Cryoablation versus anti-arrhythmic therapy for initial treatment of atrial fibrillation: a systematic review and meta-analysis

Abstract Introduction Atrial fibrillation is a common cardiac arrhythmia that affects approximately 2% of the overall population. Guidelines suggest the use of anti-arrhythmic agents as initial therapy in patients with symptomatic atrial fibrillation, however using cryoablation as a first line therapy might have increased efficacy. The safety and efficacy of cryoablation as initial therapy has not yet been established. Purpose We performed a systematic review and meta-analysis of randomized controlled trials to investigate the use of cryoballoon catheter ablation compared to anti-arrhythmic therapy as an initial intervention to prevent recurrence of atrial tachyarrhythmias in patients with atrial fibrillation. We also wanted to determine if using this initial ablative approach did not present increased adverse events. Methods A comprehensive search of multiple databases was performed to find randomized control trials that directly compared cryoablation therapy versus anti-arrhythmic therapy as initial treatment for patients with atrial fibrillation. A total of three RCTs met the inclusion criteria (724 patients) and were used in the meta-analysis. The primary outcome of our meta-analysis was recurrence of atrial tachyarrhythmias. The secondary outcome evaluated serious adverse events of each therapy. Results The results showed a statistically significant reduction of recurrence of atrial tachyarrhythmic events in patients receiving cryoablation compared to anti-arrhythmic therapy [Risk Ratio (RR): 0.60, 95% CI (0.49, 0.72), P<0.ehab724.03521, I2=0%]. There was no significant difference in serious adverse events between patients receiving cryoablation compared to patients receiving anti-arrhythmic therapy. [Risk Ratio (RR): 1.19, 95% CI (0.71, 2.00), P=0.52, I2=0%]. Conclusion Our meta-analysis showed that cryoablation therapy as an initial therapy is more efficacious than anti-arrhythmic therapy in patients with atrial fibrillation without an increased risk of serious adverse events. FUNDunding Acknowledgement Type of funding sources: None.

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The high risk of malarial recurrence in patients with Plasmodium-mixed infection after treatment with antimalarial drugs: a systematic review and meta-analysis

Parasites & Vectors ◽

10.1186/s13071-021-04792-5 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Aongart Mahittikorn ◽

Frederick Ramirez Masangkay ◽

Kwuntida Uthaisar Kotepui ◽

Giovanni De Jesus Milanez ◽

Manas Kotepui

Keyword(s):

Systematic Review ◽

Mixed Infection ◽

Subgroup Analysis ◽

Initial Treatment ◽

Meta Analysis ◽

Antimalarial Drugs ◽

Secondary Outcome ◽

Significant Heterogeneity ◽

Pooled Prevalence ◽

Significant Difference

Abstract Background Malaria mixed infections are often unrecognized by microscopists in the hospitals, and a delay or failure to treat Plasmodium-mixed infection may lead to aggravated morbidity and increased mortality. The present study aimed to quantify the pooled proportion and risk of malarial recurrences after the treatment of Plasmodium-mixed infection. The results of the study may provide benefits in the management of Plasmodium-mixed infection in co-endemic regions. Methods This systematic review and meta-analysis searched the international Prospective Register of Systematic Reviews (PROSPERO; ID = CRD42020199709), MEDLINE, Web of Science, and Scopus for potentially relevant studies in any language published between January 1, 1936, and July 20, 2020, assessing drug efficacy in patients with Plasmodium-mixed infection. The primary outcome was the pooled prevalence of Plasmodium parasitemia after initiating antimalarial treatment for Plasmodium-mixed infection. The secondary outcome was the pooled risk ratio (RR) of malarial recurrence in Plasmodium-mixed infection compared with those in Plasmodium falciparum and Plasmodium vivax mono-infection. The pooled analyses were calculated by random-effects meta-analysis. After the initial treatment in different days of recurrences (≤ 28 days or > 28 days), the risk of Plasmodium parasitemia was compared in subgroup analysis. Results Out of 5217 screened studies, 11 were included in the meta-analysis, including 4390 patients from six countries. The pooled prevalence of all recurrences of Plasmodium-mixed parasitemia was 30% (95% confidence interval (CI) 16–43; I2: 99.2%; 11 studies). The RR of malarial recurrence within 28 days after the initial treatment (clinical treatment failure) of Plasmodium-mixed parasitemia compared with the treatment of P. falciparum was 1.22 (p: 0.029; 95% CI 1.02–1.47; Cochran Q: 0.93; I2: 0%; six studies), while there was no significant difference in the risk of recurrence 28 days after initial treatment compared with the treatment of P. falciparum (p: 0.696, RR: 1.14; 95% CI 0.59–2.18; Cochran Q < 0.05; I2: 98.2%; four studies). The subgroup analysis of antimalarial drugs showed that significant malarial recurrence within 28 days was observed in patients treated with artemisinin-based combination therapies (ACTs) with no significant heterogeneity (p: 0.028, RR: 1.31; 95% CI 1.03–1.66; Cochran Q: 0.834; I2: 0%). Conclusions The present findings showed a high prevalence of malarial recurrence after the initial treatment of Plasmodium-mixed infection. Moreover, significant malaria recurrence of mixed infection occurred within 28 days after treatment with ACTs. Graphic Abstract

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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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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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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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P108 Anti-nerve growth factor (anti-NGF) antibodies as analgesia in the management of osteoarthritis

Rheumatology ◽

10.1093/rheumatology/keab247.105 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Jashmitha Rammanohar ◽

James Sutton ◽

K T Matthew Seah ◽

Wasim S Khan ◽

Kendrick To

Keyword(s):

Systematic Review ◽

Nerve Growth Factor ◽

Growth Factor ◽

Adverse Events ◽

Knee Osteoarthritis ◽

Meta Analysis ◽

Cochrane Collaboration ◽

Optimal Dosage ◽

Serious Adverse Events ◽

Nerve Growth

Abstract Background/Aims Osteoarthritis is a major cause of morbidity and disability. Much of this comes from joint pain, which is exacerbated by movement and exercise. Pharmacological analgesia therefore not only has the obvious benefit of alleviating pain, but in doing so, it also facilitates exercise (a pillar of conservative management). Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are currently the main analgesics used in this context. However, these agents can cause unwanted side effects and are contraindicated in some patients. We thus conducted a systematic review and meta-analysis using the Cochrane collaboration criteria to evaluate the efficacy of anti-nerve growth factor (anti-NGF) antibodies as potential alternative analgesics in osteoarthritis of the hip and/or knee. Whilst tanezumab has been studied extensively and monoclonal anti-NGF antibodies have been reviewed in other pain states, this is the first systematic review of three key anti-NGF antibodies: tanezumab, fulranumab and fasinumab in symptomatic hip and/or knee osteoarthritis. Methods An interdisciplinary work group conducted a literature search across seven electronic databases for the use of anti-NGF antibodies in osteoarthritis. All hip/knee osteoarthritis studies investigating anti-NGF antibodies regardless of dose regimen or phase of trial were included. Studies in which participants received NSAIDs or analgesics other than anti-NGF antibodies, or studies in which the only intervention was the administration of anti-NGF antibodies in combination with NSAIDs or other analgesics were excluded. The Jadad Scale score was used to assess the quality of each study. Results Thirteen studies involving 8,145 patients with a diagnosis of hip and/or knee osteoarthritis were analysed. Demographic information including duration of disease and Kellgren-Lawrence grades were also extracted. Anti-NGF antibodies showed significant improvements compared to placebo as rated on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) scales for pain (SMD= -0.50, 95% CI -0.71 to -0.28, P < 0.00001; I2 = 88%), physical function (SMD= -0.82, 95% CI -1.09 to -0.55, P < 0.00001; I2 = 94%) and stiffness (SMD= -0.88, 95% CI -1.22 to -0.54, P < 0.00001; I2 = 95%). These agents were not associated with a significant increase in serious adverse events but were associated with a significant increase in discontinuation due to adverse events, abnormal peripheral sensations and peripheral neuropathy. Conclusion Anti-NGF antibodies appear very promising with regard to alleviating osteoarthritic hip/knee pain but more studies are needed to determine the optimal dosage and the overall risk-to benefit ratio, particularly with long-term use. Disclosure J. Rammanohar: None. J. Sutton: None. K. Seah: None. W.S. Khan: None. K. To: None.

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Efficacy and harms of remdesivir for the treatment of COVID-19: a systematic review and meta-analysis

10.1101/2020.05.26.20109595 ◽

2020 ◽

Cited By ~ 1

Author(s):

Alejandro Piscoya ◽

Luis Fernando Ng-Sueng ◽

Angela Parra del Riego ◽

Renato Cerna-Viacava ◽

Vinay Pasupuleti ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Clinical Improvement ◽

Meta Analysis ◽

Case Series ◽

Length Of Hospital Stay ◽

Invasive Ventilation ◽

Serious Adverse Events ◽

All Cause Mortality ◽

Meta Analyses

AbstractBackgroundWe evaluated the efficacy and safety of remdesivir for the treatment of COVID-19.MethodsSystematic review in five engines, pre-print webpages and RCT registries until May 22, 2020 for randomized controlled trials (RCTs) and observational studies evaluating remdesivir on confirmed, COVID-19 adults with pneumonia and/or respiratory insufficiency. Primary outcomes were all-cause mortality, clinical improvement or recovery, need for invasive ventilation, and serious adverse events (SAE). Secondary outcomes included length of hospital stay, progression of pneumonia, and adverse events (AE). Inverse variance random effects meta-analyses were performed.ResultsTwo placebo-controlled RCTs (n=1300) and two case series (n=88) were included. All studies used remdesivir 200mg IV the first day and 100mg IV for 9 more days, and followed up until 28 days. Wang et al. RCT was stopped early due to AEs; ACTT-1 was preliminary reported at 15-day follow up. Time to clinical improvement was not decreased in Wang et al. RCT, but median time to recovery was decreased by 4 days in ACTT-1. Remdesivir did not decrease all-cause mortality (RR 0.71, 95%CI 0.39 to 1.28) and need for invasive ventilation at 14 days (RR 0.57, 95%CI 0.23 to 1.42), but had fewer SAEs (RR 0.77, 95%CI 0.63 to 0.94). AEs were similar between remdesivir and placebo arms. Risk of bias ranged from some concerns to high risk in RCTs.InterpretationThere is paucity of adequately powered and fully reported RCTs evaluating effects of remdesivir in adult, hospitalized COVID-19 patients. Remdesivir should not be recommended for the treatment of severe COVID-19.

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Serious adverse events following treatment of visceral leishmaniasis: A systematic review and meta-analysis

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009302 ◽

2021 ◽

Vol 15 (3) ◽

pp. e0009302

Author(s):

Sauman Singh-Phulgenda ◽

Prabin Dahal ◽

Roland Ngu ◽

Brittany J. Maguire ◽

Alice Hawryszkiewycz ◽

...

Keyword(s):

Systematic Review ◽

At Risk ◽

Clinical Trials ◽

Visceral Leishmaniasis ◽

Adverse Events ◽

Amphotericin B ◽

Treatment Initiation ◽

Meta Analysis ◽

Eastern Africa ◽

Serious Adverse Events

Background Despite a historical association with poor tolerability, a comprehensive review on safety of antileishmanial chemotherapies is lacking. We carried out an update of a previous systematic review of all published clinical trials in visceral leishmaniasis (VL) from 1980 to 2019 to document any reported serious adverse events (SAEs). Methods For this updated systematic review, we searched the following databases from 1st Jan 2016 through 2nd of May 2019: PUBMED, Embase, Scopus, Web of Science, Cochrane, clinicaltrials.gov, WHO ICTRP, and the Global Index Medicus. We included randomised and non-randomised interventional studies aimed at assessing therapeutic efficacy and extracted the number of SAEs reported within the first 30 days of treatment initiation. The incidence rate of death (IRD) from individual treatment arms were combined in a meta-analysis using random effects Poisson regression. Results We identified 157 published studies enrolling 35,376 patients in 347 treatment arms. Pentavalent antimony was administered in 74 (21.3%), multiple-dose liposomal amphotericin B (L-AmB) in 52 (15.0%), amphotericin b deoxycholate in 51 (14.7%), miltefosine in 33 (9.5%), amphotericin b fat/lipid/colloid/cholesterol in 31 (8.9%), and single-dose L-AmB in 17 (4.9%) arms. There was a total of 804 SAEs reported of which 793 (including 428 deaths) were extracted at study arm level (11 SAEs were reported at study level only). During the first 30 days, there were 285 (66.6%) deaths with the overall IRD estimated at 0.068 [95% confidence interval (CI): 0.041–0.114; I2 = 81.4%; 95% prediction interval (PI): 0.001–2.779] per 1,000 person-days at risk; the rate was 0.628 [95% CI: 0.368–1.021; I2 = 82.5%] in Eastern Africa, and 0.041 [95% CI: 0.021–0.081; I2 = 68.1%] in the Indian Subcontinent. In 21 study arms which clearly indicated allowing the inclusion of patients with HIV co-infections the IRD was 0.575 [95% CI: 0.244–1.355; I2 = 91.9%] compared to 0.043 [95% CI: 0.020–0.090; I2 = 62.5%] in 160 arms which excluded HIV co-infections. Conclusion Mortality within the first 30 days of VL treatment initiation was a rarely reported event in clinical trials with an overall estimated rate of 0.068 deaths per 1,000 person-days at risk, though it varied across regions and patient populations. These estimates may serve as a benchmark for future trials against which mortality data from prospective and pharmacovigilance studies can be compared. The methodological limitations exposed by our review support the need to assemble individual patient data (IPD) to conduct robust IPD meta-analyses and generate stronger evidence from existing trials to support treatment guidelines and guide future research.

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