Changes

January 2024 — reviewed. A literature search was conducted in December 2023 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. Minor structural changes have been made to the topic to align with up-to-date evidence, with no changes to the clinical recommendations.

Update

Goals

To support primary healthcare professionals to:

• Recognise risk factors for meticillin-resistant Staphylococcus aureus (MRSA).
• Confirm diagnosis with appropriate investigations.
• Manage MRSA infection with specialist advice.
• Arrange urgent assessment in secondary care if appropriate.
• Advise on self-care and infection control for people with MRSA.
• Take appropriate steps to reduce the risk of transmission of MRSA.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

Antimicrobial stewardship — Prescribing antibiotics:

• Review and, if appropriate, revise prescribing and local policies that relate to antimicrobial stewardship to ensure these are in line with NICE guidelines on antimicrobial stewardship: systems and processes for effective antimicrobial medicine use and antimicrobial stewardship: changing risk-related behaviours in the general population.
• Review and, if appropriate, optimise current prescribing practice and use implementation techniques to ensure prescribing is in line with NICE antimicrobial prescribing guidelines, guidance from the UK Health Security Agency Start smart − then focus, local trust antimicrobial guidelines, and the Antimicrobial Stewardship in Primary Care collaboration TARGET antibiotics toolkit.
• Promote the antibiotic guardian call to action and the keep antibiotics working campaign.

NICE quality standards

The following are included in the National Institute for Health and Care Excellence (NICE) Quality Standards on Infection prevention and control (QS61) and Healthcare-associated infections (QS113).

• NICE quality standards on infection prevention and control (QS61).
  • People are prescribed antibiotics in accordance with local antibiotic formularies as part of antimicrobial stewardship.
  • Organizations that provide healthcare have a strategy for continuous improvement in infection prevention and control, including accountable leadership, multi-agency working, and the use of surveillance systems.
  • People receive healthcare from healthcare workers who decontaminate their hands immediately before and after every episode of direct contact or care.
  • People who need a urinary catheter have their risk of infection minimised by the completion of specified procedures necessary for the safe insertion and maintenance of the catheter and its removal as soon as it is no longer needed.
  • People who need a vascular access device have their risk of infection minimised by the completion of specified procedures necessary for the safe insertion and maintenance of the device and its removal as soon as it is no longer needed.
  • People with a urinary catheter, vascular access device or enteral feeding tube, and their family members or carers (as appropriate), are educated about the safe management of the device or equipment, including techniques to prevent infection.

• NICE quality standards on healthcare-associated infections (QS113).
  • Hospitals monitor healthcare-associated infections and other infections of local relevance to drive continuous quality improvement.
  • Hospitals work with local health and social care organizations to assess and manage the risk of infections in hospitals from community outbreaks and incidents.
  • Hospital staff have individual objectives and appraisals on infection prevention and control linked to board-level objectives and strategies.
  • Hospitals involve infection prevention and control teams in the building, refurbishment and maintenance of hospital facilities.
  • People admitted to, discharged from, or transferred between or within hospitals have information about any infections and associated treatments shared with health and social care staff to inform their care.

[NICE, 2014; NICE, 2016]

What is it?

• Staphylococcus aureus is a Gram-positive bacterium that colonizes the skin, nose, or gut of up to a third of the general population.
  • S. aureus usually lives on intact skin harmlessly, but can cause infection (most commonly skin, soft tissue, and bone infection) if invasion through the skin or deeper tissues occurs.
• Meticillin-resistant S. aureus (MRSA) are strains of S. aureus which have developed resistance to a number of commonly used antibiotics including ß-lactam antibiotics (such as flucloxacillin).
  • MRSA colonization is defined as people carrying MRSA on their skin or in the gut or nose, but do not show symptoms and signs of infection. The most common site of colonization is the anterior nares, but MRSA can also be found in the axillae, abnormal skin (for example, eczematous skin or wounds), urine, rectum, and throat.
  • MRSA infection occurs when MRSA causes harm and requires treatment (for example boils, wounds, chest and urinary infections, or sepsis). Infection occurs when MRSA enters the body via a cut or wound and penetrates deeper tissues, resulting in a local or systemic infection. Typically this will involve symptoms of skin and soft tissue infection (for example boils, abscesses, wounds with or without exudates and signs of necrosis), chest and urinary infections, or sepsis.
• Healthcare-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA) are genetically and phenotypically distinct:
  • HA-MRSA are strains of MRSA identified in people who have had contact with healthcare services — they can present in hospital or in the community.
  • CA-MRSA are strains of MRSA identified in the community setting or within 48 hours of hospital admission typically in people with no significant past medical history or healthcare contact.
  • The definition of MRSA based on where infection is likely to have been acquired is becoming less relevant as cross-over in strain types identified in hospitals and the community becomes increasingly common.

[Bradley, 2011; Taylor, 2013; Hay, 2016; Brown, 2021; BMJ Best Practice, 2023; Vena, 2023]

What causes it?

• Clinical infection with meticillin-resistant Staphylococcus aureus (MRSA) can be caused by a person’s own colonizing bacteria or following transmission from an asymptomatic carrier or MRSA-infected person.
  • Transmission occurs through direct contact with infected skin or following contact with contaminated objects (such as razors and towels) or environmental surfaces.
  • MRSA infection occurs when MRSA enters the tissues (for example, through a cut or wound) and causes harm.
• Healthcare-associated MRSA (HA-MRSA) is usually acquired following direct or indirect contact with healthcare services, and is more likely to occur in older age groups. Risk factors include:
  • Admission to hospital or other contact with healthcare services, such as for acute or chronic disease management (including use of invasive devices, for example, urinary catheters).
  • Residence in long-term care facilities (such as care homes) or crowded conditions.
  • Previous exposure to antibiotics.
  • Past medical history of MRSA infection or colonization.
  • Contact with a person with MRSA infection or colonization.
  • Intravenous drug use.
  • Immunosuppression such as HIV.
  • Presence of a skin wound.
• Community-associated MRSA (CA-MRSA) typically occurs in people who have had no direct or indirect contact with healthcare services, but cross-over in strain types identified in hospitals and the community is becoming more common. CA-MRSA is more likely to occur in younger age groups. Risk groups include:
  • Intravenous drug users.
  • Men who have sex with men.
  • Athletes involved in particular contact sports.
  • Residents living in close proximity to others, such as in long-term care facilities or prisons.
  • Military personnel.
• Advancing age is considered an indirect risk factor for both HA-MRSA and CA-MRSA.
  • There is a higher prevalence of hospitalization, residence in a long-term care setting, and chronic medical conditions that may increase the risk of MRSA infection among people aged 65 and older.

[Taylor, 2013; Stevens, 2014; Hay, 2016; Kosar, 2017; CDC, 2019; Brown, 2021; BMJ Best Practice, 2023; Falcone, 2023; UKHSA, 2023; Vena, 2023]

How common is it?

• Staphylococcus aureus carriage
  • S. aureus nasal carriage in the general population is estimated to be up to one-third but varies between countries [den Heijer, 2013; CDC, 2019].
  • A cross-sectional study (n=32,206) of nasal swabs taken by family doctors in 9 European countries (Austria, Belgium, Croatia, France, Hungary, Spain, Sweden, the Netherlands, and the UK) found that S. aureus prevalence in adults ranged from 12·1% (Hungary) to 29·4% (Sweden) [den Heijer, 2013].
    • Of the 3156 swabs tested in adults in primary care in the UK, 25.8% were found to have S. aureus nasal carriage [CI 24.3-27.3] and 0.4% [CI 0.2-0.7) to have meticillin-resistant S. aureus (MRSA) carriage [den Heijer, 2013].
  • In the US, the Centres for Disease Control and Prevention (CDC) estimates that 2 in 100 people are carriers of MRSA [CDC, 2019].
• MRSA bacteraemia
  • Data collected from England since 2007/08 describe a substantial decrease in the number of cases of MRSA bacteraemia over a 15 year period [UKHSA, 2023]:
    • In 2022/23, 787 cases of S. aureus bacteraemia (5.7%) were identified as MRSA compared to 1116 cases (11.3%) in 2011/12 — a decrease of 49.6%.
    • Although the MRSA all-case rate for 2022/23 (1.4 per 100,000 population) is much lower than the rate in 2007/08 (8.6 per 100,000 population), the decline has slowed over recent years with rates remaining relatively constant for the past 4 years (range 1.4-1.5 per 100,000 population).
  • MRSA bacteraemia rates are highest among those aged 85 years or older [UKHSA, 2023]:
    • In 2022/23, the rate in men 85 years of age or older was 14.6/100,000 and 4.9/100,000 in women.
  • The majority of cases are community-acquired, with 295 hospital-onset and 495 community-onset cases reported in 2022/23 [UKHSA, 2023]. 
  • The percentage of MRSA cases with catheter or line as the source of bacteraemia has reduced over time [UKHSA, 2023]:
    • In 2007/08, catheters or lines were the source of 25.6% of inpatient cases of MRSA bacteraemia compared to 16.7% in 2022/23.
  • The percentage of cases caused by skin and soft tissue infections (SSTI) has increased from 16.4% in 2007/08 to 37.1% in 2022/23, although this has remained fairly consistent in recent years (excluding 2020/21, the percentage ranged from 31.1% in 2016/17 to 34.1% in 2021/22) [UKHSA, 2023].
• MRSA in long-term care facilities
  • MRSA prevalence among residents and staff at long-term care facilities, such as nursing homes, has been found to vary widely between countries from approximately 1% in Finland to around 18% in the UK and over 20% in the US [Hasanpour, 2023].
  • Rates of colonization vary for different long-term care facilities, likely dependent on the prevalence of MRSA in referring facilities, the resident population, staff colonization rates, and local infection control and prevention practices [Hasanpour, 2023].
  • Persistent carriage is high in long-term care facilities, estimated to be between 47% and 65% [Gilligan, 2010].

What is the prognosis?

Prognosis depends on individual patient characteristics (including age and co-morbidities), the severity of the meticillin-resistant Staphylococcus aureus (MRSA) infection, and promptness of diagnosis and treatment.

• MRSA bacteraemia — in England, the number of deaths within 30 days following MRSA bacteraemia has reduced markedly since 2007 [UKHSA, 2023].
  • In 2022/23 the case fatality rate (CFR) was the lowest since national surveillance was initiated at 22.5% compared to 38.9% in 2007/08 — a decrease of 42%.
  • In comparison with the previous year, the CFR decreased for both hospital-onset cases (29.6% compared with 29.7%) and community-onset cases (18.2% compared with 24.3%) during 2022/23.
• MRSA carriage
  • Following infection with MRSA, the person may become a carrier — this is a risk factor for subsequent MRSA infection and transmission of MRSA to others.
  • A US-based prospective cohort study (n=10,598 adults) with an average of 8.5 years follow up found that in crude analysis MRSA colonization was associated with a higher risk of death than no S. aureus colonization (HR 2.40, 95% CI 1.56–3.69), but after adjustment for socioeconomic status and co-morbidities (such as asthma, diabetes, cardiovascular diseases, liver disease, and cancer) this association was no longer significant [Mendy, 2016].

[Hay, 2016; BMJ Best Practice, 2023]

What are the complications?

• Meticillin-resistant Staphylococcus aureus (MRSA) can cause a wide variety of infections, which range from mild to life-threatening, including:
  • Skin and soft tissue infections such as boils, folliculitis, impetigo, cellulitis, and necrotising fasciitis.
  • Urinary tract infections.
  • Pneumonia and bronchiectasis.
  • Joint and bone infections such as osteomyelitis and septic arthritis.
  • Sepsis and toxic shock syndrome.
  • Infective endocarditis.
• Serious MRSA infections can occur in people of any age including those who are young and previously healthy — strains causing serious infections may or may not produce the pathogenic Panton-Valentine leucocidin (PVL) toxin.
  • PVL is a staphylococcal virulence factor and predisposes to necrotising soft tissue or lung infection.

[Taylor, 2013; Stevens, 2014; Hay, 2016; CDC, 2019; Brown, 2021; BMJ Best Practice, 2023; Vena, 2023]

When should I suspect MRSA?

• There are no clinical features specific to meticillin-resistant Staphylococcus aureus (MRSA) infection — MRSA can cause the same spectrum of disease as other strains of S. aureus, including:
  • Skin and soft tissue infections.
    • For more information, see the CKS topics on Boils, carbuncles, and staphylococcal carriage, Impetigo, Cellulitis - acute, and Whitlow (staphylococcal and herpetic).
  • Bone and joint infection.
  • Pneumonia.
    • For more information, see the CKS topic on Chest infections - adult.
  • Urinary tract infection.
    • For more information, see the CKS topics on Urinary tract infection - children, Urinary tract infection (lower) - men, and Urinary tract infection (lower) - women.
  • Endocarditis.
  • Sepsis.
• Consider the possibility of MRSA in all people presenting with potential staphylococcal infection, in particular if:
  • They have risk factors for MRSA (such as recent hospitalization, previous MRSA infection or colonization, nursing home contact, antibiotic use, chronic illness, surgical wounds, open ulcers, intravenous lines, or urinary catheters).
  • There is no response to first line antibiotics.
  • They have recurrent skin or soft tissue infections or a chronic non-healing ulcer, especially if purulent.

How should I assess a person with suspected MRSA?

• Take a history asking about:
  • Clinical features — onset and evolution of symptoms.
  • Previous treatment including antibiotic use.
  • Past medical history including recurrent skin infections.
  • Risk factors for MRSA such as recent hospitalization, previous MRSA infection or carriage, indwelling devices (for example urinary catheters), and previous antibiotic use.
  • Contacts with similar symptoms, recurrent skin infections, or known MRSA infection or carriage.
• Examine the person, checking:
  • Vital signs such as temperature, blood pressure, heart rate, capillary refill, and oxygen saturation – look for signs of serious illness such as sepsis.
  • The relevant systems for clinical signs of Staphylococcal infection and complications, including:
    • Skin and soft-tissue infection — such as discharging skin lesions, boils or pustules, abscess formation, central ulceration, folliculitis, impetigo, cellulitis, and necrotising fasciitis.
    • Bacteraemia or sepsis — such as tachycardia, fever, hypotension, cyanosis, bruising or petechiae suggestive of disseminated intravascular coagulation, or altered mental status.
    • Endocarditis — such as fever, cardiac murmur, tachycardia, and symptoms of congestive heart failure.
    • Joint infection — such as pain, swelling, and warmth in the affected joint with accompanying fever.
    • Pneumonia — such as fever, tachypnoea, and respiratory distress.
    • Urinary tract infection — such as abdominal pain, fever, haematuria, altered consciousness, and flank pain.
• Consider investigations:
  • If the person is well and does not require admission, take a sample from the affected area for microscopy and culture, for example, swabs of exudate from lesions or wounds, or urine or sputum samples.
  • Other investigations such as chest X-ray may be appropriate depending on the specific clinical situation.

What else might it be?

• Other conditions affecting the skin and soft tissue such as boils, folliculitis, insect bites, and cellulitis.
  • For further information, see the CKS topics on Boils, carbuncles, and staphylococcal carriage, Cellulitis - acute, Impetigo, Insect bites and stings, and Whitlow (staphylococcal and herpetic).
• Infections other than MRSA which cause chest, urinary tract, bone, joint or systemic infections.
  • For further information, see the CKS topics on Chest infections - adult, Cough - acute with chest signs in children, Urinary tract infection - children, Urinary tract infection (lower) - men, and Urinary tract infection (lower) - women.

Scenario: Management of MRSA in primary care

From birth onwards.

Search strategy

Scope of search

A literature search was conducted for guidelines and systematic reviews on primary care management of MRSA.

Search dates

September 2018 - December 2023

Key search terms

The terms listed below are the core search terms that were used for EBSCO MEDLINE (searched 27th September 2018). The strategy was adapted for The Cochrane Library databases. 

S8 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7

S7 AB (methicillin-resistant staphylococcus aureus) OR TI (methicillin-resistant staphylococcus aureus)

S6 AB (methicillin resistant staphylococcus aureus) OR TI (methicillin resistant staphylococcus aureus)

S5 AB (meticillin-resistant staphylococcus aureus) OR TI (meticillin-resistant staphylococcus aureus)

S4 AB (meticillin resistant staphylococcus aureus) OR TI (meticillin resistant staphylococcus aureus)

S3 AB HA-MRSA OR TI HA-MRSA

S2 AB MRSA OR TI MRSA

S1 (MH "Methicillin-Resistant Staphylococcus aureus")    

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• World Health Organization
• Guidelines International Network
• TRIP database
• Agency for Healthcare Research and Quality
• Institute for Clinical Systems Improvement
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Bandolier
• Drug and Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalk
• BMJ - Patient Journeys

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• LactMed
• Medicines and Healthcare products Regulatory Agency (MHRA)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
• Consistency with other providers of clinical knowledge for primary care.
• Accuracy of implementation of national guidance (in particular NICE guidelines).
• Usability.

Principles of the consultation process

• The process is inclusive and any individual may participate.
• To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
• Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
• Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
• External reviewers are not paid for commenting on the draft topics.
• Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
• All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
• All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

• Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
• Stakeholders identified from the following groups are invited to review draft topics:
  • Experts in the topic area.
  • Professional organizations and societies (for example, Royal Colleges).
  • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
  • Guideline development groups where the topic is an implementation of a guideline.
  • The British National Formulary team.
  • The editorial team that develop MeReC Publications.
• Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

• Topic selection
• Scoping of topic
• Selection of clinical scenarios
• First draft internal review
• Second draft internal review
• External review
• Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
• Outcomes have no clear evidence of clinical effectiveness
• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
  • Eligible population
  • Current interventions
  • Likely uptake of new intervention or recommendation
  • Cost of the current or new intervention mix
  • Impact on other costs
  • Condition-related costs
  • In-direct costs and service impacts
  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

• Personal financial interests
• Personal family interest
• Personal non-financial interest
• Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.