Letter to the editor re: ‘serious adverse events and deaths in PCSK9 inhibitor trials reported on ClinicalTrials.gov: a systematic review’

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 To identify relevant trials, we will search both for published and unpublished trials in major medical databases from their inception to the present.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 We will include any published or unpublished randomised clinical trial comparing one or more antidepressants with placebo, ‘active placebo’, or no intervention for adults with major depressive disorder.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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A Systematic Review of Pediatric and Adult In-Flight Medical Emergencies

International Journal of Pediatrics ◽

10.1155/2018/6596490 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Christina Sul ◽

Sherif M. Badawy

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Health Outcomes ◽

Pediatric Population ◽

Air Travel ◽

Serious Adverse Events ◽

Significant Events ◽

Medical Emergencies ◽

The Subject

In-flight medical emergencies (IMEs) are acute onboard events of illnesses or injuries with potential immediate risk to a passenger’s short- or long-term health, or life. IMEs are significant events that are related to public safety concerns. With the increasing amount of annual air travel every year, it is expected that the number of encountered IMEs will continue to grow. Thus, it will be critical to develop and implement appropriate measures to manage IMEs with the best possible outcome. Despite the fact that most IMEs are self-limited with no serious adverse events, serious IME can lead to death, disability, or other unfavorable health outcomes, particularly as a result of suboptimal medical care. In this article, we systematically reviewed the published up-to-date evidence on the subject of in-flight emergencies with a specific focus on pediatric population.

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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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Second-generation antipsychotic drugs and short-term somatic serious adverse events: a systematic review and meta-analysis

The Lancet Psychiatry ◽

10.1016/s2215-0366(19)30223-8 ◽

2019 ◽

Vol 6 (9) ◽

pp. 753-765 ◽

Cited By ~ 10

Author(s):

Johannes Schneider-Thoma ◽

Orestis Efthimiou ◽

Irene Bighelli ◽

Carola Dörries ◽

Maximilian Huhn ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Antipsychotic Drugs ◽

Second Generation ◽

Meta Analysis ◽

Short Term ◽

Serious Adverse Events ◽

Second Generation Antipsychotic

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Active and passive surveillance of yellow fever vaccine 17D or 17DD-associated serious adverse events: Systematic review

Vaccine ◽

10.1016/j.vaccine.2011.04.055 ◽

2011 ◽

Vol 29 (28) ◽

pp. 4544-4555 ◽

Cited By ~ 36

Author(s):

Roger E. Thomas ◽

Diane L. Lorenzetti ◽

Wendy Spragins ◽

Dave Jackson ◽

Tyler Williamson

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Yellow Fever ◽

Yellow Fever Vaccine ◽

Passive Surveillance ◽

Serious Adverse Events

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Long-acting muscarinic antagonists vs. long-acting β 2 agonists in COPD exacerbations: a systematic review and meta-analysis

Jornal Brasileiro de Pneumologia ◽

10.1590/s1806-37562016000000287 ◽

2017 ◽

Vol 43 (4) ◽

pp. 302-312 ◽

Cited By ~ 5

Author(s):

Israel Silva Maia ◽

Mariângela Pimentel Pincelli ◽

Victor Figueiredo Leite ◽

João Amadera ◽

Anna Maria Buehler

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Therapeutic Effects ◽

Muscarinic Antagonists ◽

Serious Adverse Events ◽

Exacerbation Rate ◽

Copd Exacerbations ◽

Long Acting

ABSTRACT Objective: To determine whether long-acting muscarinic antagonists (LAMAs) provide superior therapeutic effects over long-acting β2 agonists (LABAs) for preventing COPD exacerbations. Methods: This was a systematic review and meta-analysis of randomized clinical trials involving patients with stable, moderate to severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease criteria, treated with a LAMA (i.e., tiotropium bromide, aclidinium, or glycopyrronium), followed for at least 12 weeks and compared with controls using a LABA in isolation or in combination with a corticosteroid. Results: A total of 2,622 studies were analyzed for possible inclusion on the basis of their title and abstract; 9 studies (17,120 participants) were included in the analysis. In comparison with LABAs, LAMAs led to a greater decrease in the exacerbation rate ratio (relative risk [RR] = 0.88; 95% CI: 0.84-0.93]; a lower proportion of patients who experienced at least one exacerbation (RR = 0.90; 95% CI: 0.87-0.94; p < 0.00001); a lower risk of exacerbation-related hospitalizations (RR = 0.78; 95% CI: 0.69-0.87; p < 0.0001); and a lower number of serious adverse events (RR = 0.81; 95% CI: 0.67-0.96; p = 0.0002). The overall quality of evidence was moderate for all outcomes. Conclusions: The major findings of this systematic review and meta-analysis were that LAMAs significantly reduced the exacerbation rate (exacerbation episodes/year), as well as the number of exacerbation episodes, of hospitalizations, and of serious adverse events.

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Manipulation and Mobilization for Treating Chronic Nonspecific Neck Pain: A Systematic Review and Meta-Analysis for an Appropriateness Panel

January 2018 - Pain Physician ◽

10.36076/ppj/2019.22.e55 ◽

2019 ◽

Vol 2 (22.2) ◽

pp. E55-E70 ◽

Cited By ~ 3

Author(s):

Ian D. Coulter

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Neck Pain ◽

Meta Analysis ◽

Chronic Neck Pain ◽

Risk Of Bias ◽

Current Evidence ◽

Sample Sizes ◽

Serious Adverse Events ◽

Multiple Treatment

Background: Mobilization and manipulation therapies are widely used by patients with chronic nonspecific neck pain; however, questions remain around efficacy, dosing, and safety, as well as how these approaches compare to other therapies. Objectives: Based on published trials, to determine the efficacy, effectiveness, and safety of various mobilization and manipulation therapies for treatment of chronic nonspecific neck pain. Study Design: A systematic literature review and meta-analysis. Methods: We identified studies published between January 2000 and September 2017, by searching multiple electronic databases, examining reference lists, and communicating with experts. We selected randomized controlled trials comparing manipulation and/or mobilization therapies to sham, no treatment, each other, and other active therapies, or when combined as multimodal therapeutic approaches. We assessed risk of bias by using the Scottish Intercollegiate Guidelines Network criteria. When possible, we pooled data using random-effects meta-analysis. Grading of Recommendations, Assessment, Development, and Evaluation was applied to determine the confidence in effect estimates. This project was funded by the National Center for Complementary and Integrative Health under award number U19AT007912 and ultimately used to inform an appropriateness panel. Results: A total of 47 randomized trials (47 unique trials in 53 publications) were included in the systematic review. These studies were rated as having low risk of bias and included a total of 4,460 patients with nonspecific chronic neck pain who were being treated by a practitioner using various types of manipulation and/or mobilization interventions. A total of 37 trials were categorized as unimodal approaches and involved thrust or nonthrust compared with sham, no treatment, or other active comparators. Of these, only 6 trials with similar intervention styles, comparators, and outcome measures/timepoints were pooled for meta-analysis at 1, 3, and 6 months, showing a small effect in favor of thrust plus exercise compared to an exercise regimen alone for a reduction in pain and disability. Multimodal approaches appeared to be effective at reducing pain and improving function from the 10 studies evaluated. Health-related quality of life was seldom reported. Some 22/47 studies did not report or mention adverse events. Of the 25 that did, either no or minor events occurred. Limitations: The current evidence is heterogeneous, and sample sizes are generally small. Conclusions: Studies published since January 2000 provide low-moderate quality evidence that various types of manipulation and/or mobilization will reduce pain and improve function for chronic nonspecific neck pain compared to other interventions. It appears that multimodal approaches, in which multiple treatment approaches are integrated, might have the greatest potential impact. The studies comparing to no treatment or sham were mostly testing the effect of a single dose, which may or may not be helpful to inform practice. According to the published trials reviewed, manipulation and mobilization appear safe. However, given the low rate of serious adverse events, other types of studies with much larger sample sizes would be required to fully describe the safety of manipulation and/or mobilization for nonspecific chronic neck pain. Key words: Chronic neck pain, nonspecific, chiropractic, manipulation, mobilization, systematic review, meta-analysis, appropriateness

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Prone Positioning of Non-intubated Patients with COVID-19 - A Systematic Review and Meta-analysis

10.21203/rs.3.rs-99735/v1 ◽

2020 ◽

Author(s):

Mallikarjuna Reddy PONNAPA REDDY ◽

Ashwin SUBRAMANIAM ◽

Zheng Jie LIM ◽

Alexandr ZUBAREV ◽

Afsana AFROZ ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Prone Positioning ◽

Serious Adverse Events ◽

Lack Of Control ◽

The Impact ◽

Substantial Heterogeneity ◽

Major Adverse Events

Abstract Purpose: Several studies have reported adopting prone positioning (PP) in non-intubated patients with COVID-19-related hypoxaemic respiratory failure. This systematic review and meta-analysis evaluated the impact of PP on oxygenation and clinical outcomes.Methods: We searched PubMed, Embase and the COVID-19 living systematic review from December 1, 2019 to July 23, 2020. We included studies that reported using PP in hypoxaemic, non-intubated adult patients with COVID-19. Primary outcome measureed was the weighted mean difference (MD) in oxygenation parameters (PaO2/FiO2, PaO2 or SpO2) pre and post-PP. Results: Fifteen single arm observational studies reporting PP in 449 patients were included. Substantial heterogeneity was noted in terms of, location within hospital where PP was instituted, respiratory supports during PP, and frequency and duration of PP. Significant improvement in oxygenation was reported post-PP: PaO2/FiO2 (MD 37.6, 95% CI 18.8-56.5); PaO2 (MD 30.4 mmHg, 95% CI 10.9 to 49.9); and SpO2 (MD 5.8%, 95% CI 3.7 to 7.9). Patients with a pre-PP PaO2/FiO2 ≤150 experienced greater oxygenation improvements compared with those with a pre-PP PaO2/FiO2 >150 (MD 40.5, 95% CI -3.5 to 84.6) vs. 37, 95% CI 17.1 to 56.9). Respiratory rate decreased post-PP (MD -2.9, 95% CI -5.4 to -0.4). Overall intubation and mortality rates were 21% (90/426) and 26% (101/390) respectively. There were no major adverse events reported. Conclusions: Despite the significant variability in frequency and duration of PP and respiratory supports applied, PP was associated with improvements in oxygenation parameters without any reported serious adverse events. The results are limited by lack of control arm and adjustment for confounders. Clinical trials are required to determine the effect of awake PP on patient-centred outcomes.Systematic review registration: Registration/protocol in PROSPERO (CRD42020194080).

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