scholarly journals Current evidence on chloroquine and hydroxychloroquine and their role in the treatment and prevention of COVID-19

2020 ◽  
Author(s):  
Rephaim Mpofu ◽  
Clifford G. Banda ◽  
Hannah Gunter ◽  
Enkosi Mondleki ◽  
Gayle Tatz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Evidence ◽  
Cardiac Conduction ◽  
Current Evidence ◽  
Regulatory Agencies ◽  
Close Monitoring ◽  
Treatment And Prevention ◽  
Randomised Controlled ◽  
Meta Analyses ◽  
Robust Evidence

Although chloroquine and hydroxychloroquine have not yet been shown to be safe or effective for the treatment or prevention of COVID-19, regulatory agencies in some countries have authorised their use in Coronavirus disease 2019 (COVID-19) due to the lack of available interventions. Several large clinical trials are currently underway to investigate these agents as potential therapeutic options for COVID-19. Previous research against similar pathogens that cause severe acute respiratory syndrome and Middle East respiratory syndrome has identified chloroquine and hydroxychloroquine as possible antiviral candidates against SARS-CoV-2. Despite promising pre-clinical evidence, data have thus far failed to confirm their efficacy, and recent studies suggest potential dose-related cardiotoxicity and mortality. Close monitoring for cardiac conduction abnormalities is advised with higher-than-approved doses. Additional, robust evidence from randomised controlled trials and meta-analyses are required to make informed risk-benefit assessments. Finally, the off-label prescription of these agents should be judiciously considered, and any such use should be conducted within clinical trials, or under the Monitored Emergency Use of Unregistered and Investigational Interventions framework.

scholarly journals Current evidence on chloroquine and hydroxychloroquine and their role in the treatment and prevention of COVID-19

2020 ◽  
Author(s):  
Rephaim Mpofu ◽  
Clifford George Banda ◽  
Hannah Gunter ◽  
Enkosi Mondleki ◽  
Gayle Tatz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Evidence ◽  
Cardiac Conduction ◽  
Current Evidence ◽  
Regulatory Agencies ◽  
Close Monitoring ◽  
Treatment And Prevention ◽  
Randomised Controlled ◽  
Meta Analyses ◽  
Robust Evidence

Although chloroquine and hydroxychloroquine have not yet been shown to be safe or effective for the treatment or prevention of COVID-19, regulatory agencies in some countries have authorised their use in Coronavirus disease 2019 (COVID-19) due to the lack of available interventions. Several large clinical trials are currently underway to investigate these agents as potential therapeutic options for COVID-19. Previous research against similar pathogens that cause severe acute respiratory syndrome and Middle East respiratory syndrome has identified chloroquine and hydroxychloroquine as possible antiviral candidates against SARS-CoV-2. Despite promising pre-clinical evidence, data have thus far failed to confirm their efficacy, and recent studies suggest potential dose-related cardiotoxicity and mortality. Close monitoring for cardiac conduction abnormalities is advised with higher-than-approved doses. Additional, robust evidence from randomised controlled trials and meta-analyses are required to make informed risk-benefit assessments. Finally, the off-label prescription of these agents should be judiciously considered, and any such use should be conducted within clinical trials, or under the Monitored Emergency Use of Unregistered and Investigational Interventions framework.

scholarly journals Current evidence on chloroquine and hydroxychloroquine and their role in the treatment and prevention of COVID-19

2020 ◽  
Author(s):  
Rephaim Mpofu ◽  
Clifford G. Banda ◽  
Hannah Gunter ◽  
Enkosi Mondleki ◽  
Gayle Tatz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Evidence ◽  
Cardiac Conduction ◽  
Current Evidence ◽  
Regulatory Agencies ◽  
Close Monitoring ◽  
Treatment And Prevention ◽  
Randomised Controlled ◽  
Meta Analyses ◽  
Robust Evidence

Although chloroquine and hydroxychloroquine have not yet been shown to be safe or effective for the treatment or prevention of COVID-19, regulatory agencies in some countries have authorised their use in Coronavirus disease 2019 (COVID-19) due to the lack of available interventions. Several large clinical trials are currently underway to investigate these agents as potential therapeutic options for COVID-19. Previous research against similar pathogens that cause severe acute respiratory syndrome and Middle East respiratory syndrome has identified chloroquine and hydroxychloroquine as possible antiviral candidates against SARS-CoV-2. Despite promising pre-clinical evidence, data have thus far failed to confirm their efficacy, and recent studies suggest potential dose-related cardiotoxicity and mortality. Close monitoring for cardiac conduction abnormalities is advised with higher-than-approved doses. Additional, robust evidence from randomised controlled trials and meta-analyses are required to make informed risk-benefit assessments. Finally, the off-label prescription of these agents should be judiciously considered, and any such use should be conducted within clinical trials, or under the Monitored Emergency Use of Unregistered and Investigational Interventions framework.

scholarly journals Current evidence for COVID-19 therapies: a systematic literature review

2021 ◽  
Vol 30 (159) ◽  
pp. 200384
Author(s):  
Tobias Welte ◽  
Lucy J. Ambrose ◽  
Gillian C. Sibbring ◽  
Shehla Sheikh ◽  
Hana Müllerová ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Standard Care ◽  
Severe Disease ◽  
Therapeutic Interventions ◽  
Disease Stage ◽  
Current Evidence ◽  
Treatment And Prevention ◽  
Significant Efficacy ◽  
Immunomodulatory Therapies

Effective therapeutic interventions for the treatment and prevention of coronavirus disease 2019 (COVID-19) are urgently needed. A systematic review was conducted to identify clinical trials of pharmacological interventions for COVID-19 published between 1 December 2019 and 14 October 2020. Data regarding efficacy of interventions, in terms of mortality, hospitalisation and need for ventilation, were extracted from identified studies and synthesised qualitatively. In total, 42 clinical trials were included. Interventions assessed included antiviral, mucolytic, antimalarial, anti-inflammatory and immunomodulatory therapies. Some reductions in mortality, hospitalisation and need for ventilation were seen with interferons and remdesivir, particularly when administered early, and with the mucolytic drug, bromhexine. Most studies of lopinavir/ritonavir and hydroxychloroquine did not show significant efficacy over standard care/placebo. Dexamethasone significantly reduced mortality, hospitalisation and need for ventilation versus standard care, particularly in patients with severe disease. Evidence for other classes of interventions was limited. Many trials had a moderate-to-high risk of bias, particularly in terms of blinding; most were short-term and some included low patient numbers.This review highlights the need for well-designed clinical trials of therapeutic interventions for COVID-19 to increase the quality of available evidence. It also emphasises the importance of tailoring interventions to disease stage and severity for maximum efficacy.

Homeopathic remedies for the treatment of osteoarthritis: a systematic review

2001 ◽  
Vol 90 (01) ◽  
pp. 37-43 ◽  
Author(s):  
L Long ◽  
E Ernst
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Rheumatic Disease ◽  
Clinical Evidence ◽  
Firm Conclusion ◽  
Controlled Clinical Trials ◽  
Homeopathic Treatment ◽  
Comprehensive Search ◽  
Randomised Controlled ◽  
Homeopathic Remedies

AbstractOsteoarthritis is a common rheumatic disease. Limitations of conventional medical management of this condition indicate a real need for safe and effective treatment of osteoarthritic patients. The authors review the clinical evidence for and against the effectiveness of homeopathic medicines in the treatment of patients with osteoarthritis. A systematic review of all randomised controlled clinical trials of homeopathic treatment of patients with this condition is presented. A comprehensive search yielded four trials which are discussed in detail. The authors conclude that the small number of randomised clinical trials conducted to date, although favouring homeopathic treatment, do not allow a firm conclusion as to the effectiveness of homeopathic remedies in the treatment of patients with osteoarthritis. The clinical evidence appears promising, however, and more research into this area seems warranted.

scholarly journals The Value of Systematic Reviews and Meta-Analyses in Surgery

2021 ◽  
pp. 1-8
Author(s):  
Simon R. Knight
Keyword(s):  
Clinical Trials ◽  
Systematic Reviews ◽  
Practice Guidelines ◽  
Statistical Power ◽  
Clinical Decision Making ◽  
Learning Curves ◽  
Current Evidence ◽  
Level Of Evidence ◽  
Surgical Interventions ◽  
Meta Analyses

<b><i>Background:</i></b> Systematic reviews and meta-analyses are generally regarded as sitting atop the hierarchy of clinical evidence. The unbiased summary of current evidence that a systematic review provides, along with the increased statistical power from larger numbers of patients, is invaluable in guiding clinical decision-making and development of practice guidelines. Surgical specialties have historically lagged behind other areas of medicine in the application of evidence-based medicine, perhaps due to the unique challenges faced in the conduct of surgical clinical trials. These challenges extend to the conduct of systematic reviews, due to issues with the quality and heterogeneity of the underlying literature. <b><i>Summary:</i></b> Recent years have seen an improvement in the quality of randomized controlled trials in surgical topics and an explosion in the publication of systematic reviews. This review explores recent trends in systematic reviews in surgery and discussed some of the aspects in conducting and interpreting reviews that are unique to surgical topics, including blinding, surgical heterogeneity and learning curves, patient and clinician preference, and industry involvement. <b><i>Key Messages:</i></b> Clinical trials, and therefore systematic reviews, of surgical interventions pose unique challenges which are important to consider when conducting them or applying the findings to clinical practice. Despite the challenges, systematic reviews still represent the best level of evidence for development of surgical practice guidelines.

scholarly journals Vasoactive agents in acute mesenteric ischaemia in critical care.  A systematic review

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 453
Author(s):  
Christopher A Brennan ◽  
Peter Osei-Bonsu ◽  
Rachael Eimear McClenaghan ◽  
Ahmed Nassar ◽  
Patrice Forget ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Critical Care ◽  
Randomised Clinical Trials ◽  
Current Evidence ◽  
Mesenteric Ischaemia ◽  
Vasoactive Agents ◽  
Acute Mesenteric Ischaemia ◽  
Ovid Medline ◽  
Randomised Controlled

Background: Acute mesenteric ischaemia (AMI) is a surgical emergency which has an associated high mortality.  The mainstay of active treatment includes early surgical intervention, with resection of non-viable bowel, and revascularisation of the ischaemic bowel where possible. Due to the physiological insult of AMI however, perioperative care often involves critical care and the use of vasoactive agents to optimise end organ perfusion. A number of these vasoactive agents are currently available with varied mechanism of action and effects on splanchnic blood flow. However, specific guidance on which is the optimal vasoactive drug to use in these settings is limited. This systematic review aimed to evaluate the current evidence comparing vasoactive drugs in AMI. Methods: A systematic search of Ovid Medline, Ovid Embase, Cochrane CENTRAL and the Cochrane Database of Systematic Review was performed on the 5th of November 2020 to identify randomised clinical trials comparing different vasoactive agents in AMI on outcomes including mortality. The search was performed through the Royal College of Surgeons of England (RCSEng) search support library. Results were analysed using the Rayyan platform, and independently screened by four investigators. Results: 614 distinct papers were identified. After screening, there were no randomised clinical trials meeting the inclusion criteria. Conclusions: This review identifies a gap in literature, and therefore recommends an investigation into current practice and clinician preference in relation to vasoactive agents in AMI. Multicentre randomised controlled trials comparing these medications on clinical outcomes will therefore be required to address this question.

scholarly journals Treatment of intracerebral haemorrhage with tranexamic acid – A review of current evidence and ongoing trials

2016 ◽  
Vol 2 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Zhe Kang Law ◽  
Atte Meretoja ◽  
Stefan T Engelter ◽  
Hanne Christensen ◽  
Eugenia-Maria Muresan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Tranexamic Acid ◽  
Intracerebral Haemorrhage ◽  
Time Window ◽  
Intraventricular Haemorrhage ◽  
Current Evidence ◽  
Spot Sign ◽  
Haemostatic Agent ◽  
Significant Difference ◽  
Randomised Controlled

Purpose Haematoma expansion is a devastating complication of intracerebral haemorrhage (ICH) with no established treatment. Tranexamic acid had been an effective haemostatic agent in reducing post-operative and traumatic bleeding. We review current evidence examining the efficacy of tranexamic acid in improving clinical outcome after ICH. Method We searched MEDLINE, EMBASE, CENTRAL and clinical trial registers for studies using search strategies incorporating the terms ‘intracerebral haemorrhage’, ‘tranexamic acid’ and ‘antifibrinolytic’. Authors of ongoing clinical trials were contacted for further details. Findings We screened 268 publications and retrieved 17 articles after screening. Unpublished information from three ongoing clinical trials was obtained. We found five completed studies. Of these, two randomised controlled trials (RCTs) comparing intravenous tranexamic acid to placebo ( n = 54) reported no significant difference in death or dependency. Three observational studies ( n = 281) suggested less haematoma growth with rapid tranexamic acid infusion. There are six ongoing RCTs ( n = 3089) with different clinical exclusions, imaging selection criteria (spot sign and haematoma volume), time window for recruitment and dosing of tranexamic acid. Discussion Despite their heterogeneity, the ongoing trials will provide key evidence on the effects of tranexamic acid on ICH. There are uncertainties of whether patients with negative spot sign, large haematoma, intraventricular haemorrhage, or poor Glasgow Coma Scale should be recruited. The time window for optimal effect of haemostatic therapy in ICH is yet to be established. Conclusion Tranexamic acid is a promising haemostatic agent for ICH. We await the results of the trials before definite conclusions can be drawn.

scholarly journals The landscape of COVID-19 clinical trials in Latin America and the Caribbean: assessment and challenges

2020 ◽  
Vol 44 ◽  
pp. 1
Author(s):  
Sarah Carracedo ◽  
Ana Palmero ◽  
Marcie Neil ◽  
Anisa Hasan-Granier ◽  
Carla Saenz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Latin America ◽  
Caribbean Region ◽  
Middle Income ◽  
Middle Income Countries ◽  
Treatment And Prevention ◽  
Latin America And Caribbean ◽  
The Caribbean ◽  
Clinical Trials Registry ◽  
Robust Evidence

A considerable number of clinical trials is being conducted globally in response to the COVID-19 pandemic, including in low- and middle-income countries such as those in the Latin America and Caribbean region (LAC). Yet, an abundance of studies does not necessarily shorten the path to find safe and efficacious interventions for COVID-19. We analyze the trials for COVID-19 treatment and prevention that are registered from LAC countries in the International Clinical Trials Registry Platform, and identify a trend towards small repetitive non-rigorous studies that duplicate efforts and drain limited resources without producing meaningful conclusions on the safety and efficacy of the interventions being tested. We further assess the challenges to conducting scientifically sound and socially valuable research in the LAC region in order to inform recommendations to encourage clinical trials that are most likely to produce robust evidence during the pandemic.

scholarly journals Blood Brain-Derived Neurotrophic Factor (BDNF) and Major Depression: Do We Have a Translational Perspective?

2021 ◽  
Vol 15 ◽  
Author(s):  
Beatrice Arosio ◽  
Franca Rosa Guerini ◽  
Richard C. Oude Voshaar ◽  
Ivan Aprahamian
Keyword(s):  
Clinical Trials ◽  
Neurotrophic Factor ◽  
Peripheral Blood ◽  
Treatment Options ◽  
Measurement Techniques ◽  
Brain Derived Neurotrophic Factor ◽  
Experimental Models ◽  
Treatment Modalities ◽  
Current Evidence ◽  
Meta Analyses

Major depressive disorder (MDD) affects millions of people worldwide and is a leading cause of disability. Several theories have been proposed to explain its pathological mechanisms, and the “neurotrophin hypothesis of depression” involves one of the most relevant pathways. Brain-derived neurotrophic factor (BDNF) is an important neurotrophin, and it has been extensively investigated in both experimental models and clinical studies of MDD. Robust empirical findings have indicated an association between increased BDNF gene expression and peripheral concentration with improved neuronal plasticity and neurogenesis. Additionally, several studies have indicated the blunt expression of BDNF in carriers of the Val66Met gene polymorphism and lower blood BDNF (serum or plasma) levels in depressed individuals. Clinical trials have yielded mixed results with different treatment options, peripheral blood BDNF measurement techniques, and time of observation. Previous meta-analyses of MDD treatment have indicated that antidepressants and electroconvulsive therapy showed higher levels of blood BDNF after treatment but not with physical exercise, psychotherapy, or direct current stimulation. Moreover, the rapid-acting antidepressant ketamine has presented an early increase in blood BDNF concentration. Although evidence has pointed to increased levels of BDNF after antidepressant therapy, several factors, such as heterogeneous results, low sample size, publication bias, and different BDNF measurements (serum or plasma), pose a challenge in the interpretation of the relation between peripheral blood BDNF and MDD. These potential gaps in the literature have not been properly addressed in previous narrative reviews. In this review, current evidence regarding BDNF function, genetics and epigenetics, expression, and results from clinical trials is summarized, putting the literature into a translational perspective on MDD. In general, blood BDNF cannot be recommended for use as a biomarker in clinical practice. Moreover, future studies should expand the evidence with larger samples, use the serum or serum: whole blood concentration of BDNF as a more accurate measure of peripheral BDNF, and compare its change upon different treatment modalities of MDD.

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