Estimating the burden of antimicrobial resistance in Malawi: protocol for a prospective observational study of the morbidity, mortality and economic cost of third-generation cephalosporin resistant bloodstream infection

Introduction: Antimicrobial resistance is a global public health concern, but the problems are context specific, with each county or setting facing differing challenges. In Africa, third-generation cephalosporin resistant Enterobacterales (3GCR-E) are of particular concern, given the widespread reliance on ceftriaxone for treatment of severe infection in this setting. In Malawi, despite the rising prevalence of 3GCR-E, the health impact of these infections has not been described. This study is designed to estimate attributable mortality, morbidity and economic cost of 3GC-R bloodstream infection (BSI) in a large, urban hospital. Methods: This study will investigate the burden of antimicrobial resistance by recruiting a a prospective longitudinal cohort of patients who have bloodstream infection with 3GCR-E, at Queen Elizabeth Central Hospital, Blantyre, Malawi. Patients whose blood culture is positive for either 3GC-S or 3GC-R Enterobacterales will be enrolled and provide clinical and healthcare economic data. Patients will be followed throughout their hospital stay and to 6-months post discharge. Mortality, direct and indirect costs and other health outcomes will be compared between patients with 3GC-R and comparable 3GC-sensitive BSI. Based on our observation that some patients with clinical suspicion of sepsis and 3GC-R BSI are surviving without an effective antibiotic, we review each patient prospectively and classify what role the isolated bacteria is playing in the patient’s clinical presentation. These classifications will then be incorporated into our analysis. Ethics and dissemination: The study protocol has been approved by the Malawi College of Medicine Research Ethics Committee and by the Liverpool School of Tropical Medicine Research Ethics committee. Written informed consent will be obtained from study participants or their parents/guardians. Results will be submitted to international peer-reviewed journals, presented at international conferences and shared with participating communities and collaborators.

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Estimating the burden of antimicrobial resistance in Malawi: protocol for a prospective observational study of the morbidity, mortality and economic cost of third-generation cephalosporin resistant bloodstream infection

Wellcome Open Research ◽

10.12688/wellcomeopenres.15719.2 ◽

2020 ◽

Vol 5 ◽

pp. 29

Author(s):

Rebecca Lester ◽

Hendran Maheswaran ◽

Christopher P. Jewell ◽

David G. Lalloo ◽

Nicholas A. Feasey

Keyword(s):

Antimicrobial Resistance ◽

Blood Culture ◽

Research Ethics ◽

Bloodstream Infection ◽

Economic Cost ◽

Generation Cephalosporin ◽

Ethics Committee ◽

Third Generation ◽

Gram Negative ◽

Medicine Research

Introduction: Antimicrobial resistance (AMR) is a global public health concern, but the problems are context specific, with each county or setting facing differing challenges. In sub-Saharan Africa, third-generation cephalosporin resistant Enterobacterales (3GCR-E) are of particular concern, given the widespread reliance on ceftriaxone for treatment of severe infection in this setting. In Malawi, despite rising prevalence of 3GCR-E, the health-impact of these infections has not been described. This study is designed to estimate attributable mortality, morbidity and economic cost of 3GCR-E bloodstream infection (BSI) in a large, urban hospital. Methods: This study will investigate the burden of AMR by recruiting a a prospective longitudinal cohort of patients who have bloodstream infection with 3GCR-E, at Queen Elizabeth Central Hospital, Blantyre, Malawi. Patients whose blood culture is positive for either third-generation cephalosporin susceptible (3GC-S) or third-generation resistant (3GC-R) Enterobacterales will be enrolled and provide clinical and healthcare economic data. Patients will be followed throughout their hospital stay and to 6-months post discharge. The primary outcomes for the study are mortality and morbidity from 3GCR-E. Healthcare economic outcomes will be assessed by comparing healthcare provider costs, indirect patient costs and health-related quality of life outcomes in patients with 3GC-S and 3GC-R BSI. Based on our observation that some patients with clinical suspicion of sepsis and 3GC-R BSI are surviving without an effective antibiotic, we review each patient prospectively and classify what role the isolated bacteria is playing in the patient’s clinical presentation. Each BSI episode will be classified into the following categories: definite Gram-negative sepsis, probable Gram-negative sepsis, transient or occult bacteraemia, or contaminated blood culture. These classifications will be incorporated into our analysis. Ethics and dissemination: The study protocol has been approved by the Malawi College of Medicine Research Ethics Committee and by the Liverpool School of Tropical Medicine Research Ethics committee.

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Oxford Understanding Relationships, Sex, Power, Abuse and Consent Experiences (OUR SPACE) cross-sectional survey: a study protocol

BMJ Open ◽

10.1136/bmjopen-2021-051826 ◽

2021 ◽

Vol 11 (11) ◽

pp. e051826

Author(s):

Bridget Steele ◽

Michelle Degli Esposti ◽

Pete Mandeville ◽

Gillian Hamnett ◽

Elizabeth Nye ◽

...

Keyword(s):

Higher Education ◽

Sexual Violence ◽

Research Ethics ◽

Ethics Committee ◽

Health Concern ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Research Ethics Committee ◽

University Of Oxford ◽

The University

IntroductionSexual violence among higher education students is a public health concern, threatening the general safety of students, often with significant physical and mental health implications for victims. Establishing the prevalence estimates of sexual violence at higher education institutions (HEIs) is essential for designing and resourcing responses to sexual violence, including monitoring the effectiveness of prevention initiatives and institutional programmes. Yet, to date, there have been no rigorous studies assessing prevalence of sexual violence at HEIs in the UK.Methods and analysisInformed by guidance from Universities UK, the University of Oxford administration and the related student advocacy groups working within the University, Oxford Understanding Relationships, Sex, Power, Abuse and Consent Experiences is a cross-sectional survey of all undergraduate and graduate students over the age of 18 enrolled at the University of Oxford, UK. The survey design uses a complete sampling approach and measures adapted from previous campus climate surveys in the USA as well as the Sexual Experiences Survey (USA). The analysis will estimate the prevalence of sexual harassment and sexual violence perpetration and victimisation, and will examine whether ethnicity, gender identity, and sexual orientation are associated with these primary outcomes.Ethics and disseminationEthical approval was obtained by the Social Sciences and Humanities Interdivisional Research Ethics Committee at the University of Oxford which is a subcommittee of the Central University Research Ethics Committee (ref no.: R73805/RE001). The research team will disseminate findings through peer-reviewed journal articles and conference presentations. A report cowritten by authors and stakeholders will be shared with Oxford University students.

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Citizens, Research Ethics Committee Members and Researchers’ Attitude Toward Information and Consent for the Secondary Use of Health Data: Implications for Research Within Learning Health Systems

Journal of Empirical Research on Human Research Ethics ◽

10.1177/1556264621992214 ◽

2021 ◽

pp. 155626462199221

Author(s):

Annabelle Cumyn ◽

Roxanne Dault ◽

Adrien Barton ◽

Anne-Marie Cloutier ◽

Jean-François Ethier

Keyword(s):

Research Ethics ◽

Health Systems ◽

Ethics Committee ◽

Health Data ◽

Data Reuse ◽

Fundamental Importance ◽

Research Ethics Committee ◽

Secondary Use ◽

Public Perspectives ◽

Advance Knowledge

A survey was conducted to assess citizens, research ethics committee members, and researchers’ attitude toward information and consent for the secondary use of health data for research within learning health systems (LHSs). Results show that the reuse of health data for research to advance knowledge and improve care is valued by all parties; consent regarding health data reuse for research has fundamental importance particularly to citizens; and all respondents deemed important the existence of a secure website to support the information and consent processes. This survey was part of a larger project that aims at exploring public perspectives on alternate approaches to the current consent models for health data reuse to take into consideration the unique features of LHSs. The revised model will need to ensure that citizens are given the opportunity to be better informed about upcoming research and have their say, when possible, in the use of their data.

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Developing a policy to reduce the salt content of food consumed outside the home in Malaysia: protocol of a qualitative study

BMJ Open ◽

10.1136/bmjopen-2020-044628 ◽

2021 ◽

Vol 11 (7) ◽

pp. e044628

Author(s):

Mhairi Karen Brown ◽

Suzana Shahar ◽

Yee Xing You ◽

Viola Michael ◽

Hazreen Abdul Majid ◽

...

Keyword(s):

Medical Research ◽

Research Ethics ◽

Salt Intake ◽

Salt Content ◽

Ethics Committee ◽

Salt Reduction ◽

Reduction Strategy ◽

Research Ethics Committee ◽

School Canteen ◽

Medical Research Ethics

IntroductionCurrent salt intake in Malaysia is high. The existing national salt reduction policy has faced slow progress and does not yet include measures to address the out of home sector. Dishes consumed in the out of home sector are a known leading contributor to daily salt intake. This study aims to develop a salt reduction strategy, tailored to the out of home sector in Malaysia.Methods and analysisThis study is a qualitative analysis of stakeholder views towards salt reduction. Participants will be recruited from five zones of Malaysia (Western, Northern, Eastern and Southern regions and East Malaysia), including policy-makers, non-governmental organisations, food industries, school canteen operators, street food vendors and consumers, to participate in focus group discussions or in-depth interviews. Interviews will be transcribed and analysed using thematic analysis. Barriers will be identified and used to develop a tailored salt reduction strategy.Ethics and disseminationEthical approval has been obtained from the Universiti Kebangsaan Malaysia Medical Research Ethics Committee (UKM PPI/1118/JEP-2020–524), the Malaysian National Medical Research Ethics Committee (NMRR-20-1387-55481 (IIR)) and Queen Mary University of London Research Ethics Committee (QMERC2020/37) . Results will be presented orally and in report form and made available to the relevant ministries for example, Ministry of Health, Ministry of Education and Ministry of Trade to encourage adoption of strategy as policy. The findings of this study will be disseminated through conference presentations, peer-reviewed publications and webinars.

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Early Moves: a protocol for a population-based prospective cohort study to establish general movements as an early biomarker of cognitive impairment in infants

BMJ Open ◽

10.1136/bmjopen-2020-041695 ◽

2021 ◽

Vol 11 (4) ◽

pp. e041695

Author(s):

Catherine Elliott ◽

Caroline Alexander ◽

Alison Salt ◽

Alicia J Spittle ◽

Roslyn N Boyd ◽

...

Keyword(s):

At Risk ◽

Cohort Study ◽

Cognitive Impairment ◽

Research Ethics ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Ethics Committee ◽

Research Ethics Committee ◽

National Implementation ◽

General Movements

IntroductionThe current diagnostic pathways for cognitive impairment rarely identify babies at risk before 2 years of age. Very early detection and timely targeted intervention has potential to improve outcomes for these children and support them to reach their full life potential. Early Moves aims to identify early biomarkers, including general movements (GMs), for babies at risk of cognitive impairment, allowing early intervention within critical developmental windows to enable these children to have the best possible start to life.Method and analysisEarly Moves is a double-masked prospective cohort study that will recruit 3000 term and preterm babies from a secondary care setting. Early Moves will determine the diagnostic value of abnormal GMs (at writhing and fidgety age) for mild, moderate and severe cognitive delay at 2 years measured by the Bayley-4. Parents will use the Baby Moves smartphone application to video their babies’ GMs. Trained GMs assessors will be masked to any risk factors and assessors of the primary outcome will be masked to the GMs result. Automated scoring of GMs will be developed through applying machine-based learning to the data and the predictive value for an abnormal GM will be investigated. Screening algorithms for identification of children at risk of cognitive impairment, using the GM assessment (GMA), and routinely collected social and environmental profile data will be developed to allow more accurate prediction of cognitive outcome at 2 years. A cost evaluation for GMA implementation in preparation for national implementation will be undertaken including exploring the relationship between cognitive status and healthcare utilisation, medical costs, health-related quality of life and caregiver burden.Ethics and disseminationEthics approval has been granted by the Medical Research Ethics Committee of Joondalup Health Services and the Health Service Human Research Ethics Committee (1902) of Curtin University (HRE2019-0739).Trial registration numberACTRN12619001422112.

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Ceftolozane-tazobactam versus meropenem for definitive treatment of bloodstream infection due to extended-spectrum beta-lactamase (ESBL) and AmpC-producing Enterobacterales (“MERINO-3”): study protocol for a multicentre, open-label randomised non-inferiority trial

Trials ◽

10.1186/s13063-021-05206-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Adam G. Stewart ◽

Patrick N. A. Harris ◽

Mark D. Chatfield ◽

Roberta Littleford ◽

David L. Paterson

Keyword(s):

Bloodstream Infection ◽

Generation Cephalosporin ◽

Multidrug Resistant ◽

Definitive Treatment ◽

Resistant Organism ◽

Third Generation ◽

Beta Lactamase ◽

Open Label ◽

Extended Spectrum Beta Lactamase ◽

Extended Spectrum

Abstract Background Extended-spectrum beta-lactamase (ESBL) and AmpC-producing Enterobacterales are common causes of bloodstream infection. ESBL-producing bacteria are typically resistant to third-generation cephalosporins and result in a sizeable economic and public health burden. AmpC-producing Enterobacterales may develop third-generation cephalosporin resistance through enzyme hyper-expression. In no observational study has the outcome of treatment of these infections been surpassed by carbapenems. Widespread use of carbapenems may drive the development of carbapenem-resistant Gram-negative bacilli. Methods This study will use a multicentre, parallel group open-label non-inferiority trial design comparing ceftolozane-tazobactam and meropenem in adult patients with bloodstream infection caused by ESBL or AmpC-producing Enterobacterales. Trial recruitment will occur in up to 40 sites in six countries (Australia, Singapore, Italy, Spain, Saudi Arabia and Lebanon). The sample size is determined by a predefined quantity of ceftolozane-tazobactam to be supplied by Merck, Sharpe and Dohme (MSD). We anticipate that a trial with 600 patients contributing to the primary outcome analysis would have 80% power to declare non-inferiority with a 5% non-inferiority margin, assuming a 30-day mortality of 5% in both randomised groups. Once randomised, definitive treatment will be for a minimum of 5 days and a maximum of 14 days with the total duration determined by treating clinicians. Data describing demographic information, risk factors, concomitant antibiotics, illness scores, microbiology, multidrug-resistant organism screening, discharge and mortality will be collected. Discussion Participants will have bloodstream infection due to third-generation cephalosporin non-susceptible E. coli and Klebsiella spp. or Enterobacter spp., Citrobacter freundii, Morganella morganii, Providencia spp. or Serratia marcescens. They will be randomised 1:1 to ceftolozane-tazobactam 3 g versus meropenem 1 g, both every 8 h. Secondary outcomes will be a comparison of 14-day all-cause mortality, clinical and microbiological success at day 5, functional bacteraemia score, microbiological relapse, new bloodstream infection, length of hospital stay, serious adverse events, C. difficile infection, multidrug-resistant organism colonisation. The estimated trial completion date is December 2024. Trial registration The MERINO-3 trial is registered under the US National Institute of Health ClinicalTrials.gov register, reference number: NCT04238390. Registered on 23 January 2020.

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A Call for Better, Not Faster, Research Ethics Committee Reviews in the Covid‐19 Era

Ethics & Human Research ◽

10.1002/eahr.500104 ◽

2021 ◽

Vol 43 (5) ◽

pp. 42-44

Author(s):

Leonardo Tamariz ◽

Fred J. Hendler ◽

John M. Wells ◽

Annette Anderson ◽

Stephen Bartlett

Keyword(s):

Research Ethics ◽

Ethics Committee ◽

Research Ethics Committee

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Implementation of the StandingTall programme to prevent falls in older people: a process evaluation protocol

BMJ Open ◽

10.1136/bmjopen-2020-048395 ◽

2021 ◽

Vol 11 (7) ◽

pp. e048395

Author(s):

Morag E Taylor ◽

Chris Todd ◽

Sandra O'Rourke ◽

Lindy M Clemson ◽

Jacqueline CT Close ◽

...

Keyword(s):

Older People ◽

Research Ethics ◽

Process Evaluation ◽

Ethics Committee ◽

Community Dwelling ◽

Innovative Technology ◽

Local Health ◽

Research Ethics Committee ◽

Personal Impact ◽

The Uk

IntroductionOne in three people aged 65 years and over fall each year. The health, economic and personal impact of falls will grow substantially in the coming years due to population ageing. Developing and implementing cost-effective strategies to prevent falls and mobility problems among older people is therefore an urgent public health challenge. StandingTall is a low-cost, unsupervised, home-based balance exercise programme delivered through a computer or tablet. StandingTall has a simple user-interface that incorporates physical and behavioural elements designed to promote compliance. A large randomised controlled trial in 503 community-dwelling older people has shown that StandingTall is safe, has high adherence rates and is effective in improving balance and reducing falls. The current project targets a major need for older people and will address the final steps needed to scale this innovative technology for widespread use by older people across Australia and internationally.Methods and analysisThis project will endeavour to recruit 300 participants across three sites in Australia and 100 participants in the UK. The aim of the study is to evaluate the implementation of StandingTall into the community and health service settings in Australia and the UK. The nested process evaluation will use both quantitative and qualitative methods to explore uptake and acceptability of the StandingTall programme and associated resources. The primary outcome is participant adherence to the StandingTall programme over 6 months.Ethics and disseminationEthical approval has been obtained from the South East Sydney Local Health District Human Research Ethics Committee (HREC reference 18/288) in Australia and the North West- Greater Manchester South Research Ethics Committee (IRAS ID: 268954) in the UK. Dissemination will be via publications, conferences, newsletter articles, social media, talks to clinicians and consumers and meetings with health departments/managers.Trial registration numberACTRN12619001329156.

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