Assessing the relationship between chronic pain and cardiovascular disease: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Chronic pain is a potentially disabling condition affecting one in three people through impaired physical function and quality of life. While the psychosocial impact of chronic pain is already well established, little is known about the potential biological consequences. Chronic pain may be associated with an increased prevalence of cardiovascular disease, an effect that has been demonstrated across a spectrum of chronic pain conditions including low back pain, pelvic pain, neuropathic pain and fibromyalgia. The aim of this study was to review and summarize the evidence for a link between chronic pain and cardiovascular disease. We sought to clarify the nature of the relationship by examining the basis for a dose-response gradient (whereby increasing pain severity would result in greater cardiovascular disease), and by evaluating the extent to which potentially confounding variables may contribute to this association. METHODS: Major electronic databases MEDLINE, EMBASE, Psychinfo, Cochrane, ProQuest and Web of Science were searched for articles reporting strengths of association between chronic pain (pain in one or more body regions, present for three months or longer) and cardiovascular outcomes (cardiovascular mortality, cardiac disease, and cerebrovascular disease). Meta-analysis was used to pool data analysing the association between chronic pain and the three principal cardiovascular outcomes. The impact of pain severity, and the role of potentially confounding variables were explored narratively. RESULTS: The searches generated 11,141 studies, of which 25 matched our inclusion criteria and were included in the review. Meta-analysis (of unadjusted study outcomes) demonstrated statistically significant associations between chronic pain and mortality from cardiovascular diseases: pooled odds ratio 1.20, (95% confidence intervals 1.05-1.36); chronic pain and cardiac disease: pooled odds ratio 1.73 (95% confidence intervals 1.42-2.04); and chronic pain and cerebrovascular disease: pooled odds ratio 1.81 (95% confidence intervals 1.51-2.10). The systematic review also found evidence supporting a dose-response relationship, with greater pain intensity and distribution producing a stronger association with cardiovascular outcomes. All of the included studies were based on observational data with considerable variation in chronic pain taxonomy, methodology and study populations. The studies took an inconsistent and incomplete approach in their adjustment for potentially confounding variables, making it impossible to pool data after adjustments for confounding variables, so it cannot be concluded that these associations are causal. CONCLUSIONS: Our review supports a possible dose-response type of association between chronic pain and cardiovascular disease, supported by a range of observational studies originating from different countries. Such research has so far failed to satisfactorily rule out that the association is due to confounding variables. What is now needed are further population based longitudinal studies that are designed to allow more robust exploration of a cause and effect relationship. IMPLICATIONS: Given the high prevalence of chronic pain in developed and developing countries our results highlight a significant, but underpublicized, public health concern. Greater acknowledgement of the potentially harmful biological consequences of chronic pain may help to support regional, national and global initiatives aimed at reducing the burden of chronic pain.

A cross-sectional mixed methods study protocol to generate learning from patient safety incidents reported from general practice.

INTRODUCTION: Incident reports contain descriptions of errors and harms that occurred during clinical care delivery. Few observational studies have characterised incidents from general practice, and none of these have been from the England and Wales National Reporting and Learning System. This study aims to describe incidents reported from a general practice care setting. METHODS AND ANALYSIS: A general practice patient safety incident classification will be developed to characterise patient safety incidents. A weighted-random sample of 12,500 incidents describing no harm, low harm and moderate harm of patients, and all incidents describing severe harm and death of patients will be classified. Insights from exploratory descriptive statistics and thematic analysis will be combined to identify priority areas for future interventions. ETHICS AND DISSEMINATION: The need for ethical approval was waivered by the Aneurin Bevan University Health Board research risk review committee given the anonymised nature of data (ABHB R&D Ref number: SA/410/13). The authors will submit the results of the study to relevant journals and undertake national and international oral presentations to researchers, clinicians and policymakers.

Errors in the management of cardiac arrests: an observational study of patient safety incidents in England.

OBJECTIVE: The aim of this qualitative study is to better understand the types of error occurring during the management of cardiac arrests that led to a death. METHODS: All patient safety incidents involving management of cardiac arrests and resulting in death which were reported to a national patient safety database over a 17-month period were analysed. Structured data from each report were extracted and these together with the free text, were subjected to content analysis which was inductive, with the coding scheme emerged from continuous reading and re-reading of incidents. RESULTS: There were 30 patient safety incidents involving management of cardiac arrests and resulting in death. The reviewers identified a main shortfall in the management of each cardiac arrest and this resulted in 12 different factors being documented. These were grouped into four themes that highlighted systemic weaknesses: miscommunication involving crash number (4/30, 13%), shortfalls in staff attending the arrest (4/30, 13%), equipment deficits (11/30, 36%), and poor application of knowledge and skills (11/30, 37%). CONCLUSION: The factors identified represent serious shortfalls in the quality of response to cardiac arrests resulting in death in hospital. No firm conclusion can be drawn about how many deaths in the study population would have been averted if the emergency had been managed to a high standard. The effective management of cardiac arrests should be considered as one of the markers of safe care within a healthcare organisation.

What is the risk of death or severe harm due to bone cement implantation syndrome among patients undergoing hip hemiarthroplasty for fractured neck of femur? A patient safety surveillance study.

OBJECTIVE: To estimate the risk of death or severe harm due to bone cement implantation syndrome (BCIS) among patients undergoing hip hemiarthroplasty for fractured neck of femur. SETTING: Hospitals providing secondary and tertiary care throughout the National Health Service (NHS) in England and Wales. PARTICIPANTS: Cases reported to the National Reporting and Learning System (NRLS) in which the reporter clearly describes severe acute patient deterioration associated with cement use in hip hemiarthroplasty for fractured neck of femur (assessed independently by two reviewers). OUTCOME MEASURES: Primary-number of reported deaths, cardiac arrests and periarrests per year. Secondary-timing of deterioration and outcome in relation to cement insertion. RESULTS: Between 2005 and 2012, the NRLS received 62 reports that clearly describe death or severe harm associated with the use of cement in hip hemiarthroplasty for fractured neck of femur. There was one such incident for every 2900 hemiarthroplasties for fractured neck of femur during the period. Of the 62 reports, 41 patients died, 14 were resuscitated from cardiac arrest and 7 from periarrest. Most reports (55/62, 89%) describe acute deterioration occurring during or within a few minutes of cement insertion. The vast majority of deaths (33/41, 80%) occurred on the operating table. CONCLUSIONS: These reports provide narrative evidence from England and Wales that cement use in hip hemiarthroplasty for fractured neck of femur is associated with instances of perioperative death or severe harm consistent with BCIS. In 2009, the National Patient Safety Agency publicised this issue and encouraged the use of mitigation measures. Three-quarters of the deaths in this study have occurred since that alert, suggesting incomplete implementation or effectiveness of those mitigation measures. There is a need for stronger evidence that weighs the risks and benefits of cement in hip hemiarthroplasty for fractured neck of femur.

Patient-safety-related hospital deaths in England: thematic analysis of incidents reported to a national database, 2010-2012.

BACKGROUND: Hospital mortality is increasingly being regarded as a key indicator of patient safety, yet methodologies for assessing mortality are frequently contested and seldom point directly to areas of risk and solutions. The aim of our study was to classify reports of deaths due to unsafe care into broad areas of systemic failure capable of being addressed by stronger policies, procedures, and practices. The deaths were reported to a patient safety incident reporting system after mandatory reporting of such incidents was introduced. METHODS AND FINDINGS: The UK National Health Service database was searched for incidents resulting in a reported death of an adult over the period of the study. The study population comprised 2,010 incidents involving patients aged 16 y and over in acute hospital settings. Each incident report was reviewed by two of the authors, and, by scrutinising the structured information together with the free text, a main reason for the harm was identified and recorded as one of 18 incident types. These incident types were then aggregated into six areas of apparent systemic failure: mismanagement of deterioration (35%), failure of prevention (26%), deficient checking and oversight (11%), dysfunctional patient flow (10%), equipment-related errors (6%), and other (12%). The most common incident types were failure to act on or recognise deterioration (23%), inpatient falls (10%), healthcare-associated infections (10%), unexpected per-operative death (6%), and poor or inadequate handover (5%). Analysis of these 2,010 fatal incidents reveals patterns of issues that point to actionable areas for improvement. CONCLUSIONS: Our approach demonstrates the potential utility of patient safety incident reports in identifying areas of service failure and highlights opportunities for corrective action to save lives.

Identifying systems failures in the pathway to a catastrophic event: an analysis of national incident report data relating to vinca alkaloids.

BACKGROUND: Catastrophic errors in healthcare are rare, yet the consequences are so serious that where possible, special procedures are put in place to prevent them. As systems become safer, it becomes progressively more difficult to detect the remaining vulnerabilities. Using inadvertent intrathecal administration of vinca alkaloids as an example, we investigated whether analysis of incident report data describing low-harm events could bridge this gap. METHODS: We studied nine million patient safety incidents reported from England and Wales between November 2003 and May 2013. We searched for reports relating to administration of vinca alkaloids in patients also receiving intrathecal medication, and classified the failures identified against steps in the relevant national protocol. RESULTS: Of 38 reports that met our inclusion criteria, none resulted in actual harm. The stage of the medication process most commonly involved was 'supply, transport and storage' (15 cases). Seven cases related to dispensing, six to documentation, and four each to prescribing and administration. Defences most commonly breached related to separation of intravenous vinca alkaloids and intrathecal medication in timing (n=16) and location (n=8); potential for confusion due to inadequate separation of these drugs therefore remains. Problems involved in six cases did not align with the procedural defences in place, some of which represented major hazards. CONCLUSIONS: We identified areas of concern even within the context of a highly controlled standardised national process. If incident reporting systems include and encourage reports of no-harm incidents in addition to actual patient harm, they can facilitate monitoring the resilience of healthcare processes. Patient safety incidents that produce the most serious harm are often rare, and it is difficult to know whether patients are adequately protected. Our approach provides a potential solution.

Identification of poor performance in a national medical workforce over 11 years: an observational study.

BACKGROUND: Poorly performing doctors are a source of harm but do not commonly feature in discussions of patient safety. Few countries have national mechanisms to deal with these doctors; most opt for suspension and/or exclusion from clinical practice. This study reports on the 11-year experience of dealing with concerns about doctors' performance in the UK National Health Service (NHS). The aim of this study was to describe the frequency with which doctors were referred due to performance-related concerns, examine demographic and specialty differences, and identify the nature of the concerns prompting referral. METHODS: This observational study uses data collected by the National Clinical Assessment Service for each referral (n=6179 doctors) over an 11-year period (April 2001-March 2012) in England to examine the rate at which concerns about doctors' performance occur, understand differences in rates between practitioner groups, and changes over time. FINDINGS: The annual referral rate was five per 1000 doctors (95% CI 4.6 to 5.4). Doctors whose first medical qualification was gained outside the UK were more than twice as likely to be referred as UK-qualified doctors; male doctors were more than twice as likely to be referred as women doctors; and doctors in the late stages of their career were nearly six times as likely to be referred as early career doctors. DISCUSSION: The UK holds a consistently collected national dataset on performance concerns about doctors. This allows risk groups to be identified so that preventive action and early intervention can be targeted most effectively to reduce harm to patients. A feature of past handling of poor clinical performance has been late presentation and a lack of thematic study of causation.

Reducing the burden of surgical harm: a systematic review of the interventions used to reduce adverse events in surgery.

OBJECTIVE: To perform a systematic review of interventions used to reduce adverse events in surgery. BACKGROUND: Many interventions, which aim to improve patient safety in surgery, have been introduced to hospitals. Little is known about which methods provide a measurable decrease in morbidity and mortality. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched from inception to Week 19, 2012, for systematic reviews, randomized controlled trials (RCTs), and cross-sectional and cohort studies, which reported an intervention aimed toward reducing the incidence of adverse events in surgical patients. The quality of observational studies was measured using the Newcastle-Ottawa Scale. RCTs were assessed using the Cochrane Collaboration's tool for assessing risk of bias. RESULTS: Ninety-one studies met inclusion criteria, 26 relating to structural interventions, 66 described modifying process factors. Only 17 (of 42 medium to high quality studies) reported an intervention that produced a significant decrease in morbidity and mortality. Structural interventions were: improving nurse to patient ratios (P = 0.008) and Intensive Care Unit (ITU) physician involvement in postoperative care (P < 0.05). Subspecialization in surgery reduced technical complications (P < 0.01). Effective process interventions were submission of outcome data to national audit (P < 0.05), use of safety checklists (P < 0.05), and adherence to a care pathway (P < 0.05). Certain safety technology significantly reduced harm (P = 0.02), and team training had a positive effect on patient outcome (P = 0.001). CONCLUSIONS: Only a small cohort of medium- to high-quality interventions effectively reduce surgical harm and are feasible to implement. It is important that future research remains focused on demonstrating a measurable reduction in adverse events from patient safety initiatives.

Global research priorities to better understand the burden of iatrogenic harm in primary care: an international Delphi exercise.

Using a modified Delphi exercise, Aziz Sheikh and colleagues identify research priorities for patient safety research in primary care contexts. Please see later in the article for the Editors' Summary.

The orthopaedic error index: development and application of a novel national indicator for assessing the relative safety of hospital care using a cross-sectional approach.

OBJECTIVE: The Orthopaedic Error Index for hospitals aims to provide the first national assessment of the relative safety of provision of orthopaedic surgery. DESIGN: Cross-sectional study (retrospective analysis of records in a database). SETTING: The National Reporting and Learning System is the largest national repository of patient-safety incidents in the world with over eight million error reports. It offers a unique opportunity to develop novel approaches to enhancing patient safety, including investigating the relative safety of different healthcare providers and specialties. PARTICIPANTS: We extracted all orthopaedic error reports from the system over 1 year (2009-2010). OUTCOME MEASURES: The Orthopaedic Error Index was calculated as a sum of the error propensity and severity. All relevant hospitals offering orthopaedic surgery in England were then ranked by this metric to identify possible outliers that warrant further attention. RESULTS: 155 hospitals reported 48 971 orthopaedic-related patient-safety incidents. The mean Orthopaedic Error Index was 7.09/year (SD 2.72); five hospitals were identified as outliers. Three of these units were specialist tertiary hospitals carrying out complex surgery; the remaining two outlier hospitals had unusually high Orthopaedic Error Indexes: mean 14.46 (SD 0.29) and 15.29 (SD 0.51), respectively. CONCLUSIONS: The Orthopaedic Error Index has enabled identification of hospitals that may be putting patients at disproportionate risk of orthopaedic-related iatrogenic harm and which therefore warrant further investigation. It provides the prototype of a summary index of harm to enable surveillance of unsafe care over time across institutions. Further validation and scrutiny of the method will be required to assess its potential to be extended to other hospital specialties in the UK and also internationally to other health systems that have comparable national databases of patient-safety incidents.

The diagnosis of food allergy: protocol for a systematic review.

BACKGROUND: The literature on diagnostic tests for food allergy currently lacks clear consensus regarding the accuracy and safety of different investigative approaches. The European Academy of Allergy and Clinical Immunology is in the process of developing its Guideline for Food Allergy and Anaphylaxis, and this systematic review is one of seven inter-linked evidence syntheses that are being undertaken in order to provide a state-of-the-art synopsis of the current evidence base in relation to epidemiology, prevention, diagnosis and clinical management, and impact on quality of life, which will be used to inform the formulation of clinical recommendations. The aim of this systematic review will be to assess the diagnostic accuracy of tests aimed at supporting the clinical diagnosis of IgE-mediated food allergy. METHODS: The following databases from inception to September 30, 2012 will be searched for studies of diagnostic tests: Cochrane Library (Wiley&Sons); MEDLINE (OVID); Embase (OVID); CINAHL (Ebscohost); ISI Web of Science (Thomson Web of Knowledge); TRIP Database (web http://www.tripdatabase.com); and Clinicaltrials.gov (NIH web). These database searches will be supplemented by contacting an international panel of experts. Studies evaluating APT, SPT, specific-IgE, and component specific-IgE in participants of any age with suspected food allergy will be included. The reference standard will be DBPCFC in at least 50% of the participants. Studies will be quality assessed by using the QUADAS-2 instrument. We will report summary statistics such as sensitivity, specificity, and/or likelihood ratios. We will use the hierarchical summary ROC (HSROC) model to summarize the accuracy of each test and to compare the accuracy of two or more tests. DISCUSSION: Decisions on which tests to use need to be guided by availability of tests, populations being cared for, risks, financial considerations and test properties. This review will examine papers from around the world, covering children and adults with suspected food allergy in varying populations and concentrated on four type of tests: APT, SPT, specific-IgEs, and component specific-IgEs.

Disease-specific health-related quality of life (HRQL) instruments for food allergy: protocol for a systematic review.

BACKGROUND: The European Academy of Allergy and Clinical Immunology is in the process of developing its Guideline for Food Allergy and Anaphylaxis, and this systematic review is one of seven inter-linked evidence syntheses that are being undertaken in order to provide a state-of-the-art synopsis of the current evidence base in relation to epidemiology, prevention, diagnosis and clinical management, and impact on quality of life, which will be used to inform clinical recommendations. The aim of this systematic review will be to determine which validated instruments can be employed to enable assessment of the impact of, and investigations and interventions for, food allergy on health-related quality of life. METHODS: Seven bibliographic databases were searched from their inception to September 30, 2012 for disease-specific HRQL questionnaires that were specifically designed for use with patients/carers and any articles relating to the description, development and/or the validation of the above identified HRQLs. There were no language or geographic restrictions. We will assess the development of the instruments identified and their performance properties including: validity; generalizability; responsiveness; managing missing data; how variation in patient demography was managed; and cross-cultural and linguistic adaptation, using a previously reported quality assessment tool. DISCUSSION: Using appropriately developed and validated instruments is critical to the accurate evaluation of HRQL in people with food allergy. This review will systematically appraise the evidence on the subject and help to identify any gaps.

Patient safety in orthopedic surgery: prioritizing key areas of iatrogenic harm through an analysis of 48,095 incidents reported to a national database of errors.

BACKGROUND: With scientific and technological advances, the practice of orthopedic surgery has transformed the lives of millions worldwide. Such successes however have a downside; not only is the provision of comprehensive orthopedic care becoming a fiscal challenge to policy-makers and funders, concerns are also being raised about the extent of the associated iatrogenic harm. The National Reporting and Learning System (NRLS) in England and Wales is an underused resource which collects intelligence from reports about health care error. METHODS: Using methods akin to case-control methodology, we have identified a method of prioritizing the areas of a national database of errors that have the greatest propensity for harm. Our findings are presented using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The largest proportion of surgical patient safety incidents reported to the NRLS was from the trauma and orthopedics specialty, 48,095/163,595 (29.4%). Of those, 14,482/48,095 (30.1%) resulted in iatrogenic harm to the patient and 71/48,095 (0.15%) resulted in death. The leading types of errors associated with harm involved the implementation of care and on-going monitoring (OR 5.94, 95% CI 5.53, 6.38); self-harming behavior of patients in hospitals (OR 2.14, 95% CI 1.45, 3.18); and infection control (OR 1.91, 95% CI 1.69, 2.17). We analyze these data to quantify the extent and type of iatrogenic harm in the specialty, and make suggestions on the way forward. CONCLUSION AND LEVEL OF EVIDENCE: Despite the limitations of such analyses, it is clear that there are many proven interventions which can improve patient safety and need to be implemented. Avoidable errors must be prevented, lest we be accused of contravening our fundamental duty of primum non nocere. This is a level III evidence-based study.

The acute and long-term management of anaphylaxis: protocol for a systematic review.

BACKGROUND: The European Academy of Allergy and Clinical Immunology is in the process of developing its Guideline for Food Allergy and Anaphylaxis, and this systematic review is one of seven inter-linked evidence syntheses that are being undertaken in order to provide a state-of-the-art synopsis of the current evidence base in relation to epidemiology, prevention, diagnosis and clinical management and impact on quality of life, which will be used to inform clinical recommendations.The aims of this systematic review will be to assess the effectiveness of interventions for the acute management of anaphylaxis, and pharmacological and non-pharmacological approaches for the long-term management of anaphylaxis. METHODS: A highly sensitive search strategy has been developed, and validated study design filters will be applied to retrieve all articles pertaining to the management of anaphylaxis from electronic bibliographic databases. We will systematically review the literature on the acute management of anaphylaxis by assessing the effectiveness of epinephrine, H1-antihistamines (versus placebo), systemic glucocorticosteroids, methylxanthines or any other treatments for the emergency management of people experiencing anaphylaxis. The main interventions that have been studied in the context of long-term management are anaphylaxis management plans and allergen-specific immunotherapy. DISCUSSION: There is at present little in the way of robust evidence to guide decisions on the acute and/or long-term management of anaphylaxis. Given the risk of death and the considerable morbidity associated with anaphylaxis these evidence gaps need to be filled wherever possible; this systematic review will make a start in this area.

The acute and long-term management of food allergy: protocol for a rapid systematic review.

BACKGROUND: Allergic reactions to plant and animal derived food allergens can have serious consequences for sufferers and their families. The associated social, emotional and financial costs make it a priority to understand the best ways of managing such immune-mediated hypersensitivity responses. Conceptually, there are two main approaches to managing food allergy: those targeting immediate symptoms and those aiming to support long-term management of the condition. The European Academy of Allergy and Clinical Immunology is developing guidelines about what constitutes an effective treatment for food allergies. As part of the guidelines development process, a systematic review is planned to examine published research about the management of food allergy in adults and children. METHODS: Seven bibliographic databases were searched from their inception to September 30, 2012 for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after studies and interrupted time series. Experts were consulted for additional studies. There were no language or geographic restrictions. Studies were critically appraised using the Critical Appraisal Skills Program and Cochrane EPOC Risk of Bias tools. Only studies where people had a diagnosis of food allergy or reported a history of food allergy were included. This means that many studies of conditions that may be caused by food allergy are omitted, because only research in people with an explicit diagnosis or history was eligible. DISCUSSION: Many initiatives have been tested to treat the immediate symptoms of food allergy (acute management) and to deal with longer lasting symptoms or induce tolerability to potential allergens (long-term management). The best management strategies for people with food allergy are likely to depend on the type of allergy, symptom manifestations and age. There is a real need to increase the amount of high quality research devoted to treatment strategies for food allergy. Food allergy can be debilitating and is affecting an increasing number of children and adults. With such little known about how to effectively manage the condition and its manifestations, this appears a priority for future research.

The epidemiology of food allergy in Europe: protocol for a systematic review.

BACKGROUND: The European Academy of Allergy and Clinical Immunology is in the process of developing its Guideline for Food Allergy and Anaphylaxis, and this protocol of a systematic review is one of seven inter-linked evidence syntheses that are being undertaken in order to provide a state-of-the-art synopsis of the current evidence base in relation to epidemiology, prevention, diagnosis and clinical management and impact on quality of life, which will be used to inform the formulation of clinical recommendations.The aims of the systematic review will be to understand and describe the epidemiology of food allergy, i.e. frequency, risk factors and outcomes of patients suffering from food allergy, and to describe how these characteristics vary by person, place and time. METHODS: A highly sensitive search strategy has been developed to retrieve articles that have investigated the various aspects of the epidemiology of food allergy. The search will be implemented by combining the concepts of food allergy and its epidemiology from electronic bibliographic databases. DISCUSSION: This systematic review will provide the most up to date estimates of the frequency of food allergy in Europe. We will attempt to break these down by age and geographical region in Europe. Our analysis will take into account the suitability of the study design and the respective study biases that could affect exposure and outcome. We will examine the different methods to diagnose food allergy and the associated measures of occurrence.

Preventing food allergy: protocol for a rapid systematic review.

BACKGROUND: The European Academy of Allergy and Clinical Immunology is developing guidelines about how to prevent and manage food allergy. As part of the guidelines development process, a systematic review is planned to examine published research about the prevention of food allergy. This systematic review is one of seven inter-linked evidence syntheses that are being undertaken in order to provide a state-of-the-art synopsis of the current evidence base in relation to epidemiology, prevention, diagnosis and clinical management, and impact on quality of life, which will be used to inform clinical recommendations. The aim of this systematic review will be to assess the effectiveness of approaches for the primary prevention of food allergy. METHODS: Seven bibliographic databases will be searched from their inception to September 30, 2012 for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after studies, interrupted time series and cohort studies. Cohort studies will be included due to an inability to randomize with interventions such as breastfeeding. Studies that focused on the development of either food sensitization (a proxy measure) or food allergy will also be eligible for inclusion. Studies will be critically appraised using the Critical Appraisal Skills Program and Cochrane Risk of Bias tools, as appropriate. DISCUSSION: There is a lack of rigorous evidence to support recommendations about how to prevent the development of food allergy. It would appear that it is important to see the prevention of food allergy in the context of individual, family and wider factors that may influence its development. There is much left to learn about preventing food allergy, and this is a priority given the high societal and healthcare costs involved. This systematic review will help to further this learning.