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1.
PLoS Med ; 18(9): e1003766, 2021 09.
Article in English | MEDLINE | ID: covidwho-1470656

ABSTRACT

BACKGROUND: Amodiaquine is a 4-aminoquinoline antimalarial similar to chloroquine that is used extensively for the treatment and prevention of malaria. Data on the cardiovascular effects of amodiaquine are scarce, although transient effects on cardiac electrophysiology (electrocardiographic QT interval prolongation and sinus bradycardia) have been observed. We conducted an individual patient data meta-analysis to characterise the cardiovascular effects of amodiaquine and thereby support development of risk minimisation measures to improve the safety of this important antimalarial. METHODS AND FINDINGS: Studies of amodiaquine for the treatment or prevention of malaria were identified from a systematic review. Heart rates and QT intervals with study-specific heart rate correction (QTcS) were compared within studies and individual patient data pooled for multivariable linear mixed effects regression. The meta-analysis included 2,681 patients from 4 randomised controlled trials evaluating artemisinin-based combination therapies (ACTs) containing amodiaquine (n = 725), lumefantrine (n = 499), piperaquine (n = 716), and pyronaridine (n = 566), as well as monotherapy with chloroquine (n = 175) for uncomplicated malaria. Amodiaquine prolonged QTcS (mean = 16.9 ms, 95% CI: 15.0 to 18.8) less than chloroquine (21.9 ms, 18.3 to 25.6, p = 0.0069) and piperaquine (19.2 ms, 15.8 to 20.5, p = 0.0495), but more than lumefantrine (5.6 ms, 2.9 to 8.2, p < 0.001) and pyronaridine (-1.2 ms, -3.6 to +1.3, p < 0.001). In individuals aged ≥12 years, amodiaquine reduced heart rate (mean reduction = 15.2 beats per minute [bpm], 95% CI: 13.4 to 17.0) more than piperaquine (10.5 bpm, 7.7 to 13.3, p = 0.0013), lumefantrine (9.3 bpm, 6.4 to 12.2, p < 0.001), pyronaridine (6.6 bpm, 4.0 to 9.3, p < 0.001), and chloroquine (5.9 bpm, 3.2 to 8.5, p < 0.001) and was associated with a higher risk of potentially symptomatic sinus bradycardia (≤50 bpm) than lumefantrine (risk difference: 14.8%, 95% CI: 5.4 to 24.3, p = 0.0021) and chloroquine (risk difference: 8.0%, 95% CI: 4.0 to 12.0, p < 0.001). The effect of amodiaquine on the heart rate of children aged <12 years compared with other antimalarials was not clinically significant. Study limitations include the unavailability of individual patient-level adverse event data for most included participants, but no serious complications were documented. CONCLUSIONS: While caution is advised in the use of amodiaquine in patients aged ≥12 years with concomitant use of heart rate-reducing medications, serious cardiac conduction disorders, or risk factors for torsade de pointes, there have been no serious cardiovascular events reported after amodiaquine in widespread use over 7 decades. Amodiaquine and structurally related antimalarials in the World Health Organization (WHO)-recommended dose regimens alone or in ACTs are safe for the treatment and prevention of malaria.


Subject(s)
Amodiaquine/adverse effects , Antimalarials/adverse effects , Bradycardia/chemically induced , Heart Conduction System/drug effects , Heart Rate/drug effects , Long QT Syndrome/chemically induced , Adolescent , Adult , Bradycardia/diagnosis , Bradycardia/physiopathology , Cardiotoxicity , Child , Child, Preschool , Female , Heart Conduction System/physiopathology , Humans , Infant , Long QT Syndrome/diagnosis , Long QT Syndrome/physiopathology , Male , Middle Aged , Randomized Controlled Trials as Topic , Risk Assessment , Risk Factors , Young Adult
3.
Cochrane Database Syst Rev ; 4: CD013582, 2020 04 21.
Article in English | MEDLINE | ID: covidwho-1372688

ABSTRACT

BACKGROUND: This review is one of a series of rapid reviews that Cochrane contributors have prepared to inform the 2020 COVID-19 pandemic. When new respiratory infectious diseases become widespread, such as during the COVID-19 pandemic, healthcare workers' adherence to infection prevention and control (IPC) guidelines becomes even more important. Strategies in these guidelines include the use of personal protective equipment (PPE) such as masks, face shields, gloves and gowns; the separation of patients with respiratory infections from others; and stricter cleaning routines. These strategies can be difficult and time-consuming to adhere to in practice. Authorities and healthcare facilities therefore need to consider how best to support healthcare workers to implement them. OBJECTIVES: To identify barriers and facilitators to healthcare workers' adherence to IPC guidelines for respiratory infectious diseases. SEARCH METHODS: We searched OVID MEDLINE on 26 March 2020. As we searched only one database due to time constraints, we also undertook a rigorous and comprehensive scoping exercise and search of the reference lists of key papers. We did not apply any date limit or language limits. SELECTION CRITERIA: We included qualitative and mixed-methods studies (with a distinct qualitative component) that focused on the experiences and perceptions of healthcare workers towards factors that impact on their ability to adhere to IPC guidelines for respiratory infectious diseases. We included studies of any type of healthcare worker with responsibility for patient care. We included studies that focused on IPC guidelines (local, national or international) for respiratory infectious diseases in any healthcare setting. These selection criteria were framed by an understanding of the needs of health workers during the COVID-19 pandemic. DATA COLLECTION AND ANALYSIS: Four review authors independently assessed the titles, abstracts and full texts identified by our search. We used a prespecified sampling frame to sample from the eligible studies, aiming to capture a range of respiratory infectious disease types, geographical spread and data-rich studies. We extracted data using a data extraction form designed for this synthesis. We assessed methodological limitations using an adapted version of the Critical Skills Appraisal Programme (CASP) tool. We used a 'best fit framework approach' to analyse and synthesise the evidence. This provided upfront analytical categories, with scope for further thematic analysis. We used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in each finding. We examined each review finding to identify factors that may influence intervention implementation and developed implications for practice. MAIN RESULTS: We found 36 relevant studies and sampled 20 of these studies for our analysis. Ten of these studies were from Asia, four from Africa, four from Central and North America and two from Australia. The studies explored the views and experiences of nurses, doctors and other healthcare workers when dealing with severe acute respiratory syndrome (SARS), H1N1, MERS (Middle East respiratory syndrome), tuberculosis (TB), or seasonal influenza. Most of these healthcare workers worked in hospitals; others worked in primary and community care settings. Our review points to several barriers and facilitators that influenced healthcare workers' ability to adhere to IPC guidelines. The following factors are based on findings assessed as of moderate to high confidence. Healthcare workers felt unsure as to how to adhere to local guidelines when they were long and ambiguous or did not reflect national or international guidelines. They could feel overwhelmed because local guidelines were constantly changing. They also described how IPC strategies led to increased workloads and fatigue, for instance because they had to use PPE and take on additional cleaning. Healthcare workers described how their responses to IPC guidelines were influenced by the level of support they felt that they received from their management team. Clear communication about IPC guidelines was seen as vital. But healthcare workers pointed to a lack of training about the infection itself and about how to use PPE. They also thought it was a problem when training was not mandatory. Sufficient space to isolate patients was also seen as vital. A lack of isolation rooms, anterooms and shower facilities was a problem. Other important practical measures described by healthcare workers included minimising overcrowding, fast-tracking infected patients, restricting visitors, and providing easy access to handwashing facilities. A lack of PPE, and equipment that was of poor quality, was a serious concern for healthcare workers and managers. They also pointed to the need to adjust the volume of supplies as infection outbreaks continued. Healthcare workers believed that they followed IPC guidance more closely when they saw the value of it. Some healthcare workers felt motivated to follow the guidance because of fear of infecting themselves or their families, or because they felt responsible for their patients. Some healthcare workers found it difficult to use masks and other equipment when it made patients feel isolated, frightened or stigmatised. Healthcare workers also found masks and other equipment uncomfortable to use. The workplace culture could also influence whether healthcare workers followed IPC guidelines or not. Across many of the findings, healthcare workers pointed to the importance of including all staff, including cleaning staff, porters, kitchen staff and other support staff when implementing IPC guidelines. AUTHORS' CONCLUSIONS: Healthcare workers point to several factors that influence their ability and willingness to follow IPC guidelines when managing respiratory infectious diseases. These include factors tied to the guideline itself and how it is communicated, support from managers, workplace culture, training, physical space, access to and trust in personal protective equipment, and a desire to deliver good patient care. The review also highlights the importance of including all facility staff, including support staff, when implementing IPC guidelines.


Subject(s)
Coronavirus Infections , Cross Infection/prevention & control , Guideline Adherence , Health Personnel , Infection Control , Pandemics , Pneumonia, Viral , COVID-19 , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Guideline Adherence/standards , Health Knowledge, Attitudes, Practice , Humans , Pandemics/prevention & control , Patient Isolation , Personal Protective Equipment , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Practice Guidelines as Topic , Universal Precautions
4.
Occup Environ Med ; 78(9): 679-690, 2021 09.
Article in English | MEDLINE | ID: covidwho-1362002

ABSTRACT

OBJECTIVES: To synthesise evidence concerning the range of filtering respirators suitable for patient care and guide the selection and use of different respirator types. DESIGN: Comparative analysis of international standards for respirators and rapid review of their performance and impact in healthcare. DATA SOURCES: Websites of international standards organisations, Medline and Embase, hand-searching of references and citations. STUDY SELECTION: Studies of healthcare workers (including students) using disposable or reusable respirators with a range of designs. We examined respirator performance, clinician adherence and performance, comfort and impact, and perceptions of use. RESULTS: We included standards from eight authorities across Europe, North and South America, Asia and Australasia and 39 research studies. There were four main findings. First, international standards for respirators apply across workplace settings and are broadly comparable across jurisdictions. Second, effective and safe respirator use depends on proper fitting and fit testing. Third, all respirator types carry a burden to the user of discomfort and interference with communication which may limit their safe use over long periods; studies suggest that they have little impact on specific clinical skills in the short term but there is limited evidence on the impact of prolonged wearing. Finally, some clinical activities, particularly chest compressions, reduce the performance of filtering facepiece respirators. CONCLUSION: A wide range of respirator types and models is available for use in patient care during respiratory pandemics. Careful consideration of performance and impact of respirators is needed to maximise protection of healthcare workers and minimise disruption to care.


Subject(s)
COVID-19/epidemiology , Disposable Equipment/statistics & numerical data , Equipment Reuse/statistics & numerical data , Ventilators, Mechanical/statistics & numerical data , Disposable Equipment/standards , Equipment Reuse/standards , Health Personnel/statistics & numerical data , Humans , Pandemics/statistics & numerical data , Ventilators, Mechanical/standards
5.
R Soc Open Sci ; 8(4): 210235, 2021 Apr 13.
Article in English | MEDLINE | ID: covidwho-1231061

ABSTRACT

Hydroxychloroquine (HCQ), the hydroxyl derivative of chloroquine (CQ), is widely used in the treatment of rheumatological conditions (systemic lupus erythematosus, rheumatoid arthritis) and is being studied for the treatment and prevention of COVID-19. Here, we investigate through mathematical modelling the safety profile of HCQ, CQ and other QT-prolonging anti-infective agents to determine their risk categories for Torsade de Pointes (TdP) arrhythmia. We performed safety modelling with uncertainty quantification using a risk classifier based on the qNet torsade metric score, a measure of the net charge carried by major currents during the action potential under inhibition of multiple ion channels by a compound. Modelling results for HCQ at a maximum free therapeutic plasma concentration (free C max) of approximately 1.2 µM (malaria dosing) indicated it is most likely to be in the high-intermediate-risk category for TdP, whereas CQ at a free C max of approximately 0.7 µM was predicted to most likely lie in the intermediate-risk category. Combining HCQ with the antibacterial moxifloxacin or the anti-malarial halofantrine (HAL) increased the degree of human ventricular action potential duration prolongation at some or all concentrations investigated, and was predicted to increase risk compared to HCQ alone. The combination of HCQ/HAL was predicted to be the riskiest for the free C max values investigated, whereas azithromycin administered individually was predicted to pose the lowest risk. Our simulation approach highlights that the torsadogenic potentials of HCQ, CQ and other QT-prolonging anti-infectives used in COVID-19 prevention and treatment increase with concentration and in combination with other QT-prolonging drugs.

6.
J Infect ; 82(6): 276-316, 2021 06.
Article in English | MEDLINE | ID: covidwho-1131509

ABSTRACT

OBJECTIVE: Our objective was to describe the characteristics of patients admitted, discharged and readmitted, due to COVID-19, to a central London acute-care hospital during the second peak, in particular in relation to corticosteroids use. METHODS: We reviewed patients admitted from the community to University College Hospital (UCH) with COVID-19 as their primary diagnosis between 1st-31st December 2020. Re-attendance and readmission data were collected for patients who re-presented within 10 days following discharge. Data were retrospectively collected. RESULTS: 196 patients were admitted from the community with a diagnosis of COVID-19 and discharged alive in December 2020. Corticosteroids were prescribed in hospital for a median of 5 days (IQR 3-8). 20 patients (10.2%) were readmitted within 10 days. 11/20 received corticosteroids in the first admission of which 10 had received 1-3 days of corticosteroids. Readmission rate in those receiving 1-3 days of corticosteroids was 25%. CONCLUSIONS: Most international guidelines have recommended providing up to 10 days of corticosteroids for severe COVID-19 but stopping on discharge. Our findings show shorter courses of corticosteroids during admission are associated with an increased risk of being readmitted and support continuing the course of corticosteroids after hospital discharge monitored in the virtual ward setting.


Subject(s)
COVID-19 , Patient Readmission , Adrenal Cortex Hormones/therapeutic use , Humans , London/epidemiology , Patient Discharge , Retrospective Studies , SARS-CoV-2 , United States
7.
Ann Work Expo Health ; 65(4): 373-376, 2021 05 03.
Article in English | MEDLINE | ID: covidwho-1045892

ABSTRACT

The COVID-19 pandemic raised considerable challenges to obtain reliable guidance to help occupational health practitioners, workers, and stakeholders building up efficient prevention strategies at the workplace, between the constant increase of publications in the domain, the time required to run high-quality research and systematic reviews, and the urgent need to identify areas for prevention at the workplace. Social Media and Twitter, in particular, have already been used in research and constitute a useful source of information to identify community needs and topics of interest for prevention in the meatpacking industry. In this commentary, we introduce the methods and tools we used to screen relevant posts on Twitter. Twitter analytics is a way to capture real-time concerns of the community and help ensure compliance with the notion of social accountability. As such research has limitations in terms of exhaustiveness and level of evidence, it should be considered as provisional guidance to direct both actions at the workplace and further conventional research projects.


Subject(s)
COVID-19 , Occupational Exposure , Social Media , Humans , Pandemics , SARS-CoV-2
8.
Clin Infect Pract ; 9: 100059, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-959698

ABSTRACT

BACKGROUND: Venous thrombo-embolism is now well-recognised as a common complication of severe COVID-19 disease. Arterial thrombosis has been less well recognised, although it is increasingly reported, mostly in the context of myocardial infarction and stroke. CASE REPORT: A 63-year-old man developed a pale, cold foot with an absent dorsalis pedis pulse 7 days into his admission with COVID-19. A CT angiogram demonstrated a large thrombus in the lower thoracic aorta, which had not been present on CT pulmonary angiogram the preceding week, along with occlusion of both popliteal arteries. He was managed with therapeutic dose of low molecular weight heparin (LMWH) for 6 weeks. RESULTS: This case adds to the growing list of potential sites and consequences of thrombosis in COVID-19. CONCLUSION: This case underscores the urgent need for pathophysiological studies and clinical trials to target treatments and guidelines for thromboprophylaxis in COVID-19.

9.
Syst Rev ; 9(1): 256, 2020 11 04.
Article in English | MEDLINE | ID: covidwho-937144

ABSTRACT

BACKGROUND: The COVID-19 pandemic has created a sense of urgency in the research community in their bid to contribute to the evidence required for healthcare policy decisions. With such urgency, researchers experience methodological challenges to maintain the rigour and transparency of their work. With this in mind, we offer reflections on our recent experience of undertaking a rapid Cochrane qualitative evidence synthesis (QES). METHODS: This process paper, using a reflexive approach, describes a rapid QES prepared during, and in response to, the COVID-19 pandemic. FINDINGS: This paper reports the methodological decisions we made and the process we undertook. We place our decisions in the context of guidance offered in relation to rapid reviews and previously conducted QESs. We highlight some of the challenges we encountered in finding the balance between the time needed for thoughtfulness and comprehensiveness whilst providing a rapid response to an urgent request for evidence. CONCLUSION: The need for more guidance on rapid QES remains, but such guidance needs to be based on actual worked examples and case studies. This paper and the reflections offered may provide a useful framework for others to use and further develop.


Subject(s)
Coronavirus Infections , Decision Making , Evidence-Based Medicine , Pandemics , Pneumonia, Viral , Publishing , Research Design , Review Literature as Topic , Betacoronavirus , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Data Accuracy , Humans , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Qualitative Research , SARS-CoV-2
10.
Infect Control Hosp Epidemiol ; 42(1): 75-83, 2021 01.
Article in English | MEDLINE | ID: covidwho-892014

ABSTRACT

BACKGROUND: Shortages of personal protective equipment during the coronavirus disease 2019 (COVID-19) pandemic have led to the extended use or reuse of single-use respirators and surgical masks by frontline healthcare workers. The evidence base underpinning such practices warrants examination. OBJECTIVES: To synthesize current guidance and systematic review evidence on extended use, reuse, or reprocessing of single-use surgical masks or filtering face-piece respirators. DATA SOURCES: We used the World Health Organization, the European Centre for Disease Prevention and Control, the US Centers for Disease Control and Prevention, and Public Health England websites to identify guidance. We used Medline, PubMed, Epistemonikos, Cochrane Database, and preprint servers for systematic reviews. METHODS: Two reviewers conducted screening and data extraction. The quality of included systematic reviews was appraised using AMSTAR-2. Findings were narratively synthesized. RESULTS: In total, 6 guidance documents were identified. Levels of detail and consistency across documents varied. They included 4 high-quality systematic reviews: 3 focused on reprocessing (decontamination) of N95 respirators and 1 focused on reprocessing of surgical masks. Vaporized hydrogen peroxide and ultraviolet germicidal irradiation were highlighted as the most promising reprocessing methods, but evidence on the relative efficacy and safety of different methods was limited. We found no well-established methods for reprocessing respirators at scale. CONCLUSIONS: Evidence on the impact of extended use and reuse of surgical masks and respirators is limited, and gaps and inconsistencies exist in current guidance. Where extended use or reuse is being practiced, healthcare organizations should ensure that policies and systems are in place to ensure these practices are carried out safely and in line with available guidance.


Subject(s)
COVID-19 , Equipment Reuse/standards , Infection Control/instrumentation , Masks/virology , N95 Respirators/virology , SARS-CoV-2/isolation & purification , COVID-19/epidemiology , COVID-19/prevention & control , Humans , Infection Control/methods , Practice Guidelines as Topic , Risk Management/methods , Risk Management/standards
11.
BMJ Open Respir Res ; 7(1)2020 10.
Article in English | MEDLINE | ID: covidwho-844386

ABSTRACT

In the context of covid-19, aerosol generating procedures have been highlighted as requiring a higher grade of personal protective equipment. We investigated how official guidance documents and academic publications have classified procedures in terms of whether or not they are aerosol-generating. We performed a rapid systematic review using preferred reporting items for systematic reviews and meta-analyses standards. Guidelines, policy documents and academic papers published in english or french offering guidance on aerosol-generating procedures were eligible. We systematically searched two medical databases (medline, cochrane central) and one public search engine (google) in march and april 2020. Data on how each procedure was classified by each source were extracted. We determined the level of agreement across different guidelines for each procedure group, in terms of its classification as aerosol generating, possibly aerosol-generating, or nonaerosol-generating. 128 documents met our inclusion criteria; they contained 1248 mentions of procedures that we categorised into 39 procedure groups. Procedures classified as aerosol-generating or possibly aerosol-generating by ≥90% of documents included autopsy, surgery/postmortem procedures with high-speed devices, intubation and extubation procedures, bronchoscopy, sputum induction, manual ventilation, airway suctioning, cardiopulmonary resuscitation, tracheostomy and tracheostomy procedures, non-invasive ventilation, high-flow oxygen therapy, breaking closed ventilation systems, nebulised or aerosol therapy, and high frequency oscillatory ventilation. Disagreements existed between sources on some procedure groups, including oral and dental procedures, upper gastrointestinal endoscopy, thoracic surgery and procedures, and nasopharyngeal and oropharyngeal swabbing. There is sufficient evidence of agreement across different international guidelines to classify certain procedure groups as aerosol generating. However, some clinically relevant procedures received surprisingly little mention in our source documents. To reduce dissent on the remainder, we recommend that (a) clinicians define procedures more clearly and specifically, breaking them down into their constituent components where possible; (b) researchers undertake further studies of aerosolisation during these procedures; and (c) guideline-making and policy-making bodies address a wider range of procedures.


Subject(s)
Aerosols/classification , Betacoronavirus , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , COVID-19 , Databases, Factual , Humans , SARS-CoV-2
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