scholarly journals Meta-analysis of drug efficacy in adult vs pediatric trials of patients with PGTC seizures

Neurology ◽  
2020 ◽  
Vol 94 (17) ◽  
pp. e1845-e1852
Author(s):  
Douglas R. Nordli ◽  
Emilia Bagiella ◽  
Alexis Arzimanoglou ◽  
Jinping Wang ◽  
Dinesh Kumar ◽  
...  

ObjectiveA meta-analysis of published studies was performed to determine whether the efficacy of antiseizure drugs in adults with primary generalized tonic-clonic seizures (PGTCS) is comparable with that in the pediatric population (2–12 years of age).MethodsElectronic searches were conducted in EMBASE, Medline, and the Cochrane Central Register of Controlled Trials for clinical trials of PGTCS in adults and children 2–12 years of age. Neurologists used standardized search and study evaluations to select eligible trials. Median percent reduction in seizure frequency from baseline and ≥50% responder rates were used to compare drug efficacy in adults and children.ResultsAmong 7 adjunctive-therapy PGTCS trials in adults and children (2–12 years of age) that met evaluation criteria, effect sizes were consistent between adults and children for lamotrigine and topiramate. The baseline-subtracted median percent seizure reduction in seizure frequency ranged from 50.0% to 79.7% in children and 57.0% to 64.0% in adults. The ≥50% responder rate was similar between children and adults in a topiramate study (50% in children compared with 58% in adults).ConclusionsThis meta-analysis supports the use of drug response from antiseizure drug clinical trials for PGTCS in adults to predict comparable treatment response in children 2–12 years of age with PGTCS.

2021 ◽  
Vol 34 ◽  
Author(s):  
Michel Marcos Dalmedico ◽  
Caroline Machado de Toledo ◽  
Paula Karina Hembecker ◽  
Juliana Londero Silva Ávila ◽  
Chayane Karla Lucena de Carvalho ◽  
...  

Abstract Introduction: Cancer pain has a considerable impact on patients’ health and quality of life, and its treatment is essentially based on opioid use. Objective: To report the effectiveness of acupuncture in relieving cancer pain (secondary to the disease or to the corresponding therapy) or in decreasing opioid use compared to other interventions. Methods: A systematic review of randomized clinical trials was conducted following the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. The trials were selected from the PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Results: The search strategy resulted in the inclusion of eight trials, of which five compared acupuncture and drug therapy and three compared acupuncture and placebo. Seven trials reported decreased pain and analgesic use. The trials showed clinical heterogeneity, making a meta-analysis unfeasible. Conclusion: The findings herein provided no robust evidence to support the routine use of acupuncture as an adjuvant therapy in the treatment of cancer pain. However, its use is promising since the results showed a trend toward decreased pain and analgesic use, thus justifying further studies in the future.


2021 ◽  
Vol 11 ◽  
Author(s):  
Shixue Chen ◽  
Zhibo Zhang ◽  
Xuan Zheng ◽  
Haitao Tao ◽  
Sujie Zhang ◽  
...  

BackgroundImmune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have demonstrated promise in treating a variety of advanced cancers; however, little is known regarding their efficacy under various clinical situations, including different cancer types, treatment lines, drug combinations, and therapeutic regimens.MethodsPublished articles and conference abstracts (in English) in PubMed, Embase, the Cochrane Central Register, and Web of Science were searched up to February 10, 2020. The data were analyzed by the meta-analysis program in Stata.ResultsA total of 16,400 patients from 91 clinical trials were included in this meta-analysis. PD-1/PD-L1 inhibitors had a mean ORR of 19.56% (95% CI: 15.09–24.03), a median TTR of 2.05 months (m) (95%CI: 1.85–2.26), and a median DOR of 10.65 m (95%CI: 7.78–13.52). First-line treatment had a higher ORR (36.57% vs. 13.18%) but a shorter DOR (9.00 m vs. 13.42 m) compared to the second-line or subsequent treatment. Immunotherapy combined with chemotherapy (I+C) (46.81% [95%CI: 36.02–57.60]) had a statistically significant higher ORR compared to immunotherapy (I) (17.75% [95%CI: 14.47–21.03]) or immunotherapy combined with immunotherapy (I+O) (12.25% [95%CI: 1.56–22.94]), while I+C (8.09 m [95%CI: 6.86–9.32]) appeared to reduce the DOR compared to I (12.39 m [95%CI: 7.60–17.18]). PD-1 inhibitors were associated with better ORR (21.65% vs. 17.60%) and DOR (11.26 m vs. 10.03 m) compared to PD-L1 inhibitors. There were no significant differences in TTR under different situations.ConclusionsPD-1/PD-L1 inhibitors were promising immunotherapeutic agents to achieve satisfactory response efficacies with different cancer types, treatment lines, drug combinations, and therapeutic regimens. This comprehensive summary of the response efficacy of PD-1/PD-L1 inhibitors serves as a reference for clinicians to make evidence-based decisions.


2020 ◽  
Author(s):  
Jennifer S Cox ◽  
Rebecca Elsworth ◽  
Rachel Perry ◽  
Julian P. Hamilton-Shield ◽  
Elanor C. Hinton

Abstract Background: Eating speed is positively correlated with higher BMI. Thus, modifying pace of eating may provide a treatment opportunity for those with overweight and obesity, which may have additional, longitudinal benefits if established in childhood. Researchers have designed interventions to help both adults and children reduce eating speed as a mechanism for weight-loss. These interventions include those that change the food that is eaten, those that use technology to support a slower eating speed, and those that work to change eating speed by cognitive means. This review seeks to understand the feasibility, acceptability and benefit to using eating speed in paediatric populations who have experienced such methods as part of a clinical weight-management programme.Methods: Clinical studies that use eating speed interventions as a treatment for paediatric patients (age 5–18 years) with overweight or obesity will be included in this review. No limits to language or search date will be implemented. A systematic search of the literature will be conducted using the following databases - MEDLINE, PyschINFO and EMBASE via OVID, Web of Science and JBI, Database of systematic reviews and Implementation reports, along with trial registers NICE, ClinicalTrials.gov and Cochrane Central Register of Controlled Trials. A grey literature search will be conducted via OpenGrey, and by writing to experts in the field. Study quality will be assessed and meta-analyses for trials that use similar interventions and report similar outcomes will be undertaken where possible.Discussion: This review will synthesise evidence regarding the feasibility, acceptability and benefit of using eating speed interventions to develop a narrative review. An assessment of heterogeneity will be assessed and where there is sufficient data, we will carry out a meta-analysis; for example, on the secondary outcomes of BMISDS or eating speed change following the interventions.


2021 ◽  
Author(s):  
Hui Yan Zhao ◽  
◽  
Sungha Kim ◽  
ChangSop Yang ◽  
Mi Ju Son

Review question / Objective: How effective are acupoint catgut embedding therapy sole or with other treatment? Condition being studied: Simple obesity. Information sources: We will search for trials from the following electronic databases: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Cumulative index to Nursing and Allied Health Literature (CINAHL). Trials will also be searched from three Korean medical databases (Oriental Medicine Advanced Searching Integrated System [OASIS], Science-On and KoreaMed), a Chinese database (Chinese National Knowledge Infrastructure [CNKI]) and a Japanese database (CiNii). Ongoing trials, trials will be searched on the Clinical Trials. gov (http://www.ClinicalTrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (http://apps.who.int/trialsearch/). We will also check the reference lists of reviews and the retrieved articles for additional studies. All bibliographic information and articles will be managed using EndNote (X8.2; Clarivate Analytics, Philadelphia). If the data of study are missing or insufficient, we will contact the corresponding authors by email.


Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1537
Author(s):  
Kevin Sheng-Kai Ma ◽  
Chien-Chang Lee ◽  
Ko-Jiunn Liu ◽  
James Cheng-Chung Wei ◽  
Yuan-Ti Lee ◽  
...  

Clinical trials evaluating the safety and antibody response of strategies to manipulate prophylactic and therapeutic immunity have been launched. We aim to evaluate strategies for augmentation of host immunity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We searched clinical trials registered at the National Institutes of Health by 25 May 2021 and conducted analyses on inoculated populations, involved immunological processes, source of injected components, and trial phases. We then searched PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials for their corresponding reports published by 25 May 2021. A bivariate, random-effects meta-analysis was used to derive the pooled estimate of seroconversion and adverse events (AEs). A total of 929,359 participants were enrolled in 389 identified trials. The working mechanisms included heterologous immunity, active immunity, passive immunity, and immunotherapy, with 62.4% of the trials on vaccines. A total of 9072 healthy adults from 27 publications for 22 clinical trials on active immunity implementing vaccination were included for meta-analyses. The pooled odds ratios (ORs) of seroconversion were 13.94, 84.86, 106.03, and 451.04 (all p < 0.01) for vaccines based on protein, RNA, viral vector, and inactivated virus, compared with that of respective placebo/control treatment or pre-vaccination sera. The pooled ORs for safety, as defined by the inverse of systemic adverse events (AEs) were 0.53 (95% CI = 0.27–1.05; p = 0.07), 0.35 (95% CI = 0.16–0.75; p = 0.007), 0.32 (95% CI = 0.19–0.55; p < 0.0001), and 1.00 (95% CI = 0.73–1.36; p = 0.98) for vaccines based on protein, RNA, viral vector, and inactivated virus, compared with that of placebo/control treatment. A paradigm shift from all four immune-augmentative interventions to active immunity implementing vaccination was observed through clinical trials. The efficacy of immune responses to neutralize SARS-CoV-2 for these vaccines was promising, although systemic AEs were still evident for RNA-based and viral vector-based vaccines.


2020 ◽  
Vol 27 ◽  
Author(s):  
Peyman Nowrouzi-Sohrabi ◽  
Reza Tabrizi ◽  
Mohammad Jalali ◽  
Navid Jamali ◽  
Shahla Rezaei ◽  
...  

Introduction: A systematic review and meta-analysis of clinical trials was undertaken to evaluate the effect of diacerein intake on cardiometabolic profiles in patients with type 2 diabetes mellitus (T2DM). Methods: Electronic databases such as PubMed, EMBASE, Scopus, Web of Science, Google Scholar, and Cochrane Central Register of Controlled Trials were searched from inception to 31 July 2019. Statistical heterogeneity was evaluated using Cochran’s Q test and I-square (I2 ) statistic. Data were pooled using random-effect models and weighted mean difference (WMD). Results: From 1,733 citations, seven clinical trials were eligible for inclusion and meta-analysis. A significant reduction in hemoglobin A1c (HbA1c) (WMD -0.73; 95%CI -1.25 to -0.21; P= 0.006; I2 = 72.2%) and body mass index (BMI) (WMD -0.55; 95%CI -1.03 to -0.07; P= 0.026; I2 = 9.5%) were identified. However, no significant effect of diacerein intake was identified on fasting blood sugar (FBS) (WMD - 9.00; 95%CI -22.57 to 4.57; P= 0.194; I2 = 60.5%), homeostatic model assessment for insulin resistance (HOMA-IR) (WMD 0.39; 95%CI 0.95 to 1.73; P= 0.569; I2 = 2.2%), body weight (WMD -0.54; 95%CI -1.10 to 0.02; P= 0.059), triglycerides (WMD -0.56; 95%CI -24.16 to 23.03; P= 0.963; I2 = 0.0%), total-cholesterol (WMD -0.21; 95%CI -12.19 to 11.78; P= 0.973; I2 = 0.0%), HDL-cholesterol (WMD -0.96; 95%CI -2.85 to 0.93; P= 0.321; I2 = 0.0%), and LDL-cholesterol levels (WMD -0.09; 95%CI -8.43 to 8.25; P= 0.983; I2 = 37.8%). Conclusion: Diacerein intake may reduce HbA1c and BMI; however, no evidence of effect was observed for FBS, HOMA-IR, body weight, triglycerides, total-cholesterol, HDL-cholesterol or LDL-cholesterol.


2021 ◽  
pp. bmjspcare-2021-003065
Author(s):  
Lewis Thomas Hughes ◽  
David Raftery ◽  
Paul Coulter ◽  
Barry Laird ◽  
Marie Fallon

PurposeOpioids are recommended for moderate-to-severe cancer pain; however, in patients with cancer, impaired hepatic function can affect opioid metabolism. The aim of this systematic review was to evaluate the evidence for the use of opioids in patients with cancer with hepatic impairment.MethodsA systematic review was conducted and the following databases searched: AMED (−2021), MEDLINE (−2021), EMBASECLASSIC + EMBASE (−2021) and Cochrane Central Register of Controlled Trials (−2021). Eligible studies met the following criteria: patients with cancer-related pain, taking an opioid (as defined by the WHO Guidelines for the pharmacological and radiotherapeutic management of cancer pain in adults and adolescents); >18 years of age; patients with hepatic impairment defined using recognised or study-defined definitions; clinical outcome hepatic impairment related; and primary studies. All eligible studies were appraised using the Grading of Recommendations Assessment, Development and Evaluation system.ResultsThree studies (n=95) were eligible but heterogeneity meant meta-analysis was not possible. Each individual study focused on only one each of oxycodone±hydrocotarnine, oxycodone/naloxone and morphine. No recommendations could be formulated on the preferred opioid in patients with hepatic impairment.ConclusionsMorphine is the preferred opioid in hepatic impairment owing to clinical experience and pharmacokinetics. This review, however, found little clinical evidence to support this. Dose adjustments of morphine and the oxycodone formulations reviewed remain necessary in the absence of quality evidence. Overall, the quality of existing evidence on opioid treatments in cancer pain and hepatic impairment is low and there remains a need for high-quality clinical studies examining this.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Zhao ◽  
Chuantao Peng ◽  
Hafiz Arbab Sakandar ◽  
Lai-Yu Kwok ◽  
Wenyi Zhang

Lactobacillus (L.) plantarum strains, belong to lactic acid bacteria group, are considered indispensable probiotics. Here, we performed meta-analysis to evaluate the regulatory effects of L. plantarum on the immunity during clinical trials. This meta-analysis was conducted by searching across four most common literature databases, namely, Cochrane Central Register of Controlled Trials, Web of Science, Embase, and PubMed. Clinical trial articles that met the inclusion and exclusion criteria were analyzed by Review Manager (version 5.3). p-value &lt; 0.05 of the total effect was considered statistically significant. Finally, total of 677 references were retrieved, among which six references and 18 randomized controlled trials were included in the meta-analysis. The mean differences observed at 95% confidence interval: interleukin (IL)-4, −0.48 pg/mL (−0.79 to −0.17; p &lt; 0.05); IL-10, 9.88 pg/mL (6.52 to 13.2; p &lt; 0.05); tumor necrosis factor (TNF)-α, −2.34 pg/mL (−3.5 to −1.19; p &lt; 0.05); interferon (IFN)-γ, −0.99 pg/mL (−1.56 to −0.41; p &lt; 0.05). Therefore, meta-analysis results suggested that L. plantarum could promote host immunity by regulating pro-inflammatory and anti-inflammatory cytokines.


2021 ◽  
Vol 8 ◽  
Author(s):  
Sha Yang ◽  
Yujia J. Luo ◽  
Cong Luo

Background: There is no uniform treatment for pathological scars, including keloids and hypertrophic scars, in clinic currently. Previously, multiple randomized controlled trials have examined the clinical efficacy of different treatments. Nonetheless, the results are inconsistent, and many treatments have not been directly compared. This makes it difficult to conclude which approach is more favorable, in terms of efficacy and safety, for the treatment of pathological scarring. This study aimed at evaluating the efficacy of different injection and topical treatment strategies for hypertrophic scar and keloid.Methods: Relevant literature from PubMed, Medline, Embase, Scopus, the Cochrane Central Register of Controlled Trials (CCRCT), and WHO International Clinical Trials Registry Platform (WHO-ICTRP) were searched, from database inception through November 2020. Randomized clinical trials evaluating different treatment strategies of pathological scars, including triamcinolone acetonide (TAC), verapamil (VER), 5-fluorouracil (5-FU), botulinum toxin A (BTA), bleomycin (BLM), and silicone gels were included in the study.Results: The network meta-analysis included a total of 2,009 patients from 29 studies. A network meta-analysis of injection and topical treatment strategies showed that the efficacy of TAC combined with BTA was best in the treatment of pathological scars. Combination therapies of TAC with 5-FU and TAC with BTA significantly improved the clinical efficiency. However, there was no statistically significant difference between other treatment strategies. The order of efficacy predicted by the surface under the cumulative ranking (SUCRA) curve was as follows: TAC+BTA (82.2%) &gt; TAC+5-FU (69.8%) &gt; BTA (67.3%) &gt; 5-FU+silicone (59.4%) &gt; TAC+silicone (58.3%) &gt; 5-FU (49.8%) &gt; BLM (42.0%) &gt; TAC (26.7%) &gt; VER (26.2%) &gt; silicone (18.3%). There was no publication bias revealed based on the funnel diagram.Conclusion: This study recommends intralesional injection of TAC-BTA and TAC-5-FU combined therapies. But for patients who cannot tolerate the side effects, the use of silicone gels in combination with TAC is recommended. However, these conclusions need to be further confirmed by more randomized controlled trials.


2021 ◽  
Vol 5 (8) ◽  
pp. 2237-2244
Author(s):  
Parth Patel ◽  
Payal Patel ◽  
Meha Bhatt ◽  
Cody Braun ◽  
Housne Begum ◽  
...  

Abstract Prompt evaluation and therapeutic intervention of suspected pulmonary embolism (PE) are of paramount importance for improvement in outcomes. We systematically reviewed outcomes in patients with suspected PE, including mortality, incidence of recurrent PE, major bleeding, intracranial hemorrhage, and postthrombotic sequelae. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. We included 22 studies with 15 865 patients. Among patients who were diagnosed with PE and discharged with anticoagulation, 3-month follow-up revealed that all-cause mortality was 5.69% (91/1599; 95% confidence interval [CI], 4.56-6.83), mortality from PE was 1.19% (19/1597; 95% CI, 0.66-1.72), recurrent venous thromboembolism (VTE) occurred in 1.38% (22/1597; 95% CI: 0.81-1.95), and major bleeding occurred in 0.90% (2/221%; 95% CI, 0-2.15). In patients with a low pretest probability (PTP) and negative D-dimer, 3-month follow-up revealed mortality from PE was 0% (0/808) and incidence of VTE was 0.37% (4/1094; 95% CI: 0.007-0.72). In patients with intermediate PTP and negative D-dimer, 3-month follow-up revealed that mortality from PE was 0% (0/2747) and incidence of VTE was 0.46% (14/3015; 95% CI: 0.22-0.71). In patients with high PTP and negative computed tomography (CT) scan, 3-month follow-up revealed mortality from PE was 0% (0/651) and incidence of VTE was 0.84% (11/1302; 95% CI: 0.35-1.34). We further summarize outcomes evaluated by various diagnostic tests and diagnostic pathways (ie, D-dimer followed by CT scan).


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