scholarly journals Pharmacological treatment for bipolar mania: a systematic review and network meta-analysis of double-blind randomized controlled trials

Author(s):  
Taro Kishi ◽  
Toshikazu Ikuta ◽  
Yuki Matsuda ◽  
Kenji Sakuma ◽  
Makoto Okuya ◽  
...  

AbstractA systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological interventions for adults with acute bipolar mania. We searched PubMed, the Cochrane Library, and Embase databases for eligible studies published before March 14, 2021. Randomized controlled trials (RCTs) of oral medication monotherapy lasting ≥10 days in adults with mania were included, and studies that allowed the use of antipsychotics as a rescue medication during a trial were excluded. The primary outcomes were response to treatment (efficacy) and all-cause discontinuation (acceptability). The secondary outcomes were the improvement of mania symptoms and discontinuation due to inefficacy. Of the 79 eligible RCTs, 72 double-blind RCTs of 23 drugs and a placebo were included in the meta-analysis (mean study duration = 3.96 ± 2.39 weeks, n = 16442, mean age = 39.55 years, with 50.93% males). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed response to treatment (N = 56, n = 14503); aripiprazole, olanzapine, quetiapine, and risperidone had lower all-cause discontinuation; however, topiramate had higher all-cause discontinuation (N = 70, n = 16324). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed the improvement of mania symptoms (N = 61, n = 15466), and aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone had lower discontinuation due to inefficacy (N = 50, n = 14284). In conclusions, these antipsychotics, carbamazepine, lithium, tamoxifen, and valproate were effective for acute mania. However, only aripiprazole, olanzapine, quetiapine, and risperidone had better acceptability than the placebo.

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Sung Min Lim ◽  
Junghee Yoo ◽  
Euiju Lee ◽  
Hyun Jung Kim ◽  
Seungwon Shin ◽  
...  

The aim of this systematic review was to determine how effective acupuncture or electroacupuncture (acupuncture with electrical stimulation) is in treating poststroke patients with spasticity. We searched publications in Medline, EMBASE, and the Cochrane Library in English, 19 accredited journals in Korean, and the China Integrated Knowledge Resources Database in Chinese through to July 30, 2013. We included randomized controlled trials (RCTs) with no language restrictions that compared the effects of acupuncture or electroacupuncture with usual care or placebo acupuncture. The two investigators assessed the risk of bias and statistical analyses were performed. Three RCTs in English, 1 in Korean, and 1 in Chinese were included. Assessments were performed primarily with the Modified Ashworth Scale (MAS). Meta-analysis showed that acupuncture or electroacupuncture significantly decreased spasticity after stroke. A subgroup analysis showed that acupuncture significantly decreased wrist, knee, and elbow spasticity in poststroke patients. Heterogeneity could be explained by the differences in control, acupoints, and the duration after stroke occurrence. In conclusion, acupuncture could be effective in decreasing spasticity after stroke, but long-term studies are needed to determine the longevity of treatment effects.


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.


2020 ◽  
Vol 2;23 (4;2) ◽  
pp. 135-148
Author(s):  
Zifeng Xu

Background: The pain control effect of ketamine versus control in women during cesarean operation is not well determined. Objectives: The present meta-analysis aimed to evaluate the clinical efficacy of ketamine versus control in cesarean section anesthesia for reducing the postoperative pain and analgesia. Study Design: We used meta-analysis to address this concern. Setting: Meta-analysis-based study. Methods: The databases PubMed, Embase, and the Cochrane Library were systematically searched to identify the relevant randomized controlled trials (RCTs) of ketamine versus control in controlling pain after cesarean section from inception to August 2018. Based on the Cochrane Handbook, the combined analysis was performed using Revman 5.3 software. Results: A total of 20 RCTs with 1,737 patients who underwent cesarean section were included. Meta-analysis showed that the pain score in the ketamine group was less than that of the control group (mean difference [MD], –1.10; 95% confidence interval [CI], –1.61, –0.59; P < 0.0001). Application of ketamine during cesarean section also resulted in decreased consumption of morphine when compared with the control group (MD, –6.11 mg; 95% CI, –9.93, –2.29; P = 0.002). In addition, the first time required for analgesia was significantly longer in the ketamine group than that of the control group (MD, 72.48 minutes; 95% CI, 50.85, 94.11; P < 0.00001). Limitations: Limited patients were included with moderate strength. Conclusions: Ketamine supplementation during cesarean section reduces pain and morphine consumption and prolongs the postoperative analgesia. Key words: Ketamine, cesarean section, randomized controlled trials, meta-analysis


Author(s):  
Shima Abdollahi ◽  
Omid Toupchian ◽  
Ahmad Jayedi ◽  
David Meyre ◽  
Vivian Tam ◽  
...  

ABSTRACT The aim of this study was to determine the effect of zinc supplementation on anthropometric measures. In this systematic review and dose–response meta-analysis, we searched PubMed, Scopus, ISI Web of Science, and the Cochrane Library from database inception to August 2018 for relevant randomized controlled trials. Mean differences and SDs for each outcome were pooled using a random-effects model. Furthermore, a dose–response analysis for zinc dosage was performed using a fractional polynomial model. Quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Twenty-seven trials (n = 1438 participants) were included in the meta-analysis. There were no significant changes in anthropometric measures after zinc supplementation in the overall analysis. However, subgroup analyses revealed that zinc supplementation increased body weight in individuals undergoing hemodialysis (HD) [3 trials, n = 154 participants; weighted mean difference (WMD) = 1.02 kg; 95% CI: 0.38, 1.65 kg; P = 0.002; I2 = 11.4%] and decreased body weight in subjects who are overweight/obese but otherwise healthy (5 trials, n = 245 participants; WMD = −0.55 kg; 95% CI: −1.06, −0.04 kg; P = 0.03; I2 = 31.5%). Dose–response analyses revealed a significant nonlinear effect of supplementation dosage on BMI (P = 0.001). Our data suggest that zinc supplementation increases body weight in patients undergoing HD and decreases body weight in individuals who are overweight/obese but otherwise healthy, although after normalization for study duration, the association observed in subjects who are overweight/obese disappeared. Although more high-quality studies are needed to reach a definitive conclusion, our study supports the view that zinc may be associated with body weight.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5125-5125 ◽  
Author(s):  
Anat Gafter-Gvili ◽  
Ronit Gurion ◽  
Pia Raanani ◽  
Ofer Shpilberg ◽  
Liat Vidal

Abstract Background Bendamustine is a chemotherapeutic drug with structural similarities to both alkylating agents (nitrogen mustard derivative) and purine analogues (benzimidazole ring). Theoretically, due to its nucleoside-like properties it might be associated with more infections. Data in the literature is lacking regarding the infection-related adverse events of bendamustine-containing regimens. Thus, we aimed to assess this risk. Methods Systematic review and meta-analysis of all randomized controlled trials comparing bendamustine containing regimens (alone or combined with other chemotherapeutic agents and/or rituximab) to any other regimens. Trials evaluating bendamustine for any indication (hematological as well as solid malignancies) were included.  A comprehensive search of The Cochrane Library, MEDLINE, conference proceedings and references was conducted until July 2013. Two reviewers appraised the quality of trials and extracted data. Outcomes assessed were: any infections, grade 3-4 infections, fatal infections, grade 3-4 neutropenia and grade 3-4 lymphopenia. For dichotomous data, relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled. We used fixed effect model to pool data, unless there was significant heterogeneity, in which case we used the random effects model. Results Ten trials conducted between the years 1998 and 2013 and randomizing 2360 patients were included. We included 4 trials of patients with non-Hodgkin lymphoma (Rummel 2013, Rummel 2010, Herold 2006 and the Bright study 2013), 3 trials of CLL (Knauf 2009, Niederle 2013, LeBlond 2013), 1 trial of patients with multiple myeloma (Ponish 2006) and 2 trials of breast carcinoma patients. The bendamustine arm included: bendamustine alone (2 trials), bendamustine-rituximab (BR) (4 trials), bendamustine, vincristine, prednisone (BOP) (1 trial), bendamustine, MTX. 5FU (BMF) (2 trials) and bendamustine, prednisone (BP) (1 trial). The comparator arms in 8 of the trials included other alkylating agents: chlorambucil, R -CHOP,  cyclophosphamide, MTX, 5-FU (CMF) and melphalan-prednisone (MP) – each regimen used in 2 trials and COP used in 1 trial.  In 2 trials the comparator arm included fludarabine based regimens (alone or with rituximab). There was no statistically significant effect for bendamustine on the rate of any type of infection (RR 1.06 [95% CI 0.83, 1.34], 6 trials, figure). This analysis included only trials of hematological malignancies. There was no increase in the rate of grade 3-4 infections (RR 1.45 [95% CI 0.86, 2.45], 7 trials) or fatal infection (RR 0.69 [95% CI 0.30, 1.58], 3 trials). Data were too scarce to analyze by specific types of infections separately. There was no increase in the rate of grade 3-4 neutropenia in the bendamustine arm (RR 0.9 [95% CI 0.58, 1.42], 6 trials). This was true both when the comparator was alkylating agent containing regimens (RR 0.87 [95% CI 0.52, 1.48], 4 trials) or fludarabine containing regimens (RR 1.02 [95% CI 0.54, 1.91], 2 trials). There was a significant increase in grade 3-4 lymphopenia in the bendamustine arm compared to alkylating agent containing regimens (RR 1.95[95% CI 1.54, 2.47). Conclusions Our systematic review demonstrates no effect of bendamustine on the rate of infections when compared to either alkylating agents or fludarabine,  in hematological as well as in solid malignancies, despite an increase in lymphopenia. Thus, bendamustine remains a safe therapeutic option. The main drawback of this meta-analysis is the heterogeneity between malignancies and treatments. Disclosures: No relevant conflicts of interest to declare.


2021 ◽  
Vol 12 ◽  
Author(s):  
Guozhi Wu ◽  
Yuan Yang ◽  
Min Liu ◽  
Yuping Wang ◽  
Qinghong Guo

Background: Crohn disease (CD) is a chronic inflammatory disease that affects quality of life. There are several drugs available for the treatment of CD, but their relative efficacy is unknown due to a lack of high-quality head-to-head randomized controlled trials.Aim: To perform a mixed comparison of the efficacy and safety of biosimilars, biologics and JAK1 inhibitors for CD.Methods: We searched PubMed, Web of Science, embase and the Cochrane Library for randomized controlled trials (RCTs) up to Dec. 28, 2020. Only RCTs that compared the efficacy or safety of biosimilars, biologics and JAK1 inhibitors with placebo or another active agent for CD were included in the comparative analysis. Efficacy outcomes were the induction of remission, maintenance of remission and steroid-free remission, and safety outcomes were serious adverse events (AEs) and infections. The Bayesian method was utilized to compare the treatments. The registration number is CRD42020187807.Results: Twenty-eight studies and 29 RCTs were identified in our systematic review. The network meta-analysis demonstrated that infliximab and adalimumab were superior to certolizumab pegol (OR 2.44, 95% CI 1.35–4.97; OR 2.96, 95% CI 1.57–5.40, respectively) and tofacitinib (OR 2.55, 95% CI 1.27–5.97; OR 3.10, 95% CI 1.47–6.52, respectively) and revealed the superiority of CT-P13 compared with placebo (OR 2.90, 95% CI 1.31–7.59) for the induction of remission. Infliximab (OR 7.49, 95% CI 1.85–34.77), adalimumab (OR 10.76, 95% CI 2.61–52.35), certolizumab pegol (OR 4.41, 95% CI 1.10–21.08), vedolizumab (OR 4.99, 95% CI 1.19–25.54) and CT-P13 (OR 10.93, 95% CI 2.10–64.37) were superior to filgotinib for the maintenance of remission. Moreover, infliximab (OR 3.80, 95% CI 1.49–10.23), adalimumab (OR 4.86, 95% CI 1.43–16.95), vedolizumab (OR 2.48, 95% CI 1.21–6.52) and CT-P13 (OR 5.15, 95% CI 1.05–27.58) were superior to placebo for steroid-free remission. Among all treatments, adalimumab ranked highest for the induction of remission, and CT-P13 ranked highest for the maintenance of remission and steroid-free remission.Conclusion: CT-P13 was more efficacious than numerous biological agents and JAK1 inhibitors and should be recommended for the treatment of CD. Further head-to-head RCTs are warranted to compare these drugs.


2020 ◽  
Author(s):  
Yun Diao ◽  
Hang Yang ◽  
Yang Chun Zhou ◽  
Biao Du

Abstract Objective: The aim of this review was to evaluate the efficacy and tolerability of ubrogepant in patients with acute migraine. Methods: We systematically searched PubMed, Embase, MEDLINE, Cochrane Library, and clinicaltrials.gov from inception to JULY, 2019. Randomized controlled trials of the efficacy and/or tolerability of ubrogepant for migraine were included. Meta-analysis was conducted by RevMan 5.3 software. Results: A total of 4 RCTs involving 4 163 patients were included. The meta-analysis showed that:compared to the control group, the percentage of participants with PF, the percentage of participants with PR, the percentage of participants with SPF, the percentage of participants with SPR,the absence of phonophobia in sound,the absence of phonophobia in light and the absence of nausea (RR=1.31,95%CI:1.18~1.45,P<0.00001, RR=1.63,95%CI:1.46~1.82,P<0.00001, RR=1.22,95%CI:1.15~1.29,P<0.00001, RR=1.32,95%CI:1.22~1.42,P<0.00001, RR=1.16,95%CI:1.05~1.27,P=0.002), all the differences were statistically significant. Conclusions: For adult patients with acute migraine, ubrogepant could effectively abort the acute attack. High-quality, adequately powered RCTs are needed to fully evaluate the efficacy and tolerability of ubrogepant for acute migraine.


BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Liping Gou ◽  
Zhenghao Wang ◽  
Ye Zhou ◽  
Xiaofeng Zheng

Abstract Background A systematic review and meta-analysis was conducted to compare the safety and efficiency of nephroscopy and cystoscopy in transurethral cystolithotripsy (TUCL) for bladder stones (BS). Methods The PubMed, Web of Science, Embase, EBSCO, and Cochrane Library databases were searched up to January 2021 for studies assessing the effect of different types of endoscopes among patients who underwent TUCL. The search strategy and study selection process were in accordance with the PRISMA statement. Results Five randomized controlled trials were included in the meta-analysis. The results showed no difference in stone-free rate (RR = 1.00, CI = 0.98–1.02, p = 1.00) between the two groups and nonsignificant heterogeneity (I2 = 0%, p = 1.00), and all patients were rendered stone free. Use of the nephroscope significantly shortened the operative time compared with the cystoscope group (RR= − 26.26, CI = − 35.84 to − 16.68, p < 0.00001), and there was significant heterogeneity (I2= 87%, p < 0.00001). There was no significant difference in mean urethral entries (RR = 0.66, CI = − 0.71 to − 2.04, p = 0.35), hospitalization (MD = 0.08, 95% CI = − 0.07 to 0.23, p = 0.31) or total complication rate (RR=1.37, 95% CI = 0.47–4.00, p = 0.56) between the two groups. Conclusions In conclusion, this systematic review demonstrates that both nephroscopy and cystoscopy have high stone clearance efficiency, low rates of complications and short hospitalizations. The mean urethral entries depend on the treatment method for large stone fragments. However, the use of nephroscopy can significantly reduce the operative time.


Author(s):  
Desye Gebrie ◽  
Desalegn Getnet ◽  
Tsegahun Manyazewal

AbstractBackgroundIn spite of the global containment on prevention efforts, the spread of coronavirus disease 2019 (COVID-19) is continuing to rise, with 1.1 million confirmed cases and 60,124 deaths recorded worldwide since 04 April 2020. The outbreak has a significant threat to international health and economy. At present, there is no approved vaccine or treatment for the disease, while efforts are underway. Remdesivir, a nucleotide-analogue antiviral drug developed for Ebola, is determined to prevent and stop infections with COVID-19, while results are yet controversial. Here, we aim to conduct a systematic review and meta-analysis of randomized controlled trials to compare the effectiveness of remdesivir and placebo in patients with COVID-19.Method and analysisWe will search MEDLINE-PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Google scholar databases without restriction in year of publication. We will include randomized controlled trials that assessed the effectiveness of remdesivir versus placebo for patients confirmed with COVID-19. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA 2015) guidelines for the design and reporting of the results. The primary endpoint will be time to clinical recovery. The secondary endpoints will be all cause mortality, discharged date, frequency of respiratory progression, and treatment-emergent adverse events. Two independent authors will perform study selection, data extraction, and methodology quality assessment. RevMan 5.3 software will be used for statistical analysis. Random/fixed effect model will be carried out to calculate mean differences for continuous outcomes and risk ratio for dichotomous outcomes between remdesivir and placebo.Ethics and disseminationThis study does not require ethical approval, because no participant’s data will be involved in this systematic review and meta-analysis. The findings of this study will be published in reputable and peer-reviewed journal.RegistrationThis review protocol is submitted in PROSPERO database for registration and we will include the registration number in the revised version of the manuscript.Strengths and limitations of this study➣This systematic review and meta-analysis will be derived from only randomized controlled trials which will increase the quality of evidences.➣This systematic review and meta-analysis will be derived from only randomized controlled trials which will reduce between study heterogeneity.➣Subgroup and sensitivity analysis will be carried out to identify possible reasons that may cause significant heterogeneity between studies.➣The use of Cochrane risk of bias tool to assess risk of bias for each included studies to extract and synthesize evidence based conclusions.➣One of the limitation of this study might be the restriction of trials published in English language.


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