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Implantable cardioverter defibrillator devices: when, how and who should discuss deactivation with patients: a systematic literature review
  1. Megan Freemantle and
  2. Fliss Murtagh
  1. Wolfson Palliative Care Research Centre, Hull York Medical School, University of Hull, Hull, UK
  1. Correspondence to Megan Freemantle, Wolfson Palliative Care Research Centre, Hull York Medical School, University of Hull, Hull HU6 7RX, UK; meganfreemantle{at}


Background Implantable cardioverter defibrillators (ICDs) are used to treat life-threatening cardiac arrhythmias and prevent sudden cardiac arrest. As recipients age they may develop greater risk of dying as a result of progressive multimorbidity rather than sudden cardiac death. Defibrillation shocks may prolong an uncomfortable dying process. Deactivation of the defibrillator would prevent this, yet is not always discussed and planned.

Aim To systematically review published evidence on ICD deactivation discussions and make recommendations on when, how and who should facilitate effective and patient-centred deactivation discussions.

Methods Using standard systematic review methods, MEDLINE, EMBASE, CINAHL and PsycInfo were searched for studies published in the English language between 2010 and March 2021. Inclusion criteria were studies of adults (≥18 years) and including discussions on ICD deactivation and/or related communication. Included studies were independently reviewed, data extracted, quality assessed and data synthesised using a deductive approach.

Results Of the 8893 articles identified, 22 papers met the inclusion criteria. Deductive approach led to identification of five main themes: (1) timing of ICD deactivation discussions, (2) initiation of deactivation discussions, (3) advance directives, (4) barriers to discussions and (5) facilitators of discussions.

Conclusions Despite available guidelines, conversations on device deactivation are not being undertaken consistently. Evidence suggests lack of professional awareness of guidelines and limited training in communication skills. To prevent distress and promote comfortable dying, there needs to be a proactive clinical and policy initiative in the education of both professionals and patients and their relatives about device deactivation.

  • communication
  • education and training
  • heart failure
  • quality of life

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Key messages

What was already known?

  • Implantable cardioverter defibrillators treat arrhythmias and prevent cardiac arrest.

  • Deactivation is needed to avoid protracted distressing death.

What are the new findings?

  • Deactivation discussions are inconsistent, late or do not occur.

  • Professionals are unaware of guidelines recommending early discussion.

What is their significance?

  • Proactive clinical initiatives and training about device deactivation are needed.

  • Research is needed on the best timing for discussions.


Implantable cardioverter defibrillators (ICDs) are used to treat life-threatening cardiac arrhythmias and prevent sudden cardiac arrest.1 The device is surgically inserted to perform four key functions: automatic administration of defibrillation shocks to terminate ventricular fibrillation (VF) or fast ventricular tachycardia (VT), antibradycardia pacing often used after a defibrillation shock as the heart returns to normal sinus rhythm, antitachycardia pacing to terminate slower VT and cardioversion of VT.2 ICD should be considered as a secondary prevention for patients who have experienced one or more episodes of spontaneous, sustained VT or VF. It can also be recommended for prophylactic primary prevention in patients who have not had prior episodes of VT or VF, but are at high risk of arrhythmias, with the aim of improving symptoms, quality of life and preventing sudden death.

However, despite initial benefit, as ICD recipients age they may develop greater risk of dying as a result of progressive multimorbidity rather than sudden cardiac death. In these cases, defibrillation shocks may result in the prolongation of an uncomfortable dying process, with one in three ICD recipients experiencing multiple shocks in their last days of life, which can be both painful and futile, preventing a dignified death.3

To ensure high-quality end-of-life care, it is recommended patients should have an understanding of the impact ICDs can have during the active process of dying and how these events could be avoided if deactivation of the defibrillator was initiated, while maintaining the pacemaker function. This should be done through open, sensitive and culturally relevant communications.2

Both the British Heart Foundation (BHF) (2013) and the European Heart Rhythm Association (EHRA) (2010) advise device deactivation discussions should be included as part of a preimplantation informed consent, raising the issue of a future time whereby the patient’s general health may deteriorate to such an extent that device deactivation may be appropriate.2 4 At the time of the guideline publication, the results of the EHRA survey (2010) suggested that only 4% of implant centres were doing this.5 Indeed, current literature shows a mixed response to this proactive approach with clinicians, suggesting that raising issues related to ICD deactivation at the preimplantation stage might be inappropriate since implantation of the ICD felt like a ‘second chance at life’.6 Furthermore, it has been reported that patients have expressed how engaging in an ICD deactivation discussion before implantation may increase emotional distress.7

The goals of this review are to provide an overview of the evidence on the process of initiating ICD deactivation discussions, when they should occur, who should be involved, the use of advance directive and the barriers to these conversations, and from these to provide recommendations on how to engage in effective, patient-centred deactivation discussions.


Inherent within the aim of this systematic review is the exploration of the complexity of balancing the duty of care to consider ICD withdrawal, when the ICD is at risk of causing harm, with the potential distress of these conversations. As such, although systematic reviews traditionally focus on quantitative evidence, qualitative evidence with the potential for rich explanatory data was incorporated.

Criteria for consideration of studies for review

Prior to searching databases inclusion criteria were agreed by both authors; literature had to be published in the last 10 years in the English language and refer to an adult population (over the age of 18 years). This timeframe was chosen to reflect current practice following recommendations of national and international guidelines.2 4 To answer the research question literature had to be on the communication around ICD deactivation.

Identification and selection of studies

The aim of the search was to identify and select an inclusive list of all studies that met the inclusion criteria. MF searched the following databases from October 2019 to February 2020, with a further search in March 2021: MEDLINE, EMBASE, CINAHL and PsycInfo.

Consensus was reached between the reviewers for the specific Medical Subject Heading (MeSH) headings and keywords used for the population: implantable cardioverter defibrillator, ICD, automatic implantable cardioverter defibrillator, AICD and implantable defibrillator (in relation to both patients and professionals). Search words used for intervention included the following: communication, health communication, consult, inform, mention, discuss, verbalise, talk to, vocalise, converse, address, advance care planning, advance directive and end-of-life planning. Appropriate wildcards were inserted where necessary.

MF hand-searched the reference lists of relevant studies to identify further papers. Titles and abstracts were inspected by MF and clearly ineligible papers or duplicates were deleted. Full copies of potentially eligible papers were retrieved; if full copy of the text could not be found authors were contacted via ResearchGate. Abstracts alone could not be used as they provided insufficient data. Unpublished articles were included if they met the criteria for inclusion and the full text was available. All identified full papers were independently screened by MF.

Data extraction

A standardised electronic checklist was agreed and created by both authors to extract data on general information (author and year, type of publication, country of origin, source of funding, study characteristics, aim, study design, inclusion and exclusion criteria, recruitment procedures); participant characteristics (participants, age, gender, ethnicity, disease characteristics); number of participants included; and number and reason for withdrawal. Additionally, the extraction form included three key criteria: experience of, barriers to and facilitators of ICD deactivation communication. This was a deductive approach to answer the research question. MF extracted the data.

Data analysis

The Critical Appraisal Skills Programme (CASP) checklist (according to study type) was used by MF to assess the quality of included papers. It was anticipated that the search strategy would produce a diverse set of papers using different research methods.


Following de-duplication, 8063 studies were identified. During title/abstract screening and full-text review, 8041 studies were excluded. The primary reasons for exclusion were unrelated to study aim, ICD referred to ‘International Classification of Diseases’ or articles could not be accessed. Ten of the included studies were qualitative reviews,7–16 eight used a survey to extract data,17–24 three retrospectively reviewed data25–27 and only one study was a randomised controlled trial (RCT)28 (figure 1).

Figure 1

PRISMA flow chart showing the identification, screening and inclusion/exclusion of reports. Page MJ et al.40 PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Five included cohort studies assessed for quality using the CASP cohort checklist scored highly. Most of the studies were robust and generalisable, but it was difficult to identify how studies controlled confounding factors.22 23 25–27 Fifteen studies were qualitative and appraised using the qualitative CASP checklist. These qualitative studies rarely reflected on the interactions between participants and researchers and if all ethical considerations had been taken into account. However, for all the studies there was a clear statement of findings.7–12 15–20 24 Only one RCT was included, which was appraised using the RCT CASP checklist and scored highly in all criteria.28 See online supplemental material for full details of the quality assessments.

Supplemental material

Fourteen of the studies focused on patient experience, six on the perspectives of healthcare professionals and two on family member experiences. There is a significant gender disparity, with 93% of the studies on patient experience having a male predominance. Twelve studies were conducted in the USA and Canada, seven in the European Union and three in the UK. See table 1 for full details of included papers.

Table 1

Details of included papers

There was variation across the 22 included studies about when, where and who conducted ICD deactivation discussions. In terms of timing, four studies mentioned deactivation being discussed as part of the informed consent,7 11 15 17 seven did not specify a time,9 16 18 22 24 25 28 two during ICD replacement8 21 and eight as part of end-of-life care.10 12–14 20 23 26 27 One study described how these conversations occurred across transitions, including informed consent, after implantation and as part of end-of-life care.19 The location of these discussions was not always recorded: ten were conducted in ‘a clinical setting’,8 9 11 12 14 15 17–21 25 28 one stipulated a hospice12 and three outpatient clinics.14 15 28 There was a lack of clarity and consensus regarding the appropriate person to initiate these conversations. Some studies simply recorded ‘healthcare professionals’, and others clearly identified cardiologists, heart failure nurse specialists or palliative care consultants (further details in table 2).

Table 2

Details of when, where and who conducted conversations

Main themes

Following data extraction on the experience, barriers and facilitators of communication, five main themes were identified: (1) timing of ICD deactivation discussions, (2) initiation of deactivation discussions, (3) advance directives, (4) barriers to discussions and (5) facilitators of discussions.

Timing of ICD deactivation discussions

Informed consent is the voluntary agreement given by a fully informed, competent person and is central to both ethical and legal aspects of care. Informed consent requires effective communication between the healthcare professional and the patient to explain the benefits, risks and alternative treatment options.29 Therefore, prior to ICD implantation, as recommended by the BHF and EHRA, ICD deactivation should be discussed.2 4 Raphael et al 15 showed this recommendation is supported by patients, who when asked in an interview when they would want to discuss ICD deactivation 52% preferred discussion before implantation compared with just 22% who believed it should be delayed until they were terminally ill.15

Despite this recommendation some studies report that engaging in early discussions might increase emotional distress.7 8 10 18 A qualitative study showed that patients found talking about death too difficult as it shifts the focus away from what they consider important, which was living in the present.8 In addition, MacIver et al 7 reported the irony in having deactivation discussions prior to ICD implantation: “they put in a machine that can save me … and now they are talking about turning it off already.” Further literature also suggested it might be inappropriate to discuss deactivation early since implantation felt like ‘a second chance at life’.16

One small survey recorded only 13% (n=4) of patients had spoken with their doctor or nurse regarding deactivation. Nevertheless, many reported they would raise the question about end-of-life if they had multiple shocks (83%), repeated hospital admission with recurring heart problems (87%) or towards end-of-life (97%).24

However, it is important to acknowledge that some patients never want to discuss end-of-life issues.7 16 21–23 Thompson et al 22 found 40% of participants said they never wanted to have a conversation concerning end-of-life care; 55% of the cohort said they would want to have their ICD battery replaced even if they were seriously ill and suffering from a terminal disease. This has been supported by Miller et al,21 who found that patients who had already experienced a shock were more likely to maintain defibrillation therapy, “it saved my life, and I don’t want to live without it,” and would choose to avoid ICD deactivation discussions. One study uncovered reasons for this reluctance experienced by patients, including that information may be confusing, the decision is best left to the doctor and switching off may prematurely shorten life.15

Initiation of deactivation discussions

The BHF guideline advises ICD deactivation discussions should occur, ideally between the heart failure nurse, the patient and their chosen representative.2

However, literature suggests that many patients would prefer to leave the decision to engage in deactivation discussions solely in the hands of clinicians.8 15 23 Fluur et al 8 found that this was because patients felt clinicians knew best and trusted their judgement to decide whether or not the ICD should remain activated. Miller et al 21 reported that patients trusted clinicians so much that if they did not bring up discussion about end-of-life choices they inferred it was not important.

In terms of which specific member of the clinical team should be involved in these discussions, MacIver’s et al 7 study of 17 patients reported that 9 suggested a cardiologist and 8 suggested nurses. Similar results were supported by Hill et al,19 with healthcare professionals recommending a cardiologist (97%) or a specialist heart failure nurse (82%).

Despite the general consensus that specialist nurses have the necessary attributes to initiate a discussion about deactivation, overall data show a lack of nursing contribution to the final decision. Kramer et al 11 interviewed nurses who described how preimplantation discussions were largely physician-driven. These physicians placed a strong emphasis on the benefits of the device and less attention to future deactivation. The nurses in this study reported they would be better suited than physicians to initiate end-of-life discussions, largely because they are generally more involved with patient care and decision making after implantation. Through this greater level of interaction, the nurses learnt a great deal about their patient’s goals and preferences; these factors are important in influencing end-of-life decisions. The current lack of nurses’ involvement was explained by one study as a result of the structure of healthcare systems and the traditional role of physicians to diagnose and make treatment decisions.19 Hjelmfors et al 20 reported there may be an issue with the lack of education and training nurses receive to have these conversations. The study showed that despite most nurses thinking it appropriate for them to talk about prognosis and end-of-life decisions with the patient, 58% were hesitant due to uncertainty of knowing how to approach the topic or answer patient questions.20

The evidence suggests that perhaps clinicians should not be the only ones to initiate deactivation discussions.7 10 19 20 23 MacIver et al 7 reported that some patients would prefer that the patients themselves were the ones to start the conversation. They felt that if the physician initiated the discussion before they were ready, this could increase emotional distress. Further literature also supported this approach, stating the choice to deactivate was best left to the patient because ‘no time is really the right time’.10

Advance directives

To facilitate the topic of deactivation, an advance directive, a process of formal decision making that aims to help patients establish decisions about future care that take effect when they lose capacity can be used.30 However, literature has shown that in the case of ICD deactivation advance directives are either not being used or their purpose is not being explained fully.8 11 13 16 18 20 22 25–27 In addition, Conelius18 suggested some healthcare professionals either do not understand the advance directives themselves or do not believe they are useful. Buchhalter et al 25 found 57% of participants had advance directives and of these 48% were executed before implantation. Worryingly, only one advance directive addressed ICD deactivation. Interestingly, this patient executed his advance directive 4 months after implantation and died 10 years later, 2 days after deactivation for end-stage heart failure.

In addition to advance directives, palliative care medicine consultation (PCMC) also provides a suitable opportunity for discussing and recording ICD deactivation wishes alongside all life-prolonging treatments as an integral component to holistic assessment of physical, psychological, spiritual and social care. However, reporting on a retrospective review of the medical records of 150 patients who had undergone deactivation, Buchhalter et al 25 and Pasalic et al 26 found only two-thirds of PCMCs specifically addressed this aspect of care. They acknowledge this may reflect a lack of awareness that the patient had an ICD. It is noteworthy that PCMCs occurred significantly more frequently in patients who requested deactivation themselves, suggesting decision-making capacity.

Stoevelaar et al 16 established that not everyone was in favour of recording their preferences in a document. This was due to a range of reasons including not knowing the choices available or personal preferences for end-of-life care, knowing what they wanted but worrying that their decision would change when actually in that situation, or being doubtful that even if they expressed their choices they would be respected.

Barriers to discussions

Literature suggests making advance decisions about deactivation can be difficult for the patient and their family due to lack of information or understanding. Two studies reported how family members felt ‘left out’ from the lack of information.9 12 Fluur et al 9 described how spouses were rarely offered verbal or written information and had to rely on secondhand recollections following the consultation. Kutcher and Soroka12 reported that spouses recalled how the medical team showed great enthusiasm for implantation but great reluctance to consider deactivation. Without this support caregivers felt lost and hopeless. In both cases caregivers were forced to turn to their own network and educate themselves about the possibility and benefits of deactivation.

However, there is debate on whether family members should be involved in advance decision making.8–12 16 18 19 Fluur et al 9 revealed that spouses were often overprotective, which could have a negative impact on the patient, leading to reduced social interaction and impaired communication when it came to making advance decisions. One study reported nurses’ observation of family pressure to encourage patients to keep their device, with one nurse quoting how the patient felt the need to avoid deactivation and stay alive just for their son.11

Evidence suggests it is not family members alone who may lack an understanding on device deactivation. Conelius18 reported patients had a lack of understanding of their medical condition and treatment options and limited confidence in healthcare providers to decide their treatments. Mooney et al 24 highlighted that patient information in respect of device management and deactivation during serious illness or at end-of-life is limited. In their study, 17% and 20% of patients were unable to offer an opinion when asked if they would deactivate their ICD if receiving shocks daily or if they had serious illness. Miller et al 21 showed that understanding of the device is crucial and that when patients had increased knowledge they were more likely to consider deactivation.

Furthermore, although patients and family members may lack knowledge, clinicians can also feel underprepared to have these conversations. Hjelmfors et al 20 reported that more than half the nurses surveyed hesitated when it came to initiating end-of-life discussions; in practice they lacked confidence in answering patient questions and 91% reported a need for further training in advanced communication skills.

Facilitators of discussions

A key facilitator as reported by Goldstein et al 28 is the training of physicians. This RCT explored the impact of an interactive 90 min communication skills training session on advance care planning conversations and ICD deactivation. The single RCT involved six hospitals with heart failure programmes and an absence of protocols addressing ICD deactivation. These were randomised in a single-blinded cluster to reduce cross contamination at the level of clinicians and patients.28 The study found that patients were more likely to have goals of care conversations if the physicians had undertaken the training, compared with those cared for by clinicians in the control group (47% intervention vs 38% control; OR: 1.53; p=0.04).

Shared decision making, as described by Ali-Ahmed et al 17 and Hill et al,19 incorporates relevant facts about risks and benefits and facilitates accurate and timely information to inform treatment choices. In addition, Miller et al 21 found that increasing patient knowledge decreased unnecessary procedures including shocks in the active dying phase.

Building supporting relationships with healthcare professionals over time allows a process rather than one-off conversations to occur. Hjelmfors et al 20 reported nurses were in 100% agreement on two main facilitators for end-of-life discussions: a good relationship with the patient and repeated opportunities. Moreover, MacIver et al 7 promoted the recognition of the palliative phase of illness, identifying the best time to talk about deactivation being when the patient’s condition changes, with these transitions providing opportunity for conversations.


Alongside developments in healthcare there has been an increase in the use of ICDs to treat life -threatening cardiac arrhythmias and cardiac arrest. However, with increasing age, disease burden and comorbidities, these devices have the potential to cause harm, with many patients experiencing shocks as they approach death. The associated pain, distress and anxiety with possible prolongation of the dying experience could be avoided. This review suggests that despite guidelines2 4 recommending conversations about deactivation of the defibrillator element of the device to prevent this, these recommendations are not always translated into clinical practice. Furthermore, these conversations are fraught with difficulties for healthcare professionals, patients and families.

To answer the research question of when, how and who should have deactivation discussions, a deductive approach was constructed which yielded both quantitative and qualitative cross-national studies. Of the included studies there was only one RCT and the rest were observational or qualitative. Due to the diverse nature of selected articles it was not appropriate to use traditional synthesis methods; results were instead reported under predetermined themes. Consideration needs to be taken of the diverse healthcare systems, practices and policies when applying the relevance of this review to practice. Overall, there is little strong evidence to support practice when faced with the complexity of these conversations. Nevertheless, this review identifies significant issues that deserve further discussion.

Current guidelines recommend that device deactivation discussions should be included as part of preimplantation informed consent.2 4 The review suggests a variety of preferences when ICD deactivation conversations should occur and there is no overall defining answer from the literature. It is clear that as part of the informed consent process, where patients should receive a full explanation, of the benefits and risks of their defibrillator, ICD deactivation should be mentioned. In general, patients concur that they want to be ‘informed’ about device deactivation prior to implantation, but lengthy discussions should be avoided until a more appropriate time.

It is the role of clinicians to provide guidance and support about appropriate treatments and options at each phase of the disease trajectory. The review suggests there are some patients who are not aware that deactivation is available to them. To address this, experienced and competent clinicians could take opportunities to introduce conversations during elective ICD battery replacement, when there is functional decline, frequent hospital admissions, on referral to palliative care and as a component of resuscitation conversations. Crucial to discussions is the sensitive exploration of the patient’s readiness to talk about deactivation and tailor information and delivery to their expressed preference.

The BHF recommends that heart failure nurse specialists, who know the patient and have had advance communication training, should be the ones to initiate and revisit deactivation discussions.2 These guidelines concur with general recommendations from most of the studies reviewed. Although some studies suggest deactivation discussions are not welcomed by patients,7 16 21–23 this should not deter healthcare professionals from seeking to engage in these conversations in order to prevent distressing shocks at end-of-life. Indeed, healthcare professionals have a duty of care to consider withdrawal of non-contributory therapies and prevent the distress caused by resuscitation measures in those with a progressive and irreversible decline in their condition.31 Conversations should reassure the patient that device deactivation is painless, only discontinues the shock component and does not hasten death.2

Palliative care is an approach to improve the quality of life of patients and their families facing problems associated with life-threatening illness, offering a support system to help the patient live as actively as possible until end-of-life, and can be applicable in the early course of illness in conjunction with other life-sustaining therapies.32 ,33 Indeed, in the UK this phased transition of including palliative care alongside disease-modifying treatments has been suggested as particularly relevant for those with slowly progressive or fluctuating trajectories as with cardiovascular disease.34 Joint working between cardiology and palliative care could be a conduit for advance care planning conversations including deactivation. However, this contrasts US models, which are defined by a sharper transition to palliative care accompanied by a cessation of curative care, and is illustrated by 63 patients who received late referrals to palliative care who all had poor or terminal prognosis and for whom the median survival after deactivation was just 2 days.26

The main issue, which many studies in the review support, is that deactivation discussions are being left until the impending death of the patient. A study by Kim et al 35 suggests one possible reason is that ICD is primarily considered a life-saving therapy, and for many patients and healthcare professionals deactivation is considered a controversial issue leading to a delay in discussion.

The inclusion of cross-national literature means the review is subjected to the impact of variations in healthcare systems around the world. The American College of Cardiology/American Heart Association and Heart Rhythm Society advise patients with an ICD to make a device-specific advance directive when nearing end-of-life.36 This approach appears to differ from that in Europe, as illustrated by a six-country, cluster-randomised European advance care planning study where only 10% of patients who received the intervention had an advance directive in their hospital files. Although not specifically related to ICD deactivation, this illustrates the differences in cross-national approaches to advance directives.37

Reported barriers suggested from this literature review and supported by other studies38 include lack of professional teaching and a knowledge deficit of patients regarding deactivation. To improve professional training a quality improvement project by Javaid et al 39 found targeted teaching, compared with posters or emails, had the biggest improvement in the occurrence of deactivation discussions. Goldstein et al’s28 RCT found the intervention group that received communication training were more likely to discuss goals of care than the control. This suggests education and targeted workshops can help increase professionals’ awareness and confidence. To support patient and relative knowledge verbal information should be supplemented by written education materials. Establishing early conversations and having a process of continued dialogue with experienced healthcare professionals can help with the processing of information, resulting in appropriate timing of deactivation. This in turn may help decrease unnecessary harm and distress and promote comfortable dying.

The review highlights that despite guidelines2 4 which provide advice on how and who should be having device deactivation discussions, the opportunity for these conversations is not offered or undertaken on a consistent basis. Reasons could include a lack of professional awareness of guidelines or that current teaching practice commonly includes the reasons for implanting life-sustaining devices, but fails to acknowledge deactivation. Literature suggests without education and training in communication skills to explain these complex issues with clarity, and where possible, encourage advance care planning discussions, these conversations remain limited. One option could be to include ICD deactivation education alongside teaching on do-not-attempt-resuscitation.

A strength of this review is that only one author was involved in selecting, extracting and evaluating the available evidence, providing internal consistency. However, this increases the risk of bias by having only one reviewer. In hindsight if MF had conducted a pilot search this would have illustrated the issue of the abbreviation ICD also referring to International Classification of Diseases and would have better limited the number of studies to be filtered. Furthermore, the lack of response from authors to request full-text articles meant that potential studies were excluded.

In summary, this review shows that there needs to be a proactive clinical and policy initiative in the education of both professionals and patients and relatives about device deactivation. Moreover, healthcare professionals should be taught how to communicate these complex issues in a clear and compassionate manner to ensure timely deactivation of the shock element of the ICD to facilitate a comfortable, natural death. Further research could be conducted on the most effective way for this to be implemented.

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

Ethics statements

Patient consent for publication


Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.


  • Contributors MF participated in all aspects of the review: data searching, study selection, data extraction, quality appraisal, manuscript writing and edits. FM coordinated all aspects of the review and assisted in manuscript writing and editing.

  • Funding This review was completed as part of a research module towards a primary medical degree and received no external funding. FM is a National Institute for Health Research (NIHR) Senior Investigator. The views expressed in this article are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.