scholarly journals Currently prescribed drugs in the UK that could upregulate or downregulate ACE2 in COVID-19 disease: a systematic review

BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e040644
Author(s):  
Hajira Dambha-Miller ◽  
Ali Albasri ◽  
Sam Hodgson ◽  
Christopher R Wilcox ◽  
Shareen Khan ◽  
...  

ObjectiveTo review evidence on routinely prescribed drugs in the UK that could upregulate or downregulate ACE2 and potentially affect COVID-19 disease.DesignSystematic review.Data sourceMEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science.Study selectionAny design with animal or human models examining a currently prescribed UK drug compared with a control, placebo or sham group, and reporting an effect on ACE2 level, activity or gene expression.Data extraction and synthesisMEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science and OpenGrey from inception to 1 April 2020. Methodological quality was assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool for animal studies and Cochrane risk-of-bias tool for human studies.ResultsWe screened 3360 titles and included 112 studies with 21 different drug classes identified as influencing ACE2 activity. Ten studies were in humans and one hundred and two were in animal models None examined ACE2 in human lungs. The most frequently examined drugs were angiotensin receptor blockers (ARBs) (n=55) and ACE inhibitors (ACE-I) (n=22). More studies reported upregulation than downregulation with ACE-I (n=22), ARBs (n=55), insulin (n=8), thiazolidinedione (n=7) aldosterone agonists (n=3), statins (n=5), oestrogens (n=5) calcium channel blockers (n=3) glucagon-like peptide 1 (GLP-1) agonists (n=2) and Non-steroidal anti-inflammatory drugs (NSAIDs) (n=2).ConclusionsThere is an abundance of the academic literature and media reports on the potential of drugs that could attenuate or exacerbate COVID-19 disease. This is leading to trials of repurposed drugs and uncertainty among patients and clinicians concerning continuation or cessation of prescribed medications. Our review indicates that the impact of currently prescribed drugs on ACE2 has been poorly studied in vivo, particularly in human lungs where the SARS-CoV-2 virus appears to enact its pathogenic effects. We found no convincing evidence to justify starting or stopping currently prescribed drugs to influence outcomes of COVID-19 disease.

Author(s):  
Hajira Dambha-Miller ◽  
Ali Albasri ◽  
Sam Hodgson ◽  
Christopher R Wilcox ◽  
Shareen Khan ◽  
...  

Objective: To review evidence on routinely prescribed drugs in the UK that could up or downregulate Angiotensin Converting Enzyme 2 (ACE2) and potentially affect COVID-19 disease Design: Systematic review Data source: MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science Study selection: Any design with animal or human models examining a currently prescribed UK drug compared to a control, placebo or sham group, and reporting an effect on ACE2 level, activity or gene expression. Data extraction and synthesis: MEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science and OpenGrey from inception to 1st April 2020. Methodological quality was assessed using the SYRCLE's risk of bias tool for animal studies and Cochrane risk of bias tool for human studies. Results: We screened 3,360 titles and included 112 studies with 21 different drug classes identified as influencing ACE2 activity. Ten studies were in humans and 102 were in animal models None examined ACE2 in human lungs. The most frequently examined drugs were Angiotensin Receptor Blockers (ARBs) (n= 55) and Angiotensin-Converting Enzyme- Inhibitors (ACE-I) (n= 22). More studies reported upregulation than downregulation with ACE-I (n=22), ARBs (n=55), insulin (n=8), thiazolidinedione (n=7) aldosterone agonists (n=3), statins (n=5), oestrogens (n=5) calcium channel-blockers (n=3) GLP-1 agonists (n=2) and NSAIDs (n=2). Conclusions: There is an abundance of academic literature and media reports on the potential of drugs that could attenuate or exacerbate COVID-19 disease. This is leading to trials of repurposed drugs and uncertainty amongst patients and clinicians concerning continuation or cessation of prescribed medications. Our review indicates that the impact of currently prescribed drugs on ACE2 has been poorly studied in-vivo, particularly in human lungs where the SARS-CoV-2 virus appears to enact its pathogenic effects. We found no convincing evidence to justify starting or stopping currently prescribed drugs to influence outcomes of COVID-19 disease.


2020 ◽  
Author(s):  
Hajira Dambha-Miller ◽  
Ali Albasri ◽  
Sam Hodgson ◽  
Chris Wilcox ◽  
Nazrul Islam ◽  
...  

Abstract Background: The SARS-CoV-2 virus causing COVID-19 binds human angiotensin-converting enzyme 2 (ACE2) receptors in human tissues. ACE2 expression may be associated with COVID-19 infection and mortality rates. Routinely prescribed drugs which up- or down-regulate ACE2 expression are therefore of critical research interest as agents which might promote or reduce risk of COVID-19 infection in a susceptible population. Aim: To review evidence on routinely prescribed drug treatments in the UK that could up- or down-regulate ACE2 and potentially affect COVID-19 infection. Design and setting: Systematic review of studies published in MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science from inception to April 1st 2020. Method: A systematic review will be conducted in line with PRISMA guidelines. Inclusion criteria will be: i) assess effect of drug exposure on ACE2 level; ii) drug is included in British National Formulary (BNF) and therefore available to prescribe in UK; iii) a control, placebo or sham group is included as comparator. Exclusion criteria will be: i) ACE2 measurement in utero; ii) ACE2 measurement in children under 18 years; iii) drug not in BNF; iv) review article. Quality will be assessed using the Cochrane risk of bias tool for human studies, and the SYRCLE risk of bias tool for animal studies. Results: Data will be reported in summary tables and narrative synthesis. Conclusion: This systematic review will identify drug therapies which may increase or decrease ACE2 expression. This might identify medications increasing risk of COVID-19 transmission, or as targets for intervention in mitigating transmission.


BJGP Open ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. bjgpopen20X101115 ◽  
Author(s):  
Hajira Dambha-Miller ◽  
Ali Albasri ◽  
Sam Hodgson ◽  
Christopher Wilcox ◽  
Nazrul Islam ◽  
...  

BackgroundThe SARS-CoV-2 virus causing COVID-19 binds human angiotensin-converting enzyme 2 (ACE2) receptors in human tissues. ACE2 expression may be associated with COVID-19 infection and mortality rates. Routinely prescribed drugs that up- or down-regulate ACE2 expression are, therefore, of critical research interest as agents that might promote or reduce risk of COVID-19 infection in a susceptible population.AimTo collate evidence on routinely prescribed drug treatments in the UK that could up- or down-regulate ACE2, and thus potentially affect COVID-19 infection.Design & settingSystematic review of studies published in MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), the Cochrane Library, and Web of Science from inception to 1 April 2020.MethodA systematic review will be conducted in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Inclusion criteria will be: (1) assesses the effect of drug exposure on ACE2 level of expression or activity; (2) the drug is included in the British National Formulary (BNF) and, therefore, available to prescribe in the UK; and (3) a control, placebo, or sham group is included as comparator. Exclusion criteria will be: (1) ACE2 measurement in utero; (2) ACE2 measurement in children aged <18 years; (3) drug not in the BNF; and (4) review article. Quality will be assessed using the Cochrane risk of bias tool for human studies, and the SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) risk of bias tool for animal studies.ResultsData will be reported in summary tables and narrative synthesis.ConclusionThis systematic review will identify drug therapies that may increase or decrease ACE2 expression. This might identify medications increasing risk of COVID-19 transmission, or as targets for intervention in mitigating transmission.


2021 ◽  
pp. 030157422110195
Author(s):  
Ashish Agrawal ◽  
TM Chou

Introduction: The objective of this systematic review is to assess the effect of vibrational force on biomarkers for orthodontic tooth movement. Methods: An electronic search was conducted for relevant studies (up to December 31, 2020) on the following databases: Pubmed, Google scholar, Web of Science, Cochrane Library, Wiley Library, and ProQuest Dissertation Abstracts and Thesis database. Hand searching of selected orthodontic journals was also undertaken. The selected studies were assessed for the risk of bias in Cochrane collaboration risk of bias tool. The “traffic plot” and “weighted plot” risk of bias distribution are designed in the RoB 2 tool. The 2 authors extracted the data and analyzed it. Results: Six studies fulfilled the inclusion criteria. The risks of biases were high for 4, low and some concern for other 2 studies. The biomarkers, medium, device, frequency and duration of device, as well as other data were extracted. The outcomes of the studies were found to be heterogenous. Conclusion: One study showed highly statistically significant levels of IL-1 beta with <.001. Rate of tooth movement was correlated with levels of released biomarkers under the influence of vibrational force in 3 studies, but it was found to be significant only in 1 study. It was further observed that vibration does not have any significant reduction in pain and discomfort.


2016 ◽  
Vol 16 (2) ◽  
pp. 93-101 ◽  
Author(s):  
Iramar Baptistella do Nascimento ◽  
Willian Barbosa Sales ◽  
Raquel Fleig ◽  
Grazielle Dutra da Silva ◽  
Jean Carl Silva

Abstract Objectives: to identify bibliographically disorders related to excess weight, dyslipidemia and their complication during pregnancy and in the fetus and newborn. Methods: a systematic review including observational and interventional studies and reviews, based on MEDLINE, LILACS, Embase and the Cochrane Library between 2000 and 2015. The key-words "lipids, pregnancy, obesity and newborn" were used to establish a selective stage for inclusion/exclusion of titles, repeated studies, key-words, abstracts, methodological incompatibility and correlation with objectives. Results: 58 studies were selected, of which 36 (62%) addressed prevention and the risk in pregnancy of excess weight and lipid disorders and 19 (32.7%) suggestions and/or consequences for the fetus and newborn. Conclusions: excess weight and lipidemic disorders in pregnancy are causes for concern in scientific studies, posing risks both for the mother and the newborn. Higher prevalence of caesarian and pre-eclampsia were the two most noteworthy complications for gestational outcomes. In short, the impact on care of maternal habits and excess weight during pregnancy is highly significant, owing to the different degrees of complication in obstetric outcomes and their influence on the clinical characteristics of the newborn.


2020 ◽  
Vol 75 (4) ◽  
pp. 457-466
Author(s):  
Matteo Amoroso ◽  
Peter Apelgren ◽  
Anna Elander ◽  
Karin Säljö ◽  
Lars Kölby

BACKGROUND: Acute normovolemic hemodilution (ANH) has been proposed as a microsurgical technique to improve blood flow in free flaps. OBJECTIVE: Here, we present the first systematic review of clinical and experimental studies on the effect of ANH. METHODS: We performed a systematic literature search of PubMed, Medline, the Cochrane Library, Google Scholar, and ClinicalTrials.gov using search strategies and a review process in agreement with the PRISMA statement and the Cochrane Handbook for systematic reviews of interventions. PICO criteria were defined before bibliometric processing of the retrieved articles, which were analyzed with the SYRCLE RoB tool for risk of bias and the GRADE scale for level of evidence. RESULTS: We retrieved 74 articles from the literature search, and after processing according to PICO criteria, only four articles remained, all of which were experimental. The rating for risk of bias was uncertain according to SYRCLE RoB results, and the level of evidence was low according to GRADE evaluation. CONCLUSIONS: There is no clinical evidence for the effect of ANH on microcirculation in free flaps, and experimental studies provide weak evidence supporting the use of hemodilution in reconstructive microsurgery.


BMJ Open ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. e030536
Author(s):  
Kanika Chaudhri ◽  
Madeleine Kearney ◽  
Richard O Day ◽  
Anthony Rodgers ◽  
Emily Atkins

IntroductionForgetting to take a medication is the most common reason for non-adherence to self-administered medication. Dose administration aids (DAAs) are a simple and common solution to improve unintentional non-adherence for oral tablets. DAAs can be in the form of compartmentalised pill boxes, automated medication dispensing devices, blister packs and sachets packets. This protocol aims to outline the methods that will be used in a systematic review of the current literature to assess the impact of DAAs on adherence to medications and health outcomes.Methods and analysisRandomised controlled trials will be identified through electronic searches in databases including EMBASE, MEDLINE, CINAHL and the Cochrane Library, from the beginning of each database until January 2020. Two reviewers will independently screen studies and extract data using the standardised forms. Data extracted will include general study information, characteristics of the study, participant characteristics, intervention characteristics and outcomes. Primary outcome is to assess the effects of DAAs on medication adherence. Secondary outcome is to evaluate the changes in health outcomes. The risk of bias will be ascertained by two reviewers in parallel using The Cochrane Risk of Bias Tool. A meta-analysis will be performed if data are homogenous.Ethics and disseminationEthics approval will not be required for this study. The results of the review described within this protocol will be disseminated through publication in a peer-reviewed journal and relevant conference presentations.PROSPERO registration numberCRD42018096087


2021 ◽  
Vol 11 ◽  
Author(s):  
Alejandro López-Valenciano ◽  
David Suárez-Iglesias ◽  
Miguel A. Sanchez-Lastra ◽  
Carlos Ayán

Purpose: This systematic review aimed to analyze the impact that the COVID-19 lockdown had on the amount of physical activity performed by university students.Materials and Methods: A systematic electronic search for studies providing information regarding physical activity levels pre and during COVID-19 pandemic in university students was performed up to 20th October 2020 in the databases Cochrane Library, PubMed, SPORTDiscus, and Web of Science. The risk of bias of external validity quality of included studies was assessed by means of those the Newcastle-Ottawa Scale (NOS). The quality of the evidence for main outcomes was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Results and Conclusions: A total of 10 studies were selected. Physical activity levels were assessed by means of questionnaires (10 studies) and accelerometer (1 study). Risk of bias was regarded as low and high in six and four investigations, respectively. The quality of evidence was downgraded to low. A significant reduction of physical activity levels were observed in 9 studies. Compared to pre-lockdown values, five studies showed a reduction of light/mild physical activity (walking) between 32.5 and 365.5%, while seven studies revealed a reduction of high/vigorous physical activity between 2.9 and 52.8%. Walking, moderate, vigorous, and total physical activity levels have been reduced during the COVID-19 pandemic confinements in university students of different countries. Despite of the reductions, those who met the current minimum PA recommendations before the lockdown generally met the recommendations also during the confinements.


2020 ◽  
Vol 33 (Supplement_1) ◽  
Author(s):  
P Prasad ◽  
K Hardy ◽  
J Chmelo ◽  
M Navidi ◽  
A Phillips

Abstract   Esophagectomy is a complex procedure with associated high levels of morbidity. Rehabilitation programmes are being developed and increasingly utilised in the perioperative period and comprise a variety of physical, nutritional and psychological interventions. Such strategies may help reduce the incidence of postoperative complications, mitigate sarcopenia, prevent progressive frailty and restore quality of life. This systematic review aimed to identify and analyse studies reporting outcomes of post-esophagectomy rehabilitative interventions. Methods Major reference databases (PubMed, Medline, EMBASE, Cochrane Library and Google scholar) were interrogated and a systematic search with a pre-defined search strategy was performed up until January 2020. All eligible articles were screened in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Study quality was assessed using the MINORS (Methodological Index for Non-Randomized Studies) criteria for cohort studies and the Cochrane risk of bias tool for randomised studies. Results Three studies (n = 1 pilot study; n = 1 feasibility study and n = 1 randomised controlled trial) including some 108 patients were included in this narrative review, of whom 64 patients had undergone esophagectomy. Rehabilitative strategies utilised included a combination of physical activities such as walking and low- to moderate-intensity exercises, dietary counselling, psychological support and occupational therapy input. There was wide variation in the outcomes assessed between studies. Postoperative physical activity with exercises consistently demonstrated maximum positive impact upon cardiopulmonary fitness. The median MINORS score for included studies was 9 (8-10) and the risk of bias in the included randomised trial was low. Conclusion There is a paucity of data currently to help determine the impact that rehabilitation may have on clinical outcomes and quality of life following esophagectomy. While improved physical function has been demonstrated, there is a need to determine which interventions patients deem most important and acceptable to help them return to as close to baseline as possible. Additionally, there is a need to further understand the impact rehabilitation may have upon long-term outcomes.


2019 ◽  
Vol 43 (6) ◽  
pp. 1555-1563
Author(s):  
Ilari Rautalin ◽  
Jaakko Kaprio ◽  
Miikka Korja

AbstractAs the number of obese people is globally increasing, reports about the putative protective effect of obesity in life-threatening diseases, such as subarachnoid hemorrhage (SAH), are gaining more interest. This theory—the obesity paradox—is challenging to study, and the impact of obesity has remained unclear in survival of several critical illnesses, including SAH. Thus, we performed a systematic review to clarify the relation of obesity and SAH mortality. Our study protocol included systematic literature search in PubMed, Scopus, and Cochrane library databases, whereas risk-of-bias estimation and quality of each selected study were evaluated by the Critical Appraisal Skills Program and Cochrane Collaboration guidelines. A directional power analysis was performed to estimate sufficient sample size for significant results. From 176 reviewed studies, six fulfilled our eligibility criteria for qualitative analysis. One study found paradoxical effect (odds ratio, OR = 0.83 (0.74–0.92)) between morbid obesity (body mass index (BMI) > 40) and in-hospital SAH mortality, and another study found the effect between continuously increasing BMI and both short-term (OR = 0.90 (0.82–0.99)) and long-term SAH mortalities (OR = 0.92 (0.85–0.98)). However, according to our quality assessment, methodological shortcomings expose all reviewed studies to a high-risk-of-bias. Even though two studies suggest that obesity may protect SAH patients from death in the acute phase, all reviewed studies suffered from methodological shortcomings that have been typical in the research field of obesity paradox. Therefore, no definite conclusions could be drawn.


Sign in / Sign up

Export Citation Format

Share Document