scholarly journals Protocol: Benefits and harms of remdesivir for COVID-19 in adults: A systematic review with meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260544
Author(s):  
Asger Sand Paludan-Müller ◽  
Andreas Lundh ◽  
Matthew J. Page ◽  
Klaus Munkholm
Keyword(s):  
Systematic Review ◽  
Health Care ◽  
Adverse Events ◽  
Meta Analysis ◽  
Severe Disease ◽  
Risk Of Bias ◽  
Bibliographic Databases ◽  
Selective Reporting ◽  
Randomised Trials ◽  
Study Results

Background Effective drug treatments for Covid-19 are needed to decrease morbidity and mortality for the individual and to alleviate pressure on health care systems. Remdesivir showed promising results in early randomised trials but subsequently a large publicly funded trial has shown less favourable results and the evidence is interpreted differently in clinical guidelines. Systematic reviews of remdesivir have been published, but none have systematically searched for unpublished data, including regulatory documents, and assessed the risk of bias due to missing evidence. Methods We will conduct a systematic review of randomised trials comparing remdesivir to placebo or standard of care in any setting. We will include trials regardless of the severity of disease and we will include trials examining remdesivir for indications other than Covid-19 for harms analyses. We will search websites of regulatory agencies, trial registries, bibliographic databases, preprint servers and contact trial sponsors to obtain all available data, including unpublished clinical data, for all eligible trials. Our primary outcomes will be all-cause mortality and serious adverse events. Our secondary outcomes will be length of hospital stay, time to death, severe disease, and adverse events. We will assess the risk of bias using the Cochranes Risk of Bias 2 tool and the risk of bias due to missing evidence (e.g. publication bias, selective reporting bias) using the ROB-ME tool. Where appropriate we will synthesise study results by conducting random-effects meta-analysis. We will present our findings in a Summary of Findings table and rate the certainty of the evidence using the GRADE approach. Discussion By conducting a comprehensive systematic review including unpublished data (where available), we expect to be able to provide valuable information for patients and clinicians about the benefits and harms of remdesivir for the treatment of Covid-19. This will help to ensure optimal treatment for individual patients and optimal utilisation of health care resources. Systematic review registration CRD42021255915.

scholarly journals 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

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

P–394 Intralipid infusion at time of embryo transfer in women with history of recurrent implantation failure: a systematic review and meta-analysis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M P Rimmer ◽  
N Black ◽  
S Keay ◽  
S Quenby ◽  
B. H.A Wattar
Keyword(s):  
Systematic Review ◽  
Embryo Transfer ◽  
Meta Analysis ◽  
Small Sample ◽  
Risk Of Bias ◽  
Population Characteristics ◽  
Implantation Failure ◽  
Randomised Trials ◽  
Recurrent Implantation Failure ◽  
History Of

Abstract Study question What is the effectiveness of IV Intralipid (IVI) in improving pregnancy rates in women undergoing IVF with history of Recurrent implantation failure (RIF) to improve reproductive outcomes. Summary answer The evidence to support the use of IVI at the time of embryo transfer in women with RIF is limited. More RCTs are needed. What is known already: Optimising the implantation process following embryo transfer remains a clinical challenge with 10% of couples undergoing IVF affected by (RIF). Immunotherapy could help to optimise endometrial receptivity and increase the chances for successful conception in women with history of RIF. Intra-venous Intralipid (IVI), a fat-based emulsion of soybean oil, glycerine, phospholipids, egg, and polyunsaturated fatty acids, has been evaluated in several trials as a potential intervention to downregulate the uNK cells and macrophages as well as inhibit the pro-inflammatory mediators including T1 helper cells. Evidence synthesis is needed to evaluate the effectiveness of this intervention. Study design, size, duration We performed this systematic review using a prospectively registered protocol (CRD42019148517) and reported in accordance with the PRISMA guidelines. Participants/materials, setting, methods: We searched MEDLINE, EMBASE and CENTRAL for any randomised trials evaluating the use of IVI at the time of embryo transfer in women undergoing assisted conception until September 2020. We extracted data in duplicate and assessed risk of bias using the Cochrane Risk of Bias tools. We meta-analysed data using a random effect model and reported on dichotomous outcomes using risk ratio (RR) and 95% confidence interval (CI). Main results and the role of chance We included five randomised trials reporting on 843 women with an overall moderate risk of bias. All trials used 20% IVI solution at the time of embryo transfer compared to normal saline infusion or no intervention (routine care). The IVI group had a higher chance of clinical pregnancy (172 vs 119, RR 1.55, 95%CI 1.16–2.07, I2 44.2%) and live birth (132 vs 73, RR 1.83, 95%CI 1.42–2.35, I2 0%) post treatment compared to no intervention. Limitations, reasons for caution Our findings are limited by the small sample size and the variations in treatment protocols and population characteristics. Wider implications of the findings: Our meta-analysis offers an overview on the value of IVI to help women affected by RIF. Given the limitations and the quality of included trials, adopting the use of IVI a-la-carte to couples undergoing IVF remains immature. IVI should not be offered until larger RCTs demonstrate a persistent benefit. Trial registration number CRD42019148517

scholarly journals Racecadotril for acute diarrhoea in children: systematic review and meta-analyses

2015 ◽  
Vol 101 (3) ◽  
pp. 234-240 ◽  
Author(s):  
Morris Gordon ◽  
Anthony Akobeng
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Methodological Quality ◽  
Data Extraction ◽  
Meta Analysis ◽  
Acute Diarrhoea ◽  
Risk Of Bias ◽  
Duration Of Symptoms ◽  
Duration Of Illness ◽  
Significant Difference

ObjectiveRacecadotril is an antisecretory agent that can prevent fluid/electrolyte depletion from the bowel as a result of acute diarrhoea without affecting intestinal motility. An up-to-date systematic review is indicated to summarise the evidence on racecadotril for the treatment of acute diarrhoea in children.DesignA Cochrane format systematic review of randomised controlled trials (RCTs). Data extraction and assessment of methodological quality were performed independently by two reviewers. Methodological quality was assessed using the Cochrane risk of bias tool.PatientsChildren with acute diarrhoea, as defined by the primary studies.InterventionsRCTs comparing racecadotril with placebo or other interventions.Main outcome measursDuration of illness, stool output/volume and adverse events.ResultsSeven RCTs were included, five comparing racecadotril with placebo or no intervention, one with pectin/kaolin and one with loperamide. Moderate to high risk of bias was present in all studies. There was no significant difference in efficacy or adverse events between racecadotril and loperamide. A meta-analysis of three studies with 642 participants showed significantly shorter duration of symptoms with racecadotril compared with placebo (mean difference −53.48 h, 95% CI −65.64 to −41.33). A meta-analysis of five studies with 949 participants showed no significant difference in adverse events between racecadotril and placebo (risk ratio 0.99, 95% CI 0.73 to 1.34).ConclusionsThere is some evidence that racecadotril is more effective than placebo or no intervention in reducing the duration of illness and stool output in children with acute diarrhoea. However, the overall quality of the evidence is limited due to sparse data, heterogeneity and risk of bias. Racecadotril appears to be safe and well tolerated.

scholarly journals Should home-based ovulation predictor kits be offered as an additional approach for fertility management for women and couples desiring pregnancy? A systematic review and meta-analysis

2019 ◽  
Vol 4 (2) ◽  
pp. e001403 ◽  
Author(s):  
Ping Teresa Yeh ◽  
Caitlin E Kennedy ◽  
Sheryl Van der Poel ◽  
Thabo Matsaseng ◽  
Laura Bernard ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Observational Study ◽  
Pregnancy Rate ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Time To Pregnancy ◽  
Fertility Management ◽  
Home Based ◽  
Registration Number

IntroductionTo inform the WHO Guideline on self-care interventions, we conducted a systematic review of the impact of ovulation predictor kits (OPKs) on time-to-pregnancy, pregnancy, live birth, stress/anxiety, social harms/adverse events and values/preferences.MethodsIncluded studies had to compare women desiring pregnancy who managed their fertility with and without OPKs, measure an outcome of interest and be published in a peer-reviewed journal. We searched for studies on PubMed, CINAHL, LILACS and EMBASE through November 2018. We assessed risk of bias assessed using the Cochrane tool for randomised controlled trials (RCTs) and the Evidence Project tool for observational studies, and conducted meta-analysis using random effects models to generate pooled estimates of relative risk (RR).ResultsFour studies (three RCTs and one observational study) including 1487 participants, all in high-income countries, were included. Quality of evidence was low. Two RCTs found no difference in time-to-pregnancy. All studies reported pregnancy rate, with mixed results: one RCT from the 1990s among couples with unexplained or male-factor infertility found no difference in clinical pregnancy rate (RR: 1.09, 95% CI 0.51 to 2.32); two more recent RCTs found higher self-reported pregnancy rates among OPK users (pooled RR: 1.40, 95% CI 1.08 to 1.80). A small observational study found higher rates of pregnancy with lab testing versus OPKs among women using donor insemination services. One RCT found no increase in stress/anxiety after two menstrual cycles using OPKs, besides a decline in positive affect. No studies measured live birth or social harms/adverse events. Six studies presented end-users’ values/preferences, with almost all women reporting feeling satisfied, comfortable and confident using OPKs.ConclusionA small evidence base, from high-income countries and with high risk of bias, suggests that home-based use of OPKs may improve fertility management when attempting to become pregnant with no meaningful increase in stress/anxiety and with high user acceptability.Systematic review registration numberPROSPERO registration number CRD42019119402.

scholarly journals Laboratory Tests and Outcome for Patients with Coronavirus Disease 2019: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 5 (5) ◽  
pp. 1038-1049 ◽  
Author(s):  
Anne Alnor ◽  
Maria B Sandberg ◽  
Charlotte Gils ◽  
Pernille J Vinholt
Keyword(s):  
Systematic Review ◽  
Disease Severity ◽  
Laboratory Tests ◽  
Evidence Synthesis ◽  
Meta Analysis ◽  
Severe Disease ◽  
Risk Of Bias ◽  
Mean Difference ◽  
Routine Laboratory ◽  
Standard Mean Difference

Abstract Background Severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019 (COVID-19) and poses substantial challenges for healthcare systems. With a vastly expanding number of publications on COVID-19, clinicians need evidence synthesis to produce guidance for handling patients with COVID-19. In this systematic review and meta-analysis, we examine which routine laboratory tests are associated with severe COVID-19 disease. Content PubMed (Medline), Scopus, and Web of Science were searched until March 22, 2020, for studies on COVID-19. Eligible studies were original articles reporting on laboratory tests and outcome of patients with COVID-19. Data were synthesized, and we conducted random-effects meta-analysis, and determined mean difference (MD) and standard mean difference at the biomarker level for disease severity. Risk of bias and applicability concerns were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2. Summary 45 studies were included, of which 21 publications were used for the meta-analysis. Studies were heterogeneous but had low risk of bias and applicability concern in terms of patient selection and reference standard. Severe disease was associated with higher white blood cell count (MD, 1.28 ×109/L), neutrophil count (MD, 1.49 ×109/L), C-reactive protein (MD, 49.2 mg/L), lactate dehydrogenase (MD, 196 U/L), D-dimer (standardized MD, 0.58), and aspartate aminotransferase (MD, 8.5 U/L); all p < 0.001. Furthermore, low lymphocyte count (MD −0.32 × 109/L), platelet count (MD −22.4 × 109/L), and hemoglobin (MD, −4.1 g/L); all p < 0.001 were also associated with severe disease. In conclusion, several routine laboratory tests are associated with disease severity in COVID-19.

scholarly journals Placebo response in trials of drug treatments for cancer-related fatigue: a systematic review, meta-analysis and meta-regression

2020 ◽  
Vol 10 (4) ◽  
pp. 385-394 ◽  
Author(s):  
Rocio Roji ◽  
Patrick Stone ◽  
Federico Ricciardi ◽  
Bridget Candy
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Placebo Response ◽  
Risk Of Bias ◽  
Small Samples ◽  
Contributing Factors ◽  
Cancer Related Fatigue ◽  
Study Results ◽  
Meta Regression ◽  
Multiple Drugs

BackgroundCancer-related fatigue (CRF) is one of the most distressing symptoms experienced by patients. There is no gold standard treatment, although multiple drugs have been tested with little evidence of efficacy. Randomised controlled trials (RCTs) of these drugs have commented on the existence or size of the placebo response (PR). The objective of this systematic review was to establish the magnitude of the PR in RCTs of drugs to relieve CRF and to identify contributing factors.MethodRCTs were included in which the objective was to treat CRF. A meta-analysis was conducted using the standardised mean change (SMC) between baseline and final measurement in the placebo group. To explore factors that may be associated with the PR (eg, population or drug), a meta-regression was undertaken. Risk of bias was assessed using the revised Cochrane tool.ResultsFrom 3916 citations, 30 relevant RCTs were identified. All had limitations that increased their risk of bias. The pooled SMC in reduction in fatigue status in placebo groups was −0.23 (95% confidence intervals −0.42 to −0.04). None of the variables analysed in the meta-regression were statistically significant related to PR.ConclusionThere is some evidence, based on trials with small samples, that the PR in trials testing drugs for CRF is non-trivial in size and statistically significant. We recommend that researchers planning drug studies in CRF should consider implementing alternative trial designs to better account for PR and decrease impact on the study results.

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

2019 ◽  
Vol 2 (22.2) ◽  
pp. E55-E70 ◽  
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

scholarly journals Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis

BMJ ◽  
2021 ◽  
pp. n2321
Author(s):  
Bruno R da Costa ◽  
Tiago V Pereira ◽  
Pakeezah Saadat ◽  
Martina Rudnicki ◽  
Samir M Iskander ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Event ◽  
Adverse Events ◽  
Meta Analysis ◽  
Hip Osteoarthritis ◽  
Randomised Trials ◽  
Increased Risk ◽  
Inflammatory Drugs ◽  
Topical Nsaids ◽  
Topical Diclofenac

Abstract Objective To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose. Design Systematic review and network meta-analysis of randomised trials. Data sources Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021. Eligibility criteria for selecting studies Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis. Outcomes and measures The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed. Review methods Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo. Results 192 trials comprising 102 829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%). Conclusions Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis. Systematic review registration PROSPERO number CRD42020213656

scholarly journals Tolerability of duloxetine in the elderly and in adults: a protocol and preliminary results of a systematic review and individual participant data meta-analysis of randomized placebo-controlled trials

2020 ◽  
Author(s):  
Jean-Charles ROY ◽  
Chloé Rousseau ◽  
Alexis Jutel ◽  
Florian Naudet ◽  
Gabriel Robert
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Elderly Population ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Individual Participant Data ◽  
Younger Adults ◽  
Randomized Controlled ◽  
Individual Participant

Abstract Background. Duloxetine is an antidepressant which benefits from a wide range of approval in elderly population while its safety of use in elderly population, compared to younger adults, is not clearly assessed. A comparison of tolerability of duloxetine between elderly and younger adults would help to rule on this issue. Methods and Design. This protocol outlines a systematic review and meta-analysis of individual participant data (IPD) of all double-blind randomized controlled trials comparing the number of serious adverse events among individuals taking duloxetine in comparison to placebo between participants at least 65 years and younger adults in conditions approved by the European Medical Agency (EMA) and the Food Drug Administration (FDA). Secondarily, will be compared the number of any adverse events, clinical efficacy and quality of life between elderly and younger adults under duloxetine, in comparison to placebo. Relevant studies were selected on ClinicalTrials.gov, Clinicaltrialsregister.eu, data sharing platforms, FDA and EMA websites, and from systematic reviews and meta-analyses of duloxetine on PubMed, following Cochrane’s recommendations. Sponsors and authors from eligible studies were invited to share IPD on data sharing platform or directly with our research team. As data cannot be aggregate into a unique database, a two step-approach meta-analysis will be undertaken. Qualitative results from available data. 77 eligible randomized controlled trials were identified, representing 25303 participants. From online available data, 35 trials were assessed as being at an overall low risk of bias, 31 trials at an unclear risk of bias and 1 at high risk of bias. Evaluation of risk of bias was not feasible for 10 studies. Conclusion. This study would represent the first meta-analysis investigating the safety of duloxetine in elderly population across all conditions approved by European and American regulatory authorities with an overall low risk of bias. Registration. PROSPERO: 2019 CRD42019130488.

scholarly journals Dexmedetomidine Versus Propofol Sedation in Flexible Bronchoscopy: A Randomized Controlled Trial and a Systematic Review and Meta-Analysis

2022 ◽  
Author(s):  
Barak Pertzov ◽  
Boris Krasulya ◽  
Karam Azem ◽  
Yael Shostak ◽  
Shimon Izhakian ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Flexible Bronchoscopy ◽  
Control Groups ◽  
Randomized Controlled ◽  
Study Results ◽  
Alpha2 Adrenoceptor ◽  
And Control

Abstract Background:Dexmedetomidine (DEX), is a highly selective alpha2 adrenoceptor (α2-AR) agonist, successfully used in various procedures including flexible bronchoscopy. Randomized controlled trials (RCTs) evaluating DEX sedation during bronchoscopy report equivocal results regarding respiratory and hemodynamic outcomes. Methods We conducted an RCT to evaluate the efficacy of dexmedetomidine compared to propofol for sedation during bronchoscopy. The primary outcome was desaturation events, secondary outcomes were transcutaneous Pco2 level, hemodynamic adverse events and physician and patient satisfaction. We have also conducted A systematic review and meta-analysis of all RCTs evaluating DEX sedation during flexible bronchoscopy, included current study results.ResultsOverall, 63 patients were included, 30 and 33 in the DEX and propofol groups, respectively. The number of desaturation events was similar between groups, median (IQR) 1 (0-1) and 1 (0-2) in the DEX and control groups, respectively (P=0.29). Median desaturation time was 1 (0-2) and 1 (0-3) minutes in the DEX and control groups, respectively (P=0.48). Adverse events included hypotension, 33% vs 21.1% in intervention and control groups, respectively (P=0.04), bradycardia, cough, and delayed recovery from sedation. Total adverse events were 22 and 7 in DEX and propofol groups, respectively (P=0.009). The pooled meta-analysis included 13 trials (1604 participants) showed a significantly lower rate of desaturation events in the DEX group (RR 0.67, 95% CI 0.57 to 0.79) with a significantly higher rate of hypotension and bradycardia events (RR 1.55, 95% CI 1.16 to 2.06 and RR 1.91, 95% CI 1.04 to 3.5, respectively)ConclusionDexmedetomidine sedation resulted in a significantly reduced rate of desaturation events in comparison to propofol, midazolam and fentanyl. However, it was also associated with a higher rate of hypotension and bradycardia.Trial registration : NCT04211298, registration date: 26/12/2019

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