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Frontiers in Immunology 2021This meta-analysis compared the efficacy and safety of five kinds of COVID-19 vaccines in different age groups (young adults and older adults), aiming to analyze the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This meta-analysis compared the efficacy and safety of five kinds of COVID-19 vaccines in different age groups (young adults and older adults), aiming to analyze the difference of adverse events (AEs) rate and virus geometric mean titer (GMT) values between young and older people, in order to find a specific trend, and explore the causes of this trend through meta-analysis.
METHOD
Meta-analysis was used to analyze the five eligible articles. The modified Jadad scoring scale was used to evaluate the quality of eligible literature with a scoring system of 1 to 7. The primary endpoint of the effectiveness index was GMT. The primary endpoints of the safety index were the incidence of local AEs and systemic AEs. Stata 12.0 software was used for meta-analysis. Revman 5.0 software was used to map the risk of publication bias, and Egger's test was used to analyze publication bias.
RESULTS
The GMT values of young adults were higher than older adults (SMD = 1.40, 95% CI (0.79, 2.02), P<0.01). There was a higher incidence of local and systemic AEs in young people than in the elderly (OR = 1.10, 95% CI (1.08, 1.12), P<0.01; OR = 1.18, 95% CI (1.14, 1.22), P<0.01).
CONCLUSION
The immune effect of young people after being vaccinated with COVID-19 vaccines was better than that of the elderly, but the safety was worse than that of old people, the most common AEs were fever, rash, and local muscle pain, which were tolerable for young people. As the AEs of the elderly were lower, they can also be vaccinated safely; the reason for the low level of GMT in the elderly was related to Immunosenescence. The vaccine tolerance of people of different ages needs to be studied continuously.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antibodies, Neutralizing; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Female; Humans; Immunogenicity, Vaccine; Male; Middle Aged; SARS-CoV-2
PubMed: 34938287
DOI: 10.3389/fimmu.2021.758294 -
The Cochrane Database of Systematic... Dec 2021Epilepsy is one of the most common neurological disorders. Many people with epilepsy are drug-resistant and require add-on therapy, meaning that they concomitantly take... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Epilepsy is one of the most common neurological disorders. Many people with epilepsy are drug-resistant and require add-on therapy, meaning that they concomitantly take multiple antiepileptic drugs. Carisbamate is a drug which is taken orally and inhibits voltage-gated sodium channels. Carisbamate may be useful for drug-resistant focal epilepsy.
OBJECTIVES
To evaluate the efficacy and tolerability of carisbamate when used as an add-on therapy for drug-resistant focal epilepsy.
SEARCH METHODS
We searched the following databases on 8 April 2021: Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid) 1946 to April 07, 2021. CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, WHO ICTRP, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane review groups including Epilepsy. We also searched ongoing trials registers, checked reference lists, and contacted authors of the included trials.
SELECTION CRITERIA
Double-blind randomised controlled trials (RCTs) comparing carisbamate versus placebo or another antiepileptic drug, as add-on therapy for drug-resistant focal epilepsy. Trials could have a parallel-group or cross-over design.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected the trials for inclusion, assessed trial quality, and extracted data. The primary outcome was 50% or greater reduction in seizure frequency (responder rate). The secondary outcomes were: seizure freedom, treatment withdrawal (for any reason and due to adverse events); adverse events, and quality of life. We analysed data using the Mantel-Haenszel statistical method and according to the intention-to-treat population. We presented results as risk ratios (RRs) with 95% confidence intervals (CIs).
MAIN RESULTS
We included four RCTs involving a total of 2211 participants. All four trials compared carisbamate with placebo for drug-resistant focal epilepsy. Participants in all trials were over 16 years of age and received at least one other antiepileptic drug concomitantly. We detected substantial risk of bias across the included trials. All four trials were at high risk of attrition bias due to the incomplete reporting of attrition and the high treatment withdrawal rates noted, especially with higher doses. All four trials also had unclear risk of detection bias, as they did not specify whether outcome assessors were blinded. Meta-analysis suggested that carisbamate produced a higher responder rate compared to placebo (RR 1.36, 95% CI 1.14 to 1.62; 4 studies; moderate-certainty evidence). More participants in the carsibamate group achieved seizure freedom (RR 2.43, 95% CI 0.84 to 7.03; 1 study); withdrew from treatment for any reason (RR 1.32, 95% CI 0.82 to 2.12; 4 studies); and withdrew from treatment due to adverse events (RR 1.80, 95% CI 0.78 to 4.17; 4 studies) than in the placebo group. However, the evidence for the three outcomes was very low-certainty. There was no difference between treatment groups for the proportion of participants experiencing at least one adverse event (RR 1.10, 95% CI 0.93 to 1.30; 2 studies; low-certainty evidence). More participants in the carisbamate group than in the placebo group developed dizziness (RR 2.06, 95% CI 1.23 to 3.44; 4 studies; very low-certainty evidence) and somnolence (RR 1.82, 95% CI 1.28 to 2.58; 4 studies; low-certainty evidence), but not fatigue (RR 1.11, 95% CI 0.73 to 1.68; 3 studies); headache (RR 1.13, 95% CI 0.92 to 1.38; 4 studies); or nausea (RR 1.19, 95% CI 0.81 to 1.75; 3 studies). None of the included trials reported quality of life.
AUTHORS' CONCLUSIONS
The results suggest that carisbamate may demonstrate efficacy and tolerability as an add-on therapy for drug-resistant focal epilepsy. Importantly, the evidence for all outcomes except responder rate was of low to very low certainty, therefore we are uncertain of the accuracy of the reported effects. The certainty of the evidence is limited by the significant risk of bias associated with the included studies, as well as the statistical heterogeneity detected for some outcomes. Consequently, it is difficult for these findings to inform clinical practice. The studies were all of short duration and only included adult study populations. There is a need for further RCTs with more clear methodology, long-term follow-up, more clinical outcomes, more seizure types, and a broader range of participants.
Topics: Adult; Anticonvulsants; Carbamates; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsies, Partial; Humans; Pharmaceutical Preparations; Randomized Controlled Trials as Topic
PubMed: 34870321
DOI: 10.1002/14651858.CD012121.pub2 -
Epilepsy & Behavior : E&B Jan 2022The efficacy and safety of cenobamate relative to other antiseizure medications (ASMs) has not been evaluated. An indirect treatment comparison (network meta-analysis)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The efficacy and safety of cenobamate relative to other antiseizure medications (ASMs) has not been evaluated. An indirect treatment comparison (network meta-analysis) was performed to determine if adjunctive cenobamate increases the odds ratio (OR) for ≥50% responder rate or for withdrawals due to treatment-emergent adverse events (TEAEs) leading to ASM discontinuation versus adjunctive therapy with other ASMs.
METHODS
A systematic literature review was conducted to identify randomized, double-blind, placebo-controlled trials (maintenance phase ≥ 12 weeks) assessing adjunctive ASMs in adults with uncontrolled focal seizures. Cenobamate was compared to a group of seven other ASMs, and to subgroups of branded (brivaracetam, eslicarbazepine acetate, lacosamide, and perampanel) and older (lamotrigine, levetiracetam, and topiramate) ASMs at FDA-recommended daily maintenance doses (FDA-RDMD), at all doses, and at maximum and minimum daily doses. Statistical significance was set at p < 0.05.
RESULTS
Twenty-one studies were eligible for analysis. The placebo-adjusted ≥ 50% responder rate for FDA-RDMD of cenobamate was superior (OR 4.200; 95% CI 2.279, 7.742) to FDA-RDMD of all seven assessed (OR 2.202 95% CI 1.915, 2.532; p = 0.044) and branded ASMs (OR 2.148; 95% CI 1.849, 2.494; p = 0.037). There was no significant difference for ≥50% responder rate between FDA-RDMD of cenobamate and FDA-RDMD of older ASMs (OR 2.617; 95% CI 1.767, 3.878; p = 0.202). No significant differences were identified for ≥50% responder rate when comparing all doses and maximum/minimum doses of cenobamate to all seven, branded, and older ASMs. Cenobamate demonstrated comparable TEAE withdrawal rates to all seven ASMs, branded ASMs, and older ASMs across each of the four dose ranges (all p > 0.05).
SIGNIFICANCE
Patients receiving FDA-RDMD of cenobamate were more likely to have ≥50% seizure reduction compared with FDA-RDMD of the seven assessed ASMs and branded ASMs, without an increase in treatment discontinuation due to TEAEs.
Topics: Adult; Anticonvulsants; Carbamates; Chlorophenols; Double-Blind Method; Drug Therapy, Combination; Humans; Randomized Controlled Trials as Topic; Seizures; Tetrazoles; Treatment Outcome
PubMed: 34864380
DOI: 10.1016/j.yebeh.2021.108429 -
Journal of Medical Virology Apr 2022To systematically evaluate the efficacy and safety of arbidol and lopinavir/ritonavir (LPV/r) in the treatment of coronavirus disease 2019 (COVID-19) using a... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVES
To systematically evaluate the efficacy and safety of arbidol and lopinavir/ritonavir (LPV/r) in the treatment of coronavirus disease 2019 (COVID-19) using a meta-analysis method.
METHODS
The China Knowledge Network, VIP database, WanFang database PubMed database, Embase database, and Cochrane Library were searched for a collection of comparative studies on arbidol and lopinavir/ritonavir in the treatment of COVID-19. Meta-analysis was used to evaluate the efficacy and safety of Arbidol and lopinavir/ritonavir in the treatment of COVID-19.
RESULTS
The results of the systematic review indicated that Arbidol had a higher positive-to-negative conversion rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid on Day 7 (p = 0.03), a higher positive-to-negative conversion rate of SARS-CoV-2 nucleic acid on Day 14 (p = 0.006), a higher improvement rate of chest computed tomography on Day 14 (p = 0.02), a lower incidence of adverse reactions (p = 0.002) and lower rate of mortality (p = 0.007). There was no difference in the rate of cough disappearance on Day 14 (p = 0.24) or the rate of severe/critical illness (p = 0.07) between the two groups.
CONCLUSIONS
Arbidol may be superior to lopinavir/ritonavir in the treatment of COVID-19. However, due to the small number of included studies and the number of patients, high-quality multicenter large-sample randomized double-blind controlled trials are still needed for verification.
Topics: Antiviral Agents; COVID-19; Drug Combinations; Humans; Indoles; Lopinavir; Ritonavir; SARS-CoV-2; Sulfides; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34837230
DOI: 10.1002/jmv.27481 -
Nutrients Nov 2021There is a large and growing body of literature focusing on the use of oral magnesium (Mg) supplementation for improving glucose metabolism in people with or at risk of... (Meta-Analysis)
Meta-Analysis
Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.
There is a large and growing body of literature focusing on the use of oral magnesium (Mg) supplementation for improving glucose metabolism in people with or at risk of diabetes. We therefore aimed to investigate the effect of oral Mg supplementation on glucose and insulin-sensitivity parameters in participants with diabetes or at high risk of diabetes, compared with a placebo. Several databases were searched investigating the effect of oral Mg supplementation vs placebo in patients with diabetes or conditions at high risk of diabetes. Data were reported as standardized mean differences (SMDs) with their 95% confidence intervals (CIs) using follow-up data of glucose and insulin-sensitivity parameters. Compared with placebo, Mg supplementation reduced fasting plasma glucose in people with diabetes. In people at high risk of diabetes, Mg supplementation significantly improved plasma glucose per se, and after a 2 h oral glucose tolerance test. Furthermore, Mg supplementation demonstrated an improvement in insulin sensitivity markers. In conclusion, Mg supplementation appears to have a beneficial role and improves glucose parameters in people with diabetes. Moreover, our work indicates that Mg supplementation may improve insulin-sensitivity parameters in those at high risk of diabetes.
Topics: Blood Glucose; Diabetes Mellitus; Dietary Supplements; Double-Blind Method; Glucose Tolerance Test; Humans; Insulin Resistance; Magnesium; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34836329
DOI: 10.3390/nu13114074 -
JAMA Psychiatry Jan 2022Single-blind placebo run-in (PRI) periods are common in randomized clinical trials (RCTs) of treatment for depression. They aim to increase sensitivity to detect drug... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Single-blind placebo run-in (PRI) periods are common in randomized clinical trials (RCTs) of treatment for depression. They aim to increase sensitivity to detect drug effects; however, the association of PRI periods with study outcomes remains unclear. This is concerning given the costs of PRI periods to patients and investigators.
OBJECTIVE
To examine the association of the use of PRI periods with the placebo response, drug response, and drug-placebo difference among RCTs of antidepressants.
DATA SOURCES
MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and PsycINFO, as well as repositories of unpublished studies, were systematically searched up to July 2021.
STUDY SELECTION
Included studies were double-blind, placebo-controlled RCTs of antidepressant medication among adults with depressive disorders.
DATA EXTRACTION AND SYNTHESIS
Data were extracted into a coding sheet, including the characteristics of studies, the characteristics of PRI periods, and the outcomes of studies.
MAIN OUTCOMES AND MEASURES
Study outcomes were the primary depression symptom measure reported by the RCT. These outcomes were used to calculate effect sizes (Hedges g) of the within-group drug response and placebo response as well as the drug-placebo difference. Random-effects meta-analysis was used to calculate effect sizes, and subgroup analyses were used to compare outcomes depending on use of PRI periods.
RESULTS
A total of 347 trials (representing 89 183 participants) were included; 174 studies (50%) reported using a single-blind PRI period. Response outcome data were available for 189 studies. Studies using PRI periods reported a smaller placebo response (g = 1.05 [95% CI, 0.98-1.11]; I2 = 82%) than studies that did not use a PRI period (g = 1.15 [95% CI, 1.09-1.21]; I2 = 81%; P = .02). Subgroup analysis showed a larger drug response size among studies that did not use a PRI period (g = 1.55 [95% CI, 1.49-1.61]; I2 = 85%) than those that did use a PRI period (g = 1.42 [95% CI, 1.36-1.48]; I2 = 81%; P = .001). The drug-placebo difference did not differ by use of PRI periods (g = 0.33 [95% CI, 0.29-0.38]; I2 = 47% for use of a PRI period vs g = 0.34 [95% CI, 0.30-0.38]; I2 = 54% for no use of PRI periods; P = .92). The likelihood of response to drug vs placebo also did not differ between studies that used a PRI period (odds ratio, 1.89 [95% CI, 1.76-2.03]) and those that did not use a PRI period (odds ratio, 1.77 [95% CI, 1.65-1.89]; P = .18).
CONCLUSIONS AND RELEVANCE
This study suggests that RCTs using PRI periods yield smaller within-group changes across both placebo and drug groups compared with RCTs without PRI periods. The reduction in effect size across groups was equivalent in magnitude. Consequently, PRI studies do not observe larger drug-placebo differences, suggesting that they do not increase trial sensitivity. As such, given the resources and probable deception required and risk to external validity, the practice of using PRI periods in RCTs of antidepressants should be ended.
Topics: Antidepressive Agents; Humans; Placebos; Randomized Controlled Trials as Topic; Single-Blind Method
PubMed: 34757405
DOI: 10.1001/jamapsychiatry.2021.3204 -
Paediatrics & Child Health Oct 2021The use of intravenous acetaminophen leads to meaningful health cost increases for paediatric institutions. Therefore, strict criteria for intravenous acetaminophen...
CONTEXT
The use of intravenous acetaminophen leads to meaningful health cost increases for paediatric institutions. Therefore, strict criteria for intravenous acetaminophen administration are needed.
OBJECTIVE
To undertake a systematic review of available evidence comparing oral versus intravenous acetaminophen use in children.
METHOD
A systematic literature search was conducted on five databases. All prospective interventional studies comparing intravenous to oral acetaminophen in patients <18 years old were included. Data collection and analysis were done according to PRISMA guidelines.
RESULTS
Among 6,417 retrieved abstracts, 29 full-text articles were assessed of which 3 were retained. (1) Oral bioavailability (72% with a high inter-individual variability) was reported in 47 stable patients in a paediatric intensive care unit. (2) In a double-blind randomized controlled trial of 45 children, no difference in analgesia was found between oral and intravenous administration after cleft palate repair. (3) In an open-label prospective observational study of 200 children, temperature decreased faster after intravenous than oral administration but was similar 4 hours later.
CONCLUSIONS
Available data are insufficient to guide clinicians with a rational choice of route of administration. Oral bioavailability should be studied in paediatric populations outside the intensive care unit. Despite the widespread use of intravenous acetaminophen, there is little evidence to suggest that it improves analgesia compared to the oral formulation. Similarly, fever weans faster but whether this translates into any meaningful clinical outcome is unknown. The lack of data plus the significantly higher costs of intravenous acetaminophen should motivate further research.
PubMed: 34676011
DOI: 10.1093/pch/pxaa137 -
Journal of the International Society of... Oct 2021Previous narrative reviews have concluded that dietary nitrate (NO) improves maximal neuromuscular power in humans. This conclusion, however, was based on a limited... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Previous narrative reviews have concluded that dietary nitrate (NO) improves maximal neuromuscular power in humans. This conclusion, however, was based on a limited number of studies, and no attempt has been made to quantify the exact magnitude of this beneficial effect. Such information would help ensure adequate statistical power in future studies and could help place the effects of dietary NO on various aspects of exercise performance (i.e., endurance vs. strength vs. power) in better context. We therefore undertook a systematic review and individual participant data meta-analysis to quantify the effects of NO supplementation on human muscle power.
METHODS
The literature was searched using a strategy developed by a health sciences librarian. Data sources included Medline Ovid, Embase, SPORTDiscus, Scopus, Clinicaltrials.gov , and Google Scholar. Studies were included if they used a randomized, double-blind, placebo-controlled, crossover experimental design to measure the effects of dietary NO on maximal power during exercise in the non-fatigued state and the within-subject correlation could be determined from data in the published manuscript or obtained from the authors.
RESULTS
Nineteen studies of a total of 268 participants (218 men, 50 women) met the criteria for inclusion. The overall effect size (ES; Hedge's g) calculated using a fixed effects model was 0.42 (95% confidence interval (CI) 0.29, 0.56; p = 6.310 × 10). There was limited heterogeneity between studies (i.e., I = 22.79%, H = 1.30, p = 0.3460). The ES estimated using a random effects model was therefore similar (i.e., 0.45, 95% CI 0.30, 0.61; p = 1.064 × 10). Sub-group analyses revealed no significant differences due to subject age, sex, or test modality (i.e., small vs. large muscle mass exercise). However, the ES in studies using an acute dose (i.e., 0.54, 95% CI 0.37, 0.71; p = 6.774 × 10) was greater (p = 0.0211) than in studies using a multiple dose regimen (i.e., 0.22, 95% CI 0.01, 0.43; p = 0.003630).
CONCLUSIONS
Acute or chronic dietary NO intake significantly increases maximal muscle power in humans. The magnitude of this effect-on average, ~ 5%-is likely to be of considerable practical and clinical importance.
Topics: Athletic Performance; Dietary Supplements; Double-Blind Method; Humans; Muscle Strength; Nitrates; Randomized Controlled Trials as Topic
PubMed: 34625064
DOI: 10.1186/s12970-021-00463-z -
The Clinical Journal of Pain Dec 2021The aim of this meta-analysis was to evaluate the efficacy and safety of tanezumab for the treatment of patients with knee or hip osteoarthritis (OA). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The aim of this meta-analysis was to evaluate the efficacy and safety of tanezumab for the treatment of patients with knee or hip osteoarthritis (OA).
METHODS
PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched from inception to July 2020. Randomized-controlled trials comparing tanezumab with placebo or nonsteroidal anti-inflammatory drugs in patients with OA. Two investigators identified studies and independently extracted data, and conventional meta-analyses were conducted with Review Manager 5.3. The outcomes were pain relief, functional improvement, and risk of adverse events (AEs).
RESULTS
A total of 8 articles, comprising 9 randomized-controlled trials, were included. Overall, tanezumab was superior to placebo for relieving pain and improving function, as well as in the patient's global assessment. Tanezumab also had significant advantages over nonsteroidal anti-inflammatory drugs for relieving pain and improving function, as well as in the patient's global assessment. Significantly more patients discontinued treatment because of AEs after treatment with tanezumab. However, the differences in serious AEs and total joint replacement were not significant. Moreover, tanezumab-treated patients experienced significantly more rapid progression of osteoarthritis.
DISCUSSION
Tanezumab can alleviate pain and improve function for patients with OA of the hip or knee. Although tanezumab does not cause serious AEs, rapid progression of OA occurred in a small number of participants, so more clinical trials are needed to explore its safety.
Topics: Antibodies, Monoclonal, Humanized; Double-Blind Method; Humans; Osteoarthritis, Knee; Pain Measurement; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34608021
DOI: 10.1097/AJP.0000000000000986 -
Medicina Oral, Patologia Oral Y Cirugia... Nov 2021It is unclear if buccal articaine infiltration can be used as an alternative to standard inferior alveolar nerve block (IANB) for treating mandibular molars in pediatric... (Meta-Analysis)
Meta-Analysis
Can buccal infiltration of articaine replace traditional inferior alveolar nerve block for the treatment of mandibular molars in pediatric patients?: A systematic review and meta-analysis.
BACKGROUND
It is unclear if buccal articaine infiltration can be used as an alternative to standard inferior alveolar nerve block (IANB) for treating mandibular molars in pediatric patients. Therefore, this study aimed to pool evidence to compare the efficacy of buccal infiltration of articaine vs IANB with lignocaine for pediatric dental procedures.
MATERIAL AND METHODS
We searched the PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases for randomized controlled trials (RCTs) comparing the two techniques in pediatric patients and reporting the success of anesthesia and/or pain during treatment. PRISMA guidelines were followed.
RESULTS
Seven RCTs were included. Pooled analysis of five studies indicated no statistically significant difference in the success rates of the two anesthetic techniques (OR: 1.02; 95% CI: 0.13, 7.96; I2=69%, p=0.98). Meta-analysis of data from the four studies demonstrated no statistically significant difference in pain during the procedure with buccal infiltration of articaine or IANB with lignocaine (SMD: 0.62; 95% CI: -1.37, 0.12; I2=88%, p=0.10).
CONCLUSIONS
Evidence suggests that buccal infiltration of articaine is a viable alternative to IANB with lignocaine in pediatric patients for treating mandibular molars. Based on the confidence intervals, there may be a tendency of higher success rates with buccal infiltration of articaine.
Topics: Anesthesia, Dental; Anesthetics, Local; Carticaine; Child; Double-Blind Method; Humans; Lidocaine; Mandibular Nerve; Molar; Nerve Block; Pulpitis
PubMed: 34564678
DOI: 10.4317/medoral.24726