Microbial Preparations (Probiotics) for the Prevention of Clostridium difficile Infection in Adults and Children: An Individual Patient Data Meta-analysis of 6,851 Participants

OBJECTIVETo determine whether probiotic prophylaxes reduce the odds ofClostridium difficileinfection (CDI) in adults and children.DESIGNIndividual participant data (IPD) meta-analysis of randomized controlled trials (RCTs), adjusting for risk factors.METHODSWe searched 6 databases and 11 grey literature sources from inception to April 2016. We identified 32 RCTs (n=8,713); among them, 18 RCTs provided IPD (n=6,851 participants) comparing probiotic prophylaxis to placebo or no treatment (standard care). One reviewer prepared the IPD, and 2 reviewers extracted data, rated study quality, and graded evidence quality.RESULTSProbiotics reduced CDI odds in the unadjusted model (n=6,645; odds ratio [OR] 0.37; 95% confidence interval [CI], 0.25–0.55) and the adjusted model (n=5,074; OR, 0.35; 95% CI, 0.23–0.55). Using 2 or more antibiotics increased the odds of CDI (OR, 2.20; 95% CI, 1.11–4.37), whereas age, sex, hospitalization status, and high-risk antibiotic exposure did not. Adjusted subgroup analyses suggested that, compared to no probiotics, multispecies probiotics were more beneficial than single-species probiotics, as was using probiotics in clinical settings where the CDI risk is ≥5%. Of 18 studies, 14 reported adverse events. In 11 of these 14 studies, the adverse events were retained in the adjusted model. Odds for serious adverse events were similar for both groups in the unadjusted analyses (n=4,990; OR, 1.06; 95% CI, 0.89–1.26) and adjusted analyses (n=4,718; OR, 1.06; 95% CI, 0.89–1.28). Missing outcome data for CDI ranged from 0% to 25.8%. Our analyses were robust to a sensitivity analysis for missingness.CONCLUSIONSModerate quality (ie, certainty) evidence suggests that probiotic prophylaxis may be a useful and safe CDI prevention strategy, particularly among participants taking 2 or more antibiotics and in hospital settings where the risk of CDI is ≥5%.TRIAL REGISTRATIONPROSPERO 2015 identifier: CRD42015015701Infect Control Hosp Epidemiol2018;771–781

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Beneficial and harmful effects of antidepressants versus placebo, ‘active placebo’, or no intervention for adults with major depressive disorder: a protocol for a systematic review of published and unpublished data with meta-analyses and trial sequential analyses

Systematic Reviews ◽

10.1186/s13643-021-01705-6 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Sophie Juul ◽

Faiza Siddiqui ◽

Marija Barbateskovic ◽

Caroline Kamp Jørgensen ◽

Michael Pascal Hengartner ◽

...

Keyword(s):

Systematic Review ◽

Major Depressive Disorder ◽

Depressive Symptoms ◽

Adverse Events ◽

Depressive Disorder ◽

Meta Analysis ◽

Risk Of Bias ◽

Major Depressive ◽

Serious Adverse Events ◽

Harmful Effects

Abstract Background Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide. Antidepressants are frequently used to treat major depressive disorder. It has been shown repeatedly that antidepressants seem to reduce depressive symptoms with a statistically significant effect, but the clinical importance of the effect sizes seems questionable. Both beneficial and harmful effects of antidepressants have not previously been sufficiently assessed. The main objective of this review will be to evaluate the beneficial and harmful effects of antidepressants versus placebo, ‘active placebo’, or no intervention for adults with major depressive disorder. Methods/design A systematic review with meta-analysis will be reported as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), bias will be assessed with the Cochrane Risk of Bias tool-version 2 (ROB2), our eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, Trial Sequential Analysis will be conducted to control for random errors, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. To identify relevant trials, we will search both for published and unpublished trials in major medical databases from their inception to the present. Clinical study reports will be obtained from regulatory authorities and pharmaceutical companies. Two review authors will independently screen the results of the literature searches, extract data, and perform risk of bias assessment. We will include any published or unpublished randomised clinical trial comparing one or more antidepressants with placebo, ‘active placebo’, or no intervention for adults with major depressive disorder. The following active agents will be included: agomelatine, amineptine, amitriptyline, bupropion, butriptyline, cianopramine, citalopram, clomipramine, dapoxetine, demexiptiline, desipramine, desvenlafaxine, dibenzepin, dosulepin, dothiepin, doxepin, duloxetine, escitalopram, fluoxetine, fluvoxamine, imipramine, iprindole, levomilnacipran, lofepramine, maprotiline, melitracen, metapramine, milnacipran, mirtazapine, nefazodone, nortriptyline, noxiptiline, opipramol, paroxetine, protriptyline, quinupramine, reboxetine, sertraline, trazodone, tianeptine, trimipramine, venlafaxine, vilazodone, and vortioxetine. Primary outcomes will be depressive symptoms, serious adverse events, and quality of life. Secondary outcomes will be suicide or suicide attempt, suicidal ideation, and non-serious adverse events. Discussion As antidepressants are commonly used to treat major depressive disorder in adults, a systematic review evaluating their beneficial and harmful effects is urgently needed. This review will inform best practice in treatment and clinical research of this highly prevalent and burdensome disorder. Systematic review registration PROSPERO CRD42020220279

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Impact of body mass index on survival and serious adverse events in advanced non-small cell lung cancer treated with bevacizumab: a meta-analysis of randomized clinical trials

Current Medical Research and Opinion ◽

10.1080/03007995.2021.1900091 ◽

2021 ◽

pp. 1-1

Author(s):

Soham Shukla ◽

Zachary Babcock ◽

Laura Pizzi ◽

Luigi Brunetti

Keyword(s):

Lung Cancer ◽

Body Mass Index ◽

Clinical Trials ◽

Adverse Events ◽

Small Cell Lung Cancer ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Small Cell ◽

Small Cell Lung ◽

Serious Adverse Events

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HPV vaccines for prevention of cervical pre-cancer in adolescent girls and women

Journal of Evidence-Based Healthcare ◽

10.17267/2675-021xevidence.v1i2.2510 ◽

2019 ◽

Vol 1 (2) ◽

pp. 112

Author(s):

Jia Jian Li ◽

Jessica Stetz

Keyword(s):

Adverse Events ◽

Adolescent Girls ◽

Meta Analysis ◽

Hpv Vaccination ◽

Hpv Infection ◽

Significant Benefit ◽

Hpv Vaccines ◽

Serious Adverse Events

The evidence presented in this Cochrane meta-analysis shows the HPV vaccination confers significant benefit in preventing cervical pre-cancer. NNT of 60 for preventing one cervical pre-cancer (women 15 to 25 years old with or without HPV infection). The effect is higher for lesions associated with HPV16/18. The data also demonstrates an absence of serious adverse events. Therefore, we have assigned a color recommendation of Green (Benefit > Harm) to this vaccine.

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Efficacy and Safety of PEGPH20 in Pancreatic Cancer: A Systematic Review and Meta-Analysis

Current Cancer Therapy Reviews ◽

10.2174/1573394717666210616152341 ◽

2021 ◽

Vol 17 ◽

Author(s):

Vinod Solipuram ◽

Harish Gopalakrishna ◽

Gayatri Naira ◽

Akhila Mohan

Keyword(s):

Pancreatic Cancer ◽

Placebo Group ◽

Febrile Neutropenia ◽

Adverse Events ◽

Meta Analysis ◽

Progression Free Survival ◽

Cochrane Library ◽

Thromboembolic Events ◽

Serious Adverse Events ◽

Significant Difference

Introduction: Pancreatic cancer is an aggressive tumor that had an estimated 57,600 new cases and 47,050 deaths in 2020 in the US alone. Recent studies have targeted tumor microenvironment (TME) for better delivery of systemic chemotherapy like PEGPH20, which degrades hyaluronic acid in the extracellular matrix (ECM). A meta-analysis of these Randomized controlled trials (RCTs) to test the efficacy of PEGPH20 was performed. Methods: A systematic search was performed using PubMed, Embase, and Cochrane library without language limitations from inception to July 30, 2020. A total of 59 articles was identified, and 3 RCTs were included in the final analysis. The primary outcome was progression-free survival (PFS), and secondary outcomes were overall survival (OS), deaths from adverse events, thromboembolic events, serious adverse events (SAE), and febrile neutropenia. Results: There was no statistically significant improvement in PFS (HR= 0.94; 95%CI (0.79, 1.11)) in the PEGPH20 group when compared to the standard treatment/placebo group. There was no significant difference among OS (HR= 0.99, 95%CI (0.83, 1.17), deaths from adverse events (RR=0.97; 95%CI (0.54, 1.73)), thromboembolic events (RR= 1.49; 95%CI (0.92, 2.44)), and febrile neutropenia (RR= 0.88; 95%CI (0.45, 1.72), however, there was statistically significant increase in SAE (RR = 1.59; 95%CI (1.01, 2.52) in the PEGPH20 group compared to the placebo group. Conclusion: This meta-analysis showed that PEGPH20 did not improve the PFS or OS. Moreover, there is an increased incidence of serious adverse events with the use of PEGPH20 compared to standard therapies.

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Safety and Efficacy of Fremanezumab for the Prevention of Migraine: a Meta-analysis from Random Clinical Trails

10.21203/rs.2.22379/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Bixi Gao ◽

Nan Sun ◽

Yanbo Yang ◽

Yue Sun ◽

Mingjia Chen ◽

...

Keyword(s):

Adverse Events ◽

Neurological Diseases ◽

Meta Analysis ◽

Cochrane Library ◽

Serious Adverse Events ◽

Safety And Efficacy ◽

Therapeutic Drugs ◽

Primary Endpoints ◽

Calcitonin Gene ◽

Clinical Trails

Abstract Background Fremanezumab (TEV-48125) is a fully humanized immunoglobulin G isotype 2a selective monoclonal antibody that potently binds to calcitonin gene-related peptide (CGRP). It is one of novel therapeutic drugs for the prevention of migraine, which is one of the most common neurological diseases worldwide. Several clinical trails have been conducted to investigate the safety and efficacy of fremanezumab, but there is no systematic review of existing literature has been performed. Hence, we performed a meta-analysis to investigate the efficacy and safety of fremanezumab for prevention of migraine. Method Pubmed (MEDLINE), Embase, and Cochrane Library were searched from January 2001 to August 2019 for randomized controlled trials (RCTs). Five RCTs with 3379 patients were finally included in our study. Result We pooled 3379 patients from 5 RCTs, the primary endpoints were mean monthly migraine and headache days, baseline to week 12. We found that fremanezumab led to a significant reduction in migraine days (P < 0.0001) and headache days (P < 0.0001) during 12 weeks compared with placebo. In addition, after using fremanezumab, the risk of at least one adverse event (P=0.001) or related to the trail regimen (P=0.0005) significantly increase compared with placebo. Conclusions Fremanezumab has good efficacy for the prevention of migraine. The administration of fremanezumab can cause some mild adverse events but not serious adverse events.

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Dual– Versus Mono–Bronchodilator Therapy in Moderate to Severe COPD: A Meta-analysis

Annals of Pharmacotherapy ◽

10.1177/1060028020932134 ◽

2020 ◽

Vol 54 (12) ◽

pp. 1232-1242

Author(s):

Melissa Lipari ◽

Pramodini B. Kale-Pradhan ◽

Sheila M. Wilhelm

Keyword(s):

Adverse Events ◽

English Language ◽

Meta Analysis ◽

Dual Therapy ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Jadad Score ◽

Serious Adverse Events ◽

Bronchodilator Therapy ◽

Long Acting

Background: Chronic obstructive pulmonary disease (COPD) guidelines recommend both long-acting and dual bronchodilator therapy. It is unclear if there are differences in efficacy and safety. Objective: This meta-analysis evaluates the efficacy of dual therapy with long-acting β-agonist (LABA) + long acting muscarinic antagonist (LAMA) compared with monotherapy with LAMA for COPD. Methods: We searched PubMed, CINAHL, and Web of Science databases from inception through March 2020 to identify English-language, prospective randomized controlled trials (RCTs) that compared dual therapy with monotherapy in adult patients with COPD. Risk of bias was assessed using the Jadad score. Overall analysis was performed using Review Manager 5.3. Treatment effect was determined with the random-effects model using the Mantel-Haenszel method and was reported as mean difference (MD) with 95% CI. Results: A total of 18 RCTs were included (n = 6086; median Jadad score 5/5) that compared LAMA + LABA with LAMA. There was a greater improvement in forced expiratory volume at 1 s (FEV1) with dual therapy compared with LAMA: MD = 0.08; 95% CI = [0.05, 0.11]. There was no difference in St George Respiratory Questionnaire (SGRQ) scores between groups: OR = −0.85; 95% CI = [−1.83, 0.13]. There were no differences in overall adverse events (OR = 1.00; 95% CI = 0.92, 1.09), serious adverse events (OR = 1.01; 95% CI = 0.86, 1.18), or cardiovascular events (OR = 0.88; 95% CI = 0.58, 1.34). Conclusion and Relevance: Dual therapy improves FEV1 and is as safe as LAMA. Dual therapy does not improve SGRQ scores more than LAMA.

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Incidence of Ipilimumab-Related Serious Adverse Events in Patients with Advanced Cancer: A Meta-Analysis

Journal of Cancer ◽

10.7150/jca.28120 ◽

2019 ◽

Vol 10 (1) ◽

pp. 120-130

Author(s):

Chang-Ying Guo ◽

Si-Cong Jiang ◽

Yu-Kang Kuang ◽

Hao Hu

Keyword(s):

Adverse Events ◽

Advanced Cancer ◽

Meta Analysis ◽

Serious Adverse Events

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Safety and tolerability of calcitonin-gene-related peptide binding monoclonal antibodies for the prevention of episodic migraine – a meta-analysis of randomized controlled trials

Cephalalgia ◽

10.1177/0333102419829007 ◽

2019 ◽

Vol 39 (9) ◽

pp. 1164-1179 ◽

Cited By ~ 12

Author(s):

Da Xu ◽

Deng Chen ◽

Li-na Zhu ◽

Ge Tan ◽

Hai-jiao Wang ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Adverse Events ◽

Injection Site ◽

Meta Analysis ◽

Peptide Binding ◽

Episodic Migraine ◽

Calcitonin Gene Related Peptide ◽

Serious Adverse Events ◽

Related Peptide ◽

Calcitonin Gene

Aim To systematically evaluate the safety and tolerability of calcitonin-gene-related peptide binding monoclonal antibodies from the results of randomized controlled trials. Methods Online databases were searched on calcitonin-gene-related peptide binding monoclonal antibodies for the prevention of episodic migraine. Overall withdrawal, withdrawal due to adverse events, adverse events, serious adverse events and specific adverse events were extracted from the included studies. A meta-analysis was performed with Revman 5.3.0 software. Results Ten studies that investigated four drugs (galcanezumab, erenumab, fremanezumab and eptinezumab) with 5817 participants were included in this study. Serious adverse events, overall withdrawals, withdrawal due to adverse events and any adverse events were not significantly associated with monoclonal antibody treatment. Injection site pain and erythema were significantly higher in the calcitonin-gene-related peptide binding monoclonal antibodies treatment group than in the placebo group. The rates of serious adverse events were significantly higher in the galcanezumab 120 mg group. Injection site erythema was associated with galcanezumab 120 mg and 240 mg. Injection site pain and nasopharyngitis were associated with galcanezumab 150 mg and 5 mg, respectively. Overall adverse events were significantly higher with erenumab 70 mg and 140 mg. Treatment-related adverse events were significantly higher with fremanezumab 225 mg/month and 675 mg/quarter. Conclusions This study provides data on the safety and tolerability profiles of calcitonin-gene-related peptide binding monoclonal antibodies and confirms their potential use as preventive treatments for episodic migraine. In addition to the acceptable withdrawal rates, serious adverse events were rare, and the severity of most adverse events was mild to moderate. Injection site reaction may be the major adverse event associated with galcanezumab.

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Adverse events of exercise therapy in randomised controlled trials: a systematic review and meta-analysis

British Journal of Sports Medicine ◽

10.1136/bjsports-2018-100461 ◽

2019 ◽

Vol 54 (18) ◽

pp. 1073-1080 ◽

Cited By ~ 4

Author(s):

Andre Niemeijer ◽

Hans Lund ◽

Signe Nilssen Stafne ◽

Thomas Ipsen ◽

Cathrine Luhaäär Goldschmidt ◽

...

Keyword(s):

Systematic Review ◽

Relative Risk ◽

Adverse Events ◽

Exercise Therapy ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Control Group ◽

Controlled Trials ◽

Serious Adverse Events ◽

Randomised Controlled

ObjectiveTo evaluate the relative risk (RR) of serious and non-serious adverse events in patients treated with exercise therapy compared with those in a non-exercising control group.DesignSystematic review and meta-analysis.Data sourcesPrimary studies were identified based on The Cochrane Database of Systematic Reviews investigating the effect of exercise therapy.Eligibility criteriaAt least two of the authors independently evaluated all identified reviews and primary studies. Randomised controlled trials were included if they compared any exercise therapy intervention with a non-exercising control. Two authors independently extracted data. The RR of serious and non-serious adverse events was estimated separately.Results180 Cochrane reviews were included and from these, 773 primary studies were identified. Of these, 378 studies (n=38 368 participants) reported serious adverse events and 375 studies (n=38 517 participants) reported non-serious adverse events. We found no increase in risk of serious adverse events (RR=0.96 (95%CI 0.90 to 1.02, I2: 0.0%) due to exercise therapy. There was, however, an increase in non-serious adverse events (RR=1.19 (95%CI 1.09 to 1.30, I2: 0.0%). The number needed to treat for an additional harmful outcome for non-serious adverse events was 6 [95%CI 4 to 11).ConclusionParticipating in an exercise intervention increased the relative risk of non-serious adverse events, but not of serious adverse events. Exercise therapy may therefore be recommended as a relatively safe intervention.PROSPERO registration numberCRD42014014819.

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