scholarly journals Comparative Remission Rates and Tolerability of Drugs for Generalised Anxiety Disorder: A Systematic Review and Network Meta-analysis of Double-Blind Randomized Controlled Trials

2020 ◽  
Vol 11 ◽  
Author(s):  
Wenqiang Kong ◽  
Huiyuan Deng ◽  
Jie Wan ◽  
Yilu Zhou ◽  
Yan Zhou ◽  
...  

Background: Generalized anxiety disorder (GAD) is one of the most common psychiatric disorders associated with substantial dysfunction and socioeconomic burden. Pharmacotherapy is the first choice for GAD. Remission [Hamilton Anxiety Scale (HAM-A) score ≤7] is regarded as a crucial treatment goal for patients with GAD. There is no up-to-date evidence to compare remission rate and tolerability of all available drugs by using network meta-analysis. Therefore, the goal of our study is to update evidence and determine the best advantageous drugs for GAD in remission rate and tolerability profiles.Method: We performed a systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs). We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, wanfang data, China Biology Medicine and ClinicalTrials.gov from their inception to March 2020 to identify eligible double-blind, RCTs reporting the outcome of remission in adult patients who received any pharmacological treatment for GAD. Two reviewers independently assessed quality of included studies utilizing the Cochrane Collaboration’s risk of bias tool as described in Cochrane Collaboration Handbook and extracted data from all manuscripts. Our outcomes were remission rate (proportion of participants with a final score of seven or less on HAM-A) and tolerability (treatments discontinuations due to adverse events). We calculated summary odds ratios (ORs) and 95% confidence intervals (CIs) of each outcome via pairwise and network meta-analysis with random effects.Results: Overall, 30 studies were included, comprising 32 double-blind RCTs, involving 13,338 participants diagnosed as GAD by DSM-IV criteria. Twenty-eight trials were rated as moderate risk of bias, four trials as low. For remission rate, agomelatine (OR 2.70, 95% CI 1.74–4.19), duloxetine (OR 1.88, 95% CI 1.47–2.40), escitalopram (OR 2.03, 95% CI 1.48–2.78), paroxetine (OR 1.74, 95% CI 1.25–2.42), quetiapine (OR 1.88, 95% CI 1.39–2.55), and venlafaxine (OR 2.28, 95% CI 1.69–3.07) were superior to placebo. For tolerability, sertraline, agomelatine, vortioxetine, and pregabalin were found to be comparable to placebo. However, the others were worse than placebo in terms of tolerability, with ORs ranging between 1.86 (95% CI 1.25–2.75) for tiagabine and 5.98 (95% CI 2.41–14.87) for lorazepam. In head-to-head comparisons, agomelatine, duloxetine, escitalopram, quetiapine, and venlafaxine were more efficacious than tiagabine in terms of remission rate, ORs from 1.66 (95% CI 1.04–2.65) for duloxetine to 2.38 (95% CI 1.32–4.31) for agomelatine. We also found that agomelatine (OR 2.08, 95% CI 1.15–3.75) and venlafaxine (OR 1.76, 95% CI 1.08–2.86) were superior to vortioxetine. Lorazepam and quetiapine were poorly tolerated when compared with other drugs.Conclusions: Of these interventions, only agomelatine manifested better remission with relatively good tolerability but these results were limited by small sample sizes. Duloxetine, escitalopram, venlafaxine, paroxetine, and quetiapine showed better remission but were poorly tolerated.

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2984
Author(s):  
Stepan M. Esagian ◽  
Christos D. Kakos ◽  
Emmanouil Giorgakis ◽  
Lyle Burdine ◽  
J. Camilo Barreto ◽  
...  

The role of adjuvant transarterial chemoembolization (TACE) for patients with resectable hepatocellular carcinoma (HCC) undergoing hepatectomy is currently unclear. We performed a systematic review of the literature using the MEDLINE, Embase, and Cochrane Library databases. Random-effects meta-analysis was carried out to compare the overall survival (OS) and recurrence-free survival (RFS) of patients with resectable HCC undergoing hepatectomy followed by adjuvant TACE vs. hepatectomy alone in randomized controlled trials (RCTs). The risk of bias was assessed using the Risk of Bias 2.0 tool. Meta-regression analyses were performed to explore the effect of hepatitis B viral status, microvascular invasion, type of resection (anatomic vs. parenchymal-sparing), and tumor size on the outcomes. Ten eligible RCTs, reporting on 1216 patients in total, were identified. The combination of hepatectomy and adjuvant TACE was associated with superior OS (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.52 to 0.85; p < 0.001) and RFS (HR: 0.70, 95% CI: 0.56 to 0.88; p < 0.001) compared to hepatectomy alone. There were significant concerns regarding the risk of bias in most of the included studies. Overall, adjuvant TACE may be associated with an oncologic benefit in select HCC patients. However, the applicability of these findings may be limited to Eastern Asian populations, due to the geographically restricted sample. High-quality multinational RCTs, as well as predictive tools to optimize patient selection, are necessary before adjuvant TACE can be routinely implemented into standard practice. PROSPERO Registration ID: CRD42021245758.


2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
José Francisco Meneses-Echávez ◽  
Emilio González-Jiménez ◽  
Robinson Ramírez-Vélez

Objective. Cancer-related fatigue (CRF) is the most common and devastating problem in cancer patients even after successful treatment. This study aimed to determine the effects of supervised multimodal exercise interventions on cancer-related fatigue through a systematic review and meta-analysis.Design. A systematic review was conducted to determine the effectiveness of multimodal exercise interventions on CRF. Databases of PubMed, CENTRAL, EMBASE, and OVID were searched between January and March 2014 to retrieve randomized controlled trials. Risk of bias was evaluated using the PEDro scale.Results. Nine studiesn=772were included in both systematic review and meta-analysis. Multimodal interventions including aerobic exercise, resistance training, and stretching improved CRF symptoms (SMD=-0.23; 95% CI: −0.37 to −0.09;P=0.001). These effects were also significant in patients undergoing chemotherapyP<0.0001. Nonsignificant differences were found for resistance training interventionsP=0.30. Slight evidence of publication bias was observedP=0.04. The studies had a low risk of bias (PEDro scale mean score of 6.4 (standard deviation (SD) ± 1.0)).Conclusion. Supervised multimodal exercise interventions including aerobic, resistance, and stretching exercises are effective in controlling CRF. These findings suggest that these exercise protocols should be included as a crucial part of the rehabilitation programs for cancer survivors and patients during anticancer treatments.


2017 ◽  
Vol 11 (1) ◽  
pp. 346-354 ◽  
Author(s):  
Kannan Sridharan ◽  
Gowri Sivaramakrishnan

Introduction: Meibomian Gland Dysfunction (MGD) is a common, often overlooked, chronic condition affecting eyes for which various therapies are being evaluated. Considering the absence of a systematic review and meta-analysis, the present review was carried out. Methods: An appropriate search strategy eligibility criteria were framed and electronic databases were scrutinized for appropriate literature. Randomized Controlled Trials (RCTs) enrolling patients diagnosed with MGD were included. Outcome measures were Tear Break Up Time (TBUT), Schirmer’s test, Meibomian Gland (MG) secretion score, MG plugging score, OSDI and SPEED. Cochrane’s tool was used to assess the risk of bias and Forest plot were generated either with fixed or random effects model, with Standardized Mean Difference (SMD). Results: TBUTs, Schirmer’s test and OSDI scores for systemic antimicrobials with placebo were 1.58 [1.33, 1.83], 2.93 [0.78, 5.09] and -3.58 [-4.28, -2.89] respectively. No quantitative synthesis was attempted for either mebiomian plugging or meibomian secretion scores and no significant changes were observed with any other outcome parameter. Conclusion: Only the systemic antimicrobials were found to improve the clinical features of meibomian gland dysfunction. Varying effects of different therapeutic agents (heat therapies, omega-3-fatty acids and castor oil) were identified for MGD but the risk of bias pertaining to randomization and allocation concealment was found to be associated with most of the current RCTs. More high quality evidence is required to confirm the findings of the present review.


2020 ◽  
Vol 112 (1) ◽  
pp. 48-56
Author(s):  
Guoqi Cai ◽  
Jing Tian ◽  
Tania Winzenberg ◽  
Feitong Wu

ABSTRACT Background Clinical trials evaluating the effect of calcium supplementation on bone loss in lactating women have been small, with inconsistent results. Objectives We aimed to determine the effect of calcium supplementation on bone mineral density (BMD) in lactating women. Methods An electronic search of databases was conducted from inception to January 2020. Two authors screened studies, extracted data, and assessed the risk of bias of eligible studies. Percentage change in BMD was pooled using random-effects models and reported as weighted mean differences (WMDs) with 95% CIs. Risk of bias was assessed using the Cochrane risk of bias tool. Results Five randomized controlled trials including 567 lactating women were included. All had a high risk of bias. Mean baseline calcium intake ranged from 562 to 1333 mg/d. Compared with control groups (placebo/no intervention), calcium supplementation (600/1000 mg/d) had no significant effect on BMD at the lumbar spine (WMD: 0.74%; 95% CI: −0.10%, 1.59%; I2 = 47%; 95% CI: 0%, 81%; n = 527 from 5 trials) or the forearm (WMD: 0.53%; 95% CI: −0.35%, 1.42%; I2 = 55%; 95% CI: 0%, 85%; n = 415 from 4 trials). BMD at other sites was assessed in single trials: calcium supplementation had a small to moderate effect on total-hip BMD (WMD: 3.3%; 95% CI: 1.5%, 5.1%) but no effect on total body or femoral neck BMD. Conclusions Overall, the meta-analysis indicates that calcium supplementation does not provide clinically important benefits for BMD in lactating women. However, there was adequate dietary intake before supplementation in some studies, and others did not measure baseline calcium intake. Advising lactating women to meet the current recommended calcium intakes (with supplementation if dietary intake is low) is warranted unless new high-certainty evidence to the contrary from robust clinical trials becomes available. More research needs to be done in larger samples of women from diverse ethnic and racial groups. This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42015022092.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 489-489
Author(s):  
Victoria Chen ◽  
Andreea Zurbau ◽  
Amna Ahmed ◽  
Tauseef Khan ◽  
Cyril Kendall ◽  
...  

Abstract Objectives Current approved health claims in Canada, US and Europe recognize the ability of oat ß-glucan to lower blood cholesterol; however, its ability to improve glycemic control is less certain. We undertook a systematic review and meta-analysis of randomized controlled trials to update the evidence of the effect of oats and oat-fiber on markers of glycemic control in people with and without diabetes. Here we present data for the subgroup with diabetes. Methods MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through September 23rd, 2020. We included randomized controlled trials of ≥ 2-weeks of sources of oat ß-glucan and measures of glycemic control in diabetes. Two independent reviewers extracted relevant data and assessed the risk of bias (Cochrane Risk of Bias 2.0 Tool). The outcomes were fasting plasma glucose (FPG), 2h-plasma glucose (2h-PG) from a 75 g-oral glucose tolerance test, HbA1c and fasting plasma insulin (FPI). Data were pooled using the generic inverse variance method. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). Pooled estimates were expressed as mean differences with 95% confidence intervals (CI). GRADE assessed the certainty of the evidence. Results Eligibility criteria were met by 5 trial comparisons (N = 359) in type 2 diabetes. No trials were identified in type 1 diabetes. Consumption of oat ß-glucan sources reduced FPG (MD = −0.37 mmol/L [95% CI: −0.70, −0.05 mmol/L], P = 0.03, I2 = 0.00%, PQ = 0.76) and 2h-PG (MD = −1.24 mmol/L [95% CI: −1.97, −0.51 mmol/L], P = 0.00, I2 = 0.00%, PQ = 0.56). There were non-significant reductions in HbA1c (MD = −0.12%, [95% CI: −0.26, 0.01%], P = 0.07, I2 = 0.00%, PQ = 1.00) and FPI (MD = −4.59 pmol/L, [95% CI: −14.71, 5.52 pmol/L], P = 0.37, I2 = 40.84%, PQ = 0.19). The certainty of evidence was high for 2h-PG and moderate for FPG, HbA1c and FPI (single downgrades for imprecision in each case). Conclusions Current evidence provides a good indication that consumption of oat ß-glucan results in small improvements of glycemic control in type 2 diabetes. More high quality randomized trials are required to improve the precision of the pooled estimates. (ClinicalTrials.gov identifier, NCT04631913) Funding Sources Quaker Oats Center of Excellence, Diabetes Canada, Banting & Best Diabetes Centre, Toronto 3D foundation


Author(s):  
Sumanta Saha ◽  
Sujata Saha

Background and Purpose: The dapagliflozin’s safety profile in insulin-treated adult type-1 diabetes mellites (T1DM) patients remains poorly explored. Therefore, this systematic review and meta-analysis compared the risk of all-cause side effects, study discontinuation of participants due to side effects, urinary tract infection (UTI), diabetic ketoacidosis, and hypoglycemia between dapagliflozin 10 mg and dapagliflozin 5 mg, dapagliflozin 10 mg and placebo, and dapagliflozin 5 mg and placebo.Materials and Methods: Parallel-arm randomized controlled trials juxtaposing the above outcomes between the afore-mentioned interventions were eligible for inclusion in this study and were searched in PubMed, Embase, and Scopus. Utilizing the Cochrane tool, the risk of bias was assessed in the recruited trials. Finally, by random-effect meta-analysis, each outcome was compared among the above interventions, and the risk ratio was estimated.Results: Four trials of varying length (1-52 weeks) sourcing data from almost 1760 participants from about 32 nations were reviewed. Overall, the trials had a low or unclear risk of bias, and only one was at a high risk of bias.  Compared to the placebo, the risk of side effects was higher in those treated with dapagliflozin 5 mg (RR=1.10; 95% CI=1.02-1.18; p=0.014; I2=0%). UTI risk was less with the 10mg dapagliflozin than its lower dose (RR=0.50; 95% CI=0.32-0.79; p-value=0.003; I2=0%). All the remaining comparisons were statistically not significantly different between the juxtaposed intervention pairs.Conclusion: In contrast to placebo, dapagliflozin 5mg increased the risk of overall adversities in insulin-treated type-1 diabetes, and dapagliflozin 10 mg had a reduced risk of UTI than its 5mg preparation.


10.2196/22821 ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. e22821
Author(s):  
Negin Hesam-Shariati ◽  
Wei-Ju Chang ◽  
James H McAuley ◽  
Andrew Booth ◽  
Zina Trost ◽  
...  

Background Chronic pain is a global health problem, affecting around 1 in 5 individuals in the general population. The understanding of the key role of functional brain alterations in the generation of chronic pain has led researchers to focus on pain treatments that target brain activity. Electroencephalographic neurofeedback attempts to modulate the power of maladaptive electroencephalography frequency powers to decrease chronic pain. Although several studies have provided promising evidence, the effect of electroencephalographic neurofeedback on chronic pain is uncertain. Objective This systematic review aims to synthesize the evidence from randomized controlled trials to evaluate the analgesic effect of electroencephalographic neurofeedback. In addition, we will synthesize the findings of nonrandomized studies in a narrative review. Methods We will apply the search strategy in 5 electronic databases (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycInfo, and CINAHL) for published studies and in clinical trial registries for completed unpublished studies. We will include studies that used electroencephalographic neurofeedback as an intervention for people with chronic pain. Risk-of-bias tools will be used to assess methodological quality of the included studies. We will include randomized controlled trials if they have compared electroencephalographic neurofeedback with any other intervention or placebo control. The data from randomized controlled trials will be aggregated to perform a meta-analysis for quantitative synthesis. The primary outcome measure is pain intensity assessed by self-report scales. Secondary outcome measures include depressive symptoms, anxiety symptoms, and sleep quality measured by self-reported questionnaires. We will investigate the studies for additional outcomes addressing adverse effects and resting-state electroencephalography analysis. Additionally, all types of nonrandomized studies will be included for a narrative synthesis. The intended and unintended effects of nonrandomized studies will be extracted and summarized in a descriptive table. Results Ethics approval is not required for a systematic review, as there will be no patient involvement. The search for this systematic review commenced in July 2020, and we expect to publish the findings in early 2021. Conclusions This systematic review will provide recommendations for researchers and health professionals, as well as people with chronic pain, about the evidence for the analgesic effect of electroencephalographic neurofeedback. Trial Registration International Prospective Register of Systematic Reviews (PROSPERO) CRD42020177608; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=177608 International Registered Report Identifier (IRRID) PRR1-10.2196/22821


Author(s):  
Tarun Krishna Boppana ◽  
Saurabh Mittal ◽  
Karan Madan ◽  
Anant Mohan ◽  
Vijay Hadda ◽  
...  

There is an urgent need for effective treatment modalities for coronavirus disease 2019 (COVID-19). Data for the use of steroids in COVID-19 is emerging. We conducted this systematic review and meta-analysis to estimate the effectiveness of steroid administration in mortality reduction due to COVID-19 compared to the control group. A systematic search of the Pubmed and Embase databases was performed to extract randomized controlled trials (RCTs) regarding the use of steroid therapy for COVID-19. An overall and subgroup (based upon the type of steroid) pooled mortality analysis was performed, and odds ratios were reported. Cochrane risk of bias assessment tool was used to assess the risk of bias. Heterogeneity was assessed using the I2 statistic. Six RCTs, including 7707 patients, were selected for review. Three trials reported 28-day mortality, and two trials reported 21-day mortality, and one trial reported in-hospital mortality. There were 730 deaths among 2837 participants in the steroid group while 1342 deaths among 4870 patients randomized to the control group (Odds ratio 0.76, 95% confidence interval 0.58-1.00, p=0.05). The effect was significant in patients on oxygen or mechanical ventilation. There was no difference in the various preparations and doses of the steroids. There was heterogeneity among the trials as the I2 value was 53%, with a p-value of 0.06. There was no indication of increased serious adverse events. This meta-analysis of RCTs demonstrated that the use of systemic corticosteroids is associated with a reduction in all-cause mortality in patients with COVID-19 on oxygen or mechanical ventilation.


2013 ◽  
Vol 6;16 (6;11) ◽  
pp. E521-E532
Author(s):  
Sheng-Xi Wu

Background: Currently, there is no specific therapy for chronic pancreatitis (CP). The treatment of micronutrient antioxidant therapy for painful CP has been sporadically used for more than 30 years, however, its efficacy are still poorly understood. Objective: The purpose of this meta-analysis is to investigate the safety and efficacy of antioxidant therapy for pain relief in patients with CP. Setting: University Hospital in China Study Design: Systematic review and meta-analysis Methods: Two authors independently reviewed the search results and extracted data and disagreements were resolved by discussion. Effects were summarized using standardized mean differences (SMDs), weighted mean differences, or odds ratio (OR) according to the suitable effect model. MEDLINE, PsycINFO, Scopus, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from 1980 through December 2012. Randomized controlled trials (RCTs) that studied antioxidant supplementation for pain relief in patients with CP were analyzed. Results: Nine randomized controlled trials (RCTs) involving 390 patients were included. Overall, there was no association of antioxidant therapy with pain reduction in CP patients (SMD, −0.55; 95% CI, −1.22 to 0.12; P = 0.67). However, antioxidant therapy significantly increased blood levels of antioxidants in CP patients versus the placebo group (SMD, 1.08; 95% CI, 0.74 to 1.43; P < 0.00001). Interestingly, combined antioxidant (selenium, β-carotene, vitamin C, vitamin E, methionine) therapy was found to be associated with pain relief (SMD, -0.93; 95% CI, -1.72 to -0.14; P = 0.02), while the trials in which a single antioxidant was used revealed no significant pain relief (SMD, -0.12; 95% CI, -1.23 to 0.99; P = 0.83) in CP patients. Strong evidence was obtained that the antioxidants increased adverse effects (OR, 6.09; 95% CI, 2.29 to 16.17, P < 0.01); nevertheless, none was serious. Limitations: Because of the small sample, a consolidated conclusion cannot be reached based on current RCTs. Large-sample RCTs are needed to clarify the analgesic effect of antioxidants in CP patients. Conclusions: Combined antioxidant therapy seems to be a safe and effective therapy for pain relief in CP patients. Measures of total antioxidant status may not help to monitor the efficacy of antioxidant therapy for patients with CP. Key words: Antioxidant, pain, chronic pancreatitis, meta-analysis


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