Factors that impact on recruitment to vaccine trials in the context of a pandemic or epidemic: a qualitative evidence synthesis.

BACKGROUND: The World Health Organization declared the COVID-19 pandemic on 11 March 2020. Vaccine development and deployment were swiftly prioritised as a method to manage and control disease spread. The development of an effective vaccine relies on people's participation in randomised trials. Recruitment to vaccine trials is particularly challenging as it involves healthy volunteers who may have concerns around the potential risks and benefits associated with rapidly developed vaccines. OBJECTIVES: To explore the factors that influence a person's decision to participate in a vaccine trial in the context of a pandemic or epidemic. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was June 2021. SELECTION CRITERIA: We included qualitative studies and mixed-methods studies with an identifiable qualitative component. We included studies that explored the perspectives of adults aged 18 years or older who were invited to take part in vaccine trials in the context of a pandemic or epidemic. DATA COLLECTION AND ANALYSIS: We assessed the title, abstracts and full texts identified by the search. We used a sampling frame to identify data-rich studies that represented a range of diseases and geographical spread. We used QSR NVivo to manage extracted data. We assessed methodological limitations using an adapted version of the Critical Skills Appraisal Programme (CASP) tool for qualitative studies. We used the 'best-fit framework approach' to analyse and synthesise the evidence from our included studies. We then used the Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) assessment to assess our confidence in each finding and develop implications for practice. MAIN RESULTS: We included 34 studies in our review. Most studies related to HIV vaccine trials. The other studies related to Ebola virus, tuberculosis, Zika virus and COVID-19. We developed 20 key findings, under three broad themes (with seven subthemes), that described the factors that people consider when deciding whether to take part in a vaccine trial for a pandemic or epidemic disease. Our GRADE-CERQual confidence was high in nine of the key findings, moderate in 10 key findings and low in one key finding. The main reason for downgrading review findings were concerns regarding the relevance and adequacy of the underlying data. As a result of the over-representation of HIV studies, our GRADE-CERQual assessment of some findings was downgraded in terms of relevance because the views described may not reflect those of people regarding vaccine trials for other pandemic or epidemic diseases. Adequacy relates to the degree of richness and quantity of data supporting a review finding. Moderate concerns about adequacy resulted in a downgrading of some review findings. Some factors were considered to be under the control of the trial team. These included how trial information was communicated and the inclusion of people in the community to help with trial information dissemination. Aspects of trial design were also considered under control of the trial team and included convenience of participation, provision of financial incentives and access to additional support services for those taking part in the trial. Other factors influencing people's decision to take part could be personal, from family, friends or wider society. From a personal perceptive, people had concerns about vaccine side effects, vaccine efficacy and possible impact on their daily lives (carer responsibilities, work, etc.). People were also influenced by their families, and the impact participation may have on relationships. The fear of stigma from society influenced the decision to take part. Also, from a societal perspective, the level of trust in governments' involvement in research and trial may influence a person's decision. Finally, the perceived rewards, both personal and societal, were influencing factors on the decision to participate. Personal rewards included access to a vaccine, improved health and improved disease knowledge, and a return to normality in the context of a pandemic or epidemic. Potential societal rewards included helping the community and contributing to science, often motivated by the memories of family and friends who had died from the disease. AUTHORS' CONCLUSIONS: This review identifies many of the factors that influence a person's decision to take part in a vaccine trial, and these reflect findings from reviews that examine trials more broadly. However, we also recognise some factors that become more important in connection with a vaccine trial in the context of a pandemic or epidemic. These factors include the potential stigma of taking part, the possible adverse effects of a vaccine, the added motivation for helping society, the role of community leaders in trial dissemination, and the level of trust placed in governments and companies developing vaccines. These specific influences need to be considered by trial teams when designing, and communicating about, vaccine trials in the context of a pandemic or epidemic.

Raising awareness of antimicrobial resistance: development of an 'antibiotic footprint calculator'.

Non-academic partners can be vital in successful public engagement activities on antimicrobial resistance. With collaboration between academic and non-academic partners, we developed and launched an open-access web-based application, the 'antibiotic footprint calculator', in both Thai and English. The application focused on a good user experience, addressing antibiotic overuse and its impact, and encouraging immediate action. The application was unveiled in joint public engagement activities. From 1 Nov 2021 to 31 July 2022 (9 month period), 2554 players estimated their personal antibiotic footprint by using the application.

Zinc supplementation for preventing mortality, morbidity, and growth failure in children aged 6 months to 12 years.

BACKGROUND: Zinc deficiency is prevalent in low- and middle-income countries, and is considered a significant risk factor for morbidity, mortality, and linear growth failure. The effectiveness of preventive zinc supplementation in reducing prevalence of zinc deficiency needs to be assessed. OBJECTIVES: To assess the effects of zinc supplementation for preventing mortality and morbidity, and for promoting growth, in children aged 6 months to 12 years. SEARCH METHODS: A previous version of this review was published in 2014. In this update, we searched CENTRAL, MEDLINE, Embase, five other databases, and one trials register up to February 2022, together with reference checking and contact with study authors to identify additional studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) of preventive zinc supplementation in children aged 6 months to 12 years compared with no intervention, a placebo, or a waiting list control. We excluded hospitalized children and children with chronic diseases or conditions. We excluded food fortification or intake, sprinkles, and therapeutic interventions. DATA COLLECTION AND ANALYSIS: Two review authors screened studies, extracted data, and assessed the risk of bias. We contacted study authors for missing information and used GRADE to assess the certainty of evidence. The primary outcomes of this review were all-cause mortality; and cause-specific mortality, due to all-cause diarrhea, lower respiratory tract infection (LRTI, including pneumonia), and malaria. We also collected information on a number of secondary outcomes, such as those related to diarrhea and LRTI morbidity, growth outcomes and serum levels of micronutrients, and adverse events. MAIN RESULTS: We included 16 new studies in this review, resulting in a total of 96 RCTs with 219,584 eligible participants. The included studies were conducted in 34 countries; 87 of them in low- or middle-income countries. Most of the children included in this review were under five years of age. The intervention was delivered most commonly in the form of syrup as zinc sulfate, and the most common dose was between 10 mg and 15 mg daily. The median duration of follow-up was 26 weeks. We did not consider that the evidence for the key analyses of morbidity and mortality outcomes was affected by risk of bias. High-certainty evidence showed little to no difference in all-cause mortality with preventive zinc supplementation compared to no zinc (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.84 to 1.03; 16 studies, 17 comparisons, 143,474 participants). Moderate-certainty evidence showed that preventive zinc supplementation compared to no zinc likely results in little to no difference in mortality due to all-cause diarrhea (RR 0.95, 95% CI 0.69 to 1.31; 4 studies, 132,321 participants); but probably reduces mortality due to LRTI (RR 0.86, 95% CI 0.64 to 1.15; 3 studies, 132,063 participants) and mortality due to malaria (RR 0.90, 95% CI 0.77 to 1.06; 2 studies, 42,818 participants); however, the confidence intervals around the summary estimates for these outcomes were wide, and we could not rule out a possibility of increased risk of mortality. Preventive zinc supplementation likely reduces the incidence of all-cause diarrhea (RR 0.91, 95% CI 0.90 to 0.93; 39 studies, 19,468 participants; moderate-certainty evidence) but results in little to no difference in morbidity due to LRTI (RR 1.01, 95% CI 0.95 to 1.08; 19 studies, 10,555 participants; high-certainty evidence) compared to no zinc. There was moderate-certainty evidence that preventive zinc supplementation likely leads to a slight increase in height (standardized mean difference (SMD) 0.12, 95% CI 0.09 to 0.14; 74 studies, 20,720 participants). Zinc supplementation was associated with an increase in the number of participants with at least one vomiting episode (RR 1.29, 95% CI 1.14 to 1.46; 5 studies, 35,192 participants; high-certainty evidence). We report a number of other outcomes, including the effect of zinc supplementation on weight and serum markers such as zinc, hemoglobin, iron, copper, etc. We also performed a number of subgroup analyses and there was a consistent finding for a number of outcomes that co-supplementation of zinc with iron decreased the beneficial effect of zinc. AUTHORS' CONCLUSIONS: Even though we included 16 new studies in this update, the overall conclusions of the review remain unchanged. Zinc supplementation might help prevent episodes of diarrhea and improve growth slightly, particularly in children aged 6 months to 12 years of age. The benefits of preventive zinc supplementation may outweigh the harms in regions where the risk of zinc deficiency is relatively high.

Cardiovascular concentration-effect relationships of amodiaquine and its metabolite desethylamodiaquine: Clinical and preclinical studies.

AIMS: Amodiaquine is a 4-aminoquinoline used extensively for the treatment and prevention of malaria. Orally administered amodiaquine is largely converted to the active metabolite desethylamodiaquine. Amodiaquine can cause bradycardia, hypotension, and electrocardiograph QT interval prolongation, but the relationship of these changes to drug concentrations is not well characterized. METHODS: We conducted a secondary analysis of a pharmacokinetic study of the cardiac safety of amodiaquine (10 mg base/kg/day over 3 days) in 54 Kenyan adults (≥18 years) with uncomplicated malaria. Nonlinear mixed effects modelling was used to assess amodiaquine and desethylamodiaquine concentration-effect relationships for vital sign (pulse rate, blood pressure) and electrocardiograph interval (QT, QRS, PR) outcomes. We also measured the spontaneous beating heart rate after cumulative dosing of amodiaquine and desethylamodiaquine in isolated mouse atrial preparations. RESULTS: Amodiaquine and desethylamodiaquine caused concentration-dependent mean decreases in pulse rate (1.9 beats/min per 100 nmol/L; 95% confidence interval: 1.5-2.4), supine systolic blood pressure (1.7 mmHg per 100 nmol/L; 1.2-2.1), erect systolic blood pressure (1.5 mmHg per 100 nmol/L; 1.0-2.0) and erect diastolic blood pressure (1.4 mmHg per 100 nmol/L; 1.0-1.7). The mean QT interval prolongation was 1.4 ms per 100 nmol/L irrespective of correction factor after adjustment for residual heart rate dependency. There was no significant effect of drug concentration on postural change in blood pressure or PR and QRS intervals. In mouse atria, the spontaneous beating rate was significantly reduced by amodiaquine (n = 6) and desethylamodiaquine (n = 8) at 3 µmol/L (amodiaquine: 10 ± 2%; desethylamodiaquine: 12 ± 3%) and 10 µmol/L (amodiaquine: 50 ± 7%; desethylamodiaquine: 46 ± 6%) concentrations with no significant difference in potency between the 2 compounds. CONCLUSION: Amodiaquine and desethylamodiaquine have concentration-dependent effects on heart rate, blood pressure, and ventricular repolarization.

The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis.

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.

Cardiac TdP risk stratification modelling of anti-infective compounds including chloroquine and hydroxychloroquine.

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.

Short durations of corticosteroids for hospitalised COVID-19 patients are associated with a high readmission rate.

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.

Aortic thrombosis in COVID-19.

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.

Barreras y facilitadores del cumplimiento por parte de los trabajadores sanitarios de las directrices de prevención y control de infecciones para las enfermedades infecciosas respiratorias: una síntesis rápida de pruebas cualitativas / Barriers and facilitators to healthcare workers' adherence with infection prevention and control guidelines for respiratory infectious diseases: a rapid qualitative evidence synthesis

¿CUÁL ES EL OBJETIVO DE ESTA REVISIÓN?: Esta revisión es una de una serie de revisiones rápidas que los colaboradores de Cochrane han preparado para informar sobre la pandemia de COVID-19 de 2020. El objetivo de esta revisión Cochrane de investigación cualitativa ("síntesis de pruebas cualitativas") es explorar los factores que influyen en el cumplimiento por parte de los trabajadores sanitarios de las directrices de prevención y control de infecciones (PCI) para las enfermedades infecciosas respiratorias. Para responder a esta pregunta, se buscaron y analizaron estudios cualitativos sobre este tema. MENSAJES CLAVE: Los trabajadores de la salud señalan varios factores que influyen en su capacidad y disposición para seguir las directrices de PCI cuando se trata de enfermedades infecciosas respiratorias. Entre ellos figuran factores relacionados con la propia directriz y la forma en que se comunica, el apoyo de los directivos, la cultura del lugar de trabajo, la capacitación, el espacio físico, el acceso a los equipos de protección personal (EPI) y la confianza en ellos, y el deseo de prestar una buena atención al paciente. El examen también destaca la importancia de incluir a todo el personal de las instalaciones, incluido el personal de apoyo, al aplicar las directrices de PCI. ¿QUÉ SE HA ESTUDIADO EN ESTA REVISIÓN?: Cuando las enfermedades infecciosas respiratorias se generalizan, como durante la pandemia COVID-19, el uso de las estrategias de PCI por parte de los trabajadores sanitarios se hace aún más importante. Estas estrategias incluyen el uso de EPI como mascarillas, protectores faciales, guantes y batas; separar a los pacientes con infecciones respiratorias de los demás; y rutinas de limpieza más estrictas. Explorar la forma en que los trabajadores sanitarios ven y experimentan estas estrategias puede ayudar a las autoridades y a los centros sanitarios a aprender más sobre la mejor forma de apoyar a los trabajadores sanitarios para aplicarlas. ¿CUÁLES SON LOS DESCUBRIMIENTOS PRINCIPALES DE ESTA REVISIÓN?: Se encontraron 36 estudios relevantes y se tomaron muestras de 20 de estos para su análisis. Diez estudios eran de Asia, 4 de África, 4 de América del Norte y 2 de Australia. Los estudios exploraron las opiniones y experiencias de enfermeros, médicos y otros trabajadores de la salud al tratar el SARS, el H1N1, el MERS, la tuberculosis o la gripe estacional. La mayoría de estos trabajadores de la salud trabajaban en hospitales; otros trabajaban en entornos de atención primaria y comunitaria. Esta revisión señaló varios factores que influyeron en el cumplimiento de las pautas de PCI por parte de los trabajadores de la salud. Los siguientes factores se basan en los hallazgos evaluados como de confianza moderada a alta.- Los trabajadores sanitarios se sintieron inseguros cuando las guías locales eran largas, poco claras o no coincidían con las guías nacionales o internacionales.- Podían sentirse abrumados porque las directrices locales cambiaban constantemente.- También describieron como las estrategias de PCI conducían a un aumento de la carga de trabajo y de la fatiga, por ejemplo, porque tenían que utilizar los EPI y asumir una limpieza adicional.- Los trabajadores de la salud describieron cómo sus respuestas a las directrices de PCI se veían afectadas por el nivel de apoyo que sentían que recibían de su equipo directivo.- Se consideró vital una comunicación clara sobre las directrices de PCI.- El personal sanitario señaló la falta de formación sobre la infección en sí misma y sobre cómo utilizar los EPI.- También pensaban que era un problema cuando la formación no era obligatoria.- Tener suficiente espacio para aislar a los pacientes se consideró vital.- Demasiadas pocas habitaciones de aislamiento, antecámaras (pequeñas habitaciones que van de un pasillo a una sala de aislamiento) y duchas fueron un problema.- Otras medidas prácticas importantes descritas por los trabajadores sanitarios incluían la reducción al mínimo de las aglomeraciones de personas, la aceleración de los pacientes infectados, la restricción de las visitas y la facilitación del acceso a las instalaciones para lavarse las manos.- La falta de EPI, o que este fuese de mala calidad, era una preocupación grave para los trabajadores y administradores de la atención de la salud.- También destacaron la necesidad de ajustar la cantidad de suministros a medida que continuaban los brotes de infección.- Los trabajadores de la salud creían que seguían más de cerca la orientación de PCI cuando veían su valor.- Otros trabajadores de la salud se sentían motivados a seguir la guía por temor a infectarse a sí mismos y a sus familias, o porque se sentían responsables de sus pacientes.- Algunos trabajadores de la salud encontraron difícil usar máscaras y otros equipos cuando hacía que los pacientes se sintieran aislados, asustados o estigmatizados.- Los trabajadores sanitarios también encontraron incómodo el uso de máscaras y otros equipos.- La cultura del lugar de trabajo también puede influir en que los trabajadores sanitarios sigan o no las directrices de PCI.- En muchos de los hallazgos, los trabajadores sanitarios señalaron la importancia de incluir a todo el personal, incluido el personal de limpieza, los porteros, el personal de cocina y otro personal de apoyo al implementar las directrices de PCI. ¿CÓMO DE ACTUALIZADA ESTÁ ESTA REVISIÓN?: Se buscaron los estudios que se hubiesen publicado hasta marzo de 2020

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Performance and impact of disposable and reusable respirators for healthcare workers during pandemic respiratory disease: a rapid evidence review.

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.

Twitter Analytics to Inform Provisional Guidance for COVID-19 Challenges in the Meatpacking Industry.

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.

Extended use or reuse of single-use surgical masks and filtering face-piece respirators during the coronavirus disease 2019 (COVID-19) pandemic: A rapid systematic review.

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.

A QuESt for speed: rapid qualitative evidence syntheses as a response to the COVID-19 pandemic.

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.

Classification of aerosol-generating procedures: a rapid systematic review.

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.

COVID-19 prevention and treatment: A critical analysis of chloroquine and hydroxychloroquine clinical pharmacology.

Nicholas White and coauthors discuss chloroquine and hydroxychloroquine pharmacology in the context of possible treatment of SARS-CoV-2 infection.

Molecular epidemiology of resistance to antimalarial drugs in the Greater Mekong subregion: an observational study.

BACKGROUND: The Greater Mekong subregion is a recurrent source of antimalarial drug resistance in Plasmodium falciparum malaria. This study aimed to characterise the extent and spread of resistance across this entire region between 2007 and 2018. METHODS: P falciparum isolates from Myanmar, Thailand, Laos, and Cambodia were obtained from clinical trials and epidemiological studies done between Jan 1, 2007, and Dec 31, 2018, and were genotyped for molecular markers (pfkelch, pfcrt, pfplasmepsin2, and pfmdr1) of antimalarial drug resistance. Genetic relatedness was assessed using microsatellite and single nucleotide polymorphism typing of flanking sequences around target genes. FINDINGS: 10 632 isolates were genotyped. A single long pfkelch Cys580Tyr haplotype (from -50 kb to +31·5 kb) conferring artemisinin resistance (PfPailin) now dominates across the eastern Greater Mekong subregion. Piperaquine resistance associated with pfplasmepsin2 gene amplification and mutations in pfcrt downstream of the Lys76Thr chloroquine resistance locus has also developed. On the Thailand-Myanmar border a different pfkelch Cys580Tyr lineage rose to high frequencies before it was eliminated. Elsewhere in Myanmar the Cys580Tyr allele remains widespread at low allele frequencies. Meanwhile a single artemisinin-resistant pfkelch Phe446Ile haplotype has spread across Myanmar. Despite intense use of dihydroartemisinin-piperaquine in Kayin state, eastern Myanmar, both in treatment and mass drug administrations, no selection of piperaquine resistance markers was observed. pfmdr1 amplification, a marker of resistance to mefloquine, remains at low prevalence across the entire region. INTERPRETATION: Artemisinin resistance in P falciparum is now prevalent across the Greater Mekong subregion. In the eastern Greater Mekong subregion a multidrug resistant P falciparum lineage (PfPailin) dominates. In Myanmar a long pfkelch Phe446Ile haplotype has spread widely but, by contrast with the eastern Greater Mekong subregion, there is no indication of artemisinin combination therapy (ACT) partner drug resistance from genotyping known markers, and no evidence of spread of ACT resistant P falciparum from the east to the west. There is still a window of opportunity to prevent global spread of ACT resistance. FUNDING: Thailand Science Research and Innovation, Initiative 5%, Expertise France, Wellcome Trust.