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Impact of mRNA vaccines in curtailing SARS-CoV-2 infection and disability leave utilisation among healthcare workers during the COVID-19 pandemic: cross-sectional analysis from a tertiary healthcare system in the Greater Houston metropolitan area

Por: Vahidy · F. S. · Pan · A. P. · Hagan · K. · Bako · A. T. · Sostman · H. D. · Schwartz · R. L. · Phillips · R. · Boom · M. L.
Objectives

We provide an account of real-world effectiveness of COVID-19 vaccines among healthcare workers (HCWs) at a tertiary healthcare system and report trends in SARS-CoV-2 infections and subsequent utilisation of COVID-19-specific short-term disability leave (STDL).

Design

Cross-sectional study.

Setting and participants

Summary data on 27 291 employees at a tertiary healthcare system in the Greater Houston metropolitan area between 15 December 2020 and 5 June 2021. The initial 12-week vaccination programme period (15 December 2020 to 6 March 2021) was defined as a rapid roll-out phase.

Main outcomes and measures

At the pandemic onset, HCW testing and surveillance was conducted where SARS-CoV-2-positive HCWs were offered STDL. Deidentified summary data of SARS-CoV-2 infections and STDL utilisation among HCWs were analysed. Prevaccination and postvaccination trends in SARS-CoV-2 positivity and STDL utilisation rates were evaluated.

Results

Updated for 5 June 2021, 98.2% (n=26 791) of employees received a full or partial dose of one of the approved mRNA COVID-19 vaccines. The vaccination rate during the rapid roll-out phase was approximately 3700 doses/7 days. The overall mean weekly SARS-CoV-2 positivity rates among HCWs were significantly lower following vaccine roll-out (2.4%), compared with prevaccination period (11.8%, p

Conclusion

Despite limited generalisability of regional hospital-based studies—where factors such as the emergence of viral variants and population-level vaccine penetrance may differ—accounts of robust HCW vaccination programmes provide important guidance for sustaining a critical resource to provide safe and effective care for patients with and without COVID-19 across healthcare systems.

Minimising exposure to respiratory droplets, 'jet riders and aerosols in air-conditioned hospital rooms by a 'Shield-and-Sink strategy

Por: Hunziker · P.
Objectives

In COVID-19, transfer of respiratory materials transmits disease and drives the pandemic but the interplay of droplet and aerosol physics, physiology and environment is not fully understood. To advance understanding of disease transmission mechanisms and to find novel exposure minimisation strategies, we studied cough-driven material transport modes and the efficacy of control strategies.

Design

Computer simulations and real-world experiments were used for integrating an intensive care setting, multiphysics and physiology. Patient-focused airflow management and air purification strategies were examined computationally and validated by submicron particle exhalation imaging in volunteers.

Setting

Hospital setting during a respiratory virus pandemic with transmission by respiratory droplets and aerosols.

Participants

Healthy volunteers.

Outcome measures

Distribution of, and exposure to, potentially infectious respiratory secretions.

Results

Respiratory materials ejected by cough exhibited four transport modes: long-distance ballistic, short-distance ballistic, ‘jet rider’ and aerosol modes. Interaction with air conditioning driven flow contaminated a hospital room rapidly. Different than large droplets or aerosols, jet rider droplets travelled with the turbulent air jet initially, but fell out at a distance, were not well eliminated by air conditioning and exposed bystanders at larger distance and longer time; their size predisposes them to preferential capture in the nasal mucosa, the primordial COVID-19 infection site. ‘Cough shields’ captured large droplets but induced lateral dispersion of aerosols and jet riders. An air purification device alone had limited efficacy. A Shield and Sink’ approach combining cough shields with ‘virus sinks’ minimised exposure to all secretions in modelling and real-life experiments.

Conclusions

Jet riders have characteristics of highly efficient respiratory infection vectors and may play a role in COVID-19 transmission. Exposure to all droplet types can be minimised through an easily implemented Shield and Sink strategy.

Immunosuppression reduction when administering a booster dose of the BNT162b2 mRNA SARS-CoV-2 vaccine in kidney transplant recipients without adequate humoral response following two vaccine doses: protocol for a randomised controlled trial (BECAME study)

Por: Yahav · D. · Rozen-Zvi · B. · Mashraki · T. · Atamna · A. · Ben-Zvi · H. · Bar-Haim · E. · Rahamimov · R.
Introduction

Inadequate antibody response to mRNA SARS-CoV-2 vaccination has been described among kidney transplant recipients. Immunosuppression level and specifically, use of antimetabolite in the maintenance immunosuppressive regimen, are associated with inadequate response. In light of the severe consequences of COVID-19 in solid organ transplant recipients, we believe it is justified to examine new vaccination strategies in these patients.

Methods and analysis

BECAME is a single-centre, open-label, investigator-initiated randomised controlled, superiority trial, aiming to compare immunosuppression reduction combined with a third BNT162b2 vaccine dose versus third dose alone. The primary outcome will be seropositivity rate against SARS-CoV-2. A sample size of 154 patients was calculated for the seropositivity endpoint assuming 25% seropositivity in the control group and 50% in the intervention group. A sample of participants per arm will be also tested for T-cell response. We also plan to perform a prospective observational study, evaluating seropositivity among ~350 kidney transplant recipients consenting to receive a third vaccine dose, who are not eligible for the randomised controlled trial.

Ethics and dissemination

The trial is approved by local ethics committee of Rabin Medical Center (RMC-0192-21). All participants will be required to provide written informed consent. Results of this trial will be published; trial data will be available. Protocol amendments will be submitted to the local ethics committee.

Trail registration number

NCT04961229.

Infectious diseases experts as part of the antibiotic stewardship team in primary care: protocol for a cluster-randomised blinded study (IDASP)

Por: Ronda · M. · Padulles · A. · Simonet · P. · Rodriguez · G. · Estrada · C. · Lerida · A. · Ferro · J. J. · Cobo · S. · Tubau · F. · Gardenes · L. · Freixedas · R. · Lopez · M. · Carrera · E. · Pallares · N. · Tebe · C. · Carratala · J. · Puig-Asensio · M. · Shaw · E.
Introduction

Antibiotic overuse is directly related to antibiotic resistance, and primary care is one of the main reasons for this overuse. This study aims to demonstrate that including experts on infectious diseases (ID) within the antimicrobial stewardship (AMS) programme team in primary care settings achieves higher reductions in overall antibiotic consumption and increases the quality of prescription.

Methods and analysis

A multicentre, cluster-randomised, blinded clinical trial will be conducted between 2021 and 2023. Six primary care centres will be randomly assigned to an advanced or a standard AMS programme. The advanced AMS programme will consist of a standard AMS programme combined with the possibility that general practitioners (GP) will discuss patients’ therapies with ID experts telephonically during working days and biweekly meetings. The main endpoint will be overall antibiotic consumption, defined as daily defined dose per 1000 inhabitants per day (DHD). Secondary end-points will be: (1) unnecessary antibiotic prescriptions in patients diagnosed with upper respiratory tract or urinary tract infection, (2) adequacy of antibiotic prescription, (3) reattendance to GP or emergency room within 30 days after the initial GP visit and (4) hospital admissions for any reason within 30 days after the GP visit. Two secondary endpoints (unnecessary antibiotic therapy and adequacy of therapy) will be evaluated by blinded investigators.

We will select three clusters (centres) per arm (coverage of 147 644 inhabitants) which will allow the rejection of the null hypothesis of equal consumption with a power of 80%, assuming a moderate intracluster correlation of 0.2, an intracluster variance of 4 and a mean difference of 1 DHD. The type I error will be set at 5%.

Ethics and dissemination

The protocol was reviewed and approved by local ethics committees. The results of this study will be published in peer-reviewed journals and presented at medical conferences.

Trial registration number

NCT04848883

Invasive pneumococcal disease, pneumococcal pneumonia and all-cause pneumonia in Hong Kong during the COVID-19 pandemic compared with the preceding 5 years: a retrospective observational study

Por: Chan · K.-P. F. · Ma · T.-F. · Ip · M. S.-M. · Ho · P.-L.
Objectives

To compare the incidence and severity of invasive pneumococcal diseases (IPDs), pneumococcal pneumonia and all-cause pneumonia during the COVID-19 pandemic period with universal masking and social distancing with that of previous 5 years.

Design

Retrospective observational study on incidence of IPDs, pneumococcal pneumonia and all-cause pneumonia between January 2015–December 2019 and March 2020–March 2021. January–February 2020 was excluded from analysis as it was treated as a transitional period between normal time and pandemic.

Setting

Episode-based data by retrieval of hospitalisation records from the Hospital Authority’s territory-wide electronic medical record database in Hong Kong.

Participants

Hospitalised patients with IPD (n=742), pneumococcal pneumonia (n=2163) and all-cause pneumonia (including COVID-19 pneumonia, n=453 999) aged 18 years or above. Control diagnoses were included to assess confounding from health-seeking behaviours.

Primary and secondary outcomes

Primary outcome is the incidence of diseases between two periods. Secondary outcomes include disease severity surrogated by length of stay and mortality.

Results

Monthly average number of IPD, pneumococcal pneumonia and all-cause pneumonia hospitalisation significantly decreased by 88.9% (95% CI 79.8% to 98.0%, p

Conclusions

Incidence of IPD, pneumococcal pneumonia and all-cause pneumonia decreased during the COVID-19 pandemic. This was observed with universal masking and social distancing. We postulated this is related to reduced transmission of respiratory viruses and bacteria.

Association between previous rheumatoid arthritis and COVID-19 and its severity: a nationwide cohort study in South Korea

Por: Jung · Y. · Kwon · M. · Choi · H. G.
Objectives

The prevalence of rheumatoid arthritis (RA) among patients with COVID-19 and the association between RA and the outcome of COVID-19 remain unclear. We aimed to compare the prevalence of RA between participants with and without COVID-19; we then analysed the association between the presence of RA and the severity of COVID-19.

Design

A cross-sectional study.

Setting

Data from a nationwide COVID-19 cohort database by the Korea National Health Insurance Corporation were used.

Participants and interventions

A total of 8070 patients with COVID-19 (1 January 2020 through 4 June 2020) were matched with 32 280 control participants with regard to age, sex and income. Patients with COVID-19 were confirmed by SARS-CoV-2 PCR and controls were collected from the database. RA was confirmed using the diagnostic code (International Classification of Disease, Tenth Revision) and medication claim codes. Conditional/unconditional logistic regression was applied to analyse the association between RA and COVID-19.

Primary outcome and secondary outcome

Laboratory confirmation of SARS-CoV-2 infection was defined as the primary outcome. The secondary outcome was severe COVID-19 defined as a history of intensive care unit admission, invasive ventilation or death.

Results

The prevalence of RA in the COVID-19 (0.4%, 35/8070) and control (0.4%, 121/32,280) groups did not differ (p=0.446). After adjusting for underlying diseases, no association between RA and COVID-19 was observed (adjusted OR=1.14, 95% CI: 0.78 to 1.67) and COVID-19 severity was not associated with RA (adjusted OR=0.62, 95% CI: 0.14 to 7.29). The overall mortality rate was 2.9% (237/8070) and RA was not significantly associated with mortality (adjusted OR=1.64, 95% CI: 0.33 to 8.15).

Conclusion

We did not find an association between the presence of RA and COVID-19. In addition, RA was not associated with the severity of COVID-19.

Dutch multicentre, prospective follow-up, cohort study comparing the neurological and neuropsychological sequelae of hospitalised non-ICU- and ICU-treated COVID-19 survivors: a study protocol

Por: Klinkhammer · S. · Horn · J. · Visser-Meilij · J. M. A. · Verwijk · E. · Duits · A. · Slooter · A. J. C. · van Heugten · C. M. · the NeNeSCo study group · Aries · van Bussel · Jansen · Janssen · Postma · Santen · Magdelijns · Posthuma · van der Woude · Otten · Karakus · Bronsveld
Introduction

Owing to the novelty of COVID-19, there are still large knowledge gaps concerning its effect on the brain and the resulting impact on peoples’ lives. This large-scale prospective follow-up study investigates COVID-19-associated brain damage, neuropsychological dysfunction and long-term impact on the well-being of patients and their close ones. It is hypothesised that structural brain damage and cognitive dysfunction primarily occur in severely ill patients, as compared with moderately ill patients. Cognitive complaints, emotional distress and impact on well-being are hypothesised to be less dependent on illness severity.

Methods and analysis

For this multicentre study, 200 patients with COVID-19 (100 intensive care unit (ICU) patients and 100 non-ICU patients) formerly hospitalised in one of the six recruiting hospitals during the first European infection wave (ie, March to June 2020) and their close ones will be recruited. At minimally 6 months posthospital discharge, patients will perform a set of neuropsychological tests and are subjected to a 3T MRI scan. Patients and close ones will fill out a set of questionnaires, also at minimally 6 months posthospital discharge and again another 6 months thereafter. Data related to COVID-19 hospitalisation will be extracted from the patients’ medical records. MRI abnormalities will ultimately be related to neuropsychological test performance and questionnaire outcomes.

Ethics and dissemination

Ethics approval was granted by the medical research ethics committee of Maastricht University Medical Centre and Maastricht University (NL75102.068.20). The project is sponsored by The Brain Foundation Netherlands. Findings will be presented at national and international conferences, as well as published in peer-reviewed scientific journals.

Trial registration number

NCT04745611.

Community engagement approaches for malaria prevention, control and elimination: a scoping review protocol

Por: Awasthi · K. R. · Jancey · J. · Clements · A. C. A. · Leavy · J. E.

Community engagement (CE) is important for malaria prevention, control and ultimately elimination. As the decline of malaria has plateaued over the last 5 years, strengthening CE approaches will be necessary to enhance health promotion practice and policy to drive malaria transmission down further. Countries have adopted a wide range of public health intervention approaches for malaria prevention and control that best suit their context. This review will examine the existing evidence on the various CE approaches adopted by malaria programmes across the world and their outcomes.

Methodology and analysis

The review methodology will follow the updated Joanna Briggs Institute guide for scoping review, 2017, which is based on the framework developed by Arksey and O’Malley and further developed by Levac Colquhoun and O’Brien. Proquest, Web of Knowledge and Medline will be searched for publications from January 2000 to 31 March 2021 while Google search engine will be used to find any grey literature. The eligibility criteria will be as follows: review will include primary studies written in the English language using appropriate study designs and methods, including quantitative, qualitative and mixed methods designs; and case, programme or project reports. Information on CE approaches designed specifically for malaria prevention, control, elimination and their outcomes will be explored. Subheadings and free text terms for ‘community engagement’ and ‘malaria’ will be used for the search. The article screening and data extraction will be examined by two reviewers after the initial search, and any disputes will be resolved by a third reviewer through discussion. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews guide will be used to present the review methods and the results from the search. The scoping review results will identify and map the available evidences, sources of information and research gaps in the area of CE as one approach for malaria prevention, control and/or elimination.

Ethics and dissemination

This study only aims to review secondary sources and does not require human research ethics committee approval. The findings of the scoping review will be submitted to a peer-reviewed journal for wider dissemination.

Clinical value of laboratory indicators for predicting disease progression and death in patients with COVID-19: a retrospective cohort study

Por: Wang · Q. · Cheng · J. · Shang · J. · Wang · Y. · Wan · J. · Yan · Y.-q. · Liu · W.-b. · Zhang · H.-P. · Wang · J.-p. · Wang · X.-y. · Li · Z.-a. · Lin · J.
Objectives

As early prediction of severe illness and death for patients with coronavirus disease 2019 (COVID-19) is important, we aim to explore the clinical value of laboratory indicators in evaluating the progression and prognosis of patients with COVID-19.

Design

Retrospective cohort study.

Setting

Hospital-based study in China.

Participants

Adult patients with COVID-19 from December 15, 2019 to March 15, 2020.

End point

Disease severity and mortality.

Methods

Clinical data of 638 patients with COVID-19 were collected and compared between severe and non-severe groups. The predictive ability of laboratory indicators in disease progression and prognosis of COVID-19 was analysed using the receiver operating characteristic curve. The survival differences of COVID-19 patients with different levels of laboratory indicators were analysed utilising Kaplan-Meier analysis.

Results

29.8% (190/638) of patients with COVID-19 progressed to severe. Compared with patients with no adverse events, C reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and D-dimer were significantly higher in severe patients with adverse events, such as acute myocardial injury, respiratory failure, acute kidney injury, mechanical ventilation, intensive care unit admission, multiple organ dysfunction syndromes and death (all p

Conclusions

The combination of CRP, NLR and D-dimer could be an effective predictor for the aggravation and death in patients with COVID-19. The abnormal expression of these indicators might suggest a strong inflammatory response and multiple adverse events in patients with severe COVID-19.

Barriers and facilitators to accessing tuberculosis care in Nepal: a qualitative study to inform the design of a socioeconomic support intervention

Por: Dixit · K. · Biermann · O. · Rai · B. · Aryal · T. P. · Mishra · G. · Teixeira de Siqueira-Filha · N. · Paudel · P. R. · Pandit · R. N. · Sah · M. K. · Majhi · G. · Levy · J. · Rest · J. v. · Gurung · S. C. · Dhital · R. · Lönnroth · K. · Squire · S. B. · Caws · M. · Sidney · K. · Wingfi
Objective

Psychosocial and economic (socioeconomic) barriers, including poverty, stigma and catastrophic costs, impede access to tuberculosis (TB) services in low-income countries. We aimed to characterise the socioeconomic barriers and facilitators of accessing TB services in Nepal to inform the design of a locally appropriate socioeconomic support intervention for TB-affected households.

Design

From August 2018 to July 2019, we conducted an exploratory qualitative study consisting of semistructured focus group discussions (FGDs) with purposively selected multisectoral stakeholders. The data were managed in NVivo V.12, coded by consensus and analysed thematically.

Setting

The study was conducted in four districts, Makwanpur, Chitwan, Dhanusha and Mahottari, which have a high prevalence of poverty and TB.

Participants

Seven FGDs were conducted with 54 in-country stakeholders, grouped by stakeholders, including people with TB (n=21), community stakeholders (n=13) and multidisciplinary TB healthcare professionals (n=20) from the National TB Programme.

Results

The perceived socioeconomic barriers to accessing TB services were: inadequate TB knowledge and advocacy; high food and transportation costs; income loss and stigma. The perceived facilitators to accessing TB care and services were: enhanced championing and awareness-raising about TB and TB services; social protection including health insurance; cash, vouchers and/or nutritional allowance to cover food and travel costs; and psychosocial support and counselling integrated with existing adherence counselling from the National TB Programme.

Conclusion

These results suggest that support interventions that integrate TB education, psychosocial counselling and expand on existing cash transfer schemes would be locally appropriate and could address the socioeconomic barriers to accessing and engaging with TB services faced by TB-affected households in Nepal. The findings have been used to inform the design of a socioeconomic support intervention for TB-affected households. The acceptability, feasibility and impact of this intervention on TB-related costs, stigma and TB treatment outcomes, is now being evaluated in a pilot implementation study in Nepal.

Factors associated with COVID-19 viral and antibody test positivity and assessment of test concordance: a retrospective cohort study using electronic health records from the USA

Por: Lindsay · L. · Secrest · M. H. · Rizzo · S. · Keebler · D. S. · Yang · F. · Tsai · L.
Objectives

To identify factors associated with COVID-19 test positivity and assess viral and antibody test concordance.

Design

Observational retrospective cohort study.

Setting

Optum de-identified electronic health records including over 700 hospitals and 7000 clinics in the USA.

Participants

There were 891 754 patients who had a COVID-19 test identified in their electronic health record between 20 February 2020 and 10 July 2020.

Primary and secondary outcome measures

Per cent of viral and antibody tests positive for COVID-19 (‘positivity rate’); adjusted ORs for factors associated with COVID-19 viral and antibody test positivity; and per cent concordance between positive viral and subsequent antibody test results.

Results

Overall positivity rate was 9% (70 472 of 771 278) and 12% (11 094 of 91 741) for viral and antibody tests, respectively. Positivity rate was inversely associated with the number of individuals tested and decreased over time across regions and race/ethnicities. Antibody test concordance among patients with an initial positive viral test was 91% (71%–95% depending on time between tests). Among tests separated by at least 2 weeks, discordant results occurred in 7% of patients and 9% of immunocompromised patients. Factors associated with increased odds of viral and antibody positivity in multivariable models included: male sex, Hispanic or non-Hispanic black or Asian race/ethnicity, uninsured or Medicaid insurance and Northeast residence. We identified a negative dose effect between the number of comorbidities and viral and antibody test positivity. Paediatric patients had reduced odds (OR=0.60, 95% CI 0.57 to 0.64) of a positive viral test but increased odds (OR=1.90, 95% CI 1.62 to 2.23) of a positive antibody test compared with those aged 18–34 years old.

Conclusions

This study identified sociodemographic and clinical factors associated with COVID-19 test positivity and provided real-world evidence demonstrating high antibody test concordance among viral-positive patients.

Assessing feasibility of establishing antimicrobial stewardship programmes in two provincial-level hospitals in Vietnam: an implementation research study

Por: Huong · V. T. L. · Ngan · T. T. D. · Thao · H. P. · Quang · L. M. · Hanh · T. T. T. · Hien · N. T. · Duc · T. · Vinh · V. H. · Duc · C. M. · Dung Em · V. T. H. · Bay · P. V. B. · Oanh · N. T. T. · Hang · P. T. T. · Tu · N. T. C. · Quan · T. A. · Kesteman · T. · Dodds Ashley · E. · Anders
Objectives

To investigate the feasibility of establishing hospital-based antimicrobial stewardship (AMS) programmes comprising action-planning, educational interventions and data feedback in two provincial-level hospitals in Viet Nam.

Design and setting

This was an implementation research using participatory action process and existing resources from the Duke Antimicrobial Stewardship Outreach Network with local adjustments. A national stakeholder meeting and Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis were conducted to identify gaps and potential interventions.

Participants

Hospital AMS staff implemented activities throughout the study phases. Routinely collected patient data were analysed to support planning, implementation and evaluation.

Interventions

Hospitals were considered as a complex adaptive system and leveraged their unique characteristics and interconnections to develop 1-year plans containing core interventions (data use, educational training, prospective audit with feedback (PAF) and evaluations).

Outcome measures

We assessed feasibility using outputs from stakeholder meeting, SWOT analysis, baseline data, planning process and implementation.

Results

The stakeholder meeting identified three gaps for AMS at national level: supportive policies, AMS training and core competencies and collaboration. At the hospitals, AMS programmes took 1 year for planning due to lack of hospital-specific procedures and relevant staff competencies. Baseline data (January–December 2019) showed variations in antibiotic consumption: 951 days of therapy (DOT) per 1000 days present in the control and 496 in the intervention wards in hospital 1, and 737 and 714 in hospital 2, respectively. During 1-year implementation, clinical pharmacists audited 1890 antibiotic prescriptions in hospital 1 (June 2020–May 2021) and 1628 in hospital 2 (July 2020–July 2021), and will continue PAF in their daily work.

Conclusion

Our data confirmed the need to contextualise AMS programmes in low-income and middle-income countries (LMICs) and demonstrated the usefulness of implementation research design in assessing programme feasibility. Developing staff competencies, using local data to stimulate actions and integrating programme activities in routine hospital work are key to success in LMICs.

The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH): protocol for a prospective longitudinal cohort study of healthcare and ancillary workers in UK healthcare settings

Por: Woolf · K. · Melbourne · C. · Bryant · L. · Guyatt · A. L. · McManus · I. C. · Gupta · A. · Free · R. C. · Nellums · L. · Carr · S. · John · C. · Martin · C. A. · Wain · L. V. · Gray · L. J. · Garwood · C. · Modhwadia · V. · Abrams · K. R. · Tobin · M. D. · Khunti · K. · Pareek · M. · on beh
Introduction

The COVID-19 pandemic has resulted in significant morbidity and mortality and devastated economies globally. Among groups at increased risk are healthcare workers (HCWs) and ethnic minority groups. Emerging evidence suggests that HCWs from ethnic minority groups are at increased risk of adverse COVID-19-related outcomes. To date, there has been no large-scale analysis of these risks in UK HCWs or ancillary workers in healthcare settings, stratified by ethnicity or occupation, and adjusted for confounders. This paper reports the protocol for a prospective longitudinal questionnaire study of UK HCWs, as part of the UK-REACH programme (The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers).

Methods and analysis

A baseline questionnaire will be administered to a national cohort of UK HCWs and ancillary workers in healthcare settings, and those registered with UK healthcare regulators, with follow-up questionnaires administered at 4 and 8 months. With consent, questionnaire data will be linked to health records with 25-year follow-up. Univariate associations between ethnicity and clinical COVID-19 outcomes, physical and mental health, and key confounders/explanatory variables will be tested. Multivariable analyses will test for associations between ethnicity and key outcomes adjusted for the confounder/explanatory variables. We will model changes over time by ethnic group, facilitating understanding of absolute and relative risks in different ethnic groups, and generalisability of findings.

Ethics and dissemination

The study is approved by Health Research Authority (reference 20/HRA/4718), and carries minimal risk. We aim to manage the small risk of participant distress about questions on sensitive topics by clearly participant information that the questionnaire covers sensitive topics and there is no obligation to answer these or any other questions, and by providing support organisation links. Results will be disseminated with reports to Government and papers submitted to pre-print servers and peer reviewed journals.

Trial registration number

ISRCTN11811602; Pre-results.

Cohort profile: a migratory cohort study of US Marines who train in Australia

Por: Chan-Cuzydlo · A. · Harrison · D. J. · Pike · B. L. · Currie · B. J. · Mayo · M. · Salvador · M. G. · Hulsey · W. R. · Azzarello · J. · Ellis · J. · Kim · D. · King-Lewis · W. · Smith · J. N. · Rodriguez · B. · Maves · R. C. · Lawler · J. V. · Schully · K. L.
Purpose

In 2012, US Marines and Sailors began annual deployments to Australia to participate in joint training exercises with the Australian Defence Force and other partners in the region. During their training, US service members are exposed to a variety of infectious disease threats not normally encountered by American citizens. This paper describes a cohort of US Marines and Sailors enrolled during five rotations to Australia between 2016 and 2020.

Participants

Study participation is strictly voluntary. Group informational sessions are held prior to deployment to describe the study structure and goals, as well as the infectious disease threats that participants may encounter while in Australia. All participants provided written informed consent. Consented participants complete a pre-deployment questionnaire to collect data including basic demographic information, military occupational specialty, travel history, family history, basic health status and personal habits such as alcohol consumption. Blood is collected for serum, plasma and peripheral blood mononuclear cells (PBMC) processing. Data and specimen collection is repeated up to three times: before, during and after deployment.

Findings to date

From the five rotations that comprised the 2016–2020 Marine Rotational Force-Darwin, we enrolled 1289 volunteers. Enrolments during this period were overwhelmingly white male under the age of 24 years. Most of the enrollees were junior enlisted and non-commissioned officers, with a smaller number of staff non-commissioned officers and commissioned officers, and minimal warrant officers. Over half of the enrollees had occupational specialty designations for infantry.

Future plans

In the future, we will screen samples for serological evidence of infection with Burkholderia pseudomallei, Coxiella burnetii, Ross River virus, SARS-CoV-2 and other operationally relevant pathogens endemic in Australia. Antigenic stimulation assays will be performed on PBMCs collected from seropositive individuals to characterise the immune response to these infections in this healthy American population.

Development of influenza-associated disease burden pyramid in Shanghai, China, 2010-2017: a Bayesian modelling study

Por: Li · J. · Wang · C. · Ruan · L. · Jin · S. · Ye · C. · Yu · H. · Zhu · W. · Wang · X.
Objectives

Negative estimates can be produced when statistical modelling techniques are applied to estimate morbidity and mortality attributable to influenza. Based on the prior knowledge that influenza viruses are hazardous pathogens and have adverse health outcomes of respiratory and circulatory disease (R&C), we developed an improved model incorporating Bayes’ theorem to estimate the disease burden of influenza in Shanghai, China, from 2010 to 2017.

Design

A modelling study using aggregated data from administrative systems on weekly R&C mortality and hospitalisation, influenza surveillance and meteorological data. We constrained the regression coefficients for influenza activity to be positive by truncating the prior distributions at zero.

Setting

Shanghai, China.

Participants

People registered with R&C deaths (450 298) and hospitalisations (2621 787, from 1 July 2013), and with influenza-like illness (ILI) outpatient visits (342 149) between 4 January 2010 and 31 December 2017.

Primary outcome measures

Influenza-associated disease burden (mortality, hospitalisation and outpatient visit rates) and clinical severity (outpatient–mortality, outpatient–hospitalisation and hospitalisation–mortality risks).

Results

Influenza was associated with an annual average of 15.49 (95% credibility interval (CrI) 9.06–22.06) excess R&C deaths, 100.65 (95% CrI 48.79–156.78) excess R&C hospitalisations and 914.95 (95% CrI 798.51–1023.66) excess ILI outpatient visits per 100 000 population in Shanghai. 97.23% and 80.24% excess R&C deaths and hospitalisations occurred in people aged ≥65 years. More than half of excess morbidity and mortality were associated with influenza A(H3N2) virus, and its severities were 1.65-fold to 3.54-fold and 1.47-fold to 2.16-fold higher than that for influenza A(H1N1) and B viruses, respectively.

Conclusions

The proposed Bayesian approach with reasonable prior information improved estimates of influenza-associated disease burden. Influenza A(H3N2) virus was generally associated with higher morbidity and mortality, and was relatively more severe compared with influenza A(H1N1) and B viruses. Targeted influenza prevention and control strategies for the elderly in Shanghai may substantially reduce the disease burden.

External validation of the 4C Mortality Score for patients with COVID-19 and pre-existing cardiovascular diseases/risk factors

Por: Kuroda · S. · Matsumoto · S. · Sano · T. · Kitai · T. · Yonetsu · T. · Kohsaka · S. · Torii · S. · Kishi · T. · Komuro · I. · Hirata · K.-i. · Node · K. · Matsue · Y.
Objectives

Predictive algorithms to inform risk management decisions are needed for patients with COVID-19, although the traditional risk scores have not been adequately assessed in Asian patients. We aimed to evaluate the performance of a COVID-19-specific prediction model, the 4C (Coronavirus Clinical Characterisation Consortium) Mortality Score, along with other conventional critical care risk models in Japanese nationwide registry data.

Design

Retrospective cohort study.

Setting and participants

Hospitalised patients with COVID-19 and cardiovascular disease or coronary risk factors from January to May 2020 in 49 hospitals in Japan.

Main outcome measures

Two different types of outcomes, in-hospital mortality and a composite outcome, defined as the need for invasive mechanical ventilation and mortality.

Results

The risk scores for 693 patients were tested by predicting in-hospital mortality for all patients and composite endpoint among those not intubated at baseline (n=659). The number of events was 108 (15.6%) for mortality and 178 (27.0%) for composite endpoints. After missing values were multiply imputed, the performance of the 4C Mortality Score was assessed and compared with three prediction models that have shown good discriminatory ability (RISE UP score, A-DROP score and the Rapid Emergency Medicine Score (REMS)). The area under the receiver operating characteristic curve (AUC) for the 4C Mortality Score was 0.84 (95% CI 0.80 to 0.88) for in-hospital mortality and 0.78 (95% CI 0.74 to 0.81) for the composite endpoint. It showed greater discriminatory ability compared with other scores, except for the RISE UP score, for predicting in-hospital mortality (AUC: 0.82, 95% CI 0.78 to 0.86). Similarly, the 4C Mortality Score showed a positive net reclassification improvement index over the A-DROP and REMS for mortality and over all three scores for the composite endpoint. The 4C Mortality Score model showed good calibration, regardless of outcome.

Conclusions

The 4C Mortality Score performed well in an independent external COVID-19 cohort and may enable appropriate disposition of patients and allocation of medical resources.

Trial registration number UMIN000040598.

Utility of the FebriDx point-of-care assay in supporting a triage algorithm for medical admissions with possible COVID-19: an observational cohort study

Por: Houston · H. · Deas · G. · Naik · S. · Shah · K. · Patel · S. · Greca Dottori · M. · Tay · M. · Filson · S. A. · Biggin-Lamming · J. · Ross · J. · Vaughan · N. · Vaid · N. · Gopal Rao · G. · Amin · A. K. · Gupta-Wright · A. · John · L.
Objective

To evaluate a triage algorithm used to identify and isolate patients with suspected COVID-19 among medical patients needing admission to hospital using simple clinical criteria and the FebriDx assay.

Design

Retrospective observational cohort.

Setting

Large acute National Health Service hospital in London, UK.

Participants

All medical admissions from the emergency department between 10 August 2020 and 4 November 2020 with a valid SARS-CoV-2 RT-PCR result.

Interventions

Medical admissions were triaged as likely, possible or unlikely COVID-19 based on clinical criteria. Patients triaged as possible COVID-19 underwent FebriDx lateral flow assay on capillary blood, and those positive for myxovirus resistance protein A (a host response protein) were managed as likely COVID-19.

Primary outcome measures

Diagnostic accuracy (sensitivity, specificity and predictive values) of the algorithm and the FebriDx assay using SARS-CoV-2 RT-PCR from nasopharyngeal swabs as the reference standard.

Results

4.0% (136) of 3443 medical admissions had RT-PCR confirmed COVID-19. Prevalence of COVID-19 was 46% (80/175) in those triaged as likely, 4.1% (50/1225) in possible and 0.3% (6/2033) in unlikely COVID-19. Using a SARS-CoV-2 RT-PCR reference standard, clinical triage had sensitivity of 96% (95% CI 91% to 98%) and specificity of 61.5% (95% CI 59.8% to 63.1%), while the triage algorithm including FebriDx had sensitivity of 93% (95% CI 87% to 96%) and specificity of 86.4% (95% CI 85.2% to 87.5%). While 2033 patients were deemed not to require isolation using clinical criteria alone, the addition of FebriDx to clinical triage allowed a further 826 patients to be released from isolation, reducing the need for isolation rooms by 9.5 per day, 95% CI 8.9 to 10.2. Ten patients missed by the algorithm had mild or asymptomatic COVID-19.

Conclusions

A triage algorithm including the FebriDx assay had good sensitivity and was useful to ‘rule-out’ COVID-19 among medical admissions to hospital.

Association between cytokine levels, sepsis severity and clinical outcomes in sepsis: a quantitative systematic review protocol

Por: Gharamti · A. · Samara · O. · Monzon · A. · Scherger · S. · DeSanto · K. · Sillau · S. · Franco-Paredes · C. · Henao-Martinez · A. · Shapiro · L.
Introduction

It is widely assumed that sepsis is a life-threatening systemic inflammation caused by a dysregulated host response to infection mediated by an increase in multiple proinflammatory cytokines. The levels of key proinflammatory cytokines tumour necrosis factor, interleukin-1β and interferon are poorly characterised during sepsis. We believe this project will produce a ‘gold-standard’ document to which other reports on cytokine levels will be compared. The objective of this systematic review will be to identify key cytokine circulating levels in patients with sepsis and assess the association between these levels and morbidity and mortality outcomes related to sepsis.

Methods and analysis

We would include reports of any design except for case reports. Sepsis patients will comprise those with a diagnosis of sepsis, severe sepsis or septic shock. The primary exposure is levels of three proinflammatory cytokines. The primary outcome is mortality at 28 or 30 days. Study subjects can be of any age, sex or ethnicity. Studies will be restricted to the English language. Medline, Embase, Cochrane Library and Web of Science Core Collection will be searched for eligible studies. A database search will include studies from 1985 to May 2020. Two reviewers will independently screen and select studies, assess methodological quality and extract data. A meta-analysis will be performed, if possible, and the Grading of Recommendations Assessment Development and Evaluation Summary of Findings presented.

Ethics and dissemination

Formal ethical approval is not required as data will be extracted from existing literature. This systematic review will be disseminated through a peer-reviewed publication and at conference meetings.

PROSPERO registration number

CRD42020179800.

Host blood transcriptomic biomarkers of tuberculosis disease in people living with HIV: a systematic review protocol

Por: Mendelsohn · S. C. · Mulenga · H. · Mbandi · S. K. · Darboe · F. · Shelton · M. · Scriba · T. J. · Hatherill · M.
Introduction

Current tuberculosis triage and predictive tools offer poor accuracy and are ineffective for detecting asymptomatic disease in people living with HIV (PLHIV). Host tuberculosis transcriptomic biomarkers hold promise for diagnosing prevalent and predicting progression to incident tuberculosis and guiding further investigation, preventive therapy and follow-up. We aim to conduct a systematic review of performance of transcriptomic signatures of tuberculosis in PLHIV.

Methods and analysis

We will search MEDLINE (PubMed), WOS Core Collection, Biological Abstracts, and SciELO Citation Index (Web of Science), Africa-Wide Information and General Science Abstracts (EBSCOhost), Scopus, and Cochrane Central Register of Controlled Trials databases for articles published in English between 1990 and 2020. Case–control, cross-sectional, cohort and randomised controlled studies evaluating performance of diagnostic and prognostic host-response transcriptomic signatures in PLHIV of all ages and settings will be included. Eligible studies will include PLHIV in signature test or validation cohorts, and use microbiological, clinical, or composite reference standards for pulmonary or extrapulmonary tuberculosis diagnosis. Study quality will be evaluated using the ‘Quality Assessment of Diagnostic Accuracy Studies-2’ tool and cumulative review evidence assessed using the ‘Grading of Recommendations Assessment, Development and Evaluation’ approach. Study selection, quality appraisal and data extraction will be performed independently by two reviewers. Study, cohort and signature characteristics of included studies will be tabulated, and a narrative synthesis of findings presented. Primary outcomes of interest, biomarker sensitivity and specificity with estimate precision, will be summarised in forest plots. Expected heterogeneity in signature characteristics, study settings, and study designs precludes meta-analysis and pooling of results. Review reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies guidelines.

Ethics and dissemination

Formal ethics approval is not required as primary human participant data will not be collected. Results will be disseminated through peer-reviewed publication and conference presentation.

PROSPERO registration number

CRD42021224155.

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial

Por: Grillo · S. · Cuervo · G. · Carratala · J. · San-Juan · R. · Aguado · J. M. · Morata · L. · Gomez-Zorrilla · S. · Lopez-Contreras · J. · Gasch · O. · Gomila-Grange · A. · Iftimie · S. · Garcia-Pardo · G. · Calbo · E. · Boix-Palop · L. · Oriol · I. · Jover-Saenz · A. · Lopez-Cortes · L.
Introduction

Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia.

Methods

We will perform a superiority, randomised, open-label, phase IV–III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician.

Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation).

We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant).

Ethics and dissemination

Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders.

Trial registration number

The protocol has been approved by AEMPS with the Trial Registration Number EudraCT 2018-001207-37. ClinicalTrials.gov Identifier: NCT03959345; Pre-results.

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