Drug treatments affecting ACE2 in COVID-19 infection: a systematic review protocol

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.

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Drug treatments affecting ACE2 in COVID-19 infection: a systematic review protocol

BJGP Open ◽

10.3399/bjgpopen20x101115 ◽

2020 ◽

Vol 4 (3) ◽

pp. bjgpopen20X101115 ◽

Cited By ~ 2

Author(s):

Hajira Dambha-Miller ◽

Ali Albasri ◽

Sam Hodgson ◽

Christopher Wilcox ◽

Nazrul Islam ◽

...

Keyword(s):

Systematic Review ◽

Animal Studies ◽

Drug Exposure ◽

Meta Analysis ◽

Risk Of Bias ◽

Cochrane Library ◽

Susceptible Population ◽

Drug Treatments ◽

The Uk ◽

The Cochrane Library

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.

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

BMJ Open ◽

10.1136/bmjopen-2020-040644 ◽

2020 ◽

Vol 10 (9) ◽

pp. e040644

Author(s):

Hajira Dambha-Miller ◽

Ali Albasri ◽

Sam Hodgson ◽

Christopher R Wilcox ◽

Shareen Khan ◽

...

Keyword(s):

Systematic Review ◽

Web Of Science ◽

Angiotensin Receptor Blockers ◽

Risk Of Bias ◽

Cochrane Library ◽

Channel Blockers ◽

Human Lungs ◽

The Uk ◽

The Cochrane Library ◽

The Impact

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.

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Currently prescribed drugs in the UK that could up or downregulate ACE2 in COVID-19 disease: A systematic review

10.1101/2020.05.19.20106856 ◽

2020 ◽

Cited By ~ 1

Author(s):

Hajira Dambha-Miller ◽

Ali Albasri ◽

Sam Hodgson ◽

Christopher R Wilcox ◽

Shareen Khan ◽

...

Keyword(s):

Systematic Review ◽

Angiotensin Converting Enzyme ◽

Web Of Science ◽

Risk Of Bias ◽

Cochrane Library ◽

Converting Enzyme ◽

Human Lungs ◽

The Uk ◽

The Cochrane Library ◽

The Impact

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.

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The effect of hemodilution on free flap survival: A systematic review of clinical and experimental studies

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-200832 ◽

2020 ◽

Vol 75 (4) ◽

pp. 457-466

Author(s):

Matteo Amoroso ◽

Peter Apelgren ◽

Anna Elander ◽

Karin Säljö ◽

Lars Kölby

Keyword(s):

Systematic Review ◽

Literature Search ◽

Experimental Studies ◽

Free Flaps ◽

Risk Of Bias ◽

Cochrane Library ◽

Level Of Evidence ◽

Grade Scale ◽

Reconstructive Microsurgery ◽

The Cochrane Library

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.

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A SYSTEMATIC REVIEW OF CLINICAL OUTCOMES IN THE TREATMENT OF TEMPOROMANDIBULAR JOINT DYSFUNCTION USING ULTRASOUND GUIDED ARTHROCENTESIS AND CONVENTIONAL THERAPY

10.36106/ijsr/9303653 ◽

2021 ◽

pp. 19-22

Author(s):

Chirag Bhatia ◽

Hirkani Attarde

Keyword(s):

Systematic Review ◽

Temporomandibular Joint ◽

Operating Time ◽

Mouth Opening ◽

Risk Of Bias ◽

Temporomandibular Joint Disorders ◽

Current Evidence ◽

Cochrane Library ◽

Review Protocol ◽

Reported Data

Objective: This systematic review aimed to compare outcomes between ultrasound (US)-guided arthrocentesis and conventional arthrocentesis for the management of temporomandibular joint disorders (TMDs). Methods: PubMed, MEDLINE, Cochrane Library, Google Scholar and th EBSCOhost databases were searched up to 30 September 2020 for randomized control trials (RCTs) comparing US-guided and conventional arthrocentesis. The review protocol followed the PRISMA guidelines and was registered in PROSPERO (CRD42020211942). The risk of bias of the studies was independently evaluated using Cochrane Risk of Bias tool. Results: Four RCTs were included. It did not demonstrate any statistically signicant difference in pain or maximal mouth opening (MMO) scores after 1 week and 1 month of follow-up between US-guided and conventional arthrocentesis. Studies also reported data on intra-operative needle relocations and operating time but with conicting results. Conclusion: This study indicates that the use of US during arthrocentesis may not improve postoperative pain and MMO in the short term. Further high-quality adequately powered RCTs are required to strengthen current evidence.

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Surgery for tennis elbow: a systematic review

Shoulder & Elbow ◽

10.1177/1758573217745041 ◽

2017 ◽

Vol 11 (1) ◽

pp. 35-44 ◽

Cited By ~ 3

Author(s):

Marcus Bateman ◽

Chris Littlewood ◽

Beth Rawson ◽

Amol A. Tambe

Keyword(s):

Systematic Review ◽

Research Evidence ◽

Tennis Elbow ◽

Risk Of Bias ◽

Cochrane Library ◽

Surgical Interventions ◽

Surgical Trial ◽

The Usa ◽

Suitable Treatment ◽

The Cochrane Library

Background There is no consensus on the most suitable treatment for tennis elbow but, in the USA, surgical intervention is increasing despite a lack of supportive research evidence. The aim of this systematic review was to provide a balanced update based on all relevant published randomized controlled trials conducted to date. Methods An electronic search of MEDLINE, EMBASE, CINAHL, BNI, AMED, PsycINFO, HBE, HMIC, PubMed, TRIP, Dynamed Plus and The Cochrane Library was complemented by hand searching. Risk of bias was assessed using the Cochrane Risk of Bias Tool and data were synthesized narratively, based on levels of evidence, as a result of heterogeneity. Results Twelve studies of poor methodological quality were included. The available data suggest that surgical interventions for tennis elbow are no more effective than nonsurgical and sham interventions. Surgical technique modifications may enhance effectiveness compared to traditional methods but have not been tested against a placebo. Conclusions Current research evidence suggests that surgery for tennis elbow is no more effective than nonsurgical treatment based on evidence with significant methodological limitations. Given the recalcitrant nature of tennis elbow for some patients, further research in the form of a high-quality placebo-controlled surgical trial with an additional conservative arm is required to usefully inform clinical practice.

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Direct access cancer testing in primary care: a systematic review of use and clinical outcomes

British Journal of General Practice ◽

10.3399/bjgp18x698561 ◽

2018 ◽

Vol 68 (674) ◽

pp. e594-e603 ◽

Cited By ~ 3

Author(s):

Claire Friedemann Smith ◽

Alice C Tompson ◽

Nicholas Jones ◽

Josh Brewin ◽

Elizabeth A Spencer ◽

...

Keyword(s):

Systematic Review ◽

Poor Quality ◽

Study Data ◽

Direct Access ◽

Cochrane Library ◽

Testing Time ◽

Significant Difference ◽

The Uk ◽

The Cochrane Library ◽

Better Than

BackgroundDirect access (DA) testing allows GPs to refer patients for investigation without consulting a specialist. The aim is to reduce waiting time for investigations and unnecessary appointments, enabling treatment to begin without delay.AimTo establish the proportion of patients diagnosed with cancer and other diseases through DA testing, time to diagnosis, and suitability of DA investigations.Design and settingSystematic review assessing the effectiveness of GP DA testing in adults.MethodMEDLINE, Embase, and the Cochrane Library were searched. Where possible, study data were pooled and analysed quantitatively. Where this was not possible, the data are presented narratively.ResultsThe authors identified 60 papers that met pre-specified inclusion criteria. Most studies were carried out in the UK and were judged to be of poor quality. The authors found no significant difference in the pooled cancer conversion rate between GP DA referrals and patients who first consulted a specialist for any test, except gastroscopy. There were also no significant differences in the proportions of patients receiving any non-cancer diagnosis. Referrals for testing were deemed appropriate in 66.4% of those coming from GPs, and in 80.9% of those from consultants; this difference was not significant. The time from referral to testing was significantly shorter for patients referred for DA tests. Patient and GP satisfaction with DA testing was consistently high.ConclusionGP DA testing performs as well as, and on some measures better than, consultant triaged testing on measures of disease detection, appropriateness of referrals, interval from referral to testing, and patient and GP satisfaction.

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Emerging Nanotechnology in Non-Surgical Periodontal Therapy in Animal Models: A Systematic Review

Nanomaterials ◽

10.3390/nano10071414 ◽

2020 ◽

Vol 10 (7) ◽

pp. 1414 ◽

Cited By ~ 1

Author(s):

Adrian Brun ◽

Nicolas Moignot ◽

Marie-Laure Colombier ◽

Elisabeth Dursun

Keyword(s):

Systematic Review ◽

Animal Models ◽

Bone Loss ◽

Alveolar Bone ◽

Inflammatory Diseases ◽

Risk Of Bias ◽

Periodontal Therapy ◽

Cochrane Library ◽

Eligibility Criteria ◽

The Cochrane Library

Periodontitis is one of the most prevalent inflammatory diseases. Its treatment, mostly mechanical and non-surgical, shows limitations. The aim of this systematic review was to investigate the effect of nanoparticles as a treatment alone in non-surgical periodontal therapy in animal models. A systematic search was conducted in Medline/PubMed, Web of Science, The Cochrane Library and Science Direct. The eligibility criteria were: studies (i) using nanoparticles as chemotherapeutic agent or as delivery system; (ii) including preclinical controlled animal model (experimental periodontitis); (iii) reporting alveolar bone loss; (iv) written in English; and (v) published up to June 2019. Risk of bias was evaluated according to the SYstematic Review Centre for Laboratory Animal Experimentation. On the 1324 eligible studies, 11 were included. All reported advantages in using nanoparticles for the treatment of periodontitis, highlighted by a reduction in bone loss. Agents modulating inflammation seem to be more relevant than antibiotics, in terms of efficiency and risk of antibiotic resistance. In addition, poly(lactic-co-glycolic acid) or drugs used as their own carrier appear to be the most interesting nanoparticles in terms of biocompatibility. Risk of bias assessment highlighted many criteria scored as unclear. There are encouraging preclinical data of using nanoparticles as a contribution to the treatment of periodontitis.

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Examining the relationship between rheumatoid arthritis, multimorbidity and adverse health-related outcomes: A systematic review protocol

Journal of Comorbidity ◽

10.1177/2235042x20906657 ◽

2020 ◽

Vol 10 ◽

pp. 2235042X2090665

Author(s):

Jordan Canning ◽

Stefan Siebert ◽

Bhautesh D Jani ◽

Frances S Mair ◽

Barbara I Nicholl

Keyword(s):

Rheumatoid Arthritis ◽

Systematic Review ◽

Autoimmune Disorder ◽

Cochrane Library ◽

Systemic Complications ◽

Registration Number ◽

Health Related ◽

Review Protocol ◽

Meta Analyses ◽

The Cochrane Library

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterised by articular inflammation and systemic complications. Multimorbidity (the presence of two or more long-term health conditions) is highly prevalent in people with RA but the effect of multimorbidity on mortality and other health-related outcomes is poorly understood. Objective: To determine what is known about the effect, if any, of multimorbidity on mortality and health-related outcomes in individuals with RA. Design: Systematic review of the literature. The following electronic medical databases will be searched: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, The Cochrane Library and Scopus. Included studies will be quality appraised using the Quality in Prognostic Studies tool developed by the Cochrane Prognosis Methods Group. A narrative synthesis of findings will be undertaken and meta-analyses considered, if appropriate. This protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols 2015 guidelines, ensuring the quality of the review. Conclusions: Understanding the influence of multimorbidity on mortality and other health-related outcomes in RA will provide an important basis of knowledge with the potential to improve future clinical management of RA. PROSPERO registration number: CRD42019137756.

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Use and reporting of experience-based codesign studies in the healthcare setting: a systematic review

BMJ Quality & Safety ◽

10.1136/bmjqs-2019-009570 ◽

2019 ◽

Vol 29 (1) ◽

pp. 64-76 ◽

Cited By ~ 4

Author(s):

Theresa Green ◽

Ann Bonner ◽

Laisa Teleni ◽

Natalie Bradford ◽

Louise Purtell ◽

...

Keyword(s):

Systematic Review ◽

Health Service ◽

English Language ◽

Healthcare Setting ◽

Cochrane Library ◽

Service Improvement ◽

Consistent Manner ◽

Registration Number ◽

The Uk ◽

The Cochrane Library

BackgroundExperience-based codesign (EBCD) is an approach to health service design that engages patients and healthcare staff in partnership to develop and improve health services or pathways of care. The aim of this systematic review was to examine the use (structure, process and outcomes) and reporting of EBCD in health service improvement activities.MethodsElectronic databases (MEDLINE, CINAHL, PsycINFO and The Cochrane Library) were searched to identify peer-reviewed articles published from database inception to August 2018. Search terms identified peer-reviewed English language qualitative, quantitative and mixed methods studies that underwent independent screening by two authors. Full texts were independently reviewed by two reviewers and data were independently extracted by one reviewer before being checked by a second reviewer. Adherence to the 10 activities embedded within the eight-stage EBCD framework was calculated for each study.ResultsWe identified 20 studies predominantly from the UK and in acute mental health or cancer services. EBCD fidelity ranged from 40% to 100% with only three studies satisfying 100% fidelity.ConclusionEBCD is used predominantly for quality improvement, but has potential to be used for intervention design projects. There is variation in the use of EBCD, with many studies eliminating or modifying some EBCD stages. Moreover, there is no consistency in reporting. In order to evaluate the effect of modifying EBCD or levels of EBCD fidelity, the outcomes of each EBCD phase (ie, touchpoints and improvement activities) should be reported in a consistent manner.Trial registration numberCRD42018105879.

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