical remission with MH with an AUC of 0.73, and patients in corticosteroid-free clinical remission with MH with an AUC of 0.75. A cutoff value of 13 points identified patients in clinical remission after vedolizumab therapy with 92% sensitivity, patients in corticosteroid-free remission with 94% sensitivity, patients with MH with 98% sensitivity, patients with clinical remission and MH with 100% sensitivity, and patients with corticosteroid-free clinical remission with MH with 100% sensitivity. CONCLUSIONS: We developed and validated a scoring system to identify patients with CD most likely to respond to 26 weeks of vedolizumab therapy. Further studies are needed to optimize its accuracy in select populations and determine its cost-effectiveness.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/administração & dosagem , Quimioterapia de Indução/estatística & dados numéricos , Índice de Gravidade de Doença , Adulto , Área Sob a Curva , Proteína C-Reativa/análise , Feminino , Humanos , Quimioterapia de Indução/métodos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Resultado do Tratamento
14.
BMC Geriatr ; 18(1): 93, 2018 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-29661156

RESUMO

BACKGROUND: Physical exercise, cognitive training, and vitamin D are low cost interventions that have the potential to enhance cognitive function and mobility in older adults, especially in pre-dementia states such as Mild Cognitive Impairment (MCI). Aerobic and progressive resistance exercises have benefits to cognitive performance, though evidence is somewhat inconsistent. We postulate that combined aerobic exercise (AE) and progressive resistance training (RT) (combined exercise) will have a better effect on cognition than a balance and toning control (BAT) intervention in older adults with MCI. We also expect that adding cognitive training and vitamin D supplementation to the combined exercise, as a multimodal intervention, will have synergistic efficacy. METHODS: The SYNERGIC trial (SYNchronizing Exercises, Remedies in GaIt and Cognition) is a multi-site, double-blinded, five-arm, controlled trial that assesses the potential synergic effect of combined AE and RT on cognition and mobility, with and without cognitive training and vitamin D supplementation in older adults with MCI. Two-hundred participants with MCI aged 60 to 85 years old will be randomized to one of five arms, four of which include combined exercise plus combinations of dual-task cognitive training (real vs. sham) and vitamin D supplementation (3 × 10,000 IU/wk. vs. placebo) in a quasi-factorial design, and one arm which receives all control interventions. The primary outcome measure is the ADAS-Cog (13 and plus modalities) measured at baseline and at 6 months of follow-up. Secondary outcomes include neuroimaging, neuro-cognitive performance, gait and mobility performance, and serum biomarkers of inflammation (C reactive protein and interleukin 6), neuroplasticity (brain-derived neurotropic factor), endothelial markers (vascular endothelial growth factor 1), and vitamin D serum levels. DISCUSSION: The SYNERGIC Trial will establish the efficacy and feasibility of a multimodal intervention to improve cognitive performance and mobility outcomes in MCI. These interventions may contribute to new approaches to stabilize and reverse cognitive-mobility decline in older individuals with MCI. TRIAL REGISTRATION: Identifier: NCT02808676. https://www.clinicaltrials.gov/ct2/show/NCT02808676 .


Assuntos
Cognição/fisiologia , Disfunção Cognitiva/reabilitação , Suplementos Nutricionais , Terapia por Exercício/métodos , Tolerância ao Exercício/fisiologia , Marcha/fisiologia , Treinamento de Resistência/métodos , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/psicologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
15.
Aliment Pharmacol Ther ; 47(7): 940-950, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29460418

RESUMO

BACKGROUND: The validity of the eosinophilic oesophagitis (EoE) histologic scoring system (EoEHSS) has been demonstrated, but only preliminary reliability data exist. AIM: Formally assess the reliability of the EoEHSS and additional histologic features. METHODS: Four expert gastrointestinal pathologists independently reviewed slides from adult patients with EoE (N = 45) twice, in random order, using standardised training materials and scoring conventions for the EoEHSS and additional histologic features agreed upon during a modified Delphi process. Intra- and inter-rater reliability for scoring the EoEHSS, a visual analogue scale (VAS) of overall histopathologic disease severity, and additional histologic features were assessed using intra-class correlation coefficients (ICCs). RESULTS: Almost perfect intra-rater reliability was observed for the composite EoEHSS scores and the VAS. Inter-rater reliability was also almost perfect for the composite EoEHSS scores and substantial for the VAS. Of the EoEHSS items, eosinophilic inflammation was associated with the highest ICC estimates and consistent with almost perfect intra- and inter-rater reliability. With the exception of dyskeratotic epithelial cells and surface epithelial alteration, ICC estimates for the remaining EoEHSS items were above the benchmarks for substantial intra-rater, and moderate inter-rater reliability. Estimation of peak eosinophil count and number of lamina propria eosinophils were associated with the highest ICC estimates among the exploratory items. CONCLUSION: The composite EoEHSS and most component items are associated with substantial reliability when assessed by central pathologists. Future studies should assess responsiveness of the score to change after a therapeutic intervention to facilitate its use in clinical trials.


Assuntos
Esofagite Eosinofílica/diagnóstico , Técnicas Histológicas , Adulto , Esofagite Eosinofílica/patologia , Eosinófilos/patologia , Feminino , Técnicas Histológicas/normas , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Escala Visual Analógica
16.
Cochrane Database Syst Rev ; 1: CD011450, 2018 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-29338066

RESUMO

BACKGROUND: Endoscopic assessment of mucosal disease activity is routinely used to determine eligibility and response to therapy in clinical trials of ulcerative colitis. The operating properties of the existing endoscopic scoring indices are unclear. OBJECTIVES: A systematic review was undertaken to evaluate the development and operating characteristics of endoscopic scoring indices for the evaluation of ulcerative colitis. SEARCH METHODS: We searched MEDLINE, Embase and CENTRAL from inception to 5 July 2016. We also searched references and conference proceedings (Digestive Disease Week, United European Gastroenterology Week, European Crohn's and Colitis Organization). SELECTION CRITERIA: Any study design (e.g. randomized controlled trials, cohort studies, case series) that evaluated endoscopic indices for evaluation of ulcerative colitis disease activity were considered for inclusion. Eligible participants were adult patients (> 16 years), diagnosed with ulcerative colitis using conventional clinical, radiologic and endoscopic criteria. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed the studies identified from the literature search. These authors also independently extracted and recorded data on the number of patients enrolled; number of patients per treatment arm; patient characteristics including age and gender distribution; endoscopic index; and outcomes such as reliability (intra-rater and inter-rater), validity (content, construct, criterion), responsiveness and feasibility. Any disagreements regarding study inclusion or data extraction were resolved by discussion and consensus with a third author. Risk of bias was assessed by determining whether assessors were blinded to clinical information and whether assessors scored the endoscopic index independently. We also assessed the methodological quality of the validation studies using the COSMIN checklist MAIN RESULTS: A total of 23 reports of 20 studies met the pre-defined inclusion criteria and were included in the review. Of the 20 included validation studies, 19 endoscopic scoring indices were assessed, including the Azzolini Classification, Baron Score, Blackstone Endoscopic Interpretation, Chinese Grading System of Ulcerative Colitis, Endoscopic Activty Index, Jeroen Score, Magnifying Colonoscopy Grade, Matts Score, Mayo Clinic Endoscopic Subscore, Modified Baron Score, Modified Mayo Clinic Endoscopic Subscore, Osada Score, Rachmilewtiz Endoscopic Score, St. Mark's Index, Ulcerative Colitis Colonoscopic Index of Serverity (UCCIS), endoscopic component of the Ulcerative Colitis Disease Activity Index (UCDAI), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), Witts Sigmoidoscopic Score and Watson Grade. The individuals who performed the endoscopic scoring were blinded to clinical and/or histologic information in ten of the included studies, not blinded to clinical and/or histologic information in one of the included studies, and it was unclear whether blinding occurred in the remaining nine included studies. Independent observation was confirmed in four of the included studies, unclear in five of the included studies, and non-applicable (since inter-rater reliability was not assessed) in the remaining eleven included studies. The methodological quality (COSMIN checklist) of most of the included studies was rated as 'good' or 'excellent'. One study that assessed responsiveness was rated as 'fair'. The inter-rater reliability of nine endoscopic scoring indices including the Baron Score, Blackstone Endoscopic Interpretation, Endoscopic Activity Index, Matts Score, Mayo Clinic Endoscopic Subscore, Osada Score, UCCIS, UCEIS, Watson Grade was assessed in seven studies, with estimates of correlation, ƙ, ranging from 0.44 to 0.97. The iIntra-rater reliability of seven endoscopic scoring indices including the Baron Score, Blackstone Endoscopic Interpretation, Matts Score, Mayo Clinic Endoscopic Subscore, Osada Score, UCCIS and UCEIS was assessed in three studies, with estimates of correlation, ƙ, ranging from 0.41 to 0.86. No studies assessed content validity. Three studies evaluated the criterion validity of three endoscopic scoring indices including the Rachmilewitz Endoscopic Score, Magnifying Colonoscopy Grade and the UCCIS. These indices were correlated with objective markers of disease activity including albumin, blood leukocytes, C-reactive protein, fecal calprotectin, hemoglobin, mucosal interleukin-8 concentration and platelet count. Correlation estimates ranged from r = -0.19 to 0.83. Thirteen endoscopic scoring indices were tested for construct validity in 13 studies. Estimates of correlation between the endoscopic scoring indices and other measures of disease activity ranged from r = 0.27 to 0.93. Two studies explored the responsiveness of four endoscopic scoring indices including the Mayo Endoscopic Subscore, Modified Baron Score, Modified Mayo Endoscopic Subscore and UCEIS. One study concluded that the Modified Baron Score, Modified Mayo Endoscopic Subscore and UCEIS had similar responsiveness for detecting disease change in ulcerative colitis. The other included study concluded that the UCEIS may be the most accurate endoscopic scoring tool. None of the included studies formally assessed feasibility. AUTHORS' CONCLUSIONS: While the UCEIS, UCCIS and Mayo Clinic Endoscopic Subscore have undergone extensive validation, none of these instruments have been fully validated and only two studies assessed responsiveness. Further research on the operating properties of these indices is needed given the lack of a fully-validated endoscopic scoring instrument for the evaluation of disease activity in ulcerative colitis.


Assuntos
Colite Ulcerativa/diagnóstico , Colonoscopia , Colite Ulcerativa/patologia , Humanos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Sigmoidoscopia
17.
Stat Methods Med Res ; 27(8): 2478-2503, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-27932666

RESUMO

Double-sampling schemes using one classifier assessing the whole sample and another classifier assessing a subset of the sample have been introduced for reducing classification errors when an infallible or gold standard classifier is unavailable or impractical. Inference procedures have previously been proposed for situations where an infallible classifier is available for validating a subset of the sample that has already been classified by a fallible classifier. Here, we consider the case where both classifiers are fallible, proposing and evaluating several confidence interval procedures for a proportion under two models, distinguished by the assumption regarding ascertainment of two classifiers. Simulation results suggest that the modified Wald-based confidence interval, Score-based confidence interval, two Bayesian credible intervals, and the percentile Bootstrap confidence interval performed reasonably well even for small binomial proportions and small validated sample under the model with the conditional independent assumption, and the confidence interval derived from the Wald test with nuisance parameters appropriately evaluated, likelihood ratio-based confidence interval, Score-based confidence interval, and the percentile Bootstrap confidence interval performed satisfactory in terms of coverage under the model without the conditional independent assumption. Moreover, confidence intervals based on log- and logit-transformations also performed well when the binomial proportion and the ratio of the validated sample are not very small under two models. Two examples were used to illustrate the procedures.


Assuntos
Modelos Estatísticos , Fatores Etários , Teorema de Bayes , Simulação por Computador , Intervalos de Confiança , Anormalidades Congênitas/epidemiologia , Humanos , Funções Verossimilhança , Malária/epidemiologia , Prevalência
18.
Cochrane Database Syst Rev ; 9: CD011572, 2017 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-28886205

RESUMO

BACKGROUND: It is important to minimize placebo rates in randomised controlled trials (RCTs) to efficiently detect treatment differences between interventions. Historically, high placebo rates have been observed in clinical trials of ulcerative colitis (UC). A better understanding of factors influencing placebo rates may lead to more informed clinical trial design. OBJECTIVES: A systematic review and meta-analysis was conducted to evaluate placebo response and remission rates in RCTs evaluating UC treatments in adult patients. SEARCH METHODS: Electronic databases (i.e. MEDLINE, EMBASE, and CENTRAL) were searched from inception to 1 March 2017 with no language restrictions applied. Reference lists and conference proceedings of major gastroenterology meetings were also handsearched to identify additional studies. SELECTION CRITERIA: Placebo-controlled RCTs of adult patients with UC treated with corticosteroids, aminosalicylates, immunosuppressives or biologics were eligible, provided enrolment and outcome assessment was conducted using the Ulcerative Colitis Disease Activity Index (UCDAI) or the Mayo Clinic Score. The minimum trial duration was two weeks for induction trials and four months maintenance trials. DATA COLLECTION AND ANALYSIS: Pairs of authors independently determined study eligibility and extracted data with any disagreements resolved through consensus. Outcomes of interest included the proportion of patients with clinical response and remission. Trial characteristics such as the design, participant demographics and disease history, interventions, and enrolment and assessment criteria were also recorded. The methodological quality of the included studies was evaluated using the Cochrane risk of bias tool. Pooled placebo response and remission rates and 95% confidence intervals (95% CI) were calculated using a binomial normal model for proportions. Induction of remission and maintenance studies were pooled separately. The impact of study-level characteristics on placebo response and remission rates was investigated using mixed-effects meta-regression analyses with logits of event rates as the outcome variables. An assessment of pooled placebo rates over time was conducted using a cumulative meta-analysis based on date of publication. Publication bias was examined using funnel plots. MAIN RESULTS: The screening process identified 61 included studies which encompass 58 induction phases (5111 patients randomised to placebo) and 12 maintenance phases (1579 patients randomised to placebo). For induction trials, the pooled estimate of placebo response was 33% (95% CI 30% to 36%) while the pooled estimate of placebo remission was 12% (95% CI 9% to 15%). For maintenance trials, the pooled estimate of placebo response was 23% (95% CI 19% to 28%) while the pooled estimate of placebo remission was 17% (95% CI 10% to 27%).Studies enrolling patients with more active disease confirmed objectively by endoscopy were associated with significantly lower placebo remission and response rates than trials enrolling patients with less active disease (27% versus 4%, OR 2.60, 95% CI 1.25 to 5.42, P = 0.01 for UCDAI endoscopy sub score ≥1 versus ≥ 2 for remission; and 27% versus 4%, OR 1.70, 95% CI 1.02 to 2.82, P = 0.02 for UCDAI endoscopy sub score greater than or equal to one versus greater than or equal to two for response). With respect to drug class, the lowest placebo response and remission rates were observed in trials evaluating corticosteroids (23%; 95% CI 19 to 29%, and 5%; 95% CI 2 to 11%, respectively). Trials of biologics had the highest placebo response rate (35%; 95% CI 30 to 41%), while trials evaluating aminosalicylates had the highest placebo remission rate (18%; 95% CI 12 to 24%). Disease duration of greater than five years prior to enrolment was associated with a significantly lower placebo response rate compared to disease duration of less than or equal to five years (29% versus 47%, respectively; OR 0.54, 95% CI 0.32 to 0.92, P = 0.02). The requirement of a minimum rectal bleeding score for study eligibility was associated with an increased placebo response rate compared to studies that did not use rectal bleeding for trial eligibility (37% versus 32%, respectively; OR 1.70, 95% CI 1.02 to 2.82, P = 0.02). Finally, the time point of primary outcome assessment was found to be significantly associated with placebo remission rates such that every one week increment in endpoint assessment was associated with a 6% increase in the placebo remission rate (OR 1.06, 95% CI 1.02 to 1.10, P = 0.01).Cumulative meta-analysis indicated a consistent increase in the placebo response rate from 1987 to 2007 (from 13% to 33%), although rates have remained constant from 2008 to 2015 (32% to 34%). Similarly, placebo remission rates increased from 1987 to 2007 (5% to 14%) but have remained constant from 2008 to 2015 (12 to 14%). On meta-regression, there were no statistically significant differences between the 1987-2007 and 2008-2015 point estimates for both response (P = 0.81) and remission (P = 0.32). AUTHORS' CONCLUSIONS: Placebo response and remission rates vary according to endoscopic disease severity and rectal bleeding score at trial entry, class of agent, disease duration, and the time point at which the primary outcome was measured. These observations have important implications for the design and conduct of future clinical trials in UC and will help researchers design trials, determine required sample sizes and also provide useful information about trial design features which should be considered when planning new trials.


Assuntos
Ácidos Aminossalicílicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Produtos Biológicos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Quimioterapia de Indução , Quimioterapia de Manutenção , Adulto , Hemorragia Gastrointestinal/complicações , Hemorragia Gastrointestinal/diagnóstico , Humanos , Quimioterapia de Indução/estatística & dados numéricos , Quimioterapia de Manutenção/estatística & dados numéricos , Efeito Placebo , Ensaios Clínicos Controlados Aleatórios como Assunto , Reto
19.
Gastrointest Endosc ; 86(6): 1079-1087, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28760533

RESUMO

BACKGROUND AND AIMS: EUS is a potentially useful modality to assess severity of inflammation in ulcerative colitis (UC). We assessed the reliability of existing EUS indices and correlated them with endoscopic and histologic scores. METHODS: Four blinded endosonographers assessed 58 endoscopic and EUS videos in triplicate, from patients with UC. Intrarater and interrater reliability of the hyperemia and Tsuga scores were estimated by using intra-class correlation coefficients (ICCs). Correlation with the Mayo endoscopy score, modified Baron score (MBS), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and Geboes histopathology score (GHS) were calculated by using bootstrapping methods. A RAND consensus process led to development of standardized definitions and a revised EUS-UC score. RESULTS: ICCs for intrarater reliability were 0.76 (95% confidence interval [CI], 0.71-0.80) for the hyperemia score and 0.85 (95% CI, 0.79-0.89) for the Tsuga score. Corresponding values for interrater reliability were 0.34 (95% CI, 0.25-0.42) and 0.36 (95% CI, 0.24-0.46). Correlation between hyperemia and Tsuga scores to Mayo scoring system, MBS, UCEIS, and the GHS were 0.39 (95% CI, 0.15-0.61) and 0.28 (95% CI, 0.04-0.51), 0.38 (95% CI, 0.16-0.57) and 0.25 (95% CI, -0.01-0.48), 0.41 (95% CI, 0.16-0.62) and 0.27 (95% CI, 0.01-0.50), 0.37 (95% CI, -0.01-0.48) and 0.24 (95% CI, 0.13-0.57), respectively. The revised EUS-UC score included bowel wall thickening, depth of inflammation, and hyperemia. CONCLUSIONS: Although substantial to almost perfect intrarater agreement existed for EUS indices in UC, interrater agreement was fair. Standardization of item definitions with development of a revised evaluative instrument has potential application as an evaluative and prognostic tool for UC. (Clinical trial registration number: NCT01852760.).


Assuntos
Colite Ulcerativa/diagnóstico por imagem , Colite Ulcerativa/patologia , Endossonografia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colonoscopia , Feminino , Humanos , Hiperemia/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Método Simples-Cego , Gravação em Vídeo , Adulto Jovem
20.
Aliment Pharmacol Ther ; 46(3): 292-302, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28568974

RESUMO

BACKGROUND: High concentration mesalazine formulations are more convenient than conventional low concentration formulations for the treatment of ulcerative colitis (UC). AIM: To compare the efficacy and safety of 1600 mg and 400 mg tablet mesalazine formulations. METHODS: Patients with mild-to-moderate active UC (Mayo Clinic Score >5; N=817) were randomised to 3.2 g of oral mesalazine, administered as two 1600 mg tablets once, or four 400 mg tablets twice daily. We hypothesised that treatment with the 1600 mg tablet was non-inferior (within a 10% margin) to the 400 mg tablet for induction of clinical and endoscopic remission at week 8. Open-label treatment with the 1600 mg tablet continued for 26-30 weeks based on induction response. Predictors of treatment response were also explored. RESULTS: At week 8, remission occurred in 22.4% and 24.6% of patients receiving the 1600 mg and 400 mg tablets, respectively (absolute difference -2.2%, 95% CI: -8.1% to 3.8%, non-inferiority P=.005). Endoscopic and histopathologic disease activity, leucocyte concentration and age were significantly associated with clinical remission (P=.022, .042, .014 and .023, respectively). At week 38, 43.9% (296/675) of patients who continued treatment with the 1600 mg formulation were in remission, including 70.3% (142/202) of patients who received a reduced dose of mesalazine (1.6 g/d). The overall incidence of serious adverse events was low. CONCLUSIONS: Induction therapy with 3.2 mg mesalazine using two 1600 mg tablets once-daily was statistically and clinically non-inferior to a twice-daily regimen using four 400 mg tablets (NCT01903252).


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Mesalamina/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Química Farmacêutica , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Indução de Remissão , Comprimidos
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