Fluvoxamine for Outpatient COVID-19 to Prevent Hospitalization: A Systematic Review and Meta-Analysis

Importance: Widely available and affordable options for the outpatient management of COVID-19 are needed, particularly therapies that prevent hospitalization. Objective: Perform a meta-analysis of the available randomized clinical trial evidence for fluvoxamine in the outpatient management of COVID-19. Data Sources: World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. Study Selection: Completed outpatient trials with available results which compared fluvoxamine to placebo. Data Extraction and Synthesis: We followed the PRISMA 2020 guidelines. We extracted study details in terms of inclusion criteria, trial demographics and the pre-specified outcome of all-cause hospitalization. Risk of bias was assessed by the Cochrane Risk of Bias 2 tool. We conducted a frequentist random effects meta-analysis, as well as two sensitivity analyses using a Bayesian random effects meta-analysis with different estimates of prior probability: a weakly neutral prior (50% chance of efficacy with 95% confidence interval for Risk Ratio [RR] between 0.5 and 2) and a moderately optimistic prior (85% chance of efficacy). We contextualized the results by estimating the probability of any effect (RR ≤1) and moderate effect (RR ≤0.9) on reducing hospitalization. Main Outcome(s) and Measure(s): All cause hospitalization. Results: 2196 participants were included from 3 identified trials. The risk ratios for hospitalization were 0.75 (95%CI, 0.57-0.97) for the frequentist analysis, 0.78 (95%CI 0.58-1.08) for the Bayesian weakly neutral prior, and 0.73 (95%CI, 0.53-1.01) for the Bayesian moderately optimistic prior. Depending on the scenario, the probability of any effect on hospitalization ranged from 94.1% to 98.3% and a moderate effect from 81.6% to 91.1%. Conclusions and Relevance: Under a variety of assumptions, fluvoxamine shows a high probability of preventing hospitalization in outpatients with COVID-19. While ongoing randomized trials are important to evaluate alternative doses, explore the effectiveness in vaccinated patients, and provide further refinement to these estimates, fluvoxamine could be recommended as a treatment option, particularly in resource-limited settings or persons without access to SARS-CoV-2 monoclonal antibody therapy or direct antivirals.

Download Full-text

Prevalence of retinopathy in prediabetes: protocol for a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-040997 ◽

2021 ◽

Vol 11 (1) ◽

pp. e040997

Author(s):

Varo Kirthi ◽

Paul Nderitu ◽

Uazman Alam ◽

Jennifer Evans ◽

Sarah Nevitt ◽

...

Keyword(s):

Systematic Review ◽

Diabetic Retinopathy ◽

Data Extraction ◽

Meta Analysis ◽

International Diabetes Federation ◽

Current Data ◽

Risk Of Bias ◽

Fundus Photography ◽

Primary Data ◽

Cochrane Library

IntroductionThere is growing evidence of a higher than expected prevalence of retinopathy in prediabetes. This paper presents the protocol of a systematic review and meta-analysis of retinopathy in prediabetes. The aim of the review is to estimate the prevalence of retinopathy in prediabetes and to summarise the current data.Methods and analysisThis protocol is developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines. A comprehensive electronic bibliographic search will be conducted in MEDLINE, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Google Scholar and the Cochrane Library. Eligible studies will report prevalence data for retinopathy on fundus photography in adults with prediabetes. No time restrictions will be placed on the date of publication. Screening for eligible studies and data extraction will be conducted by two reviewers independently, using predefined inclusion criteria and prepiloted data extraction forms. Disagreements between the reviewers will be resolved by discussion, and if required, a third (senior) reviewer will arbitrate.The primary outcome is the prevalence of any standard features of diabetic retinopathy (DR) on fundus photography, as per International Clinical Diabetic Retinopathy Severity Scale (ICDRSS) classification. Secondary outcomes are the prevalence of (1) any retinal microvascular abnormalities on fundus photography that are not standard features of DR as per ICDRSS classification and (2) any macular microvascular abnormalities on fundus photography, including but not limited to the presence of macular exudates, microaneurysms and haemorrhages. Risk of bias for included studies will be assessed using a validated risk of bias tool for prevalence studies. Pooled estimates for the prespecified outcomes of interest will be calculated using random effects meta-analytic techniques. Heterogeneity will be assessed using the I2 statistic.Ethics and disseminationEthical approval is not required as this is a protocol for a systematic review and no primary data are to be collected. Findings will be disseminated through peer-reviewed publications and presentations at national and international meetings including Diabetes UK, European Association for the Study of Diabetes, American Diabetes Association and International Diabetes Federation conferences.PROSPERO registration numberCRD42020184820.

Download Full-text

Effect of consumption of animal milk compared to infant formula for non-breastfed/mixed-fed infants 6–11 months of age: a systematic review (protocol)

BMJ Open ◽

10.1136/bmjopen-2020-046370 ◽

2021 ◽

Vol 11 (2) ◽

pp. e046370

Author(s):

Aamer Imdad ◽

Julie Melissa Ehrlich ◽

Joseph Catania ◽

Emily Tanner-Smith ◽

Abigail Smith ◽

...

Keyword(s):

Systematic Review ◽

Infant Formula ◽

Breast Feeding ◽

Meta Analysis ◽

Risk Of Bias ◽

World Health ◽

Control Group ◽

Breastfed Infants ◽

Evaluation Approach ◽

Animal Milk

IntroductionPrevalence rates of breastfeeding remain low even though the World Health Organization (WHO) and the American Academy of Pediatrics recommend exclusive breast feeding for the first 6 months of life in combination with appropriate complementary feeding beyond six 6 months of age. There have been several studies that address the implication of drinking animal milk and/or infant formula on children’s health and development when breast feeding is not offered during the first year of life. Vast improvements have been made in infant formula design, which may increase its benefits compared with animal’s milk. The objective of this review is therefore to synthesise the most recent evidence on the effects of the consumption of animal milk compared with infant formula in non-breastfed or mixed breastfed infants aged 6–11 months.Methods and analysisWe will conduct a systematic review and meta-analysis of studies that assessed the effect of animal milk compared with formula or mixed-fed (breastmilk and formula) on infants aged 6–11 months. The primary outcomes of interest include anaemia, gastrointestinal blood loss, weight for age, height for age and weight for height. We will include randomised and non-randomised studies with a control group. We will use the Cochrane risk of bias tools to assess the risk of bias. We will use meta-analysis to pool findings if the identified studies are conceptually homogenous and data are available from more than one study. We will assess the overall quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach.Ethics and disseminationThis is a systematic review, so no patients will be directly involved in the design or development of this study. The findings from this systematic review will be disseminated to relevant patient populations and caregivers and will guide the WHO’s recommendations on formula consumption versus animal milk in infants aged 6–11 months.Trial registration numberCRD42020210925.

Download Full-text

Effectiveness of Antalgic Therapies in Patients with Vertebral Bone Metastasis: A Protocol for a Systematic Review and Meta-Analysis

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18083991 ◽

2021 ◽

Vol 18 (8) ◽

pp. 3991

Author(s):

Antonio Jose Martin-Perez ◽

María Fernández-González ◽

Paula Postigo-Martin ◽

Marc Sampedro Pilegaard ◽

Carolina Fernández-Lao ◽

...

Keyword(s):

Systematic Review ◽

Bone Metastasis ◽

Data Extraction ◽

Meta Analysis ◽

Risk Of Bias ◽

Cochrane Library ◽

Pharmacological Intervention ◽

Vertebral Metastasis ◽

Randomized Controlled Clinical Trials

There is no systematic review that has identified existing studies evaluating the pharmacological and non-pharmacological intervention for pain management in patients with bone metastasis. To fill this gap in the literature, this systematic review with meta-analysis aims to evaluate the effectiveness of different antalgic therapies (pharmacological and non-pharmacological) in the improvement of pain of these patients. To this end, this protocol has been written according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) and registered in PROSPERO (CRD42020135762). A systematic search will be carried out in four international databases: Medline (Via PubMed), Web of Science, Cochrane Library and SCOPUS, to select the randomized controlled clinical trials. The Risk of Bias Tool developed by Cochrane will be used to assess the risk of bias and the quality of the identified studies. A narrative synthesis will be used to describe and compare the studies, and after the data extraction, random effects model and a subgroup analyses will be performed according to the type of intervention, if possible. This protocol aims to generate a systematic review that compiles and synthesizes the best and most recent evidence on the treatment of pain derived from vertebral metastasis.

Download Full-text

Effects of open-label placebos in clinical trials: a systematic review and meta-analysis

Scientific Reports ◽

10.1038/s41598-021-83148-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Melina von Wernsdorff ◽

Martin Loef ◽

Brunna Tuschen-Caffier ◽

Stefan Schmidt

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Medical Condition ◽

Data Extraction ◽

Meta Analysis ◽

Risk Of Bias ◽

Open Label ◽

Cancer Related Fatigue ◽

Promising Treatment ◽

Irritable Bowel

AbstractOpen-label placebos (OLPs) are placebos without deception in the sense that patients know that they are receiving a placebo. The objective of our study is to systematically review and analyze the effect of OLPs in comparison to no treatment in clinical trials. A systematic literature search was carried out in February 2020. Randomized controlled trials of any medical condition or mental disorder comparing OLPs to no treatment were included. Data extraction and risk of bias rating were independently assessed. 1246 records were screened and thirteen studies were included into the systematic review. Eleven trials were eligible for meta-analysis. These trials assessed effects of OLPs on back pain, cancer-related fatigue, attention deficit hyperactivity disorder, allergic rhinitis, major depression, irritable bowel syndrome and menopausal hot flushes. Risk of bias was moderate among all studies. We found a significant overall effect (standardized mean difference = 0.72, 95% Cl 0.39–1.05, p < 0.0001, I2 = 76%) of OLP. Thus, OLPs appear to be a promising treatment in different conditions but the respective research is in its infancy. More research is needed, especially with respect to different medical and mental disorders and instructions accompanying the OLP administration as well as the role of expectations and mindsets.

Download Full-text

Predictability of rotational tooth movement with orthodontic aligners comparing software-based and achieved data: A systematic review and meta-analysis of observational studies

Journal of Orthodontics ◽

10.1177/14653125211027266 ◽

2021 ◽

pp. 146531252110272

Author(s):

Despina Koletsi ◽

Anna Iliadi ◽

Theodore Eliades

Keyword(s):

Effect Size ◽

Tooth Movement ◽

Data Extraction ◽

Meta Analysis ◽

Risk Of Bias ◽

Patient Treatment ◽

Qualitative Synthesis ◽

Meta Analyses ◽

Enamel Reduction

Objective: To evaluate all available evidence on the prediction of rotational tooth movements with aligners. Data sources: Seven databases of published and unpublished literature were searched up to 4 August 2020 for eligible studies. Data selection: Studies were deemed eligible if they included evaluation of rotational tooth movement with any type of aligner, through the comparison of software-based and actually achieved data after patient treatment. Data extraction and data synthesis: Data extraction was done independently and in duplicate and risk of bias assessment was performed with the use of the QUADAS-2 tool. Random effects meta-analyses with effect sizes and their 95% confidence intervals (CIs) were performed and the quality of the evidence was assessed through GRADE. Results: Seven articles were included in the qualitative synthesis, of which three contributed to meta-analyses. Overall results revealed a non-accurate prediction of the outcome for the software-based data, irrespective of the use of attachments or interproximal enamel reduction (IPR). Maxillary canines demonstrated the lowest percentage accuracy for rotational tooth movement (three studies: effect size = 47.9%; 95% CI = 27.2–69.5; P < 0.001), although high levels of heterogeneity were identified (I2: 86.9%; P < 0.001). Contrary, mandibular incisors presented the highest percentage accuracy for predicted rotational movement (two studies: effect size = 70.7%; 95% CI = 58.9–82.5; P < 0.001; I2: 0.0%; P = 0.48). Risk of bias was unclear to low overall, while quality of the evidence ranged from low to moderate. Conclusion: Allowing for all identified caveats, prediction of rotational tooth movements with aligner treatment does not appear accurate, especially for canines. Careful selection of patients and malocclusions for aligner treatment decisions remain challenging.

Download Full-text

EXPRESS: A meta-analysis of aspirin and subarachnoid haemorrhage in patients with intracranial aneurysms yields different results to the general population

International Journal of Stroke ◽

10.1177/17474930211004888 ◽

2021 ◽

pp. 174749302110048

Author(s):

Frederick Ewbank ◽

Jacqueline Birks ◽

Diederik Bulters

Keyword(s):

General Population ◽

Subarachnoid Haemorrhage ◽

Confidence Intervals ◽

Random Effects ◽

Intracranial Aneurysms ◽

Meta Analysis ◽

Risk Of Bias ◽

Random Effects Models ◽

Hazard Ratios ◽

Unruptured Intracranial Aneurysms

Abstract Background Some studies have shown a protective association between aspirin use and subarachnoid haemorrhage (SAH). Other studies have found no relationship or the reverse. These studies differ in their study populations and definitions of SAH. Aims Our aim was to establish 1) if there is an association between aspirin and SAH, 2) how this differs between the general population and those with intracranial aneurysms. Summary of review Studies reporting aspirin use and the occurrence of SAH were included and grouped based on population (general population vs aneurysm population). Odds ratios, hazard ratios and confidence intervals were combined in random-effects models. 11 studies were included. Overall, there was an association between aspirin and SAH (OR 0.68 [0.48, 0.96]). However, populations were diverse and heterogeneity between studies high (p<0.00001), questioning the validity of combining these studies and justifying analysis by population. In the general population there was no difference in aspirin use between individuals with and without SAH (OR 1.15 [0.96, 1.38]). In patients with intracranial aneurysms, aspirin use was greater in patients without SAH (OR 0.37 [0.24, 0.58]), although these studies were at higher risk of bias. Conclusions There is an association between aspirin use and SAH in patients with intracranial aneurysms. This apparent protective relationship is not seen in the general population. Prospective randomised studies are required to further investigate the effect of aspirin on unruptured intracranial aneurysms.

Download Full-text

Clinical effectiveness of convalescent plasma in hospitalized patients with COVID-19: a systematic review and meta-analysis

Therapeutic Advances in Respiratory Disease ◽

10.1177/17534666211028077 ◽

2021 ◽

Vol 15 ◽

pp. 175346662110280

Author(s):

Roberto Ariel Abeldaño Zuñiga ◽

Ruth Ana María González-Villoria ◽

María Vanesa Elizondo ◽

Anel Yaneli Nicolás Osorio ◽

David Gómez Martínez ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Clinical Improvement ◽

Data Extraction ◽

Meta Analysis ◽

Clinical Effectiveness ◽

Risk Of Bias ◽

Hospitalized Patients ◽

Low Risk ◽

Controlled Clinical Trials

Aims: Given the variability of previously reported results, this systematic review aims to determine the clinical effectiveness of convalescent plasma employed in the treatment of hospitalized patients diagnosed with COVID-19. Methods: We conducted a systematic review of controlled clinical trials assessing treatment with convalescent plasma for hospitalized patients diagnosed with SARS-CoV-2 infection. The outcomes were mortality, clinical improvement, and ventilation requirement. Results: A total of 51 studies were retrieved from the databases. Five articles were finally included in the data extraction and qualitative and quantitative synthesis of results. The overall risk of bias in the reviewed articles was established at low-risk only in two trials. The meta-analysis suggests that there is no benefit of convalescent plasma compared with standard care or placebo in reducing the overall mortality and the ventilation requirement. However, there could be a benefit for the clinical improvement in patients treated with plasma. Conclusion: Current results led to assume that the convalescent plasma transfusion cannot reduce the mortality or ventilation requirement in hospitalized patients diagnosed with SARS-CoV-2 infection. More controlled clinical trials conducted with methodologies that ensure a low risk of bias are still needed. The reviews of this paper are available via the supplemental material section.

Download Full-text

Risk of dementia in gout and hyperuricaemia: a meta-analysis of cohort studies

BMJ Open ◽

10.1136/bmjopen-2020-041680 ◽

2021 ◽

Vol 11 (6) ◽

pp. e041680

Author(s):

Shu-Yue Pan ◽

Rui-Juan Cheng ◽

Zi-Jing Xia ◽

Qiu-Ping Zhang ◽

Yi Liu

Keyword(s):

Cohort Studies ◽

Quality Assessment ◽

Publication Bias ◽

Data Extraction ◽

Meta Analysis ◽

Sensitivity Analyses ◽

Cochrane Library ◽

Crystal Formation ◽

Medical Subject Headings ◽

Eligibility Criteria

ObjectivesGout, characterised by hyperuricaemia with monosodium urate crystal formation and inflammation, is the most common inflammatory arthritis in adults. Recent studies have found that elevated uric acid levels are related to the occurrence of dementia. We conducted a study to investigate the association between dementia and gout or hyperuricaemia.DesignSystematic review and meta-analysis of cohort studies.Data sourcesStudies were screened from inception to 28 June 2019 by searching Medline, Embase and the Cochrane Library databases.Eligibility criteriaCohort studies comparing the risk of dementia in patients with gout and hyperuricaemia versus non-gout and non-hyperuricaemia controls were enrolled.Data extraction and analysisTwo reviewers separately selected studies and extracted data using the Medical Subject Headings without restriction on languages or countries. The adjusted HRs were pooled using the DerSimonian and Laird random effects model. Sensitivity analyses were conducted to evaluate the stability of the results. Publication bias was evaluated using Egger’s and Begg’s tests. Quality assessment was performed according to the Newcastle-Ottawa Scale.ResultsFour cohort studies that met the inclusion criteria were included in our meta-analysis. We found that gout and hyperuricaemia did not increase the risk of dementia, with a pooled HR of 0.94 (95% CI 0.69 to 1.28), but might decrease the risk of Alzheimer’s disease (AD), with a pooled HR of 0.78 (95% CI 0.64 to 0.95). There was little evidence of publication bias. Quality assessment of the included studies was high (range: 6–8 points).ConclusionsOur study shows that gout and hyperuricaemia do not increase the risk of dementia. However, gout and hyperuricaemia might have a protective effect against AD. Due to the limited number of research articles, more investigations are needed to demonstrate the potential relationship between dementia and gout or hyperuricaemia.

Download Full-text

1241. PfSPZ Vaccine Administered by Direct Venous Inoculation to Prevent Plasmodium falciparum Malaria is as Safe as Normal Saline – a Meta-analysis of 12 Randomized Controlled Clinical Trials

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1426 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S639-S640

Author(s):

L W Preston Church

Keyword(s):

Plasmodium Falciparum ◽

Random Effects ◽

Normal Saline ◽

Meta Analysis ◽

Laboratory Data ◽

Plasmodium Falciparum Malaria ◽

Sub Saharan Africa ◽

Sensitivity Analyses ◽

Double Blind ◽

Significant Difference

Abstract Background Sanaria’s PfSPZ Vaccine prevents Plasmodium falciparum (Pf) infection transmitted in the field and by controlled human malaria infection. Safety of PfSPZ Vaccine has been demonstrated in 12 randomized, double-blind, placebo-controlled trials (RCT) varying in regimen from 3 to 5 doses over 4 to 20 weeks and in size from 18 to 332 subjects in adults in the US and EU and 5-month to 65-year-olds in 5 countries in sub-Saharan Africa. This study was conducted to analyze solicited adverse event (AE) and laboratory data by random effects meta-analysis. Methods PfSPZ Vaccine is composed of radiation-attenuated, aseptic, purified, cryopreserved Pf sporozoites (SPZ) administered by direct venous inoculation (DVI). Normal saline (NS) is always the placebo. Data from all completed RCTs were included as either age > 18 years (n=598) or age 5 months to 17 years (n=641). Any subject receiving at least one dose was included. A random-effects model was used to study vaccine safety and I2 to evaluate heterogeneity. Analysis was performed for any systemic solicited AE and for the most frequently observed AEs and laboratory abnormalities. Sensitivity analyses were performed by removal of trials with zero events to evaluate potential bias. Results When examined individually, only 1 trial had a significant difference between PfSPZ Vaccine and NS for any AE (myalgias in adults). In the adult meta-analysis, there was no difference in the random effects risk ratios (RR) for having any vaccine-related AEs (1.40, 95% confidence interval (CI) 0.88-2.28), or for fever (0.75, 0.24-2.35), headache (1.23, 0.74-2.02), fatigue (0.72, 0.19-2.54), or myalgia (1.09, 0.26-4.68). In the pediatric meta-analysis there was no difference between the RR for PfSPZ Vaccine and NS for any AE (0.84, 0.59-1.18) or for fever (1.09, 0.44-2.69). No significant differences in the most common grade 2 or higher laboratory abnormalities – declines in hemoglobin, neutrophil or platelet count – were detected. Sensitivity analysis did not change the results. Conclusion There was no difference in risk for AEs or lab abnormalities between PfSPZ Vaccine and NS, indicating that PfSPZ Vaccine administered by DVI was extremely safe and well tolerated in 5-month- to 65-year-olds. Disclosures LW Preston Church, MD, FIDSA, Sanaria Inc. (Employee)

Download Full-text

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

Archives of Disease in Childhood ◽

10.1136/archdischild-2015-309676 ◽

2015 ◽

Vol 101 (3) ◽

pp. 234-240 ◽

Cited By ~ 14

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.

Download Full-text