RESUMO
OBJECTIVE: A lack of universal definitions for response and remission in pediatric obsessive-compulsive disorder (OCD) has hampered the comparability of results across trials. To address this problem, we conducted an individual participant data diagnostic test accuracy meta-analysis to evaluate the discriminative ability of the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) in determining response and remission. We also aimed to generate empirically derived cutoffs on the CY-BOCS for these outcomes. METHOD: A systematic review of PubMed, PsycINFO, Embase and CENTRAL identified 5,401 references; 42 randomized controlled clinical trials were considered eligible, and 21 provided data for inclusion (N = 1,234). Scores of ≤2 in the Clinical Global Impressions Improvement and Severity scales were chosen to define response and remission, respectively. A 2-stage, random-effects meta-analysis model was established. The area under the curve (AUC) and the Youden Index were computed to indicate the discriminative ability of the CY-BOCS and to guide for the optimal cutoff, respectively. RESULTS: The CY-BOCS had sufficient discriminative ability to determine response (AUC = 0.89) and remission (AUC = 0.92). The optimal cutoff for response was a ≥35% reduction from baseline to posttreatment (sensitivity = 83.9, 95% CI = 83.7-84.1; specificity = 81.7, 95% CI = 81.5-81.9). The optimal cutoff for remission was a posttreatment raw score of ≤12 (sensitivity = 82.0, 95% CI = 81.8-82.2; specificity = 84.6, 95% CI = 84.4-84.8). CONCLUSION: Meta-analysis identified empirically optimal cutoffs on the CY-BOCS to determine response and remission in pediatric OCD randomized controlled clinical trials. Systematic adoption of standardized operational definitions for response and remission will improve comparability across trials for pediatric OCD.
Assuntos
Transtorno Obsessivo-Compulsivo , Criança , Humanos , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Projetos de PesquisaRESUMO
BACKGROUND: Trichotillomania (TTM) is a difficult-to-treat psychiatric condition with no first-line medications approved by the Food and Drug Administration. Individuals with TTM often feel that clinicians know little about this disorder. Here, we present an updated meta-analysis of randomized controlled trials (RCTs) examining treatments for TTM. METHODS: Pubmed, PsychINFO, Embase, and CENTRAL were searched with the terms "Trichotillomania OR Hair Pulling Disorder" to identify randomized controlled clinical trials evaluating treatments for TTM. RESULTS: Twenty-four trials involving 26 comparisons and 857 participants were included in this meta-analysis. Behavioral therapy with habit-reversal training components (BT-HRT) demonstrated a large benefit compared to control conditions (standardized mean difference [SMD] [95% CI] = -1.22 [-1.71, -0.73], p < .0001) for improving TTM symptoms. Clomipramine (SMD [95% CI] = -0.71 [-1.38, -0.05], p = .036), N-acetylcysteine (SMD [95% CI] = -0.75 [-1.36, -0.13], p = .017) and olanzapine (SMD [95% CI] = -0.94 [-1.77, -0.12], p = .025) demonstrated significant benefits compared to placebo in RCTs. CONCLUSIONS: BT-HRT has demonstrated the largest treatment effects and has the strongest evidence base for reducing TTM symptoms. In contrast, several pharmacological agents have demonstrated efficacy in single randomized clinical trials that would benefit from replication. Additional trials are needed to identify other effective medications for TTM and determine the relative efficacy of available agents.
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Tricotilomania , Acetilcisteína , Terapia Comportamental , Clomipramina/uso terapêutico , Humanos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Tricotilomania/tratamento farmacológicoRESUMO
Objectives: In clinical trials of pediatric trichotillomania (TTM), three instruments are typically employed to rate TTM severity: (1) the Massachusetts General Hospital Hair Pulling Scale (MGH-HPS), (2) the National Institute of Mental Health Trichotillomania Severity Scale (NIMH-TSS), and (3) the Trichotillomania Scale for Children (TSC). These instruments lack standardized definitions of treatment response, which lead researchers to determine their own definitions of response post hoc and potentially inflate results. We performed a meta-analysis to provide empirically determined accuracy measures for percentage reduction cut points in these three instruments. Methods: MEDLINE was searched for TTM clinical trials. A total of 67 studies were initially identified, but only 5 were clinical trials focused on TTM in pediatric populations and therefore were included in this meta-analysis (n = 180). A Clinical Global Impressions Improvement score ≤2 was used to define clinical response. Receiver operating characteristic principles were employed to determine accuracy measures for percentage reduction cut points on each one of the instruments. Meta-DiSc software was employed to provide pooled accuracy measures for each cut point for each instrument. The Youden Index and the distance to corner methods were used to determine the optimal cut point. Results: The optimal cut points to determine treatment response were a 45% reduction on the MGH-HPS (Youden Index 0.40, distance to corner 0.20), a 35% reduction on the NIMH-TSS (Youden Index 0.42, distance to corner 0.17), a 25% reduction on the TSC child version (TSC-C; Youden Index 0.40, distance to corner 0.18), and a 45% (distance to corner 0.30) or 50% reduction (Youden Index 0.33) on the TSC parent version (TSC-P). The TSC-C had less discriminative ability at determining response in younger children in comparison to older children; no age-related differences were observed on the TSC-P. Conclusions: This study provides empirically determined cut points of treatment response on three instruments that rate TTM severity. These data-driven cut points will benefit future research on pediatric TTM.
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Tricotilomania/terapia , Adolescente , Fatores Etários , Criança , Humanos , Índice de Gravidade de Doença , Resultado do Tratamento , Tricotilomania/fisiopatologiaRESUMO
PURPOSE: To investigate the effects of exenatide on renal injury in streptozotocin-induced diabetic rats. METHODS: Fifty SD rats were randomly divided into normal control, model, exenatide-1, exenatide-2 and exenatide-3 groups, 10 rats in each group. The diabetic nephropathy model was constructed in later 4 groups. Then, the later 3 groups were treated with 2, 4 and 8 µg/kg exenatide for 8 weeks, respectively. The serum and urine biochemical indexes and oxidative stress and inflammatory indexes in renal tissue were determined. RESULTS: Compared to the model group, in exenatide-3 group the serum fasting plasma glucose and hemoglobin A1c levels were significantly decreased, the fasting insulin level was significantly increased, the renal index and blood urea nitrogen, serum creatinine and 24 h urine protein levels were significantly decreased, the renal tissue superoxide dismutase and glutathione peroxidase levels were significantly increased, the malondialdehyde level was significantly decreased, and the renal tissue tumor necrosis factor alpha, interleukin 6, hypersensitive C-reactive protein and chemokine (C-C motif) ligand 5 levels were significantly decreased P<0.05). CONCLUSIONS: Exenatide can mitigate the renal injury in diabetic rats. The mechanisms may be related to its resistance of oxidative stress and inflammatory response in renal tissue.
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Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Exenatida/uso terapêutico , Animais , Diabetes Mellitus Experimental/fisiopatologia , Nefropatias Diabéticas/prevenção & controle , Modelos Animais de Doenças , Rim/efeitos dos fármacos , Masculino , Estresse Oxidativo , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
Purpose:To investigate the effects of exenatide on renal injury in streptozotocin-induced diabetic rats.Methods:Fifty SD rats were randomly divided into normal control, model, exenatide-1, exenatide-2 and exenatide-3 groups, 10 rats in each group. The diabetic nephropathy model was constructed in later 4 groups. Then, the later 3 groups were treated with 2, 4 and 8 μg/kg exenatide for 8 weeks, respectively. The serum and urine biochemical indexes and oxidative stress and inflammatory indexes in renal tissue were determined.Results:Compared to the model group, in exenatide-3 group the serum fasting plasma glucose and hemoglobin A1c levels were significantly decreased, the fasting insulin level was significantly increased, the renal index and blood urea nitrogen, serum creatinine and 24 h urine protein levels were significantly decreased, the renal tissue superoxide dismutase and glutathione peroxidase levels were significantly increased, the malondialdehyde level was significantly decreased, and the renal tissue tumor necrosis factor alpha, interleukin 6, hypersensitive C-reactive protein and chemokine (C-C motif) ligand 5 levels were significantly decreased P<0.05).Conclusions:Exenatide can mitigate the renal injury in diabetic rats. The mechanisms may be related to its resistance of oxidative stress and inflammatory response in renal tissue.(AU)
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Animais , Ratos , Incretinas/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/análise , Diabetes Mellitus Experimental , Injúria Renal Aguda/tratamento farmacológico , Modelos Animais de DoençasRESUMO
Abstract Purpose: To investigate the effects of exenatide on renal injury in streptozotocin-induced diabetic rats. Methods: Fifty SD rats were randomly divided into normal control, model, exenatide-1, exenatide-2 and exenatide-3 groups, 10 rats in each group. The diabetic nephropathy model was constructed in later 4 groups. Then, the later 3 groups were treated with 2, 4 and 8 μg/kg exenatide for 8 weeks, respectively. The serum and urine biochemical indexes and oxidative stress and inflammatory indexes in renal tissue were determined. Results: Compared to the model group, in exenatide-3 group the serum fasting plasma glucose and hemoglobin A1c levels were significantly decreased, the fasting insulin level was significantly increased, the renal index and blood urea nitrogen, serum creatinine and 24 h urine protein levels were significantly decreased, the renal tissue superoxide dismutase and glutathione peroxidase levels were significantly increased, the malondialdehyde level was significantly decreased, and the renal tissue tumor necrosis factor alpha, interleukin 6, hypersensitive C-reactive protein and chemokine (C-C motif) ligand 5 levels were significantly decreased P<0.05). Conclusions: Exenatide can mitigate the renal injury in diabetic rats. The mechanisms may be related to its resistance of oxidative stress and inflammatory response in renal tissue.