case study medicine bmj

Search the world's largest collection of clinical case reports

Browse case reports by:

Publish in BMJ Case Reports

Global health case reports.

These are case reports that focus on the causes of ill health, the social determinants of health and access to healthcare services, prevailing local and national issues that affect health and wellbeing, and the challenges in providing care to vulnerable populations or with limited resources.

Read the full collection now

Case Reports: Unusual presentation of more common disease/injury :

2 August 2023

Images in… :

7 June 2023

14 July 2023

Case Reports: Rare disease :

5 July 2023

18 July 2023

Case Reports: Adverse drug reactions and complications :

6 June 2023

Case Reports: Unusual association of diseases/symptoms :

1 June 2023

10 July 2023

Case Reports by specialty

Anaesthesia
Dentistry and oral medicine
Dermatology
Emergency medicine
Endocrinology
General practice and family medicine
Geriatric medicine
Haematology
Infectious diseases
Obstetrics and gynaecology
Ophthalmology
Orthopaedics
Paediatrics
Respiratory medicine
Rheumatology

AltmetricsTEST4

Global Health Competition

Every year BMJ Case Reports selects authors of global health case reports to join our editorial team as a global health associate editor.

This is an opportunity to gain some editorial experience or join our team on research and educational projects. Students and graduates may apply.

Simply select Global Health Competition when you submit.

Latest Articles

Rheumatology :

31 May 2024

Log in using your username and password

Search More Search for this keyword Advanced search
Latest content
Call for Papers
BMJ Journals More You are viewing from: Google Indexer

http://orcid.org/0000-0003-1141-7613 Sergi Fàbregues 1 and
Michael D Fetters 2
1 Department of Psychology and Education , Universitat Oberta de Catalunya , Barcelona , Spain
2 Department of Family Medicine , University of Michigan , Ann Arbor , Michigan , USA
Correspondence to Dr Sergi Fàbregues, Department of Psychology and Education, Universitat Oberta de Catalunya, Rambla del Poblenou, 156, 08018, Barcelona, Spain; sfabreguesf{at}uoc.edu

The aim of this article is to introduce family medicine researchers to case study research, a rigorous research methodology commonly used in the social and health sciences and only distantly related to clinical case reports. The article begins with an overview of case study in the social and health sciences, including its definition, potential applications, historical background and core features. This is followed by a 10-step description of the process of conducting a case study project illustrated using a case study conducted about a teaching programme executed to teach international family medicine resident learners sensitive examination skills. Steps for conducting a case study include (1) conducting a literature review; (2) formulating the research questions; (3) ensuring that a case study is appropriate; (4) determining the type of case study design; (5) defining boundaries of the case(s) and selecting the case(s); (6) preparing for data collection; (7) collecting and organising the data; (8) analysing the data; (9) writing the case study report; and (10) appraising the quality. Case study research is a highly flexible and powerful research tool available to family medicine researchers for a variety of applications.

Case study research
research design
mixed methods
family practice
primary care
general practice

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0

https://doi.org/10.1136/fmch-2018-000074

Statistics from Altmetric.com

Request permissions.

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Significance statement

Given their potential for answering ‘how’ and ‘why’ questions about complex issues in their natural setting, case study designs are being increasingly used in the health sciences. Conducting a case study can, however, be a complex task because of the possibility of combining multiple methods and the need to choose between different types of case study designs. In order to introduce family medicine and community health researchers to the fundamentals of case study research, this article reviews its definition, potential applications, historical background and main characteristics. It follows on with a practical, step-by-step description of the case study process that will be useful to researchers interested in implementing this research design in their own practice.

Introduction

This article provides family medicine and community health researchers a concise resource to conduct case study research. The article opens with an overview of case study in the social and health sciences, including its definition, potential applications, historical background and core features. This is followed by a 10-step description of the process of conducting a case study project, as described in the literature. These steps are illustrated using a case study about a teaching programme executed to teach international medical learners sensitive examination skills. The article ends with recommendations of useful articles and textbooks on case study research.

Origins of case study research

Case study is a research design that involves an intensive and holistic examination of a contemporary phenomenon in a real-life setting. 1–3 It uses a variety of methods and multiple data sources to explore, describe or explain a single case bounded in time and place (ie, an event, individual, group, organisation or programme). A distinctive feature of case study is its focus on the particular characteristics of the case being studied and the contextual aspects, relationships and processes influencing it. 4 Here we do not include clinical case reports as these are beyond the scope of this article. While distantly related to clinical case reports commonly used to report unusual clinical case presentations or findings, case study is a research approach that is frequently used in the social sciences and health sciences. In contrast to other research designs, such as surveys or experiments, a key strength of case study is that it allows the researcher to adopt a holistic approach—rather than an isolated approach—to the study of social phenomena. As argued by Yin, 3 case studies are particularly suitable for answering ‘how’ research questions (ie, how a treatment was received) as well as ‘why’ research questions (ie, why the treatment produced the observed outcomes).

Given its potential for understanding complex processes as they occur in their natural setting, case study increasingly is used in a wide range of health-related disciplines and fields, including medicine, 5 nursing, 6 health services research 1 and health communication. 7 With regard to clinical practice and research, a number of authors 1 5 8 have highlighted how insights gained from case study designs can be used to describe patients’ experiences regarding care, explore health professionals’ perceptions regarding a policy change, and understand why medical treatments and complex interventions succeed or fail.

In anthropology and sociology, case study as a research design was introduced as a response to the prevailing view of quantitative research as the primary way of undertaking research. 9 From its beginnings, social scientists saw case study as a method to obtain comprehensive accounts of social phenomena from participants. In addition, it could complement the findings of survey research. Between the 1920s and 1960s, case study became the predominant research approach among the members of the Department of Sociology of the University of Chicago, widely known as ‘The Chicago School’. 10 11 During this period, prominent sociologists, such as Florian Znaniecki, William Thomas, Everett C Hughes and Howard S Becker, undertook a series of innovative case studies (including classical works such as The Polish peasant in Europe and America or Boys in White ), which laid the foundations of case study designs as implemented today.

In the 1970s, case study increasingly was adopted in the USA and UK in applied disciplines and fields, such as education, programme evaluation and public policy research. 12 As a response to the limitations of quasi-experimental designs for undertaking comprehensive programme evaluations, researchers in these disciplines saw in case studies—either alone or in combination with experimental designs—an opportunity to gain additional insights into the outcomes of programme implementation. In the mid-1980s and early 1990s, the case study approach became recognised as having its own ‘logic of design’ (p46). 13 This period coincides with the publication of a considerable number of influential articles 14–16 and textbooks 4 17 18 on case study research.

These publications were instrumental in shaping contemporary case study practice, yet they reflected divergent views about the nature of case study, including how it should be defined, designed and implemented (see Yazan 19 for a comparison of the perspectives of Yin, Merriam and Stake, three leading case study methodologists). What these publications have in common is that case study revolves around four key features.

First, case study examines a specific phenomenon in detail by performing an indepth and intensive analysis of the selected case. The rationale for case study designs, rather than more expansive designs such as surveys, is that the researcher is interested in investigating the particularity of a case, that is, the unique attributes that define an event, individual, group, organisation or programme. 2 Second, case study is conducted in natural settings where people meet, interact and change their perceptions over time. The use of the case study design is a choice in favour of ‘maintaining the naturalness of the research situation and the natural course of events’ (p177). 20

Third, case study assumes that a case under investigation is entangled with the context in which it is embedded. This context entails a number of interconnected processes that cannot be disassociated from the case, but rather are part of the study. The case study researcher is interested in understanding how and why such processes take place and, consequently, uncovering the interactions between a case and its context. Research questions concerning how and why phenomena occur are particularly appropriate in case study research. 3

Fourth, case study encourages the researcher to use a variety of methods and data types in a single study. 20 21 These can be solely qualitative, solely quantitative or a mixture of both. The latter option allows the researcher to gain a more comprehensive understanding of the case and improve the accuracy of the findings. The four above-mentioned key features of case study are shown in table 1 , using the example of a mixed methods case study evaluation. 22

View inline

Key features of case study as presented by Shultz et al 22

There are many potential applications for case study research. While often misconstrued as having only an exploratory role, case study research can be used for descriptive and explanatory research (p7–9). 3 Family medicine and community health researchers can use case study research for evaluating a variety of educational programmes, clinical programmes or community programmes.

Case study illustration from family medicine

In the featured study, Japanese family medicine residents received standardised patient instructor-based training in female breast, pelvic, male genital and prostate examinations as part of an international training collaboration to launch a new family medicine residency programme. 22 From family medicine residents, trainers and staff, the authors collected and analysed data from post-training feedback, semistructured interviews and a web-based questionnaire. While the programme was perceived favourably, they noted barriers to reinforcement in their home training programme, and taboos regarding gender-specific healthcare appear as barriers to implementing a similar programme in the home institution.

A step-by-step description of the process of carrying out a case study

As shown in table 2 and illustrated using the article by Shultz et al , 22 case study research generally includes 10 steps. While commonly conducted in this order, the steps do not always occur linearly as data collection and analysis may occur over several iterations or implemented with a slightly different order.

Ten steps for conducting a case study

Examples of published studies using the four types of case study designs suggested by Yin 3

Step 1. Conduct a literature review

During the literature review, researchers systematically search for publications, select those most relevant to the study’s purpose, critically appraise them and summarise the major themes. The literature review helps researchers ascertain what is and is not known about the phenomenon under study, delineate the scope and research questions of the study, and develop an academic or practical justification for the study. 23

Step 2. Formulate the research questions

Research questions critically define in operational terms what will be researched and how. They focus the study and play a key role in guiding design decisions. Key decisions include the case selection and choice of a case study design most suitable for the study. According to Fraenkel et al , 24 the key attributes of good research questions are (1) feasibility, (2) clarity, (3) significance, (4) connection to previous research identified in the literature and (5) compliance with ethical research standards.

Step 3. Ensure that a case study is appropriate

Before commencing the study, researchers should ensure that case study design embodies the most appropriate strategy for answering the study questions. The above-noted four key features—in depth examination of phenomena, naturalness, a focus on context and the use of a combination of methods—should be reflected in the research questions as well as subsequent design decisions.

Step 4. Determine the type of case study design

Researchers need to choose a specific case study design. Sometimes, researchers may define the case first (step 5), for example, in a programme evaluation, and the case may need to be defined before determining the type. Yin’s 3 typology is based on two dimensions, whether the study will examine a single case or multiple cases, and whether the study will focus on a single or multiple units of analysis. Figure 1 illustrates these four types of design using a hypothetical example of a programme evaluation. Table 3 shows an example of each type from the literature.

Download figure
Open in new tab
Download powerpoint

Types of case study designs. 3 21

In type 1 holistic single case design , researchers examine a single programme as the sole unit of analysis. In type 2 embedded single case design , the interest is not exclusively in the programme, but also in its different subunits, including sites, staff and participants. These subunits constitute the range of units of analysis. In type 3 holistic multiple case design , researchers conduct a within and cross-case comparison of two or more programmes, each of which constitutes a single unit of analysis. A major strength of multiple case designs is that they enable researchers to develop an in depth description of each case and to identify patterns of variation and similarity between the cases. Multiple case designs are likely to have stronger internal validity and generate more insightful findings than single case designs. They do this by allowing ‘examination of processes and outcomes across many cases, identification of how individual cases might be affected by different environments, and the specific conditions under which a finding may occur’ (p583). 25 In type 4 embedded multiple case design , a variant of the holistic multiple case design, researchers perform a detailed examination of the subunits of each programme, rather than just examining each case as a whole.

Step 5. Define the boundaries of the case(s) and select the case(s)

Miles et al 26 define a case as ‘a phenomenon of some sort occurring in a bounded context’ (p28). What is and is not the case and how the case fits within its broader context should be explicitly defined. As noted in step 4, this step may occur before choice of the case study type, and the process may actually occur in a back-and-forth fashion. A case can entail an individual, a group, an organisation, an institution or a programme. In this step, researchers delineate the spatial and temporal boundaries of the case, that is, ‘when and where it occurred, and when and what was of interest’ (p390). 9 Aside from ensuring the coherence and consistency of the study, bounding the case ensures that the planned research project is feasible in terms of time and resources. Having access to the case and ensuring ethical research practice are two central considerations in case selection. 1

Step 6. Prepare to collect data

Before beginning the data collection, researchers need a study protocol that describes in detail the methods of data collection. The protocol should emphasise the coherence between the data collection methods and the research questions. According to Yin, 3 a case study protocol should include (1) an overview of the case study, (2) data collection procedures, (3) data collection questions and (4) a guide for the case study report. The protocol should be sufficiently flexible to allow researchers to make changes depending on the context and specific circumstances surrounding each data collection method.

Step 7. Collect and organise the data

While case study is often portrayed as a qualitative approach to research (eg, interviews, focus groups or observations), case study designs frequently rely on multiple data sources, including quantitative data (eg, surveys or statistical databases). A growing number of authors highlight the ways in which the use of mixed methods within case study designs might contribute to developing ‘a more complete understanding of the case’ (p902), 21 shedding light on ‘the complexity of a case’ (p118) 27 or increasing ‘the internal validity of a study’ (p6). 1 Guetterman and Fetters 21 explain how a qualitative case study can also be nested within a mixed methods design (ie, be considered the qualitative component of the design). An interesting strategy for organising multiple data sources is suggested by Yin. 3 He recommends using a case study database in which different data sources (eg, audio files, notes, documents or photographs) are stored for later retrieval or inspection. See guidance from Creswell and Hirose 28 for conducting a survey and qualitative data collection in mixed methods and DeJonckheere 29 on semistructured interviewing.

Step 8. Analyse the data

Bernard and Ryan 30 define data analysis as ‘the search for patterns in data and for ideas that help explain why these patterns are there in the first place’ (p109). Depending on the case study design, analysis of the qualitative and quantitative data can be done concurrently or sequentially. For the qualitative data, the first step of the analysis involves segmenting the data into coding units, ascribing codes to data segments and organising the codes in a coding scheme. 31 Depending on the role of theory in the study, an inductive, data-driven approach can be used where meaning is found in the data, or a deductive, concept-driven approach can be adopted where predefined concepts derived from the literature, or previous research, are used to code the data. 32 The second step involves searching for patterns across codes and subsets of respondents, so major themes are identified to describe, explain or predict the phenomenon under study. Babchuk 33 provides a step-by-step guidance for qualitative analysis in this issue. When conducting a single case study, the within-case analysis yields an in depth, thick description of the case. When the study involves multiple cases, the cross-comparison analysis elicits a description of similarities and divergence between cases and may generate explanations and theoretical predictions regarding other cases. 26

For the quantitative part of the case study, data are entered in statistical software packages for conducting descriptive or inferential analysis. Guetterman 34 provides a step-by-step guidance on basic statistics. In case study designs where both data strands are analysed simultaneously, analytical techniques include pattern matching, explanation building, time-series analysis and creating logic models (p142–167). 3

Step 9. Write the case study report

The case study report should have the following three characteristics. First, the description of the case and its context should be sufficiently comprehensive to allow the reader to understand the complexity of the phenomena under study. 35 Second, the data should be presented in a concise and transparent manner to enable the reader to question, or to re-examine, the findings. 36 Third, the report should be adapted to the interests and needs of its primary audience or audiences (eg, academics, practitioners, policy-makers or funders of research). Yin 3 suggests six formats for organising case study reports, namely linear-analytic, comparative, chronological, theory building, suspense and unsequenced structures. To facilitate case transferability and applicability to other similar contexts, the case study report must include a detailed description of the case.

Step 10. Appraise quality

Although presented as the final step of the case study process, quality appraisal should be considered throughout the study. Multiple criteria and frameworks for appraising the quality of case study research have been suggested in the literature. Yin 3 suggests the following four criteria: construct validity (ie, the extent to which a study accurately measures the concepts that it claims to investigate), internal validity (ie, the strength of the relationship between variables and findings), external validity (ie, the extent to which the findings can be generalised) and reliability (ie, the extent to which the findings can be replicated by other researchers conducting the same study). Yin 37 also suggests using two separate sets of guidelines for conducting case study research and for appraising the quality of case study proposals. Stake 4 presents a 20-item checklist for critiquing case study reports, and Creswell and Poth 38 and Denscombe 39 outline a number of questions to consider. Since these quality frameworks have evolved from different disciplinary and philosophical backgrounds, the researcher’s approach should be coherent with the epistemology of the study. Figure 2 provides a quality appraisal checklist adapted from Creswell and Poth 38 and Denscombe. 39

Checklist for evaluating the quality of a case study. 38 39

The challenges to conducting case study research include rationalising the literature based on literature review, writing the research questions, determining how to bound the case, and choosing among various case study purposes and designs. Factors held in common with other methods include analysing and presenting the findings, particularly with multiple data sources.

Other resources

Resources with more in depth guidance on case study research include Merriam, 17 Stake 4 and Yin. 3 While each reflects a different perspective on case study research, they all provide useful guidance for designing and conducting case studies. Other resources include Creswell and Poth, 38 Swanborn 2 and Tight. 40 For mixed methods case study designs, Creswell and Clark, 27 Guetterman and Fetters, 21 Luck et al , 6 and Plano Clark et al 41 provide guidance. Byrne and Ragin’s 42 The SAGE Handbook of Case-Based Methods and Mills et al ’s 43 Encyclopedia of case study research provide guidance for experienced case study researchers.

Conclusions

Family medicine and community health researchers engage in a wide variety of clinical, educational, research and administrative programmes. Case study research provides a highly flexible and powerful research tool to evaluate rigorously many of these endeavours and disseminate this information.

Acknowledgments

The authors would like to acknowledge the help of Dick Edelstein and Marie-Hélène Paré in editing the final manuscript.

Cresswell K ,
Robertson A , et al
Walshe CE ,
Caress AL ,
Chew-Graham C , et al
Jackson D ,
Adelman C ,
Eurepos G ,
Eurepos G , et al
Lincoln YS ,
Eisenhardt KM
Hijmans E ,
Guetterman TC ,
Shultz CG ,
Yajima A , et al
Fraenkel J ,
Huberman A ,
Creswell J ,
DeJonckheere M
Bernard H ,
Guetterman T
Denscombe M
Plano Clark VL ,
Walton JB , et al
Little SH ,
Motohara S ,
Miyazaki K , et al
Peterson JC ,
Rogers EM ,
Cunningham-Sabo L , et al
Halladay JR ,
Reed D , et al

Contributors SF and MDF conceived and drafted the manuscript, and approved the final version of the manuscript.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests None declared.

Patient consent for publication Not required.

Provenance and peer review Not commissioned; internally peer reviewed.

Read the full text or download the PDF:

Global Health

Educational curriculum, writing a global health case report, access the global health archive, access the bmj case reports global health blogs.

Journal of Medical Case Reports

In the era of evidence-based practice, we need practice-based evidence. The basis of this evidence is the detailed information from the case reports of individual people which informs both our clinical research and our daily clinical care. Each case report published in this journal adds valuable new information to our medical knowledge. Prof Michael Kidd AO, Editor-in- Chief

Join the Editorial Board

We are recruiting Associate Editors to join our Editorial Board. Learn more about the role and how to apply here !

Meet the Editors

Get to know the Editors behind Journal of Medical Case Reports !

megaflopp / Getty Images / iStock

Requirements for case reports submitted to JMCR

• Patient ethnicity must be included in the Abstract under the Case Presentation section.

• Consent for publication is a mandatory journal requirement for all case reports . Written informed consent for publication must be obtained from the patient (or their parent or legal guardian in the case of children under 18, or from the next of kin if the patient has died). For more information, please see our editorial policies .

Report of the Month

Superior mesenteric vein thrombosis due to covid-19 vaccination.

Vaccines have made a significant contribute to sowing the spread of the COVID-19 infection. However, side effects of the vaccination are beginning to appear, and one of which, thrombosis, is a particular problem as it can cuase serious complications. While cases of splanchnic venous thrombosis (SVT) after ChAdOx1 nCoV-19 vaccinations have been reported, cases of SVT mRNA-1273 vaccines are rare.

In this case report, clinicians describe a patient presenting with superior mesentric vein thrombosis following a COVID-19 vaccination, and examine the relationship between the mRNA-1273 vaccines and intestinal ischemia.

Most accessed

Case analysis of hepatotoxicity caused by vancomycin

Authors: Jiayao Wu and Yulu Zhou

Endovascular stenting using a sagittal sinus approach for sigmoid sinus wall dehiscence related to intractable pulsatile tinnitus: a case series

Authors: Luis Alberto Ortega-Porcayo, Guillermo Gonzalez-Garibay, Ángel Lee, Juan A. Ponce-Gómez, Victor Alcocer-Barradas, Samuel Romano-Feinholz and Marco Antonio Zenteno Castellanos

Surgical intervention of Lemierre’s syndrome: a case report and review of the literature

Authors: Yiqi Pan, Zhihong Shi, Bin Ye, Qian Da, Chaofu Wang, Yilin Shen and Mingliang Xiang

Severe hypotension and postoperative cardiac arrest caused by 5-aminolevulinic acid: a case report

Authors: Taishi Miyazaki, Shinya Taguchi, Norihiko Obata and Satoshi Mizobuchi

Hemodynamic instability caused by pneumorrachis and pneumomediastinum following epidural analgesia: a case report

Authors: Maria Fountoulaki, Emmanouil I. Kapetanakis, Niki Kouna, Nikolaos Papagiannis and Tatiana Sidiropoulou

Most recent articles RSS

View all articles

An itchy erythematous papular skin rash as a possible early sign of COVID-19: a case report

Authors: Alice Serafini, Peter Konstantin Kurotschka, Mariabeatrice Bertolani and Silvia Riccomi

Red ear syndrome precipitated by a dietary trigger: a case report

Authors: Chung Chi Chan and Susmita Ghosh

How to choose the best journal for your case report

Authors: Richard A. Rison, Jennifer Kelly Shepphird and Michael R. Kidd

The Erratum to this article has been published in Journal of Medical Case Reports 2017 11 :287

COVID-19 with repeated positive test results for SARS-CoV-2 by PCR and then negative test results twice during intensive care: a case report

Authors: Masafumi Kanamoto, Masaru Tobe, Tomonori Takazawa and Shigeru Saito

Recurrent knee arthritis diagnosed as juvenile idiopathic arthritis with a 10-year asymptomatic period after arthroscopic synovectomy: a case report

Authors: Atsushi Teramoto, Kota Watanabe, Yuichiro Kii, Miki Kudo, Hidenori Otsubo, Takuro Wada and Toshihiko Yamashita

Most accessed articles RSS

A Guide to Writing and Using Case Reports

This thematic series, published in 2016, provides a valuable resource for clinicians who are considered producing a case report. It comprises of a special editorial series of guides on writing, reviewing and using case reports.

Aims and scope

Journal of Medical Case Reports will consider any original case report that expands the field of general medical knowledge, and original research relating to case reports.

Case reports should show one of the following:

Unreported or unusual side effects or adverse interactions involving medications
Unexpected or unusual presentations of a disease
New associations or variations in disease processes
Presentations, diagnoses and/or management of new and emerging diseases
An unexpected association between diseases or symptoms
An unexpected event in the course of observing or treating a patient
Findings that shed new light on the possible pathogenesis of a disease or an adverse effect

Suitable research articles include but are not limited to: N of 1 trials, meta-analyses of published case reports, research addressing the use of case reports and the prevalence or importance of case reporting in the medical literature and retrospective studies that include case-specific information (age, sex and ethnicity) for all patients.

Article accesses

Throughout 2022, articles were accessed from the journal website more than 4.17 million times; an average of over 11 ,400 accesses per day.

Latest Tweets

Your browser needs to have JavaScript enabled to view this timeline

Peer Review Mentoring Scheme

The Editors at Journal of Medical Case Reports endorse peer review mentoring of early career researchers.

If you are a senior researcher or professor and supervise an early career researcher with the appropriate expertise, we invite you to co-write and mentor them through the peer review process. Find out how to express your interest in the scheme here .

Call for Papers

The Journal of Medical Case Reports is calling for submissions to our Collection on COVID-19 – a look at the past, present and future of the pandemic . Guest Edited by Dr. Jean Karl Soler, The Family Practice Malta, Malta

About the Editor-in-Chief

Professor Michael Kidd AO FAHMS is foundation Director of the Centre for Future Health Systems at the University of New South Wales in Sydney, Australia, and Professor of Global Primary Care and Future Health Systems with the Nuffield Department of Primary Care Health Sciences at the University of Oxford. During the COVID-19 pandemic, Prof Kidd was the Deputy Chief Medical Officer and Principal Medical Advisor with the Australian Government Department of Health and Aged Care, and Professor of Primary Care Reform at the Australian National University. He holds honorary appointments with the University of Toronto, the University of Melbourne, Flinders University, and the Murdoch Children's Research Institute, and is the Emeritus Director of the World Health Organization Collaborating Centre on Family Medicine and Primary Care. He is an elected Fellow of the Australian Academy of Health and Medical Sciences (FAHMS). In the 2023 King's Birthday Honours List he was made an Officer of the Order of Australia. Prof Kidd served as president of the World Organization of Family Doctors (WONCA) from 2013-2016, and as president of the Royal Australian College of General Practitioners from 2002-2006. He is the founder and Editor-in-Chief of the Journal of Medical Case Reports, the world's first PubMed-listed journal devoted to publishing case reports from all medical disciplines.

Editorial Board
Manuscript editing services
Instructions for Editors
Sign up for article alerts and news from this journal

Annual Journal Metrics

2022 Citation Impact 1.0 - 2-year Impact Factor 0.628 - SNIP (Source Normalized Impact per Paper) 0.284 - SJR (SCImago Journal Rank)

2023 Speed 33 days submission to first editorial decision for all manuscripts (Median) 148 days submission to accept (Median)

2023 Usage 4,048,208 downloads 2,745 Altmetric mentions

More about our metrics

ISSN: 1752-1947

Submission enquiries: Access here and click Contact Us
General enquiries: [email protected]

Log in using your username and password

Search More Search for this keyword Advanced search
Latest content
Current issue
BMJ Journals More You are viewing from: Google Indexer

http://orcid.org/0000-0001-5502-5975 Mohammad Hassan Murad 1 ,
Shahnaz Sultan 2 ,
Samir Haffar 3 ,
Fateh Bazerbachi 4
1 Evidence-Based Practice Center, Mayo Clinic , Rochester , Minnesota , USA
2 Division of Gastroenterology, Hepatology, and Nutrition , University of Minnesota, Center for Chronic Diseases Outcomes Research, Minneapolis Veterans Affairs Healthcare System , Minneapolis , Minnesota , USA
3 Digestive Center for Diagnosis and Treatment , Damascus , Syrian Arab Republic
4 Department of Gastroenterology and Hepatology , Mayo Clinic , Rochester , Minnesota , USA
Correspondence to Dr Mohammad Hassan Murad, Evidence-Based Practice Center, Mayo Clinic, Rochester, MN 55905, USA; murad.mohammad{at}mayo.edu

https://doi.org/10.1136/bmjebm-2017-110853

Statistics from Altmetric.com

Request permissions.

epidemiology

In 1904, Dr James Herrick evaluated a 20-year-old patient from Grenada who was studying in Chicago and suffered from anaemia and a multisystem illness. The patient was found to have ‘freakish’ elongated red cells that resembled a crescent or a sickle. Dr Herrick concluded that the red cells were not artefacts because the appearance of the cells was maintained regardless of how the smear slide was prepared. He followed the patient who had subsequently received care from other physicians until 1907 and questioned whether this was syphilis or a parasite from the tropics. Then in 1910, in a published case report, he concluded that this presentation strongly suggested a previously unrecognised change in the composition of the corpuscle itself. 1 Sickle cell disease became a diagnosis thereafter.

Case reports and case series have profoundly influenced the medical literature and continue to advance our knowledge in the present time. In 1985, the American Medical Association reprinted 51 papers from its journal that had significantly changed the science and practice of medicine over the past 150 years, and five of these papers were case reports. 2 However, concerns about weak inferences and the high likelihood of bias associated with such reports have resulted in minimal attention being devoted to developing frameworks for approaching, appraising, synthesising and applying evidence derived from case reports/series. Nevertheless, such observations remain the bread and butter of learning by pattern recognition and integral to advancing medical knowledge.

Guidance on how to write a case report is available (ie, a reporting guideline). The Case Report (CARE) guidelines 3 were developed following a three-phase consensus process and provide a 13-item checklist that can assist researchers in publishing complete and meaningful exposition of medical information. This checklist encourages the explicit presentation of patient information, clinical findings, timeline, diagnostic assessment, therapeutic interventions, follow-up and outcomes. 3 Yet, systematic reviewers appraising the evidence for decision-makers require tools to assess the methodological quality (risk of bias assessment) of this evidence.

In this guide, we present a framework to evaluate the methodological quality of case reports/series and synthesise their results, which is particularly important when conducting a systematic review of a body of evidence that consists primarily of uncontrolled clinical observations.

Definitions

In the biomedical published literature, a case report is the description of the clinical course of one individual, which may include particular exposures, symptoms, signs, interventions or outcomes. A case report is the smallest publishable unit in the literature, whereas case series report aggregates individual cases in one publication. 4

If a case series is prospective, differentiating it from a single-arm uncontrolled cohort study becomes difficult. In one clinical practice guideline, it was proposed that studies without internal comparisons can be labelled as case series unless they explicitly report having a protocol before commencement of data collection, a definition of inclusion and exclusion criteria, a standardised follow-up and clear reporting of the number of excluded patients and those lost to follow-up. 6

Evaluating methodological quality

Pierson 7 provided an approach to evaluate the validity of a case report based on five components: documentation, uniqueness, objectivity, interpretation and educational value, resulting in a score with a maximum of 10 (a score above 5 was suggested indicate a valid case report). This approach, however, was rarely used in subsequent work and seems to conflate methodological quality with other constructs. For case reports of adverse drug reactions, other systems classify an association as definite, probable, possible or doubtful based on leading questions. 8 9 These questions are derived from the causality criteria that was established in 1965 by the English epidemiologist Bradford Hills. 10 Lastly, we have adapted the Newcastle Ottawa scale 11 for cohort and case–control studies by removing items that relate to comparability and adjustment (which are not relevant to non-comparative studies) and retained items that focused on selection, representativeness of cases and ascertainment of outcomes and exposure. This tool was applied in several published systematic reviews with good inter-rater agreement. 12–16

Proposed tool

The previous criteria from Pierson, 7 Bradford Hills 10 and Newcastle Ottawa scale modifications 11 converge into eight items that can be categorised into four domains: selection, ascertainment, causality and reporting. The eight items with leading explanatory questions are summarised in table 1 .

View inline

Tool for evaluating the methodological quality of case reports and case series

For example, a study that explicitly describes all the cases who have presented to a medical centre over a certain period of time would satisfy the selection domain. In contrast, a study that reports on several individuals with unclear selection approach leaves the reader with uncertainty to whether this is the whole experience of the researchers and suggests possible selection bias. For the domain of ascertainment, self-report (of the exposure or the outcome) is less reliable than ascertainment using administrative and billing codes, which in turn is less reliable than clinical records. For the domain of causality, we would have stronger inference in a case report of an adverse drug reaction that has resolved with cessation of the drug and reoccurred after reintroduction of the drug. Lastly, for the domain of reporting, a case report that is described with sufficient details may allow readers to apply the evidence derived from the report in their practice. On the other hand, an inadequately reported case will likely be unhelpful in the course of clinical care.

We suggest using this tool in systematic reviews of case reports/series. One option to summarise the results of this tool is to sum the scores of the eight binary responses into an aggregate score. A better option is not to use an aggregate score because numeric representation of methodological quality may not be appropriate when one or two questions are deemed most critical to the validity of a report (compared with other questions). Therefore, we suggest making an overall judgement about methodological quality based on the questions deemed most critical in the specific clinical scenario.

Synthesis of case reports/series

A single patient case report does not allow the estimation of an effect size and would only provide descriptive or narrative results. Case series of more than one patient may allow narrative or quantitative synthesis.

Narrative synthesis

A systematic review of the cases with the rare syndrome of lipodystrophy was able to suggest core and supportive clinical features and narratively summarised data on available treatment approaches. 17 Another systematic review of 172 cases of the infrequently encountered glycogenic hepatopathy was able to characterise for the first time patterns of liver enzymes and hepatic injury in this disease. 18

Quantitative synthesis

Quantitative analysis of non-comparative series does not produce relative association measures such as ORs or relative risks but can provide estimates of prevalence or event rates in the form of a proportion (with associated precision). Proportions can be pooled using fixed or random effects models by means of the various available meta-analysis software. For example, a meta-analysis of case series of patients presenting with aortic transection showed that mortality was significantly lower in patients who underwent endovascular repair, followed by open repair and non-operative management (9%, 19% and 46%, respectively, P<0.01). 19

A common challenge, however, occurs when proportions are too large or too small (close to 0 or to 1). In this situation, the variance of the proportion becomes very small leading to an inappropriately large weight in meta-analysis. One way to overcome this challenge is to transform prevalence to a variable that is not constrained to the 0–1 range and has approximately normal distribution, conduct the meta-analysis and then transform the estimate back to a proportion. 20 This is done using logit transformation or using the Freeman-Tukey double arcsine transformation, 21 with the latter being often preferred. 20

Another type of quantitative analysis that may be utilised is regression. A meta-analysis of 47 published cases of hypocalcaemia and cardiac dysfunction used univariate linear regression analysis to demonstrate that both QT interval and left ventricular ejection fraction were significantly correlated with corrected total serum calcium level. 22 Meta-regression, which is a regression in which the unit of analysis is a study, not a patient, can also be used to synthesise case series and control for study-level confounders. A meta-regression analysis of uncontrolled series of patients with uveal melanoma treated with proton beam therapy has shown that this treatment was associated with better outcomes than brachytherapy. 23 It is very important, however, to recognise that meta-regression results can be severely affected by ecological bias.

From evidence to decision

Several authors have described various important reasons to publish case reports/series ( table 2 ). 7 24 25

Role of case reports/series in the medical literature

It is paramount to recognise that a systematic review and meta-analysis of case reports/series should not be placed at the top of the hierarchy in a pyramid that depicts validity. 26 The certainty of evidence derived from a meta-analysis is contingent on the design of included studies, their risk of bias, as well as other factors such as imprecision, indirectness, inconsistency and likelihood of publication bias. 27 Commonly, certainty in evidence derived from case series/reports will be very low. Nevertheless, inferences from such reports can be used for decision-making. In the example of case series of aortic transection showing lower mortality with endovascular repair, a guideline recommendation was made stating ‘We suggest that endovascular repair be performed preferentially over open surgical repair or non-operative management’. This was graded as a weak recommendation based on low certainty evidence. 28 The strength of this recommendation acknowledged that the recommendation might not universally apply to everyone and that variability in decision-making was expected. The certainty in evidence rating of this recommendation implied that future research would likely yield different results that may change the recommendation. 28

The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach clearly separates the certainty of evidence from the strength of recommendation. This separation allows decision-making based on lower levels of evidence. For example, despite low certainty evidence (derived from case series) regarding the association between aspirin and Reye’s syndrome in febrile children, a strong recommendation for using acetaminophen over aspirin is possible. 29 GRADE literature also describes five paradigmatic situations in which a strong recommendation can be made based on low quality evidence. 30 One of which is when the condition is life threatening. An example of which would be using hyperbaric oxygen therapy for purpura fulminans, which is only based on case reports. 31

Guideline developers and decision-makers often struggle when dealing with case reports/case series. On occasions, they ignore such evidence and focus the scope of guidelines on areas with higher quality evidence. Sometimes they label recommendations based on case reports as expert opinion. 32 We propose an approach to evaluate the methodological quality of case reports/series based on the domains of selection, ascertainment, causality and reporting and provide signalling questions to aid evidence-based practitioners and systematic reviewers in their assessment. We suggest the incorporation of case reports/series in decision-making based on the GRADE approach when no other higher level of evidence is available.

In this guide, we have made the case for publishing case reports/series and proposed synthesis of their results in systematic reviews to facilitate using this evidence in decision-making. We have proposed a tool that can be used to evaluate the methodological quality in systematic reviews that examine case reports and case series.

Gagnier JJ ,
Altman DG , et al
Grimes DA ,
Abu-Zidan FM ,
Schünemann HJ ,
Naranjo CA ,
Sellers EM , et al
9. ↵ The World health Organization-Uppsala Monitoring Centre . The use of the WHO-UMC system for standardised case causality assessment . https://www.who-umc.org/media/2768/standardised-case-causality-assessment.pdf ( accessed 20 Sep 2017 ).
O’Connell D , et al
Bazerbachi F ,
Prokop L , et al
Vargas EJ , et al
Watt KD , et al
Szarka LA , et al
Hussain MT , et al
Farah W , et al
Leise MD , et al
Malgor R , et al
Barendregt JJ ,
Lee YY , et al
Freeman MF ,
Newman DB ,
Fidahussein SS ,
Kashiwagi DT , et al
Schild SE , et al
Vandenbroucke JP
Alsawas M , et al
Matsumura JS ,
Mitchell RS , et al
Guyatt GH ,
Vist GE , et al
Domecq JP ,
Murad MH , et al
Mestrovic J , et al
Alvarez-Villalobos N ,
Shah R , et al
Conboy EE ,
Mounajjed T , et al
Gottlieb MS
Coodin FJ ,
Uchida IA ,
Goldfinger SE
Lennox BR ,
Jones PB , et al

Contributors MHM drafted the paper and all coauthors critically revised the manuscript. All the authors contributed to conceive the idea and approved the final submitted version.

Competing interests None declared.

Provenance and peer review Not commissioned; externally peer reviewed.

Read the full text or download the PDF:

Log in using your username and password

Search More Search for this keyword Advanced search
Latest content
Current issue
BMJ Journals More You are viewing from: Google Indexer

P Daniel Patterson 1 ,
Matthew Weaver 2 ,
Sunday Clark 3 ,
Donald M Yealy 1
1 Department of Emergency Medicine, University of Pittsburgh School of Medicine, Center for Emergency Medicine of Western PA Inc, Pittsburgh, Pennsylvania, USA
2 Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
3 Center for Research on Health Care (CRHC) Data Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Correspondence to Dr Daniel Patterson, Department of Emergency Medicine, University of Pittsburgh School of Medicine, Center for Emergency Medicine of Western PA Inc, 3600 Forbes Avenue, Iroquois Bldg, Suite 400A, Pittsburgh, PA 15261, USA; pattersond{at}upmc.edu

Research begins with a clearly stated question, problem or hypothesis. The selection of a study design appropriate to the task is the next key step. This paper provides guidance for the use of case report and case series designs by describing the ‘what’, ‘when’ and ‘how’ of both designs. Also described is the use of case reports and case series study designs in prehospital emergency research and the quality of published literature from 2000 to mid-2008.

Case report
case series
emergency medical services
epidemiology
prehospital care
study design

https://doi.org/10.1136/emj.2009.073668

Statistics from Altmetric.com

Request permissions.

Research begins with a clearly stated question, problem or hypothesis. The selection of a study design—the method to address the question, problem or hypothesis—occurs next. The choice of a design is dictated by the weight of current evidence, the availability of resources, the frequency of exposure or outcome being studied and the abilities of the investigative team. Whereas a randomised controlled trial (RCT) is the most rigorous design and allows the best opportunity to link cause and effect, it is resource intensive. Also, an RCT is best deployed with a mature research question, adequate resources and pragmatic capabilities (subjects and willingness of all involved).

For less mature questions in which no or few data exist, or in the absence of adequate resources or sufficient refining evidence, investigators can deploy other study designs that include cross-sectional studies, case–control studies and cohort studies. The case report and case series (aka case conferences) often appear at or near the bottom of the study design hierarchy. Each provides an opportunity to describe the entirety of a clinical condition, possibly with unique or infrequently described signs, symptoms, treatments or outcomes. These cases enhance clinical knowledge, broadening potential differential diagnoses, and prompting consideration of conditions not often encountered during the course of care. Whereas case reports and case series require fewer resources compared with more complex study designs, they are important in building bodies of knowledge. 1 2 Although these designs can identify associations, the ability to draw casual links is limited. In case reports and case series, the experiences of a case can also be described more holistically, with case definitions designed to encompass systems or the interdependence of a system's parts.

We describe the ‘what’, ‘when’ and ‘how’ of both designs, the use of these designs in prehospital emergency research and the quality of the published literature from 2000 to mid-2008.

The ‘what’ of case reports and case series

The case report is a detailed description of a single case, or perhaps two or three cases. A case series is an extension of the case report, including more cases with similar diagnoses or salient features/outcomes over an interval. A case report or case series should not be confused with a case study, which is used frequently in health services research to study whole practices, hospitals and other systems. Case reports identify new and unusual medical occurrences, often diseases or adverse effects, and can help generate hypotheses. 3

Whether using a case report or a case series, the investigator must first define what constitutes the case. From a clinician's perspective, the case is most often the individual(s). While case definitions vary at the author's discretion and there is no singular optimal approach to defining a case, epidemiologists stress specificity and consistency when defining cases. Broad case definitions of traumatic brain injury, for example, may include cases identified based on treatment in the emergency department, signs and symptoms recorded in the field or a variety of practitioner diagnoses. Cases identified in the emergency department probably include a high proportion of vehicular-related traumatic brain injury cases and correspond to a higher degree of damage. Cases identified by primary care practitioners may be more likely to result from a less acute insult sustained during sports activities and may present with different signs and symptoms. Those identified by a neurosurgeon may include only patients with anatomical or persistent physiological dysfunction. When defining the case, the investigator should consider the multiple ways in which a case can present itself to different practitioners. An appreciation of the comprehensiveness and multidimensional nature of a case can improve the specificity of a case definition and clarify the generalisability of the spectrum of diseases under study in the case report or case series.

The ‘when’ of case reports and case series

It is appropriate to use the case report or case series design at early points in the knowledge–maturity of a particular condition or issue under study. The case report and case series are first steps in information and knowledge generation on a particular disease or condition ( figure 1 ), providing the foundation for the development of a research agenda on a new or existing condition or procedure. 4

Download figure
Open in new tab
Download powerpoint

Major epidemiological study designs.

Cross-sectional studies, case–control studies, cohort studies and other observational designs are commonly used to study a condition on a much broader scale and typically include a comparison group. Cross-sectional designs provide a means for measuring the prevalence (frequency) of a condition and hypothesis generation. Existing data sources, typically administrative data sources, or data collected through primary means such as surveys, are the most commonly used in cross-sectional studies. 5 Group proportions and means are common summary measures generated from cross-sectional studies. The cross-sectional study design is not particularly useful when the condition of interest is short in duration and rare. 6 The case–control design is commonly used as one of the first steps towards exploring the aetiology of a condition, but is also useful for searching out causes of adverse health outcomes. 7 In contrast to the cross-sectional design, case–control studies are well suited for studying rare conditions and multiple exposures of interest. 4 Another contrast between the cross-sectional and case–control design is the statistical summary measures used. When cross-sectional designs permit calculating the frequency of disease within a population, the case–control design is not well suited for such measures. Instead, risk ratios are used in case–control studies to compare the risk of developing a condition based on the proportion of cases/controls exposed to a factor or factors of interest. The cohort study design is used to estimate the average risk of a disease or condition. Subjects are followed over a specified duration of time to determine the development of the outcome of interest. Differences in exposure are calculated by establishing incidence rates in exposed versus unexposed subjects. Epidemiologists consider the cohort study design the most straightforward of all observational designs. 8

The ‘how’ of case reports and case series

Case reports and case series are often initiated by a healthcare professional who observes an unusual disease, outcome or set of patient characteristics. Once the case(s) is identified, the investigator presents the details of the case, describes the potential importance, and describes links to aetiology and therapy. Readers can identify the clinical picture of the case, the protocol of care used, and health system challenges encountered by the patient and provider. Such detailed descriptions can help refine what is known and not known about a particular clinical condition.

Unlike a cross-sectional, case–control, or cohort study design, a case report or case series lacks a comparison group. This prevents the identification of factors more frequently present or absent among the cases compared with another group of individuals. Case series can be used to describe the frequency of particular characteristics within a group of individuals with the same disease or outcome. Although it is not possible to test for the presence of valid statistical associations, properly conducted case series may allow the investigator to identify characteristics that are associated with good or bad outcomes among the cases.

Use of case reports and case series in prehospital emergency care research

With assistance from a medical research librarian, we identified all emergency medicine and prehospital emergency care case reports and case series published from 1 January 2000 to 30 July 2008 in Medline, EMBASE and CINAHL databases. Search terms used included: ambulance, case, emergency, EMS, EMT, medical, paramedic, prehospital, report, series, services, studies, technician and triage. The search was not limited by the language of publication. The search returned 6125 possible articles. Figure 2 is an illustration of the trend in use of both designs, which has increased steadily from 2000 to 2007. A significant percentage of the articles were published in trade journals, which also appear in the MEDLINE, EMBASE, and CINAHL databases. These articles were not manually reviewed to determine inclusion.

Number of emergency medicine and prehospital emergency care articles in MEDLINE, EMBASE, or CINAHL as case report or case series from 2000 to 2007.

To evaluate the quality of case reports and case series in the prehospital emergency care literature, we identified research efforts published in six of the most highly circulated peer-reviewed journals. We manually reviewed all case reports and case series published in the Emergency Medicine Journal , Annals of Emergency Medicine , Academic Emergency Medicine , Prehospital Emergency Care , European Journal of Emergency Medicine and the Canadian Journal of Emergency Medicine and identified 809 possible articles. We further limited our review to all case reports and case series focusing on prehospital emergency care published in these journals from 1 January 2007 to 30 July 2008. The remaining 132 articles were reviewed by PDP and MW for quality of presentation. Our quality rating was based on a previously prescribed rating scheme for observational designs. 1 One point was assigned for the fulfilment of each of the following eight criteria: (1) clearly defined question; (2) well-described study population; (3) well-described intervention; (4) use of validated outcome measures; (5) appropriate statistical analysis; (6) well-described results; (7) discussions/conclusions supported by data; and (8) acknowledgement of the source of funding. Articles meeting none to two criteria received a ‘poor’ rating. Articles meeting three to four criteria received a ‘fair’ rating, five to six criteria corresponded to a ‘good’ rating, and seven to eight criteria resulted in an ‘excellent’ rating. The table in appendix 1 (available online only) displays the quality rating of 115 case reports and 17 case series as well as the perspective (prehospital only or inhospital (emergency department)) from which the case is presented. The classifications were not made independently; rather consensus was achieved for all articles reviewed.

Overall, the mean total quality score for all 132 articles was 6.2 (SD 1.22). No case report or case series satisfied less than three criteria to receive a ‘poor’ rating. The research question and case definition were clearly defined in 97% of all occurrences. The authors utilised an appropriate statistical analysis in 96% of all articles reviewed. The results were adequately described in 55% of all case reports. Acknowledgement of the source of funding was the criteria satisfied the least, listed in 14% of all articles reviewed.

Among case reports, the mean total score for all case reports was 6.0 (SD 1.16). Eleven per cent of case reports received a ‘fair’ rating, 47% received a ‘good’ rating, and 42% achieved an ‘excellent’ rating. Ninety-seven per cent possessed a well-described research question, 97% outlined an appropriate case definition, 77% listed an adequately described intervention, 87% utilised validated outcome measures, 97% detailed an appropriate statistical analysis, 50% adequately described the results of the case, 89% supported the discussions and conclusions with data from the case, and 8% acknowledged the source of funding for the article.

Among case series, the mean total score for all case series was 7.2 (SD 1.03). Six per cent were assigned a ‘fair’ rating, 6% received a ‘good’ rating and 88% of case series achieved an ‘excellent’ rating. All articles contained a clearly defined research question, a well-described intervention and a discussion and conclusion section supported with data obtained during the study. Most (94%) case series adequately outlined the case definition with inclusion and exclusion criteria, and also utilised validated outcome measures. Eighty-eight per cent utilised an appropriate statistical analysis and described the results adequately. Fifty-nine per cent of case series acknowledged the source of funding for the study.

Conclusions

The case report or case series study is well suited for investigations that are at the earliest stages of enquiry. Such studies can reveal a wealth of information about unique clinical cases and can be used as a guide for future research beginning with hypothesis generation.

Acknowledgments

The authors would like to thank Dr Ahlam Saleh for her assistance with searching and retrieving the literature for this article. PDP is supported by Grant Number KL2 RR024154 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Information on NCRR is available at http://www.ncrr.nih.gov/ . Information on Re-engineering the Clinical Research Enterprise can be obtained from http://nihroadmap.nih.gov/clinicalresearch/overview-translational.asp .

Hennekens CH ,
Koepsell TD ,
Fletcher RH ,
Fletcher SW ,

Supplementary materials

Web only data.

Files in this Data Supplement:

web only data app 1
web only data app 2

Competing interests None.

Provenance and peer review Not commissioned; externally peer reviewed.

Read the full text or download the PDF:

BMJ Case Reports overview

The largest collection of peer-reviewed clinical case reports

BMJ Case Reports

casereports. bmj .com

The largest collection of peer-reviewed clinical case reports An invaluable opportunity for your institution ! BMJ Case Reports is an online, peer-reviewed journal that publishes clinically-important cases on common and rare conditions from all specialties. Subscribe your institution to a fellowship and provide the faculty, staff and students the opportunity to have their work published, and access an invaluable library of case reports from around the world. Support case-based learning and publishing An institutional fellowship (subscription) is an excellent, cost-effective way to get involved in a unique publishing community focused on education, and raise the profile of your institution.

Benefits include: • Unlimited case report submissions—averages 38 % acceptance rate • Access to all published reports—more than 2 6 ,000 cases • Downloadable images and permission to reuse content • Interactive capabilities—rate and comment on other cases • Author tools, such as peer review, report templates and copy editing • Links to related content across BMJ products • Promotion of cases through Medline/PubMed indexing

What others are saying: Review published in the Journal of the Medical Library Association “C ompared to similar resources, BMJ Case Reports is a somewhat unique product. The resources available through BMJ Case Reports are easy to find and are presented logically.”

2 6 ,000 cases published from 70+ countries

Access to 2 6 ,000 cases covering rare and common diseases Author benefits • U nlimited case report submissions— eases the publishing pathway

Educational resources • R euse material for teaching—no further permission needed Logical organization • S earch by specialty, case type, patient demographics and publication date • B rowse tabs organized by recent cases, most-read articles, specialties and top-rated cases Interactive tools • R ate and comment on cases through e-letters and blogs • S ocial media integration allows fellows to share cases and network

• F ast and supportive peer review and rapid publication • T hirty-day decision and continuous online publishing • Cases are d eposited in PubMed Central • C ase types include: - Learning from errors - Myth exploded - New disease - Novel treatment - Unexpected outcome (positive or negative) - Images in... and more!

In North America uss ales @ bmj.com , in L atin America & t he Caribbean latams ales @bmj.com to inquire about a fellowship for your institution.

Case Reports Overview 9 /2 3

www.bmj.com

Log in using your username and password

Search More Search for this keyword Advanced search
Latest content
Publish with us
About the journal
Meet the editors
Specialist reviews
BMJ Journals More You are viewing from: Google Indexer

Ge Chen 1 ,
Zhengmin (Min) Qian 2 ,
Junguo Zhang 1 ,
Shiyu Zhang 1 ,
http://orcid.org/0000-0002-7003-6565 Zilong Zhang 1 ,
Michael G Vaughn 3 ,
Hannah E Aaron 2 ,
Chuangshi Wang 4 ,
Gregory YH Lip 5 , 6 and
http://orcid.org/0000-0002-3643-9408 Hualiang Lin 1
1 Department of Epidemiology , Sun Yat-Sen University , Guangzhou , China
2 Department of Epidemiology and Biostatistics, College for Public Health and Social Justice , Saint Louis University , Saint Louis , Missouri , USA
3 School of Social Work, College for Public Health and Social Justice , Saint Louis University , Saint Louis , Missouri , USA
4 Medical Research and Biometrics Centre , Fuwai Hospital, National Centre for Cardiovascular Diseases, Peking Union Medical College , Beijing , China
5 Liverpool Centre for Cardiovascular Science , University of Liverpool and Liverpool Heart and Chest Hospital , Liverpool , UK
6 Department of Clinical Medicine , Aalborg University , Aalborg , Denmark
Correspondence to Dr Hualiang Lin, Department of Epidemiology, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China; linhualiang{at}mail.sysu.edu.cn

Objective To examine the effects of fish oil supplements on the clinical course of cardiovascular disease, from a healthy state to atrial fibrillation, major adverse cardiovascular events, and subsequently death.

Design Prospective cohort study.

Setting UK Biobank study, 1 January 2006 to 31 December 2010, with follow-up to 31 March 2021 (median follow-up 11.9 years).

Participants 415 737 participants, aged 40-69 years, enrolled in the UK Biobank study.

Main outcome measures Incident cases of atrial fibrillation, major adverse cardiovascular events, and death, identified by linkage to hospital inpatient records and death registries. Role of fish oil supplements in different progressive stages of cardiovascular diseases, from healthy status (primary stage), to atrial fibrillation (secondary stage), major adverse cardiovascular events (tertiary stage), and death (end stage).

Results Among 415 737 participants free of cardiovascular diseases, 18 367 patients with incident atrial fibrillation, 22 636 with major adverse cardiovascular events, and 22 140 deaths during follow-up were identified. Regular use of fish oil supplements had different roles in the transitions from healthy status to atrial fibrillation, to major adverse cardiovascular events, and then to death. For people without cardiovascular disease, hazard ratios were 1.13 (95% confidence interval 1.10 to 1.17) for the transition from healthy status to atrial fibrillation and 1.05 (1.00 to 1.11) from healthy status to stroke. For participants with a diagnosis of a known cardiovascular disease, regular use of fish oil supplements was beneficial for transitions from atrial fibrillation to major adverse cardiovascular events (hazard ratio 0.92, 0.87 to 0.98), atrial fibrillation to myocardial infarction (0.85, 0.76 to 0.96), and heart failure to death (0.91, 0.84 to 0.99).

Conclusions Regular use of fish oil supplements might be a risk factor for atrial fibrillation and stroke among the general population but could be beneficial for progression of cardiovascular disease from atrial fibrillation to major adverse cardiovascular events, and from atrial fibrillation to death. Further studies are needed to determine the precise mechanisms for the development and prognosis of cardiovascular disease events with regular use of fish oil supplements.

Health policy
Nutritional sciences
Public health

Data availability statement

Data are available upon reasonable request. UK Biobank is an open access resource. Bona fide researchers can apply to use the UK Biobank dataset by registering and applying at http://ukbiobank.ac.uk/register-apply/ .

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/ .

https://doi.org/10.1136/bmjmed-2022-000451

Statistics from Altmetric.com

Request permissions.

WHAT IS ALREADY KNOWN ON THIS TOPIC

Findings of the effects of omega 3 fatty acids or fish oil on the risk of cardiovascular disease are controversial

Most previous studies focused on one health outcome and did not characterise specific cardiovascular disease outcomes (eg, atrial fibrillation, myocardial infarction, stroke, heart failure, and major adverse cardiovascular events)

Whether fish oil could differentially affect the dynamic course of cardiovascular diseases, from atrial fibrillation to major adverse cardiovascular events, to other specific cardiovascular disease outcomes, or even to death, is unclear

WHAT THIS STUDY ADDS

In people with no known cardiovascular disease, regular use of fish oil supplements was associated with an increased relative risk of atrial fibrillation and stroke

In people with known cardiovascular disease, the beneficial effects of fish oil supplements were seen on transitions from atrial fibrillation to major adverse cardiovascular events, atrial fibrillation to myocardial infarction, and heart failure to death

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE, OR POLICY

Regular use of fish oil supplements might have different roles in the progression of cardiovascular disease

Further studies are needed to determine the precise mechanisms for the development and prognosis of cardiovascular disease events with regular use of fish oil supplements

Introduction

Cardiovascular disease is the leading cause of death worldwide, accounting for about one sixth of overall mortality in the UK. 1 2 Fish oil, a rich source of omega 3 fatty acids, containing eicosapentaenoic acid and docosahexaenoic acid, has been recommended as a dietary measure to prevent cardiovascular disease. 3 The UK National Institute for Health and Care Excellence recommends that people with or at high risk of cardiovascular disease consume at least one portion of oily fish a week, and the use of fish oil supplements has become popular in the UK and other western countries in recent years. 4 5

Although some epidemiological and clinical studies have assessed the effect of omega 3 fatty acids or fish oil on cardiovascular disease and its risk factors, the findings are controversial. The Agency for Healthcare Research and Quality systematically reviewed 37 observational studies and 61 randomised controlled trials, and found evidence indicating the beneficial effects of higher consumption of fish oil supplements on ischaemic stroke, whereas no beneficial effect was found for atrial fibrillation, major adverse cardiovascular events, myocardial infarction, total stroke, or all cause death. 6 In contrast, the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) reported a decreased risk of major adverse cardiovascular events with icosapent ethyl in patients with raised levels of triglycerides, regardless of the use of statins. 7 Most of these findings, however, tended to assess the role of fish oil at a certain stage of cardiovascular disease. For example, some studies restricted the study population to people with a specific cardiovascular disease or at a high risk of cardiovascular disease, 8 9 whereas others evaluated databases of generally healthy populations. 10 All of these factors might preclude direct comparison of the effects of omega 3 fatty acids on atrial fibrillation events or on further deterioration of cardiovascular disease. Few studies have fully characterised specific cardiovascular disease outcomes or accounted for differential effects based on the complex disease characteristics of participants. Hence, in this study, we hypothesised that fish oil supplements might have harmful, beneficial, or no effect on different cardiovascular disease events in patients with varying health conditions.

Most previous studies on the association between fish oil and cardiovascular diseases generally focused on one health outcome. Also, no study highlighted the dynamic progressive course of cardiovascular diseases, from healthy status (primary stage), to atrial fibrillation (secondary stage), major adverse cardiovascular events (tertiary stage), and death (end stage). Clarifying this complex pathway in relation to the detailed progression of cardiovascular diseases would provide substantial insights into the prevention or treatment of future disease at critical stages. Whether fish oil could differentially affect the dynamic course of cardiovascular disease (ie, from atrial fibrillation to major adverse cardiovascular events, to other specific cardiovascular disease outcomes, or even to death) is unclear.

To deal with this evidence gap, we conducted a longitudinal cohort study to estimate the associations between fish oil supplements and specific clinical cardiovascular disease outcomes, including atrial fibrillation, major adverse cardiovascular events, and all cause death in people with no known cardiovascular disease or at high risk of cardiovascular disease for the purpose of primary prevention. We also assessed the modifying effects of fish oil supplements on the disease process, from atrial fibrillation to other outcomes, in people with known cardiovascular disease for the purpose of secondary prevention.

The UK Biobank is a community based cohort study with more than half a million UK inhabitants aged 40-69 years at recruitment. 11–13 Participants were invited to participate in this study if they were registered with the NHS and lived within 35 km of one of 22 Biobank assessment centres. Between 1 March 2006 and 31 July 2010, a baseline survey was conducted, based on a touch screen questionnaire and face-to-face interviews, to collect detailed personal, socioeconomic, and lifestyle characteristics, and information on diseases. 11–13

We excluded patients who had a diagnosis of atrial fibrillation (n=8326), heart failure (n=2748), myocardial infarction (n=11 949), stroke (n=7943), or cancer (n=48 624) at baseline; who withdrew from the study during follow-up (n=1299); or who had incomplete or outlier data for the main information (n=11 748). Because we focused only on a specific sequence of progression of cardiovascular disease (ie, from healthy status to atrial fibrillation, to major adverse cardiovascular events, and then to death), we excluded 1983 participants with other transition patterns. The remaining 415 737 participants were included in this analysis ( figure 1 ).

Download figure
Open in new tab
Download powerpoint

Flowchart of selection of participants in study. The count of diagnosed diseases does not equate to the total number of individuals, because each person could have multiple diagnoses

Determining use of fish oil supplements

Information on regular use of fish oil supplements was collected from a self-reported touchscreen questionnaire during the baseline survey. 14 15 Each participant was asked whether they regularly used any fish oil supplement. Trained staff conducted a verbal interview with participants, asking if they were currently receiving treatments or taking any medicines, including omega 3 or fish oil supplements. Based on this information, we classified participants as regular users of fish oil supplements and non-users.

Follow-up and outcomes

Participants were followed up from the time of recruitment to death, loss to follow-up, or the end date of follow-up (31 March 2021), whichever came first. Incident cases of interest, including atrial fibrillation, heart failure, stroke, and myocardial infarction, were identified by linkage to death registries, primary care records, and hospital inpatient records. 11 Information on deaths was obtained from death registries of the NHS Information Centre, for participants in England and Wales, and from the NHS Central Register Scotland, for participants in Scotland. 11 Outcomes were defined by a three character ICD-10 (international classification of diseases, 10th revision) code. In this study, atrial fibrillation was defined by ICD-10 code I48, and major adverse cardiovascular events was determined by a combination of heart failure (I50, I11.0, I13.0, and I13.2), stroke (I60-I64), and myocardial infarction (I21, I22, I23, I24.1, and I25.2) codes.

We collected baseline data on age (<65 years and ≥65 years), sex (men and women), ethnic group (white and non-white), Townsend deprivation index (with a higher score indicating higher levels of deprivation), smoking status (never, previous, and current smokers), and alcohol consumption (never, previous, and current drinkers). Data for sex were taken from information in UK Biobank rather than from patient reported gender. Baseline dietary data were obtained from a dietary questionnaire completed by the patient or by an interviewer. The questionnaire was established for each nation (ie, England, Scotland, and Wales) to assess an individual's usual food intake (oily fish, non-oily fish, vegetables, fruit, and red meat). Diabetes mellitus was defined by ICD-10 codes E10-E14, self-reported physician's diagnosis, self-reported use of antidiabetic drugs, or haemoglobin A1c level ≥6.5% at baseline. Hypertension was defined by ICD-10 code I10 or I15, self-reported physician's diagnosis, self-reported use of antihypertensive drugs, or measured systolic and diastolic blood pressure ≥130/85 mm Hg at baseline. Information on other comorbidities (obesity (ICD-10 code E66), chronic obstructive pulmonary disease (J44), and chronic renal failure (N18)) was extracted from the first occurrence (UKB category ID 1712). Information on the use of drugs, including antihypertensive drugs, antidiabetic drug, and statins, was extracted from treatment and drug use records. Biochemistry markers were measured immediately at the central laboratory from serum samples collected at baseline. Binge drinking was defined as consumption of ≥6 standard drinks/day for women or ≥8 standard drinks/day for men. Detailed information on alcohol consumption and binge drinking in the UK Biobank was reported previously. 16

Statistical analysis

Characteristics of participants are summarised as number (percentages) for categorical variables and mean (standard deviation (SD)) for continuous variables. Comparisons between regular users of fish oil supplements and non-users were made with the χ 2 test or Student's t test.

We used a multi-state regression model to assess the role of regular use of fish oil supplements in the temporal disease progression from healthy status to atrial fibrillation, to major adverse cardiovascular events, and subsequently to death. The multi-state model is an extension of competing risks survival analysis. 17–19 The model allows simultaneous estimation of the role of risk factors in transitions from a healthy state to atrial fibrillation (transition A), healthy state to major adverse cardiovascular events (transition B), healthy state to death (transition C), atrial fibrillation to major adverse cardiovascular events (transition D), atrial fibrillation to death (transition E), and major adverse cardiovascular events to death (transition F) (transition pattern I, figure 2 ). The focus on these six transitions rather than on all possible health state transitions was preplanned and evidence based. If participants entered different states on the same date, we used the date of the theoretically previous state as the entry date of the latter state minus 0.5 days.

Numbers of participants in transition pattern I, from baseline to atrial fibrillation, major adverse cardiovascular events, and death

We further examined the effects of regular use of fish oil supplements on other pathways. For example, we divided major adverse cardiovascular events into three individual diseases (heart failure, stroke, and myocardial infarction), resulting in three independent pathways (transition patterns II, III, and IV, online supplemental figures S1–S3 ). All models were adjusted for age, sex, ethnic group, Townsend deprivation index, consumption of oily fish, consumption of non-oily fish, smoking status, alcohol consumption, obesity, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, chronic renal failure, and use of statins, antidiabetic drugs, and antihypertensive drugs.

Supplemental material

We conducted several sensitivity analyses for the multi-state analyses of transition pattern A: additionally adjusting for setting (urban and rural), body mass index (underweight, normal, overweight, and obese), and physical activity (low, moderate, and high) in the model; adjusting for binge drinking rather than alcohol consumption; additionally adjusting for other variables of dietary intake (consumption of vegetables, fruit, and red meat); calculating participants' entry date into the previous state with different time intervals (0.5 years, one year, and two years); excluding participants who entered different states on the same date; excluding events occurring in the first two years of follow-up; restricting the follow-up date to 31 March 2020 to evaluate the influence of the covid-19 pandemic; and the use of the inverse probability weighted method to deal with biases between the regular users and non-users of fish oil supplements. Also, we conducted grouped analyses for sex, age group, ethnic group, smoking status, consumption of oily fish, consumption of non-oily fish, hypertension, and drug use, to examine effect modification. The interactions were tested with the likelihood ratio test. All analyses were carried out with R software (version 4.0.3), and the multi-model analysis was performed with the mstate package. A two tailed P value <0.05 was considered significant.

Patient and public involvement

Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. Participants were involved in developing the ethics and governance framework for UK Biobank and have been engaged in the progress of UK Biobank through follow-up questionnaires and additional assessment visits. UK Biobank keeps participants informed of all research output through the study website ( https://www.ukbiobank.ac.uk/explore-your-participation ), participant events, and newsletters.

A total of 415 737 participants (mean age 55.9 (SD 8.1) years; 55% women), aged 40-69 years, were analysed, and 31.4% (n=1 30 365) of participants reported regular use of fish oil supplements at baseline ( figure 1 ). Table 1 shows the characteristics of regular users (n=130 365) and non-users (n=285 372) of fish oil supplements. In the group of regular users of fish oil supplements, we found higher proportions of elderly people (22.6% v 13.9%), white people (95.1% v 94.2%), and women (57.6% v 53.9%), and higher consumption of alcohol (93.1% v 92.0%), oily fish (22.1% v 15.4%), and non-oily fish (18.0% v 15.4%) than non-users. The Townsend deprivation index (mean −1.5 (SD 3.0) v −1.3 (3.0)) and the proportion of current smokers (8.1% v 11.4%) were lower in regular users of fish oil supplements. Online supplemental table S1 provides more details on patient characteristics and online supplemental table S2 compares the basic characteristics of included and excluded people.

View inline

Baseline characteristics of study participants grouped by use of fish oil supplements

Over a median follow-up time of of 11.9 years, 18 367 participants had atrial fibrillation (transition A) and 17 826 participants had major adverse cardiovascular events (transition B); 14 902 participants died without having atrial fibrillation or major adverse cardiovascular events (transition C). Among patients with incident atrial fibrillation, 4810 developed major adverse cardiovascular events (transition D) and 1653 died (transition E). Among patients with incident major adverse cardiovascular events, 5585 died during follow-up (transition F, figure 2 ). In separate analyses for individual diseases (transition patterns II, III, and IV, online supplemental figures S1–S3 ), in patients with atrial fibrillation, 3085 developed heart failure, 1180 had a stroke, and 1415 had a myocardial infarction. During follow-up, 2436, 2088, and 2098 deaths occurred in patients with heart failure, stroke, and myocardial infarction, respectively.

Multi-state regression results

Table 2 shows the different roles of regular use of fish oil supplements in transitions from healthy status to atrial fibrillation, to major adverse cardiovascular events, and then to death. For individuals in the primary stage (healthy status), we found that the use of fish oil supplements had a harmful effect on the transition from health to atrial fibrillation, with an adjusted hazard ratio of 1.13 (95% CI 1.10 to 1.17, transition A). The hazard ratio for transition B (from health to major adverse cardiovascular events) was 1.00 (95% CI 0.97 to 1.04) and for transition C (from health to death) was 0.98 (0.95 to 1.02).

Hazard ratios (95% confidence intervals) for each transition, for different transition patterns for progressive cardiovascular disease by regular use of fish oil supplements

For individuals in the secondary stage (atrial fibrillation) at the beginning of the study, regular use of fish oil supplements decreased the risk of major adverse cardiovascular events (transition D, hazard ratio 0.92, 95% CI 0.87 to 0.98), and had a borderline protective effect on the transition from atrial fibrillation to death (transition E, 0.91, 0.82 to 1.01). For transition F, from major adverse cardiovascular events to death, after adjusting for covariates, the hazard ratio was 0.99 (0.94 to 1.06, transition pattern I, table 2 ).

We divided major adverse cardiovascular events into three individual diseases (ie, heart failure, stroke, and myocardial infarction) and found that regular use of fish oil supplements was marginally associated with an increased risk of stroke in people with a healthy cardiovascular state (hazard ratio 1.05, 95% CI 1.00 to 1.11), whereas a protective effect was found in transitions from healthy cardiovascular states to heart failure (0.92, 0.86 to 0.98). For patients with atrial fibrillation, we found that the beneficial effects of regular use of fish oil supplements were for transitions from atrial fibrillation to myocardial infarction (0.85, 0.76 to 0.96), and from atrial fibrillation to death (0.88, 0.81 to 0.95) for transition pattern IV. For patients with heart failure, we found a protective effect of regular use of fish oil supplements on the risk of mortality (0.91, 0.84 to 0.99) (transition patterns II, III, and IV, table 2 ).

Stratified and sensitivity analyses

We found that age, sex, smoking, consumption of non-oily fish, prevalent hypertension, and use of statins and antihypertensive drugs modified the associations between regular use of fish oil supplements and the transition from healthy states to atrial fibrillation ( online supplemental figure S4 ). We found that the association between regular use of fish oil supplements and risk of transition from healthy states to major adverse cardiovascular events was greater in women (hazard ratio 1.06, 95% CI 1.00 to 1.11, P value for interaction=0.005) and non-smoking participants (1.06, 1.06 to 1.11, P value for interaction=0.001) ( online supplemental figure S4 ). The protective effect of regular use of fish oil supplements on the transition from healthy states to death was greater in men (hazard ratio 0.93, 95% CI 0.89 to 0.98, P value for interaction=0.003) and older participants (0.91, 0.86 to o 0.96, P value for interaction=0.002) ( online supplemental figures S5 and S6 ). The results were not substantially changed in the sensitivity analyses ( online supplemental table S3 ).

Principal findings

Our study characterised the regular use of fish oil supplements on the progressive course of cardiovascular disease, from a healthy state (primary stage), to atrial fibrillation (secondary stage), major adverse cardiovascular events (tertiary stage), and death (end stage). In this prospective analysis of more than 400 000 UK adults, we found that regular use of fish oil supplements could have a differential role in the progression of cardiovascular disease. For people with a healthy cardiovascular profile, regular use of fish oil supplements, a choice of primary prevention, was associated with an increased risk of atrial fibrillation. For participants with a diagnosis of atrial fibrillation, however, regular use of fish oil supplements, as secondary prevention, had a protective effect or no effect on transitions from atrial fibrillation to major adverse cardiovascular events, atrial fibrillation to death, and major adverse cardiovascular events to death. When we divided major adverse cardiovascular events into three individual diseases (ie, heart failure, stroke, and myocardial infarction), we found associations that could suggest a mildly harmful effect between regular use of fish oil supplements and transitions from a healthy cardiovascular state to stroke, whereas potential beneficial associations were found between regular use of fish oil supplements and transitions from atrial fibrillation to myocardial infarction, atrial fibrillation to death, and heart failure to death.

Comparison with other studies

Primary prevention.

The cardiovascular benefits of regular use of fish oil supplements have been examined in numerous studies but the results are controversial. Extending previous reports, our study estimated the associations between regular use of fish oil supplements and specific clinical cardiovascular disease outcomes in people with no known cardiovascular disease. Our findings are in agreement with the results of several previous randomised controlled trials and meta-analyses. The Long-Term Outcomes Study to Assess Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridaemia (STRENGTH) reported that consumption of 4 g/day of marine omega 3 fatty acids was associated with a 69% higher risk of new onset atrial fibrillation in people at high risk of cardiovascular disease. 20 A meta-analysis of seven randomised controlled trials showed that users of marine omega 3 fatty acids supplements had a higher risk of atrial fibrillation events, with a hazard ratio of 1.25 (95% CI 1.07 to 1.46, P=0.013). 21 The Vitamin D and Omega-3 Trial (VITAL Rhythm study), a large trial of omega 3 fatty acids for the primary prevention of cardiovascular disease in adults aged ≥50 years, however, found no effects on incident atrial fibrillation, major adverse cardiovascular events, or cardiovascular disease mortality among those treated with 840 mg/day of marine omega 3 fatty acids compared with placebo. 10 22

One possible explanation for the inconsistent results in these studies is that adverse effects might be related to dose and composition. Higher doses of omega 3 fatty acids used in previous studies might have had an important role in causing an adverse effect on atrial fibrillation. 21 One study found that high concentrations of fish oil altered cell membrane properties and inhibited Na-K-ATPase pump activity, whereas a low concentration of fish oil minimised peroxidation potential and optimised activity. 23 In another study, individuals with atrial fibrillation or flutter had higher percentages of total polyunsaturated fatty acids, and n-3 and n-6 polyunsaturated fatty acids, on red blood cell membranes than healthy controls. 24

In terms of composition of omega 3 fatty acids, a recent meta-analysis showed that eicosapentaenoic acid alone can be more effective at reducing the risk of cardiovascular disease than the combined effect of eicosapentaenoic acid and docosahexaenoic acid. 25 Similar outcomes were reported in the INSPIRE study, which showed that higher levels of docosahexaenoic acid reduced the cardiovascular benefits of eicosapentaenoic acid when given as a combination. 26 Another possible explanation is that age, sex, ethnic group, smoking status, dietary patterns, and use of statins and antidiabetic drugs by participants might modify the effects of regular use of fish oil supplements on cardiovascular disease events. Despite these differences in risk estimates, our findings do not support the use of fish oil or omega 3 fatty acid supplements for the primary prevention of incident atrial fibrillation or other specific clinical cardiovascular disease events in generally healthy individuals. Caution might be warranted when fish oil supplements are used for primary prevention because of the uncertain cardiovascular benefits.

Secondary prevention

Our large scale cohort study assessed the role of regular use of fish oil supplements on the disease process, from atrial fibrillation to more serious cardiovascular disease stages, to death, in people with known cardiovascular disease. Contrary to the observations for primary prevention, we found associations that could suggest beneficial effects between regular use of fish oil supplements and most cardiovascular disease transitions. No associations were found between regular use of fish oil supplements and transitions from atrial fibrillation to death, or from major adverse cardiovascular events to death.

Consistent with our hypothesis, the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI) Prevenzione study reported an association between administration of low dose prescriptions of n-3 polyunsaturated fatty acids and reduced cardiovascular events in patients with recent myocardial infarction. 27 A meta-analysis of 16 randomised controlled trials also reported a tendency towards a greater beneficial effect for secondary prevention in patients with cardiovascular disease. 28 Why patients with previous atrial fibrillation benefit is unclear. These findings indicate that triglyceride independent effects of omega 3 fatty acids might in part be responsible for the benefits in cardiovascular disease seen in previous trials. 29–31 No proven biological mechanism for this explanation exists, however, and the dose and formulation of omega 3 fatty acids used in clinical practice are not known.

For the disease process, from cardiovascular disease to death, our findings are consistent with the results of secondary prevention trials of omega 3 fatty acids, which have mostly shown a weak or neutral preventive effect in all cause mortality with oil fish supplements. The GISSI heart failure trial (GISSI-HF), conducted in 6975 patients with chronic heart failure, reported that supplemental omega 3 fatty acids reduced the risk of all cause mortality by 9% (hazard ratio 0.91, 95% CI 0.833 to 0.998, P=0.041). 32 Zelniker et al showed that omega 3 fatty acids were inversely associated with a lower incidence of sudden cardiac death in patients with non-ST segment elevation acute coronary syndrome. 33 A meta-analysis found that use of omega 3 supplements of ≤1 capsule/day was not associated with all cause mortality, but among participants with a risk of cardiovascular disease, taking a higher dose was associated with a reduction in cardiac death and sudden death. 28 Individuals who might benefit the most from fish oil or omega 3 fatty acid supplements are possibly more vulnerable individuals, such as those with previous cardiovascular diseases and those who can no longer live in the community. How fish oil supplements stop further deterioration of cardiovascular disease is unclear, but the theory that supplemental omega 3 fatty acids might protect the coronary artery is biologically plausible, suggesting that omega 3 fatty acids have anti-inflammatory and anti-hypertriglyceridaemia effects, contributing to a reduction in thrombosis and improvement in endothelial function. 34–41 Nevertheless, the effects of omega 3 fatty acids vary according to an individual's previous use of statins, which might partly explain the different effects of fish oil supplements in people with and without cardiovascular disease.

Many studies of omega 3 fatty acids, including large scale clinical trials and meta-analyses, have not produced entirely consistent results. 21 25 42 Our study mainly explored the varied potential effects of regular use of fish oil supplements on progression of cardiovascular disease, offering an initial overview of this ongoing discussion. Our findings suggest caution in the use of fish oil supplements for primary prevention because of the uncertain cardiovascular benefits and adverse effects. Further studies are needed to determine whether potential confounders modify the effects of oil fish supplements and the precise mechanisms related to the development and prognosis of cardiovascular disease events.

Strengths and limitations of this study

The strengths of our study were the large sample size, long follow-up period, which allowed us to analyse clinically diagnosed incident diseases, and complete data on health outcomes. Another strength was our analytical strategy. The multi-state model gives less biased estimates than the conventional Cox model, and distinguished the effect of regular use of fish oil supplements on each transition in the course of cardiovascular disease.

Our study had some limitations. Firstly, as an observational study, no causal relations can be drawn from our findings. Secondly, although we adjusted for multiple covariates, residual confounding could still exist. Thirdly, information on dose and formulation of the fish oil supplements was not available in this study, so we could not evaluate potential dose dependent effects or differentiate between the effects of different fish oil formulations. Fourthly, the use of hospital inpatient data for determining atrial fibrillation events could have excluded some events triggered by acute episodes, such as surgery, trauma, and similar conditions, resulting in underestimation of the true risk because undiagnosed atrial fibrillation is a common occurrence. 43 Fifthly, most of the participants in this study were from the white ethnic group and whether the findings can be generalised to other ethnic groups is not known. Finally, our study did not consider behavioural changes in populations with different cardiovascular profiles because of limited information, and variations in outcomes for different cardiovascular states merits further exploration.

Conclusions

This large scale prospective study of a UK cohort suggested that regular use of fish oil supplements might have differential roles in the course of cardiovascular diseases. Regular use of fish oil supplements might be a risk factor for atrial fibrillation and stroke among the general population but could be beneficial for disease progression, from atrial fibrillation to major adverse cardiovascular events, and from atrial fibrillation to death. Further studies are needed to determine whether potential confounders modify the effects of oil fish supplements and the precise mechanisms for the development and prognosis of cardiovascular disease events.

Ethics statements

Patient consent for publication.

Consent obtained directly from patients.

Ethics approval

The UK Biobank study obtained ethical approval from the North West Multicentre Research ethics committee, Information Advisory Group, and the Community Health Index Advisory Group (REC reference for UK Biobank 11/NW/0382). Participants gave informed consent to participate in the study before taking part.

Acknowledgments

This study was conducted with UK Biobank Resource (application No: 69550). We appreciate all participants and professionals contributing to UK Biobank.

Mensah GA ,
Johnson CO , et al
Gao MM , et al
Saravanan P ,
Davidson NC ,
Schmidt EB , et al
National Institute for Health and Care Excellence
Lichtenstein AH ,
Vadiveloo M , et al
Djuricic I ,
Miller M , et al
Kesse-Guyot E ,
Czernichow S , et al
Klemsdal TO ,
Sandvik L , et al
Manson JE ,
Lee I-M , et al
Gallacher J ,
Allen N , et al
Littlejohns TJ ,
Sudlow C , et al
Allen NE , et al
Zhong W-F ,
Liu S , et al
Wu Z , et al
Gallagher C ,
Elliott AD , et al
Qian SE , et al
Nicholls SJ ,
Lincoff AM ,
Garcia M , et al
Djousse L ,
Al-Ramady OT , et al
Bassuk SS ,
Cook NR , et al
Cazzola R ,
Della Porta M ,
Castiglioni S , et al
Viviani Anselmi C ,
Ferreri C ,
Novelli V , et al
Khan MS , et al
Knowlton K , et al
Marchioli R ,
Bomba E , et al
Olmastroni E ,
Gazzotti M , et al
Al Rifai M , et al
Tavazzi L ,
Maggioni AP ,
Marchioli R , et al
Zelniker TA ,
Morrow DA ,
Scirica BM , et al
Limonte CP ,
Zelnick LR ,
Ruzinski J , et al
Nelson JR ,
Miller PE ,
Van Elswyk M ,
Alexander DD
Mozaffarian D ,
Bornfeldt KE
Harris WS ,
Ginsberg HN ,
Arunakul N , et al
Markozannes G ,
Tsapas A , et al
Svennberg E ,
Engdahl J ,
Al-Khalili F , et al

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.

Data supplement 1
Data supplement 2

GYL and HL are joint senior authors.

Contributors HL supervised the whole project and designed the work. GC and HL directly accessed and verified the underlying data reported in the manuscript. GC contributed to data interpretation and writing of the report. ZQ, SZ, JZ, ZZ, MGV, HEA, CW, and GYHL contributed to the discussion and data interpretation, and revised the manuscript. All authors had full access to all of the data in the study and had final responsibility for the decision to submit for publication. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. HL is the guarantor. Transparency: The lead author (guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Funding This work was supported by the Bill and Melinda Gates Foundation (grant No INV-016826). Under the grant conditions of the foundation, a creative commons attribution 4.0 generic license has already been assigned to the author accepted manuscript version that might arise from this submission. The funder had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication.

Competing interests All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from Bill and Melinda Gates Foundation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

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.

Read the full text or download the PDF:

Log in using your username and password

Search More Search for this keyword Advanced search
Latest content
Current issue
BMJ Journals More You are viewing from: Google Indexer

http://orcid.org/0000-0003-4249-1947 Matthew Woodward 1 ,
http://orcid.org/0000-0002-5915-0041 Mary Dixon-Woods 1 ,
http://orcid.org/0000-0002-0934-3806 Wendy Randall 2 ,
Caroline Walker 2 ,
Chloe Hughes 2 ,
Sarah Blackwell 2 ,
Louise Dewick 3 ,
Rachna Bahl 3 , 4 ,
http://orcid.org/0000-0002-1825-4864 Tim Draycott 3 , 5 ,
Cathy Winter 6 ,
Akbar Ansari 1 ,
http://orcid.org/0000-0003-2524-5357 Alison Powell 1 ,
http://orcid.org/0000-0002-7886-3223 Janet Willars 1 ,
http://orcid.org/0000-0003-4393-0956 Imogen A F Brown 1 ,
http://orcid.org/0000-0003-3792-0575 Annabelle Olsson 1 ,
http://orcid.org/0000-0001-5673-751X Natalie Richards 1 ,
http://orcid.org/0000-0002-6093-8709 Joann Leeding 1 ,
http://orcid.org/0000-0002-6082-3151 Lisa Hinton 1 ,
http://orcid.org/0000-0002-0037-274X Jenni Burt 1 ,
http://orcid.org/0000-0002-2099-006X Giulia Maistrello 7 ,
Charlotte Davies 7 ,
Thiscovery Authorship Group ,
ABC Contributor Group ,
Jan W van der Scheer 1
1 THIS Institute (The Healthcare Improvement Studies Institute) , Department of Public Health and Primary Care, University of Cambridge , Cambridge , UK
2 The Royal College of Midwives , London , UK
3 Royal College of Obstetricians and Gynaecologists , London , UK
4 University Hospitals Bristol and Weston NHS Foundation Trust , Bristol , UK
5 North Bristol NHS Trust , Westbury on Trym , UK
6 PROMPT Maternity Foundation , Bristol , UK
7 RAND Europe , Cambridge , UK
Correspondence to Dr Jan W van der Scheer, THIS Institute (The Healthcare Improvement Studies Institute), University of Cambridge, Cambridge, CB1 8RN, UK; jan.vanderscheer{at}thisinstitute.cam.ac.uk

Clinical tools for use in practice—such as medicine reconciliation charts, diagnosis support tools and track-and-trigger charts—are endemic in healthcare, but relatively little attention is given to how to optimise their design. User-centred design approaches and co-design principles offer potential for improving usability and acceptability of clinical tools, but limited practical guidance is currently available. We propose a framework (FRamework for co-dESign of Clinical practice tOols or ‘FRESCO’) offering practical guidance based on user-centred methods and co-design principles, organised in five steps: (1) establish a multidisciplinary advisory group; (2) develop initial drafts of the prototype; (3) conduct think-aloud usability evaluations; (4) test in clinical simulations; (5) generate a final prototype informed by workshops. We applied the framework in a case study to support co-design of a prototype track-and-trigger chart for detecting and responding to possible fetal deterioration during labour. This started with establishing an advisory group of 22 members with varied expertise. Two initial draft prototypes were developed—one based on a version produced by national bodies, and the other with similar content but designed using human factors principles. Think-aloud usability evaluations of these prototypes were conducted with 15 professionals, and the findings used to inform co-design of an improved draft prototype. This was tested with 52 maternity professionals from five maternity units through clinical simulations. Analysis of these simulations and six workshops were used to co-design the final prototype to the point of readiness for large-scale testing. By codifying existing methods and principles into a single framework, FRESCO supported mobilisation of the expertise and ingenuity of diverse stakeholders to co-design a prototype track-and-trigger chart in an area of pressing service need. Subject to further evaluation, the framework has potential for application beyond the area of clinical practice in which it was applied.

Healthcare quality improvement
Human factors
Obstetrics and gynecology
Quality improvement methodologies
Trigger tools

https://doi.org/10.1136/bmjqs-2023-016196

Statistics from Altmetric.com

Request permissions.

Key messages

Much research and debate focuses on the validity and reliability of clinical tools for practice, but far less attention has been given to how to optimise their design and usability.

We propose a framework (FRamework for co-dESign of Clinical practice tOols or ‘FRESCO’) offering practical guidance for developing prototype clinical tools, drawing on user-centred design methods and co-design principles.

FRESCO successfully supported co-design of a prototype chart for detecting and responding to possible fetal deterioration during labour.

By codifying existing methods and principles into a single framework, FRESCO has potential to facilitate pragmatic, flexible and inclusive co-design of clinical practice tools, but will require further evaluation.

Clinical practice tools—ranging from medicine reconciliation charts through to diagnosis support tools and track-and-trigger charts—are endemic in healthcare. 1–3 While much research and debate focus on the validity and reliability of such tools, 4 far less attention has been given to how to optimise their design. 5–8 Yet, features of design, including usability, 9–11 are among the most important influences on effective implementation. 3 7 12 It is now clear that merely meeting technical specifications is insufficient. 6 Critical to the effective deployment, implementation, and impact of clinical practice tools is early and continued engagement with end-users and broader stakeholders so that their priorities are addressed through design processes. 6 13 Currently, however, thinking about how to optimise design of clinical practice tools either does not happen at all, or is deferred until far too late in the process of tool development, leading to a high level of waste associated with non-adoption or poor implementation. 14 15 Though a range of design methods is available and widely used in other industries, 8 their use in development of clinical practice tools has been strikingly limited. 5 6 12 In this article, we propose that practical, action-oriented guidance could help to address this problem.

User-centred design is among the most well established of the various approaches that can support better usability of clinical tools, 16 and is already a staple in the development of medical devices. 6 9 10 17 18 Seeking to enhance usability of products and systems through a focus on user needs and perspectives, 16 user-centred methods are distinguished by their systematic and typically iterative approach to optimising design through consideration of contexts of use, usability goals, user characteristics, environment, tasks, and workflow. 16 19–21 By taking into account human capacities and limitations such as effects of stress on cognition, influence of fatigue, overload through multitasking, and limited memory capacity, 9 19 21 user-centred approaches have potential to enable systematic consideration of safety, effectiveness, and efficiency when designing clinical practice tools. 22–24

A user-centred approach to development of clinical practice tools is valuably complemented by co-design principles. 6 18 25 Such principles encourage developers and users—including, for example, healthcare professionals, patients, human factors engineers, and graphic designers—to nurture collective creativity and to work in partnership. 25–27 Application of these principles to development of clinical practice tools could strengthen or expand user-centred approaches, 6 18 in particular by emphasising the need for early and continued engagement of end-users and broader stakeholders throughout the design process, 6 17 18 28 29 and mobilisation of multiple forms of expertise. 6 17 One established methodological framework for co-design describes involvement of users and developers across pre-design , generative, evaluative, and post-design phases ( table 1 ). 28 Some evidence has already demonstrated the usefulness of this approach to developing products and systems for healthcare. 29 30

View inline

The methodological framework for co-design by Sanders and Stappers 28

One example of a pressing need for improving usability and design processes is found in track-and-trigger charts for detecting and responding to patient deterioration. 12 31 32 These widely used charts are based on the principle that there may be periods during which clinical deterioration is detectable by ‘tracking’ a predefined set of clinical parameters over time, with specific thresholds ‘triggering’ action. 33 Track-and-trigger charts are particularly likely to benefit from user-centred design, since they seek to support clinical decision-making and action in often pressurised situations where clarity around responding to a potentially deteriorating situation is essential, and where human capacities and limitations (eg, memory capacity, effects of stress on cognition) are key influences on patient safety. 12 34 Despite their potential value, track-and-trigger charts have been challenged by issues in acceptability, adoption, and use. 35–37 These issues are likely to be linked to suboptimal design, 12 34 including inadequate user involvement prior to implementation. 32 37 38

Despite burgeoning literature on both user-centred design (and variants, including human-centred design) and co-design, 17 18 22–24 26–30 39 practical guidance for combined use of these methods and principles in the development of clinical practice tools remains limited. In this article, we address this gap. We propose a five-step framework with recommended actions for each step, and we describe a case study of its application in developing a prototype track-and-trigger chart.

The FRamework for co-dESign of Clinical practice tOols (FRESCO) we propose seeks to codify existing user-centred design methods and co-design principles into a single framework to guide the development of clinical practice tools to the point of readiness for large-scale testing ( table 2 ). FRESCO recognises that development of tools usually benefits from iterative prototyping. Accordingly, it includes user-centred methods for formal prototype testing, 11 13 19 40 and application of the co-design principle of using prototypes as tools for discovery, understanding, and learning. 28 41 42

The FRamework for co-dESign of Clinical tOols

Using five steps outlined in table 2 , FRESCO aims to facilitate a process of collective creativity through structured co-design activities, 17 18 29 39 with involvement of users, developers, and other stakeholders in roles of design partners, informants, or testers. 18 This process is informed throughout by findings from systematic user-centred evaluations (see steps 2–4 in table 2 ).

The first step is to establish a multidisciplinary advisory group that offers voice to a diversity of experience and expertise throughout the process (see step 1). Following a pre-design phase of co-design (see steps 1 and 2), FRESCO facilitates proceeding through a generative phase (including gathering ideas from users based on concept prototypes produced by developers, see steps 2 and 3) to an evaluative co-design phase (including testing of co-designed prototypes, see steps 4 and 5). The movements from pre-design to generative to evaluative co-design phases align with, and are informed by, key user-centred design techniques such as heuristic evaluation (see step 2), think-aloud usability evaluations (see step 3) and simulations (see step 4). The last step of FRESCO aligns with completing the evaluative phase of co-design (see step 5), working towards a final prototype ready for further testing in real-life settings as part of the post-design phase (see table 1 ).

We used FRESCO in a case study, aiming to co-design a track-and-trigger chart for detection and response to suspected intrapartum fetal deterioration ( Box 1 ).

Case study: Avoiding Brain Injury in Childbirth (ABC) programme

In 2021, the UK’s Department of Health and Social Care commissioned the Avoiding Brain Injury in Childbirth (ABC) programme, a collaboration between the Royal College of Midwives (RCM), Royal College of Obstetricians and Gynaecologists (RCOG), and The Healthcare Improvement Studies Institute at the University of Cambridge. Colleagues from these institutions formed the ABC programme team.

A key aim of the ABC Programme was to co-design a standardised approach for detecting and responding to possible fetal deterioration during labour, including a track-and-trigger chart. The need for this work had been identified as critical and urgent because problems in intrapartum monitoring and response remain major and persistent hazards in maternity care, contributing to poor outcomes at birth and clinical negligence claims.

Current approaches to fetal monitoring during labour focus primarily on assessment of fetal heart rate features, which can be done either using intermittent auscultation (for lower-risk labours) or electronic fetal monitoring with cardiotocography (for higher-risk labours). A key innovation of the ABC programme was to combine monitoring of fetal heart rate features with other evidence-based intrapartum risk factors into a track-and-trigger tool, informed by earlier work of a task force of the RCM and RCOG. The intention of the ABC programme was to co-design an improved prototype tool, ready for deployment in a future national programme of testing, implementation, and evaluation.

Below, we explain how each step of the framework guided the Avoiding Brain Injury in Childbirth (ABC) programme’s co-design of a prototype chart for detecting and responding to suspected fetal deterioration during labour ( figure 1 ).

Download figure
Open in new tab
Download powerpoint

Step 1: establish a multidisciplinary advisory group

Optimising a tool for detecting and responding to possible fetal deterioration during labour requires access to a range of expertise and experience, including scientific knowledge, clinical expertise, lived experience of labour and using maternity services, graphic design, human factors/ergonomics, and social science. We identified individuals with one or more of these forms of expertise or experience using intentional outreach and inclusive methods of recruitment. 43 We sought to be purposeful in ensuring diversity as well as addressing the potential for power imbalances. 43 44 For example, we included a mix of seniority among the maternity professionals and ensured that service user representation included multiple viewpoints. As detailed in online supplemental file 1 , the group included the following:

Supplemental material

twelve maternity professionals (six midwives and six obstetricians),

five maternity service users (representing a range of maternity experiences and experience of advocating for improvement and inclusion of under-represented voices), and

five other specialists (human factors engineer with expertise in user-centred design, graphic designer, consensus-building specialist, and two specialists in facilitating patient and public involvement [PPI]).

As part of the pre-design phase (including preparation of the group for the co-design process), 28 roles and responsibilities across different stages of work were explicitly allocated to support efficient and effective decision-making. 45 46 This, for example, meant that not all advisory group members needed to be involved in all activities of all steps, as further detailed in figure 1 and across steps 2–5 below.

The group’s specialists in human factors engineering, consensus-building, and PPI facilitated or led exchanges, meetings, workshops, and other co-design activities. 47 48 The PPI facilitators were particularly important in ensuring that everyone’s voices could be heard during meetings, 43 44 as well as facilitating separate activities for maternity service users, in the interests of addressing potential power imbalances. The activities of the advisory group that were part of the generative and evaluative co-design phases 28 are further detailed across steps 2–5 below.

Step 2: develop initial drafts of the prototype

In accordance with the pre-design and generative phase of co-design, 28 41 we set out to understand stakeholders’ experiences of the work system under consideration. 19–21 49 This included developing two alternative prototypes of the track-and-trigger tool to explore which design elements worked best for maternity professionals. 13 49

Prior to the programme, a task force from two national bodies ( Box 1 ) had developed an initial draft prototype (‘Design 1’, see figure 1 and online supplemental file 2 ). It included the evidence-based clinical information required for detection and responding to possible fetal deterioration, but was focused more on clinical content than on design. A human factors engineer evaluated the draft prototype against usability heuristics, 34 50 51 while alert to the contexts of use 20 such as intended or expected users, tasks, physical environment, social and organisational milieu, and technical and environmental constraints. 19–21

A second prototype (‘Design 2’, see figure 1 and online supplemental file 2 ) was then developed with support of the graphic designer, based on the clinical information and heuristic evaluation of Design 1 as well as the factors identified in analysis of the context of use description of the tool (see overview in online supplemental file 3 ). 20 Design 2 applied established user-interface design principles (detailed in online supplemental file 3 ), such as the need to be attentive to limitations of memory and attention while executing a task, 51–53 and the need for consistent use of colour coding and for grouping-related information together. 34 50–54

Though the clinical content of both designs was the same, they used alternative page formats, colours, font types and sizes, ways of recording observations, visuals indicating actions and information structures (see details in online supplemental file 3 ). These alternatives were designed to enable comparison and to prompt discussions with participants about preferences in subsequent think-aloud usability evaluation (see step 3 below). 55

Step 3: conduct think-aloud usability evaluations

As part of the generative co-design phase, 13 28 41 we conducted think-aloud formative usability sessions with 15 maternity professionals of varied backgrounds ( online supplemental file 4 ). 10 11 19 Asking people to work with designs 1 and 2 (see figure 1 ), the sessions were aimed at understanding processes of cognition and identifying usability flaws (and their causes) with a small group of representative end-users. 11 19 46

In advance of the session, participants received print-outs of the two draft prototypes, examples of the drafts with recorded observations, and clinical scenarios. Each session took part during a video call hosted on an online platform 1 , and was facilitated by a moderator (trained interviewer or human factors engineer). Sessions were organised so that designs 1 and 2 were covered in a sequence counterbalanced across participants to mitigate order effects. The moderator started with an exercise to encourage the participant to think aloud in describing their experiences while interacting with the prototype, 10 11 19 with prompts used to elicit experiences of particular design elements. Following this think-aloud exercise, the moderator used a semistructured interview guide (see online supplemental file 4 ) to ask about preferences for elements of one of the designs, elicit further views on design aspects that could be improved and use of the chart in practice. 6 10 29 56

The sessions took about one hour each. They were audio-recorded and transcribed verbatim. Analysis focused on preferences for elements of the two designs and identification of design principles to guide future prototype iterations. 56–58 Participants preferred the detail contained within Design 1, but found Design 2 easier to complete and interpret ( table 3 ). These findings reflected the tension between high data density and information overload. 54 They highlight that a particular consideration in developing clinical practical tools is striking a balance between: (1) including sufficient information to support task completion, and (2) preventing high data density that can increase search times and mental workload, particularly if information is poorly structured. 59 Further qualitative analysis identified five requirements to inform further prototype iterations and future implementation ( table 4 ), such as the need for optimising flow of information. 54

Examples of analysis on the number of participants who preferred specific design elements of Design 1 versus Design 2 (see online supplemental file 1 for details on design elements)

Identified requirements to inform further prototype iterations based on qualitative analysis of the think-aloud exercises and follow-up interviews

The analysis informed a set of co-design activities with advisory group maternity professionals for the next prototype iteration. 13 41 42 46 This included structured email exchange and online meetings facilitated by the human factors engineer or consensus facilitator to reach a professional consensus on which elements of designs 1 and 2 to incorporate in an improved draft prototype (‘Design 3’, see figure 1 ). Design 3 combined these elements—guided by the heuristic evaluation of step 2, the think-aloud evaluation findings of step 3 and clinical expertise—to feature:

selective use of colour to indicate trigger values and trend lines used for recording observations,

showing a ‘start of labour risk assessment’ on the same page as the intrapartum risk factors recorded during labour,

an A3-sized format to improve legibility while accommodating for the content detail preferred by participants, and

implementation of a simplified action diagram for escalation.

Step 4: test the prototype in clinical simulations

The evaluative phase of co-design included clinical simulation, 13 28 41 which is increasingly valued for its ability to support quality improvement in health systems. 60 61 Simulations have a role in both user-centred 7 40 60 61 and co-design approaches. 28 41 One key advantage of clinical simulation is that rare but potentially catastrophic events or conditions can be reproduced. 62 Design 3 (see figure 1 ) was tested in close approximations of real-life settings, since this is critical to safety checks, understanding how a tool might be used in practice and identifying how to improve work systems. 61

We conducted clinical simulations involving 52 maternity professionals from five different National Health Service maternity units ( online supplemental file 5 ). These units were recruited through convenience sampling based on availability. The simulations were designed as quality improvement activities (see Ethics approval below) guided by the ‘TEACH Sim’ framework, 63 focusing on: (1) testing usability of the Design 3 prototype, (2) comparing care with the prototype with usual care with the unit’s existing documentation, and (3) informing the next iteration of the prototype. TEACH Sim helped to specify the simulation’s objectives, audience, scenario script, equipment, actors, and team composition. 63

As simulation is especially well suited for conducting controlled tests exposing one group but not the other to a new prototype, 60 64 we employed the same clinical scenario twice in each round of simulation: first with a team using usual care and the second time with a different team using the Design 3 prototype ( figure 1 ). Facilitated by an experienced midwife from the advisory group, simulations in two units took place in situ, that is, in the participants’ own clinical settings where care is routinely performed. 60 61 Due to clinical pressures, simulations in other units took place in a dedicated simulation laboratory or a clinical teaching setting.

Simulations were audio and video-recorded, with one camera fixed above the desk to capture participants making recordings on intrapartum tools. A trained ethnographer 65 used a fieldnote form to record observations on aspects such as teamwork, professional roles and boundaries, communication, and social atmosphere during the simulation, with a focus on use of the intrapartum tools.

Each simulation was followed by an audio-recorded, verbatim-transcribed debrief 7 66 67 and focus group 6 10 65 session with the participants, facilitated by the ethnographer and an advisory group midwife using a topic guide ( online supplemental file 5 ). The debriefing and focus group discussions with the teams involved in the simulation aided learning, through reflecting on experiences of the scenario, contextual and environment issues, safety concerns, acceptability and usability of the usual care and prototype tools, as well as identifying opportunities for better teamwork, equipment set-ups, escalation systems, and design of tools. 61 67 The focus group discussions also helped generate further ideas to improve the draft prototype. 6 10 65

Following the focus group, participants completed the Ottawa Acceptability of Decision Rules Instrument. 68 This validated survey instrument further complemented assessment of reported usability, 10 and comparison between groups providing usual care and prototype care. 68 69

Analysis 57 70 focused on four areas: (1) recording errors and corrections made on the prototype charts, (2) if triggers during the simulation safety checks consistently led to the required actions for safe care, (3) the role of the intrapartum tools in communication (both within the team and with those in labour and their birth partners), and (4) suggestions for improving the usability of the draft prototype. Data analysis used narrative summaries and observational checklists to code the behaviour of simulation participants based on video recordings or direct observations of the sociotechnical system during the simulations. 70 Quantitative usability analysis assessed use errors and corrections on the charts. 19 58 71

The findings of the simulations ( table 5 ) informed meetings with maternity professionals from the advisory group, facilitated by the human factors engineer and consensus specialist. One key discussion point was the need to support transfer across settings, that is, from low-risk settings where intermittent auscultation is used to higher-risk settings where cardiotocography is used. The group reached a consensus on a single prototype (‘Design 4’, see figure 1 ). Design 4 required users to refer to a second page for actions (compared with the original single-page format—see online supplemental files 2 and 3 ). The group viewed this as an acceptable trade-off given that the single prototype would support transfer across settings.

Examples and key findings of the analysis of the simulations

Step 5: generating a final prototype using co-design workshops

Step 4 identified a need for further input to (i) improve use of the prototype in terms of communication with the person in labour and (ii) finalise the action diagram. To complete the evaluative co-design phase, 28 this was addressed with the advisory group through workshops. These have shown potential for practical and effective ways to finalise a prototype. 13 17 18 39 41 46 To address potential power imbalances, workshops were organised with subgroups ( figure 1 ). Facilitators supported agenda-setting, procedures, and consensus rules, 72 73 and were mindful of power dynamics. 44

The PPI facilitators introduced Design 4 to the five service user representatives and gained feedback on it during three discussion workshops ( figure 1 ), exploring in particular how the prototype might impact communication with those in labour. The maternity professionals and human factors engineer joined the discussions upon invitation by the PPI facilitators or service users. These workshops led to the inclusion of an additional item—‘is the woman concerned?’—in the final prototype, as this was a key proposal made by the representatives.

To address the identified use difficulties with the flow chart actions, an alternative grid format (vs the original flow chart format) was developed. 10 46 The human factors engineer facilitated three workshops with maternity professionals from the advisory group, in which the flow chart and grid formats were used alongside each other with reference to written clinical scenarios ( figure 1 ). 10 They reached a consensus that the grid layout provided better usability—through its better conveyance of the data 34 54 —and should be implemented in the final prototype. The final prototype (see online supplemental file 6 ) was prepared by the human factors engineer and graphic designer, reviewed by the advisory group and considered ready for use in large-scale testing.

Clinical practice tools have not routinely benefited from systematic combination of user-centred design methods and co-design principles applied to their development, 6 17 18 despite the availability of well-established techniques with a good track record in improving design and usability in a range of clinical applications. 11 13 16 29 30 One likely reason for this is the limited practical guidance about how to deploy these approaches in a pragmatic yet systematic manner for development of clinical practice tools. The framework (FRESCO) proposed in this article codifies existing user-centred design methods and co-design principles into practical guidance for enabling mobilisation of multiple forms of expertise for development of clinical practice tools. Our case study illustrates application of the framework in an area of pressing need, leading to a viable track-and-trigger prototype tool ready for large-scale testing. The study also helps to address the call for better reporting of healthcare improvement activities that align with principles of co-design. 18 39 74

FRESCO builds on an established co-design framework ( table 1 ), 28–30 including use of pre-design, generative, and evaluative phases that can inform future post-design implementation phases with the produced prototype. One of its contributions is in sensitising developers of clinical practice tools to systematic consideration of the needs and priorities of users—through application of principles of collective creativity and inclusivity central to co-design into a series of actionable steps 25–27 —while employing a user-centred design approach that supports safety, effectiveness, and efficiency. 22–24 The case study also illustrates that employment of FRESCO is consistent with a design process moving from medium to high structural restrictiveness . 55 The generative phase started with various concept prototypes that encouraged the co-design group to explore alternative ideas, which helped prevent the risk of premature closure around one solution. During the evaluative phase, the best elements of the concept prototypes were then integrated through iterative cycles into a single prototype, using high structural restrictiveness to increase decision-making precision. 55

Findings of the case study suggest that FRESCO supports inclusive ways of co-designing prototype clinical practice tools and enabled improvements based on voices that are often under-represented in development of clinical practice tools. As an example, a novel prompt—‘is the woman concerned?’—was included in the prototype to help ensure optimal communication with those in labour and their birth partners, following input of service user representatives. This helped address the imperative to include patient/family concern in track-and-trigger systems 75 as well as the broader concern to listen better to families and involve them in their own care. 76 The in situ simulations helped to understand how the prompt could be best used in practice. Key to achieving co-design in this way is commitment to inclusion, facilitation that focuses on hearing everyone’s voices and managing power dynamics through, for example, organising separate activities for service users when needed. These findings suggest that FRESCO can contribute to the need for effective ways of co-design with patients, as called for in models for co-creation of healthcare services. 77

Strengths and limitations of the framework

While FRESCO helped develop a prototype track-and-trigger tool, further evaluation will be needed to determine clinical and service user experience, efficiency, implementability, sustainability of change, impact on clinical outcomes, and any unintended consequences. 78 79 Piloting and large-scale, national testing will be important in supporting this. Further examples of use cases outside of this context would help to refine and test the framework, for example to: (1) determine whether clinical practice tools produced using the framework offer advantages over others, (2) establish the resourcing needed for minimal and optimal execution of each step, and (3) assess the extent to which steps may need to be adapted for use in lower-resourced settings. There is also a need to generate learning on how to sustain engagement and involvement of users in the design process.

Although the resource implications of using FRESCO are significant, so too are the costs of developing the technical components of clinical practice tools. 14 Moreover, deploying suboptimally designed tools introduces multiple risks and potential for waste. 3 5 12 71 Ultimately, FRESCO could help to prevent the characteristic dysfunctions associated with exclusively bottom-up or top-down innovation for quality improvement, 80 such as lack of access to specific expertise common in locally led, bottom-up approaches, 15 and risk of perverse incentives associated with top-down approaches. 81 For example, using the framework as a practical guide to developing a prototype clinical practice tool could help prevent suboptimal implementation owing to inadequate or absent exploration of usability or acceptability, 7 38 78 82 83 or waiting until the end of the development cycle when the sunk costs may limit improvement. 7 12 83

Limitations of the case study

The pandemic conditions in which the case study was conducted imposed some limitations, including the need to adapt established in-person think-aloud methods and conduct of observations. These adaptations did highlight the flexibility inherent to our proposed framework. Ongoing pressures caused by the pandemic also required the use of convenience sampling of units for the simulations and use of clinical simulation laboratories instead of in situ settings in some units, so representativeness was difficult to determine.

The proposed framework (FRESCO), combining user-centred design methods and co-design principles, was successfully deployed to develop a prototype clinical practice tool for detecting and responding to possible fetal deterioration during labour. By codifying existing methods and principles into a single actionable framework, FRESCO has potential to facilitate pragmatic, flexible, and inclusive co-design of clinical practice tools using methods that can be standardised, replicated, and potentially scaled when needed, but will require further evaluation. Future work can also help identify the kinds of applications the framework works best for and where its limits lie.

Ethics statements

Patient consent for publication.

Not required.

Ethics approval

This study involves human participants. The usability evaluations received ethics approval from the University of Cambridge Psychology Research Ethics Committee (PRE.2021.067). All participants provided written informed consent and were invited to join the ABC authorship group. The UK’s Health Research Authority decision tool ( http://www.hra-decisiontools.org.uk/research/ ) showed that ethics approval was not required for the simulations, as they were classified as quality improvement activities, in which all of the participants provided written informed consent and were invited to join the ABC authorship group.

Acknowledgments

For recruitment and communications support, we thank the Avoiding Brain Injury in Childbirth (ABC) communications team including members from THIS Institute, RCOG and RCM. We are grateful for the many and varied contributions from colleagues across the ABC programme team and external to the team, including the graphic designers (Dan Gould Design, Soapbox) and video agency (Hobson Curtis).

Chapman SM ,
Oulton K , et al
Almanasreh E ,
Carayon P ,
Hoonakker P ,
Hundt AS , et al
Lugg-Widger FV , et al
Rodriguez NM ,
Burleson G ,
Linnes JC , et al
Doughty C ,
Arnold J , et al
Bitkina OV ,
Daniels J ,
Kushniruk A , et al
Jaspers MWM
Gale-Andrews L , et al
Coulentianos M ,
Rodriguez-Calero I ,
Daly S , et al
Wynants L ,
Rijnhart E , et al
Dixon-Woods M ,
Pronovost PJ
Kushniruk A ,
Woudstra K ,
Rovers M , et al
Göttgens I ,
Oertelt-Prigione S
Kushniruk AW ,
Holden RJ ,
↵ International organization for standardization, IEC 62366-1:2015. Medical devices — part 2: guidance on the application of usability engineering to medical devices . 2021 . Available : https://www.iso.org/standard/63179.html
↵ International organization for standardization, ISO 9241-210:2019. Ergonomics of human-system interaction — part 210: human-centred design for interactive systems . 2019 . Available : https://www.iso.org/standard/77520.html
↵ International organization for standardization, IEC 62366-1:2015. Medical devices — part 1: application of usability engineering to medical devices . 2021 . Available : https://www.iso.org/standard/63179.html
Sanders EBN ,
Stappers PJ
Masterson D ,
Areskoug Josefsson K ,
Robert G , et al
Williams O , et al
Clausen C ,
Pedersen S , et al
Noorbergen TJ ,
Roxburgh M , et al
Credland N ,
Connolly F ,
Lydon S , et al
O’Connell A ,
Flabouris A ,
Thompson CH
Preece MHW ,
Horswill MS , et al
van Galen LS ,
Struik PW ,
Driesen BEJM , et al
Elliott D ,
McKinley S , et al
Mackintosh N ,
Rance S , et al
Perry L , et al
Grindell C ,
Croot L , et al
Saldana C ,
Craig K , et al
Sanders EB-N ,
Sanders E-N ,
Garfield S ,
Franklin BD , et al
Brewster L ,
Aveling E-L ,
Martin G , et al
Andersen PVK ,
Coupland C ,
Hignett S ,
Miller D , et al
Visser FS ,
Stappers PJ ,
van der Lugt R , et al
Johnson TR ,
Patel VL , et al
Shneiderman B
Dashevsky SG
Sanders MS ,
McCormick EJ
Bateman N ,
Bresciani S
Militello LG ,
Patel H , et al
Henshall C ,
Kenyon S , et al
Moacdieh NM ,
Dixon-Woods M
Gettrust L , et al
Benishek LE ,
Lazzara EH ,
Gaught WL , et al
Bonafide CP ,
Roberts KE ,
Weirich CM , et al
Phillips EC ,
Tallentire V , et al
Brehaut JC ,
Graham ID ,
Wood TJ , et al
Auerbach M ,
Hunt EA , et al
Khajouei R ,
Peute LWP ,
Hasman A , et al
Greenhalgh T ,
Finlay T , et al
Murphy MK ,
Lamping DL , et al
Bazzano AN ,
Martin J , et al
Massie S , et al
Batalden M ,
Batalden P ,
Margolis P , et al
Wherton J ,
Papoutsi C , et al
Collins GS ,
Reitsma JB ,
Altman DG , et al
van der Scheer JW ,
Woodward M ,
Ansari A , et al
Mukamel DB ,
Haeder SF ,
O’Malley D ,
Cithambaram K
Salwei ME ,
Carayon P , et al

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.

Data supplement 1

Twitter @MaryDixonWoods & @THIS_Institute, @LisaHinton4, @janvdscheer

Collaborators Thiscovery Authorship Group: Ruth Cousens, Jordan Moxey, Luke Steer, Andy Paterson, André Sartori. ABC Contributor Group: Aiesha Lake, Amar M Karia, Anna MA Croot, Bethan Everson, Bothaina Attal, Carlo Personeni, Charity Khoo, Charity LK Khoo, Charlotte Vale, Clare Shakespeare, Cossor Anwar, Daniel Wolstenholme, Daisy V Westaway, Emma Crookes, Evleen Price, Georgina Brehaut, Hannah K Twinney, Hannah Sharpe, Helena Bull, Ilaria Medda, Jayden J Mills, Jennifer Jardine, Julia F Bodle, Julie McKay, Karen Hooper, Katarina Tvarozkova, Katie Cornthwaite, Libby Shaw, Louise Houghton, Lucy M Saunders, M Nwandison, Margaret Blott, Mary Edmondson, Megan Gailey, Nina Johns, Pauline Hewitt, Phil Steer, Sophie Relph, Subhadeep Roy, Susanna Stanford, Theresa Fitzpatrick, Zeba Ismaeljibai, Zenab Barry.

Contributors All authors read and approved the final manuscript. Their specific contributions, following CRediT (Contributor Roles Taxonomy), are as follows: MW contributed to conceptualisation, formal analysis, investigation, methodology, project administration, writing (original draft preparation) and writing (review and editing). MD-W contributed to conceptualisation, funding acquisition, methodology, project administration, supervision, writing (original draft preparation) and writing (review and editing). WR contributed to investigation, methodology, project administration, resources, supervision and writing (review and editing). CW contributed to investigation, project administration, resources and writing (review and editing). CH contributed to investigation, project administration, resources and writing (review and editing). SB contributed to investigation, project administration, resources and writing (review and editing). LD contributed to investigation, project administration, resources and writing (review and editing). RB contributed to conceptualisation, methodology, supervision and writing (review and editing). TD contributed to conceptualisation, funding acquisition, methodology, project administration, supervision and writing (review and editing). CW contributed to methodology, resources and writing (review and editing). AP contributed to formal analysis, project administration, investigation, methodology and writing (review and editing). AA contributed to formal analysis, project administration and writing (review and editing). JW contributed to formal analysis, investigation, methodology and writing (review and editing). IAFB contributed to formal analysis and writing (review and editing). AO contributed to formal analysis and writing (review and editing). NR contributed to formal analysis and writing (review and editing). JL contributed to formal analysis, investigation, methodology, project administration and writing (review and editing). LH contributed to formal analysis, conceptualisation, investigation, methodology, project administration, supervision and writing (review and editing). JB contributed to conceptualisation, formal analysis, funding acquisition, methodology, project administration, supervision, writing (original draft preparation) and writing (review and editing). GM contributed to formal analysis, project administration and writing (review and editing). CD contributed to formal analysis and writing (review and editing). JWvdS contributed to conceptualisation, formal analysis, methodology, project administration, supervision, writing (original draft preparation) and writing (review and editing). The final version of the manuscript was also read and approved by the members of the Thiscovery Authorship Group and the ABC Contributor Group (see the Acknowledgements section). JWvdS is the guarantor of the study.

Funding The Department of Health and Social Care (UK) provided funding for the Avoiding Brain Injury in Childbirth (ABC) programme. The methodological work presented in this paper was supported by THIS Institute, which is funded by the Health Foundation (Grant/Award Number: RHZF/001 - RG88620), an independent charity committed to bringing about better health and health care for people in the UK. Contributions of Mary Dixon-Woods to the work were supported by the National Institute for Health and Care Research (MD-W was an NIHR Senior Investigator [NF-SI-0617-10026] during conduct of the study).

Competing interests None declared.

Provenance and peer review Not commissioned; externally peer reviewed.

↵ https://thiscovery.org/about

Linked Articles

Editorial Effective use of interdisciplinary approaches in healthcare quality: drawing on operations and visual management Nicola Bateman BMJ Quality & Safety 2024; 33 216-219 Published Online First: 06 Mar 2024. doi: 10.1136/bmjqs-2023-016947

Read the full text or download the PDF:

Log in using your username and password

Search More Search for this keyword Advanced search
Latest Content
For authors
BMJ Journals More You are viewing from: Google Indexer

http://orcid.org/0000-0002-1648-8835 Ramon Pi-Rusiñol 1 ,
http://orcid.org/0000-0001-9227-8234 Evert Verhagen 2 ,
Miriam Blanch 3 ,
Gil Rodas Font 1 , 4
1 FC Barcelona Medical Department, FIFA Medical Excellence Center, and Barça Innovation Hub , Barcelona , Spain
2 Amsterdam Collaboration on Health & Safety in Sports, Department of Public and Occupational Health, Amsterdam Movement Sciences , Amsterdam UMC , Amsterdam , Netherlands
3 ITEREM BPM Consulting Barcelona Spain , Barcelona , Spain
4 Barnaclinic Sports Medicine Unit , Barcelona , Spain
Correspondence to Dr Ramon Pi-Rusiñol; ramon.pi{at}fcbarcelona.cat

Objective This paper presents an exploratory case study focusing on the applicability and value of process mining in a professional sports healthcare setting. We explore whether process mining can be retrospectively applied to readily available data at a professional sports club (Football Club Barcelona) and whether it can be used to obtain insights related to care flows.

Design Our study used discovery process mining to detect patterns and trends in athletes’ Post-Pre-Participation Medical Evaluation injury route, encompassing five phases for analysis and interpretation.

Results We examined preprocessed data in event log format to determine the injury status of athletes in respective baseline groups (healthy or pathological). Our analysis found a link between thigh muscle injuries and later ankle joint problems. The process model found three loops with recurring injuries, the most common of which were thigh muscle injuries. There were no differences in injury rates or the median number of days to return to play between the healthy and pathological groups.

Conclusions This study explored the applicability and value of process mining in a professional sports healthcare setting. We established that process mining can be retrospectively applied to readily available data at a professional sports club and that this approach can be used to obtain insights related to sports healthcare flows.

Sporting injuries
Data Science
Sports & exercise medicine

Data availability statement

The data supporting the conclusions of this article can be requested from the corresponding author upon reasonable request.

https://doi.org/10.1136/bmjsem-2024-001890

Statistics from Altmetric.com

Request permissions.

WHAT IS ALREADY KNOWN ON THIS TOPIC

Athlete healthcare in professional sports has proven challenging, while this context provides a dynamic multidisciplinary environment that poses specific challenges. Process mining has emerged in healthcare as an effective tool for interpreting and improving complicated care processes. Its application has led to improvements in, among other things, the quality of care, patient safety, patient satisfaction and resource optimisation.

WHAT THIS STUDY ADDS

Our study demonstrates the feasibility of employing exploratory process mining to extract valuable insights into readily available data injury data in a professional sports setting.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

Understanding injury pathways could provide insights into where, to whom, and when we should focus resources. In doing so, process mining might help navigate some of the known implementation barriers in sports.

Introduction

In professional sports, injuries constitute a major concern, with severe repercussions for athlete performance, career longevity and team success. 1–3 Hence, professional sports organisations’ capacity to prevent and respond to injuries proactively is of great significance. Over the years, research has provided a vast library of evidence to support and protect athletes’ health. 4 However, effectively using this evidence in professional sports has proven challenging, 5–7 while this context provides a dynamic multidisciplinary environment that poses specific challenges. 8–10

Recent studies have explored the role of sports medicine professionals as members of a high-performance support team. 11–14 This work has outlined that healthcare in professional sports is complex and requires flexible athlete care processes. This brings forward the concept of ‘process mining’ as an interesting opportunity to explore in professional sports healthcare. Process mining aims to improve operational processes (ie, processes with repeated execution of activities to deliver products or services) through a data-driven systematic analysis of event data. 15 The outcome is a detailed identification of trends, patterns and bottlenecks of processes in practice. 15–17 Process mining methods can encompass retrospective analyses, such as identifying the origins of a bottleneck in a process and prospective analyses, like forecasting the remaining processing time of an ongoing case or offering suggestions to reduce the incidence of failures. Both retrospective and prospective analyses have the potential to prompt interventions, such as implementing measures to resolve performance or compliance issues.

Process mining has been successfully applied in many fields, including healthcare, where it has emerged as an effective tool for interpreting and improving complicated care processes. 18–20 These outcomes have improved, among other things, the quality of care, patient safety, patient satisfaction and resource optimisation. 19–22 Given such positive results, exploring the applicability and value of process mining in a professional sports healthcare setting is only reasonable. Understanding injury pathways could provide insights into where, to whom, and when we should focus resources. In doing so, process mining might help navigate some of the known implementation barriers in sports. 8 23–25

In this paper, we present an exploratory case study focusing on the applicability and value of process mining in a professional sports healthcare setting. We explore whether process mining can be retrospectively applied to readily available data at a professional sports club (Football Club Barcelona; FCB) and if it can be used to obtain insights related to care flows. Specifically, we were interested in investigating the relationship between the presence of clinical antecedents when players entered the club with subsequent injury risk, injury severity and return to play (RTP).

We used ‘discovery process mining’ for our study. This technique uses data mining to discover patterns, trends and insights about an existing process, specifically for our study, the longitudinal injury pathway of athletes after a Pre-Participation Medical Evaluation (PPME). Our discovery process mining entailed five phases, which we outline below. We describe the methodology for each phase below instead of providing an overarching methods section. The first four phases are graphically summarised in figure 1 . The fifth phase concerns analysing and interpreting the discovered model, leading to suggestions to improve care processes.

Download figure
Open in new tab
Download powerpoint

Flowchart of the evolutive phases of the study. RTP, return to play.

Phase 1—data collection

In this first phase, we collected relevant data from our athletic FCB Medical Services management system, representing 12 different sports (COR Database V.1.0 FCB. Spain). 26 This system electronically records all PPME data, periodic check-ups and pathological episodes of illnesses and injuries. The OSICS V.10 code was used to code all episodes in the system. 27 Past encodings in IDC9 and IDC10 were transferred to OSICS V.10 to standardise the data. Our current analysis used data from all 2574 athletes over 25 months: from 1 January 2008 to 1 March 2020 (the start of the SARS-COVID-19 pandemic) ( table 1 ). The findings of this observational study have been disclosed in conformity with the Helsinki Declaration. 28 Before entering the club, all athletes completed a consent form.

View inline

Demographics of available athletes in the FCB Medical Services management system

Outcome measures

The athlete’s health status at the PPME is the independent variable in our further analyses. Athletes were considered healthy when no clinical antecedents were detected in the anamnesis at the PPME (‘Healthy’ group; n=1020). Athletes with pathology were characterised as having clinical history at the time of club entrance (‘pathology’ group; n=1534). 26 As dependent variables in the analysis, we examined future injury.

We collected clinical information and data related to the type of injury, time loss (TL) or medical attention (MA) and the time to RTP. These metrics were obtained based on consensus definitions and data collection procedures suggested by the Union of European Football Associations. 29 30 TL injuries included any injury during a training session or match that caused the player to be absent for at least the next training session or match. In contrast, MA injuries did not result in TL from training sessions and scheduled matches. We calculated RTP as the recovery time (in days) from the day of the injury until the player returned to training or competition after TL. Finally, we defined recurrent injury as any injury of the same type and at the same anatomic location as a previous injury in the same individual within 2 months after RTP.

Phase 2—preprocessing

Before further analysing the data, the database had to be preprocessed to ensure its quality and usability. As we found 21 981 records for 2559 individual pathological cases in our database, it was necessary to perform data filtering to derive useful findings. There were 1100 different OSICS V.10 codes among all accessible cases. This made us concentrate on the four most common OSICS code categories of location (Thigh, Knee, Foot and Ankle) combined with the four most common injury types (muscle, tendon, haematoma and joint). This yielded a data set for analysis in 1439 athletes (815 in a Pathology Group; PG, and 624 in a Healthy Group; HG).

Phase 3—event log creation

In this step, we transformed the preprocessed data into an event log format for further analysis. An event log reflects how a process has been executed and describes the sequence of activities that were performed, when they were executed, and by whom and for whom. 31 Specifically, for our study, this step described the injury status and severity of athletes from their designated baseline groups (HG or PG) through follow-up. Both groups had similar dynamics, distribution and data flow during follow-up ( figure 2 ).

Event log describing the evolution of athletes in our study.

Healthy group

In the HG, we registered 2511 injury episodes in 624 athletes. Athletes with injury were, on average, 25.2 (SD±12.1) days with an open injury case. Of these, among 542 athletes, 1447 injuries resulted in an average of 21.2 (SD±9.3) days of TL.

Pathology group

The PG included 2877 injury episodes in 815 athletes. Injury cases were open for an average of 24.9 (SD±10.6) days. Of these. 1636 injuries led to an average of 19.5 (SD±10.7) days of TL in 689 athletes.

Phase 4—process model discovery

Using Process Mining in Disco by Fluxicon, 32 33 we analysed the event log to discover our process model. Using this mining algorithm, we filtered data progressively to establish injury patterns. The outcome of this process is graphically presented in a Directly-Follows Graph in figure 3 . The Figure is primitive in that it presents all athletes’ data, regardless of their baseline PPME outcome. We can, as such, only observe pathways of injury. We also note that these outcomes are only representable for our club as these pathways are present under the influence of our care provided to the athletes. Consequently, these results cannot be extrapolated to other settings or situations outside our club or study.

Directly follows graph on all injuries in our database. This figure includes 5388 time loss (TL) and medical attention (MA) injury episodes in 1439 athletes, regardless of their baseline PPME outcome. PPME, Pre-Participation Medical Evaluation.

Figure 3 highlights a pathway between thigh muscle injuries and subsequent ankle joint injuries. From the 1944 thigh muscle injuries recorded as the primary injury, we distinguished two main ‘fluxes’: one back to thigh muscle injury (n=821) and one to ankle joint injury (n=239). This should be interpreted as that just less than half of all thigh muscle injuries were linked to recurrent thigh muscle injuries, and about one-fifth to subsequent ankle injury. Similarly, for ankle joint injuries, out of 1271 cases, 236 were linked to subsequent thigh muscle injury and 322 to ankle joint injury. No fluxes were established from knee joint injuries. We must iterate that these fluxes do not imply causal relationships; they only show the injury pathway of athletes.

Our process model identified three loops with recurrent injuries that require further attention ( table 2 ). The most commonly recurring injuries were thigh muscle injuries (362 cases; rate 6.7 %), followed by ankle joint injuries (279 cases; rate 5.2 %) and knee joint injuries (102 cases; rate 1.9 %). For none of these injuries, we found a difference in injury rates nor the median number of days to RTP between the HG and PG groups. Our process model revealed a difference in the cumulative duration of thigh muscle injuries (HG 22.3 years vs PG 33.1 years), but this is because the number of thigh injuries in the PG group was larger than in the HG group (362 vs 167). Such differences were not found for the ankle and knee.

Our process model established the three most common recurrent injuries

Phase 5—optimisation

The main goal of process mining is to unravel processes’ performance, reveal bottlenecks and find areas for improvement. 15 18 21 31 As mentioned, for our study, we were interested in the injury pathway of athletes from entry at FCB to their career at our club. We were particularly interested in the potential differing pathways of athletes with clinical antecedents as assessed through our PPME. For this latter interest, we can be brief in saying that during their stay at our club, the injury pathways between HG and PG did not differ. Hence, current care processes appear suited to both groups of athletes.

The high recurrence rates for specific injuries are of interest; in our process, these were related to the thigh, ankle and knee. Our results also found relationships and trends between different injuries, frequently leading to injuries in other anatomical regions. For example, we found a pattern of bijective correlation between posterior thigh muscle injuries and ankle joint injuries. Following these results, the central actions in optimising our care process would focus on the possibility of avoiding injury recurrences and preventing subsequent injuries. 34–36

This study explored the applicability and value of process mining in a professional sports healthcare setting. Process mining has proven to be a valuable tool for extracting meaningful insights into large and seemingly chaotic datasets, also in healthcare settings. 18 We established that process mining can be retrospectively applied to readily available data at a professional sports club and that this approach can be used to obtain insights related to sports healthcare flows.

We should emphasise that these outcomes only say something about the process, not the relationships established in this process. This holds especially true for athletic injury and health data like ours, where previous research has established certain risk factors, like previous injury, that predispose to future injury. 37–41 For example, our study focused on the relationship between clinical antecedents when players entered the club and subsequent injury risk, injury severity and RTP. We did not find any of such relationships to exist in our processes. That is not to say these athletes do not have an increased risk of injury; we can only conclude that this relationship was not found in the healthcare structure of FCB. Process mining is an approach that evaluates an operational process in which decisions are made and, in our case, healthcare is provided. A multidisciplinary philosophy strongly guides FCB Medical Services’ medical care for our athletes. Once an athlete entered FCB, individualised care was provided when the PPME detected the presence of clinical antecedents. As a result, the medical team, physiotherapists, physical trainers and coaches may have played a critical role in preserving athlete health and reducing injury risks. This could explain why the injury rates in our study did not differ between the HG and PG groups. Consequently, we concluded no optimisation in our processes is needed at the PPME. At the same time, this highlights that our study is limited to FCB’s specific situation and population, subject to specific monitoring conditions and prevention and maintenance mechanisms that differ in other contexts. Hence, our findings cannot be generalised to other clubs or populations; they can only be used to demonstrate the value of process mining in improving clinical care processes in a professional sports setting.

In our study, we employed process discovery as our process mining approach. This approach entails a discovery technique that produces a process model based on event log data without using additional information. 15 This rudimentary approach only provides a descriptive outcome, that is, what happens in practice. Our outcomes do not indicate what is going well in the healthcare process at FCB and what elements demand improvement. This implies that process discovery is not a one-stop shop. We must continue to study the trends and patterns we discovered and understand why these exist at FCB so that we can implement improvements. Then, after processes are revised, we must monitor whether any changes improve these processes and not create bottlenecks elsewhere.

Process discovery is only one of four described basic process mining types. There is also conformance checking, process re-engineering and operational support. Conformance checking aims to detect differences and commonalities between a predefined process model and actual event logs, for example, to see if athlete injury pathways in practice follow the pathway (model) we expect. 42 Process engineering resembles conformance checking. However, the goal is to change the process model instead of diagnosing differences, for example, how can we improve our understanding to reflect the observed athlete’s injury pathway better? Operational support aims to directly influence a process by providing warnings, predictions or recommendations, arguably coming close to health monitoring in sports healthcare. 15 At first sight, these additional types of process mining hold value for a sports healthcare setting. However, this should be further explored and validated in various contexts.

Even though further work is needed, we want to draw attention to ‘operational support’ process mining. Other process mining types work on event data, that is, analysing events that have already occurred and only providing us with post hoc insights. Even though providing important insights, our understanding of care processes remains static when our insights are limited to only two points: the beginning (eg, screening) and the end (eg, injury). We are unaware of the dynamic processes that connect these moments and the data’s similarities and differences. This is important as the injury’s complex and dynamic aetiology has been well described. 9 43 44 This complex aetiology consists of visible athlete-related factors that can be measured and ‘soft’ factors such as quality of care, leadership and communication strategies. 10 13 45–47 This dictates that proactive measures to protect athletes’ health demand multidisciplinary prevention plans across a professional sports organisation to mitigate multiple risk factors effectively. 7 10 48 49 In current professional sports, numerous data sources are regularly updated in (near) real time, and there is ample computing power to analyse events promptly. 50–53 Consequently, ‘operational support’ process mining might be a powerful approach to provide the sports organisation with information on which athlete may benefit from what intervention, where in the process, this intervention should be provided, and by whom this intervention should best be provided.

This paper explored the applicability and value of process mining in a professional sports healthcare context. We presented a case study involving FCB PPME and injury data to gain insights into athletes’ injury pathways after they entered the club. Our study has demonstrated the feasibility of extracting valuable insights into readily available data in a professional sports setting.

Ethics statements

Patient consent for publication.

Not applicable.

Raysmith BP ,
Charlton PC
Hägglund M ,
Magnusson H , et al
Williams S ,
Trewartha G ,
Kemp SPT , et al
Gouttebarge V ,
Finch CF , et al
Owoeye OBA ,
Verhagen EALM , et al
Verhagen E ,
van Nassau F
O’Brien J ,
Pruna R , et al
Bolling C ,
van Mechelen W ,
Pasman HR , et al
Mellette J ,
Konin J , et al
Cruickshank A ,
Fletcher D ,
Arnold R , et al
Salcinovic B ,
Dijkstra P , et al
Leonardi G ,
Panzarasa S ,
Quaglini S , et al
Ji L , et al
De Weerdt J ,
Fernández-Llatas C , et al
Munoz-Gama J ,
Fernandez-Llatas C , et al
Subrahmanya SVG ,
Shetty DK ,
Patil V , et al
Schonenberg M ,
Song M , et al
Saint-Pierre C ,
Herskovic V , et al
Santner E ,
Donaldson A ,
Callaghan A ,
Bizzini M , et al
Pi-Rusiñol R ,
Sanz-de la Garza M ,
Grazioli G , et al
World Medical A
Ekstrand J ,
Bengtsson H , et al
van der Aalst WMP
Clarsen B ,
Verhagen E , et al
Vicenzino B ,
Bahr R , et al
Räisänen AM , et al
Ekenros L ,
von Rosen P
Kniewasser C ,
Hollander K , et al
Johnson MI ,
Francis P , et al
Mailuhu AKE ,
van Rijn RM ,
Stubbe JH , et al
Oosterhoff JHF ,
Moen M , et al
van der Aalst W ,
Adriansyah A ,
van Dongen B
Bittencourt NFN ,
Meeuwisse WH ,
Mendonça LD , et al
Tyreman H ,
Hagel B , et al
Marino KR ,
Vishnubala D ,
Ahmed OH , et al
Lundqvist D ,
Lagerbäck L , et al
Davison M , et al
Ageberg E ,
Brodin EM ,
Linnéll J , et al
Nassis GP ,
Brito J , et al
Figueiredo P , et al
Claudino JG ,
Capanema D de O ,
de Souza TV , et al
Gabbett TJ ,
Oetter E , et al

X @ramonpi32, @evertverhagen

Contributors RP and GR developed the rationale behind this study. RP prepared the initial drafts of this manuscript. MB and EV supported the analyses and provided critical feedback and input on manuscript drafts. GR is the guarantor of the study.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests Ramon Pi-Rusiñol and Gil Rodas work at the FC Barcelona Medical Department. Evert Verhagen is the Editor-in-Chief of BMJ Open Sport & Exercise Medicine .

Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

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

Read the full text or download the PDF:

Log in using your username and password

Search More Search for this keyword Advanced search
Latest Content
BMJ Journals More You are viewing from: Google Indexer

http://orcid.org/0009-0007-8086-2231 Basma Aabdi 1 ,
Ghizlane Kharrasse 1 ,
Abdelkrim Zazour 2 ,
Hajar Koulali 2 ,
Ouiam Elmqaddem 2 ,
Ismaili Zahi 1
1 Gastroenterology , Mohammed VI University Hospital Oujda, Morocco , Oujda , Morocco
2 Digestive Disease Research Laboratory (LARMAD) , Mohammed I University, Faculty of Medicine and Pharmacy, Oujda, Morocco , Oujda , Morocco
Correspondence to Dr Basma Aabdi; basma.aabdi{at}ump.ac.ma

Objective Dieulafoy’s lesions (DLs) are a rare but potentially life-threatening source of gastrointestinal (GI) haemorrhage. They are responsible for roughly 1%–6.5% of all cases of acute non-variceal GI bleeding.

Here, we describe retrospectively the clinical and endoscopic features, review the short-term and long-term outcomes of endoscopic management of bleeding DLs and we identify rate and risk factors, of recurrence and mortality in our endoscopic unit.

Design Data were collected from patients presenting with GI haemorrhagic secondary to DLs between January 2018 and August 2023. Patients’ medical records as well as endoscopic databases were retrospectively reviewed. Demographic data, risk factors, bleeding site, outcomes of endoscopy techniques, recurrence and mortality rate were taken into account.

Results Among 1170 cases of GI bleeding, we identified only seven cases involving DLs. Median age was 74 years, with a male-to-female ratio of 2.5. 75% of patients had significant comorbidities, mainly cardiovascular diseases. Only anticoagulant and antiplatelet agents were significantly associated with DLs. All patients were presented with GI bleeding as their initial symptom. The initial endoscopy led to a diagnosis in 85% of the cases. Initial haemostasis was obtained in all patients treated endoscopically. Nevertheless, the study revealed early recurrence in two out of three patients treated solely with epinephrine injection or argon plasma coagulation. In contrast, one of three patients who received combined therapy, experienced late recurrence (average follow-up of 1 year). Pathological diagnosis was necessary in one case. One patient (14%) died of haemorrhagic shock. Average length of hospital stay was 3 days.

Conclusion Although rare, DLs may be responsible for active, recurrent and unexplained GI bleeding. Thanks to the emergence of endoscopic therapies, the recurrence rate has decreased and the prognosis has highly improved. Therefore, the endoscopic approach remains the first choice to manage bleeding DLs.

GASTROINTESTINAL BLEEDING
ENDOSCOPIC PROCEDURES
GASTROINTESTINAL HAEMORRHAGE

Data availability statement

No data are available.

https://doi.org/10.1136/bmjgast-2023-001299

Statistics from Altmetric.com

Request permissions.

WHAT IS ALREADY KNOWN ON THIS TOPIC

Dieulafoy’s lesion (DL) is responsible for active, recurrent and unexplained non-variceal gastrointestinal bleeding.

DL is classically located in the stomach, particularly along the lesser curvature.

The gold standard treatment in endoscopic therapy with high haemostasis rate.

Selective arterial embolisation through angiography or wedge resection as the preferred surgical procedure are two management options for recurrent and uncontrolled DLs.

WHAT THIS STUDY ADDS

The majority of cases of bleeding DL are diagnosed by endoscopic techniques and, in some cases, endoscopy is non-diagnostic and no bleeding site could be identified.

Prognosis mainly depends on patient comorbidities.

Anticoagulants and antiplatelet agents emerge as significant risk factors in the occurrence of DL bleeding.

Endoscopic banding ligation or haemoclipping are the most effective and successful option of treatment of DL and epinephrine injection is a suboptimal treatment.

Combined therapy gave better results than monotherapy in terms of permanent haemostasis. However, re-bleeding can also be shown with combined therapy.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

When oesophagogastroduodenal endoscopy and colonoscopy are unremarkable in suspected haemorrhagic DL, gastroenterologists should proceed with alternative techniques (single or double balloon enteroscopies for distal small bowel/CT angiography or surgery) to identify the bleeding site.

Mechanical therapy and combined therapy should not rule out the risk of re-bleeding.

Recurrence risk factors should be sought if bleeding DL was suspected. But, their absence does not rule out the diagnosis of re-bleeding.

Introduction

Dieulafoy’s lesion (DL) can be defined as a rupture of an abnormally large submucosal artery protruding into the mucosa through a small defect in the gastrointestinal (GI) wall. It could be responsible for 2% of acute GI haemorrhages and 5.8% of non-variceal upper GI bleeding but also rare lower GI bleeding. 1 2 The stomach, along the lesser curvature, is the most common site of the majority of DLs. 3 4 Although rare, DLs could be an important cause of life-threatening GI bleeding especially in the elderly. In addition, the mortality rate has declined from 80% to 9% with the advent of endoscopic approaches.

During this study, we retrospectively outlined the epidemiological, clinical and endoscopic features of bleeding DL. The aim objective was to assess our institutional experience in the management of DLs and to juxtapose the resulting outcomes with existing data in the medical literature.

This section outlines the experimental design, the materials used and the specific methodology adopted in conducting this study. This study was carried out in the Hepato-Gastroenterology and Digestive Endoscopy Department, University Hospital Center, spanning from January 2018 to August 2023.

Endoscopic data were retrospectively reviewed from emergent oesophagogastroduodenal endoscopy (OGD) and colonoscopy procedures conducted on 1170 patients presenting with GI bleeding. Furthermore, data were collected from two distinct digestive endoscopy units, namely the emergency unit and the interventional endoscopy unit. Procedures were carried out either by certified endoscopists or by emerging endoscopists under the guidance of an experienced team.

The seven patients who were diagnosed with DLs received intravenous proton pump inhibitors before endoscopic treatment. Thirteen patients presenting GI bleeding of unknown cause were excluded from this study.

All endoscopic examinations were performed according to international guidelines using two types of standard video endoscopes: PENTAX MEDCIAL 27″ Radiance, SC-WU27-G1522, 90X0660 and FUJIFILM 26″ Radiance, G2 HB, SC-WU26-A1511, 90XO623.

The endoscopic criteria employed for diagnosing DLs included the following: active arterial oozing, a bleeding point lacking visible underlying ulceration, micropulsatile streaming through a minute mucosal defect and visualisation of an adherent clot with a point of attachment to a tiny mucosal defect or the surrounding normal mucosa.

Various endoscopic haemostasis techniques were available; however, the choice of treatment approach was left to the discretion of the endoscopist and depended on the availability of equipment. The therapeutic methods used consisted of epinephrine injection (1:10 000 dilution) into and around the DL, argon plasma coagulation (APC) and haemoclipping.

To assess the success of therapeutic endoscopy, particular attention was given to the absence of bleeding from the DLs until the endoscope was withdrawn. Furthermore, follow-up endoscopy was conducted within a 24-hour to 48-hour timeframe following the initial procedure to confirm healing at the previous bleeding site.

Re-bleeding was defined as the presence of haemorrhagic shock accompanied by signs of ongoing blood loss following the initial transfusion and stabilisation. In cases where early recurrence (within 72 hours) was suspected, patients underwent endoscopic relook and retreatment. Surgical intervention was considered only when bleeding persisted after the second endoscopy or when the bleeding source could not be identified. To assess the possibility of late recurrence bleeding, long-term follow-up (up to 1 year) was conducted for all patients who had undergone endoscopic treatment.

Various factors were taken into consideration, including demographic data (age, gender, bleeding site and comorbidities), risk factors for GI bleeding such as medication use (non-steroidal anti-inflammatory drugs (NSAIDs), anticoagulants and antiplatelet agents), mode of presentation, laboratory results, blood transfusion requirements before and after endoscopic management, endoscopic techniques and outcomes, as well as re-bleeding and mortality rates.

Descriptive statistics were used to summarise patients’ data using Windows-based Excel software, V.2013. Categorical and continuous data were reported as percentages and medians (with IQR).

Among the 1020 OGD and 150 colonoscopies performed for acute GI bleeding in our endoscopy department between January 2018 and August 2023, DLs were identified as the aetiological factor in approximately 0.6% of patients presenting with acute GI bleeding.

In the study group, seven patients were diagnosed with DLs. Among these cases, five were male (71%), while two were female (28%). The median age of the patients was 74 years, with the youngest being 50 years old and the oldest 90. All of the cases presented with significant cardiovascular risk factors. Notable comorbidities included high blood pressure in two patients, heart disease in four patients and type II diabetes in three patients. Furthermore, a combination of comorbidities was observed in two patients.

Among the seven patients, only three were not taking any medications at the time of presentation. Two patients were on direct oral anticoagulants, one due to valvular heart disease and the other for severe heart failure. A single patient was taking acenocoumarol for arrhythmia-related heart disease, and an antiplatelet agent was prescribed for the patient with aortic valvular stenosis.

Five patients presented with isolated melena, one patient experienced both haematemesis and melena, and one patient had haematemesis along with haemodynamic instability necessitating a blood transfusion. No cases of rectal bleeding were reported.

The mean haemoglobin level at presentation was 74 g/L. Blood transfusion requirements varied from 2 to 5 units of packed red blood cells (mean of 2.8 units per patient). All patients exhibited preserved biological haemostasis parameters.

Demographic and clinical data of these series are summarised in online supplemental table 1 .

Supplemental material

DLs were identified in the stomach in two patients, specifically within the fundus. In two other cases, these lesions were located in the second duodenal portion. Additionally, one case was found to be situated in the bulb.

Throughout the study period, there was only one reported case of colonic DL, which was located in the right colic angle. Another case of ileal DL was also reported.

Six cases of DLs were diagnosed only by standard video endoscopes. The mean of 2.5 endoscopy sessions (range 1–4) was required for diagnosing and management of the DLs.

Different endoscopic haemostasis techniques were used. Initial haemostasis was achieved for six patients.

Epinephrine injection (1:10 000 dilution) was performed in only one patient (16%), allowing initial haemostasis. The maximal injection volume was 10 mL. However, the patient had re-bleeding (within 24 hours). Permanent haemostasis was achieved by using both APC and haemoclipping during subsequent endoscopy.

In our analysis, only two patients (33% of the cases) were managed solely with APC, without subsequent administration of epinephrine.

In one of these cases, early re-bleeding occurred, necessitating a second-look endoscopy to regain haemorrhage control. Unfortunately, the patient succumbed to haemorrhagic shock prior to endoscopic intervention.

In the remaining three patients in our study, a combination of therapeutic modalities was employed. Specifically, two cases were treated with both epinephrine injection and haemoclipping, as shown in figure 1 , while the third case underwent haemoclipping followed by APC application. In these three instances, the initial interventions successfully achieved haemostasis. Nevertheless, one of these cases experienced delayed recurrent bleeding 1 year after the initial treatment.

Download figure
Open in new tab
Download powerpoint

Illustrative pictures of patient with active bleeding from fundic DL and haemostatic success after endoscopic treatment. (A) Voluminous gastric blood clot with punctiform sheet bleeding on the lesser curvature. (B) Endoscopic management with both epinephrine injection and haemoclipping.

There were no post-endoscopy complications. Table 1 summarises the earlier findings.

View inline

Endoscopic data before and after endoscopic therapies in patients with bleeding Dieulafoy’s lesions

In one case, upper endoscopy initially failed to detect any indications of haemorrhage. Subsequent colonoscopy, however, revealed the presence of blood in the ileum, although the precise origin of the bleeding remained unclear. CT angiography subsequently showed active contrast extravasation within the central section of the small bowel, devoid of any visible mass. Unfortunately, both arterial embolisation and enteroscopy were unfeasible in the emergency setting. Concurrently, the patient’s haemodynamic condition deteriorated rapidly leading to an emergent exploratory laparotomy which successfully localised the site of bleeding, a segmental resection of the small bowel was performed. Subsequent pathological analysis confirmed the presence of a DL in the proximal ileum ( figures 2 and 3 ).

Surgical specimen showing a blood clot in the ileum.

Pathology specimen showing Dieulafoy’s lesion in the ileum.

The average length of hospital stay was 3 days. During the 1-year follow-up period, a single patient exhibited delayed recurrent bleeding attributed to DL. One patient (14% of cases), was died from bleeding-related complications.

DL was initially reported by Gallard in 1884. Another French surgeon, Georges Dieulafoy, described this lesion in 1898 as ‘Exulceratio simplex’. 3 DLs account for approximately 1.5% of all cases of acute upper GI bleeding and 3.5% of cases of jejunoileal bleeding. 5 In our study, 0.6% of patients presented with acute GI bleeding secondary to DLs (seven cases). Although it is rare, DL could be responsible for severe, active and recurrent haemorrhages. 6

Although old publications report a predilection towards advanced age, DLs can affect individuals of all age groups, with a median age in the sixth decade. We observed a distinct male predominance, with a sex ratio of two men to one woman. 3 6 Our patients fell within the same age range as reported in previous studies. However, we noted a significant male predominance, twice that which is mostly described in the literature. Moreover, the majority of affected patients are elderly with several comorbidities. In our series, as in other studies, 85% of patients were older than 65 years.

DL is anatomically defined as a vascular malformation characterised by an aberrant, tortuous, consistently large submucosal artery that causes bleeding in the absence of ulcers, aneurysms or erosions. In the literature we reviewed, a congenital anomaly has been suggested as a cause in younger individuals, whereas an acquired malformation has been proposed for elderly. 6

The presence of cardiovascular comorbidities, high blood pressure, chronic renal failure and diabetes are recognised as risk factors for the development of DLs. Several studies have suggested a correlation between bleeding DLs and chronic NSAID and anticoagulant use (in more than 40% of patients). Our findings are consistent with the role of anticoagulants and antiplatelet agents as risk factors in the occurrence of bleeding DLs. However, other authors have contested this causal association. No causal link has been established between alcohol or tobacco consumption and the occurrence of DLs. 6–9

DLs are primarily found in the stomach. Up to 80% of these lesions are located 6–10 cm from the gastro-oesophageal junction, along the lesser curvature of the stomach. Elsewhere, as reported in several studies, DLs can also occur in other locations, including the duodenum, the distal stomach and the oesophagus. 3 4 6 8 In our series, DLs were identified in both the stomach and the duodenum at similar rates (28% each).

Barbier et al 10 reported colonic DLs as an unusual cause of lower GI bleeding in 1985. Actually, this location is extremely rare, with fewer than 30 cases documented in the literature. Baxter and Aly 3 reported that colonic DLs accounted for 2% of their review of 45 case reports.

Ileal DLs represent an uncommon site for GI bleeding, comprising less than 1% of all DLs cases, 3 According to the literature review, approximately 10 cases of histologically proven ileal DLs have been reported. 11

Recent case reports have also described DLs occurrences in the cecum, appendix, jejunum and ano-rectum. 12–14 Nikolaidis et al 9 described that 43% of DLs cases were located at surgical anastomosis sites.

DLs are often asymptomatic. 15 The most common clinical presentation includes melena, followed by haematemesis or haematochezia. Haemoptysis or haemorrhagic shock has also been reported. The association of haematemesis and melena was found in almost 50% of patients. 6 In contrast, in our case series, 71% of patients presented with isolated melena, 14% presented only with haematemesis and 14% presented with both haematemesis and melena. Due to the severity and recurrence of GI bleeding, laboratory abnormalities were frequently observed. In our findings, 71% of our patients required transfusion of packed red blood cells, with a mean of 2.8 units.

According to the literature review, initial endoscopy has enabled a diagnosis in 65%–90% of cases. In the studies by Kasapidis et al 2 and Norton et al 16 an average of 1.9 or 1.3 endoscopic sessions were required for diagnosing DLs. In our study, DLs were diagnosed in 85% of patients during the initial endoscopy, with an average of 2.5 endoscopic sessions. The endoscopic criteria necessary for diagnosis included active arterial oozing, the presence of a bleeding point with no visible underlying ulceration, a protruding vessel, and visualisation of an adherent clot with attachment to a normal mucosal defect or through the surrounding normal mucosa. 6 8 In the current study, 28% of patients had an adherent clot, and approximately 71% of patients presented with active bleeding, either as spurting or oozing.

Indeed, in 33% of cases, establishing the diagnosis required more than one endoscopy. 8 In our study, approximately 20% of patients needed more than one endoscopy to confirm the diagnosis. Our findings were consistent with the literature.

Some unusual locations of bleeding DLs were challenging to diagnose. For instance, ileal DLs may be overlooked and inaccessible to conventional endoscopy. High volume bleeding may also be a factor that limits the sensitivity of endoscopy. Recently, single or double balloon enteroscopies identified DLs of the distal small bowel in 3.5% of patients. 5 Moreover, CT angiography may be useful to determine the site of bleeding. It can be shown as contrast extravasation from an eroded tortuous artery, 8 17 as in our case of ileal DL.

Pathological diagnosis, while may not be a routine practice, can become indispensable in diagnosis of DLs, especially in certain rare and challenging anatomical sites. Actually in our ileal case of DL, the diagnosis was exclusively established through histological examination.

Surgical wedge resection has been the standard treatment of DLs. Through emergent endoscopy, this option gradually replaced surgery and became first-line treatment for DLs. 18 However, no consensus is recommended for endoscopic management.

Actually, the majority of data collected on treatment approaches consist of small case series or limited retrospective reports. Three main endoscopic haemostatic techniques can be used 3 17 : thermal (heat probe coagulation or APC, regional injection (epinephrine or norepinephrine) and sclerotherapy, mechanical therapy (endoscopic band ligation (EBL) and haemoclipping).

Although the results of endoscopic haemostatic therapies were variable, the rate of permanent haemostasis was high, reaching 90%. In a retrospective study, APC was found to be very effective for management of bleeding DLs. 19 In our study, a re-bleeding was observed in one patient treated with APC, while permanent haemostasis was achieved in the other. Mechanical haemostasis provided by EBL or haemoclipping is the most effective option in the treatment of DLs with a high success rates (95%) and low risk of recurrence <10%. 20 21 Due to the risk of re-bleeding, epinephrine injection is considered as a suboptimal treatment and it is not recommended to be used alone. 8 These results are consistent with data achieved by this study. The use of combined therapy gave better results than monotherapy in terms of permanent haemostasis and low rate of re-bleeding. 8 22 By contrast, in this study, one patient treated by combined therapy including epinephrine and haemoclipping had a recurrent bleeding during the follow-up period.

Comparative results of endoscopic therapies from retrospective studies are summarised in table 2 .

Summary of findings from the literature on endoscopic therapy of patients with Dieulafoy’s lesions

Based on the current literature, the rate of re-bleeding is 9%–40% and increases with endoscopic monotherapy. 8 The overall risk of recurrence in the short-term (<72 hours) is around 10%. 23 In instances of recurrent and uncontrolled bleeding, two management options have been documented for DLs 6 8 : selective arterial embolisation through angiography or wedge resection as the preferred surgical procedure.

Thanks to emergent endoscopy, the mortality of DLs has significantly decreased from 80% to 8.6%. In the current study, one patient died from haemorrhagic shock (14%).

This study is subject to several inherent limitations. First, the relatively rare incidence of DLs has resulted in a limited sample size, which may compromise the ability to establish statistical significance for the findings. Furthermore, being a retrospective investigation, there is a potential for inaccuracies in the recorded medical histories and risk factors.

Notwithstanding these constraints, the study reveals a robust association between cardiovascular diseases and episodes of bleeding attributed to DLs. Additionally, the use of anticoagulants and antiplatelet agents emerges as significant risk factors in the development of DLs.

While uncommon, DL is unequivocally acknowledged as a potentially life-threatening source of acute GI haemorrhage, particularly among the elderly. Timely diagnosis and prompt endoscopic management, especially in elderly individuals with multiple risk factors, can be invaluable and lifesaving.

Haemoclipping and combined therapeutic modalities are emerging as the most efficacious approaches, demonstrating superior haemostasis rates when compared with injection therapy. Nevertheless, to establish the optimal endoscopic treatment for DLs, further comprehensive studies will be imperative in the future.

Ethics statements

Patient consent for publication.

Not applicable.

Ethics approval

This retrospective analysis was conducted according to the ethical principles of the Declaration of Helsinki and local legislation, informed consent was obtained from the seven participants for this retrospective study.

Walmsley RS ,
Kasapidis P ,
Georgopoulos P ,
Delis V , et al
Ofosu A , et al
Dulic-Lakovic E ,
Hubner D , et al
Sreenarasimhaiah J ,
Tang S , et al
Nikolaidis N ,
Giouleme O , et al
Barbier P ,
Triller J , et al
Shibutani S ,
Ono S , et al
Lee SH , et al
Johnson A ,
Capovilla M
Baccaro L ,
Sakharpe A , et al
Tang SJ , et al
Norton ID ,
Petersen BT ,
Sorbi D , et al
Kim HS , et al
Iacopini F ,
Petruzziello L ,
Marchese M , et al
Baran M , et al
Wang S , et al
Katsinelos P ,
Paroutoglou G ,
Mimidis K , et al
Park YS , et al

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.

Data supplement 1

Contributors BA: manuscript writing and analysis. GK: manuscript correction. AZ: verification of the overall reproducibility of the results. HK: evolution of the general aims and objectives of research. OE: methodology development. IZ: data visualisation and presentation. BA and IZ confirm and accept full responsibility for the overall content of the work as guarantors.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests None declared.

Provenance and peer review Not commissioned; externally peer reviewed.

Read the full text or download the PDF:

- Google Chrome

Intended for healthcare professionals

Access provided by Google Indexer
My email alerts
BMA member login
Username * Password * Forgot your log in details? Need to activate BMA Member Log In Log in via OpenAthens Log in via your institution

Search form

Advanced search
Search responses
Search blogs
News & Views
Gender medicine in the...

Gender medicine in the US: how the Cass review failed to land

Related content
Peer review
Jennifer Block , freelance journalist
writingblock{at}protonmail.com

A landmark investigation with bearing on the future of gender identity services for children and adolescents has been pivotal in the UK—and largely ignored by US medical organisations and media. Jennifer Block reports on how America has resisted the push for a more holistic approach

The newly released Cass review on transgender care for under 18s has had a seismic effect across the United Kingdom and Europe. 1 Scotland and Wales promptly followed the NHS in England in ceasing the prescription of puberty “blocking” drugs outside of research protocols. The UN special rapporteur on violence against women and girls, Reem Alsalem, called the independent inquiry’s findings and recommendations “seminal” and stated that policies on gender treatments have “breached fundamental principles” of children’s human rights, with “devastating consequences.” Some charities and clinicians are disappointed with last month’s final review report. But the tone of major print and broadcast media in the UK has shifted: outlets that have previously reported criticism of gender services as transphobic now note how, as the Guardian reported, “the lack of high quality research, highlighted by Cass, has been a subject of growing unease among doctors.”

The review by Hilary Cass, paediatrician and former president of the Royal College of Paediatrics and Child Health, was commissioned by the NHS and built on the findings of Cass’s 2022 interim report. Then, she found that the evidence underpinning the treatment intensive, “gender affirming” model of care for distressed young people was “limited” and “inconclusive.” The final report is even clearer: “The reality is that we have no good evidence on the long term outcomes of interventions to manage gender related distress.”

But in the United States, where the gender affirming model is the norm, the effect of Cass’s four year investigation and final report isn’t yet obvious. “Unfortunately, Cass does not seem to be penetrating the public consciousness,” says Zhenya Abbruzzese, cofounder of the four year old Society for Evidence Based Gender Medicine (SEGM), a group of researchers and clinicians that has pushed for systematic reviews and an evidence based approach.

Cracks in medical consensus

Of the eight systematic reviews that Cass commissioned, two looked at nearly two dozen professional guidelines and found that most lack “developmental rigour.” 2 3 More concerning, Cass exposed how they are built on “circularity,” drawn from years old versions of guidelines issued by the World Professional Association for Transgender Health (WPATH) and the Endocrine Society, each of which refer to the other rather than to high quality evidence. “This approach may explain why there has been an apparent consensus on key areas of practice despite the evidence being poor,” writes Cass. Neither group responded to The BMJ .

The American Academy of Paediatrics (AAP) and the Endocrine Society have stood by their guidelines. The Cass review “does not contain any new research that would contradict” them, the Endocrine Society said in a statement. 4 WPATH issued an email statement that Cass “is rooted in the false premise that non-medical alternatives to care will result in less adolescent distress,” and added on 17 May that its own guidelines were “based on far more systematic reviews [than] the Cass review.” 5 As The BMJ reported last year, 6 WPATH’s own systematic review, one of an unknown number commissioned for the eighth version of its Standards of Care —just two were published—concluded that the strength of the evidence to support the mental health benefits of hormones was “low” and that it was “impossible” to conclude how they affect suicide risk.

Under pressure from some members, the AAP announced last year that it would commission an independent systematic review of the evidence for the affirmative model—at the same time that it reconfirmed its 2018 statement in support. 7 The BMJ obtained a new resolution dated 1 April that asks the organisation to “issue an interim update to the 2018 policy statement based on the best available evidence to date.”

“The time has passed for yet another systematic review,” says Julia Mason, an Oregon paediatrician and member of SEGM who has submitted several resolutions, including the April 2024 one, to AAP for more evidence based guidance. “We now have a dozen high quality reviews (eight Cass, two NICE, one Swedish, one German) all pointing to significant issues with the purely affirmative model of care,” she says. “Parents and their children are being misled in clinics all over the country. There is no evidence that giving puberty blockers followed by hormones and surgery is lifesaving care, and there is mounting evidence that the harms might outweigh the advantages.” The AAP did not respond to The BMJ ’s request for comment.

The American Psychological Association, American Psychiatric Association, and American College of Obstetricians and Gynecologists, which have position statements in support of the affirmative model, have remained silent about Cass. Only the psychology group responded to The BMJ , saying that it is studying the Cass report, but “we stand by the statement.”

Not all relevant professional groups have joined the consensus. Scot Glasberg, past president of the American Society of Plastic Surgeons, now president of the Plastic Surgery Foundation, told The BMJ that the organisation will issue “trustworthy, high quality” guidelines, but “like Dr Cass, we’ve found that the literature is of low quality and low value to dictate surgical care . . . We are trying to be very measured and not get into the difficulty that some of the other organisations have gotten into.” The American Academy of Family Physicians sought to develop a clinical practice guideline in 2020 but hasn’t yet produced one. 8 The organisation declined to comment.

Some people in the psychology community are emboldened by Cass to break their silence, even if it means facing hostility from their peers. Brooke Laufer is a clinical psychologist based outside of Chicago and among the 300 clinicians who’ve joined the organisation Therapy First, which promotes psychotherapy as first line treatment for gender exploration. She told The BMJ that she is a politically liberal feminist who has “marched in Pride marches.” Recently, she posted about the Cass review to a listserv of therapists and was reprimanded by several members for promoting “misinformation” and “hate speech.” In February, another listserv member who posted about a Therapy First webinar was met with eight separate complaints to the state medical board.

Laufer says that the American Psychological Association should “gather its integrity and put out a statement that says we’re taking the Cass report seriously and we recommend puberty blockers to be paused unless it’s in the context of a clinical trial.” She adds: “What’s at stake are human lives and a generation of kids. This is about standing up and being adults and saying sorry, we got some of this wrong.”

The American Psychiatric Association met in New York this month for its annual conference. It had just one panel discussion on the topic of gender medicine, about “promoting public policy for evidence based transgender care,” focused on the negative effects of state legislation restricting treatments. In stark contrast, the European Society for Child and Adolescent Psychiatry released a new policy statement on safeguarding gender distressed youth from “experimental and unnecessarily invasive treatments with unproven psychosocial effects.” 9

Hesitant media response

US media and the political landscape in general are notoriously polarised. Trusted LGBT+ advocacy groups have been unequivocal about the merits of the affirming model. GLAAD, which journalists founded in the 1980s to combat “grossly defamatory” media reporting about HIV/AIDS, protested the New York Times ’s coverage of gender medicine, which has included the voices of former patients who feel they’ve been harmed. Last year, GLAAD parked a truck outside the paper of record’s offices: its electronic billboard stated, “The science is settled.”

Some hoped that Cass would offer an impartial beacon. And a few legacy and left leaning newsrooms covered the report in earnest—Reuters, the New York Times , the Nation , NBC, and the Economist . The Wall Street Journal ’s editorial board said that the review “shows wisdom and humility on treatment of young people, in contrast to the ideological conformity in US medical associations.” The Washington Post and Boston Globe also ran opinions that amplified Cass to argue for a more precautionary path forward.

But many outlets historically aligned with advocacy positions have held back on any ink. STAT News, which “delivers trusted and authoritative journalism about health, medicine, and the life sciences,” has so far ignored Cass (as well as The BMJ ’s request for comment). So has CNN. Jesse Singal, one of the first American journalists to expose the potential harms of youth gender treatment, reported on his Substack that the legacy news network had recycled the pronouncement that “gender affirming care is medically necessary, evidence based care” in 35 separate articles over the past two years, practically verbatim. 10 (CNN did not explain, and did not respond to a query from The BMJ .) “Many outlets dug themselves into a deep hole on this issue by simply acting as stenographers and megaphones for activist groups rather than doing their jobs,” wrote Singal.

Singal has also called out Scientific American for not covering the Cass report, while on 20 April running a question and answer piece with a prominent advocate of gender affirming care titled “Anti-trans efforts use misinformation, epistemological violence, and gender essentialism.” The oldest continuously published magazine in the US, Scientific American , has run several articles favourable to the affirmative model in recent years. In “Why anti-trans laws are anti-science,” written in 2021 and republished in 2023, the magazine’s editors stated that it is “unscientific and cruel” to claim that treatments are “unproven and dangerous” or that “legislation is necessary to protect children.” According to a 2022 article, “What the science on gender affirming care for transgender kids really shows,” data “consistently show that access to gender affirming care is associated with better mental health outcomes.” “Decades of data support the use and safety of puberty pausing medications,” declared one 2023 piece. 11

The magazine’s editor in chief, Laura Helmuth, has promoted these pieces on Twitter/X with declarations like, “The research is clear, and all the relevant medical organisations agree”; policies that restrict treatments are “dangerous, cruel, bigoted, and contrary to all the best scientific and medical evidence.” She’s also disparaged inquiries on the subject. In a February 2023 tweet, Helmuth included gender affirming care among a list of “things we don’t need to be both-sidesing, be ‘objective,’ or be ‘just asking questions!’ about.” Neither Helmuth nor the magazine’s publisher, Springer Nature, responded to a detailed email referencing the articles and more than 15 tweets.

A political lens

US reporting in the main is sympathetic with, if not following the lead of, authoritative sources such as the US Department of Health and Human Services (HHS), which informs that “research demonstrates that gender affirming care improves the mental health and overall wellbeing of gender diverse children and adolescents” and calls puberty blockers “reversible.” 12 On 24 April, a congressman confronted Xavier Becarra, secretary of the department, about these statements, holding up a thick printed copy of the Cass review. “I can assure you that we look at all studies,” said Becarra. “When we talk about a standard of care, it’s not something we make up. It’s based on what the major medical associations [say].” The US Department of Health and Human Services did not respond to The BMJ ’s request for comment.

Rachel Levine, US assistant secretary for health, told National Public Radio in October 2022 that “there is no argument among medical professionals . . . about the value and importance of gender affirming care.” Yale paediatrician Meredithe McNamara, who coauthored a November 2022 commentary in the New England Journal of Medicine titled “Protecting transgender health and challenging science denialism,” told PBS NewsHour the same month, “The evidence base is strong.” McNamara has called puberty blockers “one of the most compassionate things that a parent can consent to for a transgender child,” 11 and in testimony to the US Congress, warned that when gender affirming care “is interrupted or restricted, suicide, depression, anxiety, disordered eating, and poor quality of life follow.” 13

In professional training, journalists have been led to interpret dissent as part of a “misinformation climate,” as in a two part Poynter Institute webinar called “Transgender coverage: avoiding rhetoric to deliver meaningful journalism,” recorded on 18 April and 2 May. Cass’s final review no doubt qualified as “medical and peer reviewed research findings”—one of the learning goals—yet it went unmentioned in all three hours of discussion. McNamara, the only medical speaker, listed the mental health benefits of gender treatments and showed a chart of five “misinformation themes,” among them “low quality evidence” and “guidelines are not trustworthy.” In part two, when asked about European countries restricting treatment, Jo Yurcaba, a reporter for NBC Out, the LGBTQ section of NBC News, told attendees that “transition related care is highly politicised in Europe, in the same way it is in the US.” These webinars were required viewing for reporters applying for an $11 500 grant for journalists interested in covering transgender issues. A spokesperson for Poynter, which also publishes the fact checking site Politifact, told The BMJ that it “strives to present an accurate, current, and well rounded overview” for journalists in training and that, by 9 April when Cass’s final report was released, “our curriculum and learning objectives had been set and our subject matter experts had prepared their materials.”

So far, outspoken thought leaders have not reconciled their statements with the growing list of systematic reviews that stand in contradiction. In an emailed response to The BMJ , McNamara said that she “noted with great interest, the systematic reviews that the Cass review relied on deemed several of the studies it assessed as ‘moderate’ in quality.” Although other advocates have seized on this apparent discrepancy, it is a known feature of systematic reviews: individual studies within a body of evidence might be rated moderate, yet when taken as a whole, that evidence may still be, as Cass put it, “remarkably weak.”

Some prominent activists attempted to discredit other aspects of Cass, both the review and the person. Alejandra Caraballo, a Harvard Law School instructor with more than 160 000 followers on X, posted in advance of the report’s release that it had “disregarded nearly all studies,” a claim that Cass called “misinformation.” The activist Erin Reed, who has a quarter of a million followers between X and Substack and is a go-to media source, accused Cass of having “collaborated on a trans care ban in Florida.” Cass spoke with a clinical member of the state’s board of medicine as part of her review. On the Majority Report, a podcast with 1.5 million subscribers, Reed said that Cass represents “the playbook for how to ban trans care.”

For science reporters and editors who have repeatedly delivered the “science is settled” boilerplate, these denunciations offer a tempting way around correcting the record. A 10 May article in Mother Jones took that route, casting the report as a political document: “It’s like the DeSantis administration wrote it.”

Medical leaders and media professionals “should engage with the content,” says Abbruzzese, which she notes is in English, freely accessible, and transparent in its rigour. “What the Cass review did was evaluate the gender clinic model of care and concluded that, when delivered in this exceptionalised way, every child who walks through the door is viewed as a trans child who is there to be medically transitioned. Cass concluded that model is fundamentally flawed because these children’s significant pre-existing mental health problems are effectively ignored in the false expectation that transition will cure them.”

“The Cass report is going to stand the test of time,” says Erica Anderson, a clinical psychologist and former president of the US Professional Association for Transgender Health. “I’m already hearing from the boards of directors and trustees of some hospital systems who are starting to get nervous about what they’ve permitted. So I think that’s going to accelerate change within American healthcare.”

In the face of criticism, Cass has been unwavering: “It wouldn’t be too much of a problem if people were saying ‘This is clinical consensus, and we’re not sure.’ But what some organisations are doing is doubling down on saying the evidence is good,” she told the New York Times . “And I think that’s where you’re misleading the public.”

Provenance and peer review: Commissioned, peer reviewed.

This feature has been funded by the BMJ Investigations Unit. For details see bmj.com/investigations .

Competing interests: The author declares having contributed a commentary to Scientific American in 2019 that was removed for unspecified reasons following a social media campaign. Helmuth, who became editor-in-chief in 2020, was not involved.

↵ Cass H. Independent review of gender identity services for children and young people: final report. April 2024. https://cass.independent-review.uk/?page_id=936
Heathcote C ,
Hewitt CE ,
Langton T ,
↵ Endocrine Society. Endocrine Society statement in support of gender-affirming care. Endocrine Society. 2024. https://www.endocrine.org/news-and-advocacy/news-room/2024/statement-in-support-of-gender-affirming-care
↵ World Professional Association for Transgender Health,. US Professional Association for Transgender Health. WPATH AND USPATH comment on the Cass review. 2024. https://www.wpath.org/media/cms/Documents/Public%20Policies/2024/17.05.24%20Response%20Cass%20Review%20FINAL%20with%20ed%20note.pdf?_t=1716075965
↵ Agency for Healthcare Research and Quality. Treatments for gender dysphoria in transgender youth. 17 Jul 20. https://effectivehealthcare.ahrq.gov/get-involved/nominated-topics/treatments-gender-dysphoria-transgender-youth
Drobnič Radobuljac M ,
Grošelj U ,
Kaltiala R ,
ESCAP Policy Division ,
ESCAP Board
↵ Singal J. Why is the same misleading language about youth gender medicine copied and pasted into dozens of CNN.Com articles? Singal-Minded. 22 Mar 2024. https://jessesingal.substack.com/p/why-is-the-same-misleading-language
↵ Parshall A. What are puberty blockers, and how do they work? Scientific American. 1 May 2023. https://web.archive.org/web/20240329141001/https://www.scientificamerican.com/article/what-are-puberty-blockers-and-how-do-they-work/
↵ US Department of Health and Human Services. Office of Population Affairs. Gender-affirming care and young people. https://www.opa.hhs.gov/sites/default/files/2022-03/gender-affirming-care-young-people-march-2022.pdf
↵ US House of Representatives. Meeting: examining proposals that provide access to care for patients and support research for rare diseases. 14 June 2023. https://docs.house.gov/Committee/Calendar/ByEvent.aspx?EventID=116121

Log in using your username and password

Search More Search for this keyword Advanced search
Latest content
Current issue
BMJ Journals More You are viewing from: Google Indexer

http://orcid.org/0000-0002-9551-2150 John Hatheway 1 ,
Alexander Hersel 2 ,
Jonathan Song 3 ,
Mitchell Engle 4 ,
Genaro Gutierrez 5 ,
Vishal Khemlani 6 ,
Leonardo Kapural 7 ,
Gregory Moore 8 ,
Reginald Ajakwe 9 ,
Drew Trainor 10 ,
Jennifer Hah 11 ,
Peter S Staats 12 ,
Paul Lynch 13 ,
James Makous 14 ,
Gary Heit 15 ,
http://orcid.org/0000-0001-6686-3587 Shilpa Kottalgi 16 and
http://orcid.org/0000-0001-6870-9436 Mehul J Desai 17
1 Northwest Pain Care , Spokane , Washington , USA
2 Pain Management and Injury Relief , Thousand Oaks , California , USA
3 Arizona Pain Specialists , Scottsdale , Arizona , USA
4 Institute of Precision Pain Medicine , Corpus Christi , Texas , USA
5 Pain Specialists of America , Austin , Texas , USA
6 Columbia Pain Management , Portland , Oregon , USA
7 Center for Clinical Research , Carolinas Pain Institute , Winston-Salem , North Carolina , USA
8 Pacific Sports and Spine , Eugene , Oregon , USA
9 Comprehensive Spine & Pain Physicians , Burbank , California , USA
10 Denver Spine and Pain Institute , Denver , Colorado , USA
11 Division of Pain Medicine , Stanford University , Palo Alto , California , USA
12 Premier Pain Ctr , Shrewsbury , New Jersey , USA
13 US Pain Care , Scottsdale , Arizona , USA
14 Makous Research, LLC , Carlsbad , California , USA
15 Hue University of Medicine and Pharmacy , Hue , Thua Thien Hue , Viet Nam
16 Nalu Medical Inc , Carlsbad , California , USA
17 International Spine, Pain & Performance Center , Washington , District of Columbia , USA
Correspondence to Shilpa Kottalgi, Nalu Medical Inc, Carlsbad CA 92008, California, USA; skottalgi{at}nalumed.com

Background We report the results from the first large, postmarket, multicentre, randomised controlled trial (RCT) evaluating peripheral nerve stimulation (PNS) for the treatment of chronic peripheral pain with a micro-implantable pulse generator (micro-IPG).

Methods Subjects meeting eligibility were randomised (2:1) to either the active arm receiving PNS and conventional medical management (CMM) or the control arm receiving CMM alone. Treatments were limited to the following areas: lower back, shoulder, knee and foot/ankle.

Results At 6 months, the active arm achieved an 88% responder rate with a 70% average reduction in pain. At the 3-month primary endpoint, the active arm achieved an 84% responder rate with an average pain reduction of 67% compared with the control arm, which achieved a 3% responder rate with an average pain reduction of 6%. Both responder rate and pain reduction in the active arm were significantly better than in the control arm (p<0.001). A majority of patient-reported outcomes also reached statistical significance. There have been no reports of pocket pain and no serious adverse device effects. 81% of subjects found the external wearable component of the PNS system to be comfortable.

Conclusions This study successfully reached its primary endpoint—the active arm achieved a statistically significant superior responder rate as compared with the control arm at 3 months. These RCT results demonstrated that PNS, with this micro-IPG, is efficacious and safe. This ongoing study will follow subjects for 3 years, the results of which will be reported as they become available.

CHRONIC PAIN
Peripheral Nerve Injuries
Pain Management

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Not Applicable.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, an indication of whether changes were made, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ .

https://doi.org/10.1136/rapm-2023-105264

Statistics from Altmetric.com

Request permissions.

WHAT IS ALREADY KNOWN ON THIS TOPIC

Peripheral nerve stimulation (PNS) has been widely used for over 50 years to treat intractable chronic pain of peripheral nerve origin.

However, there is a paucity of data from randomised clinical trials. A previous PNS randomised controlled trial (RCT) showed borderline-positive outcomes.

WHAT THIS STUDY ADDS

This study showed, through a well-controlled RCT using validated outcome instruments, that PNS therapy delivered by a micro-implantable pulse generator device significantly reduced pain and improved functional outcomes in over 80% of subjects treated.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

The outcomes of this study provide a basis for clinical evidence in support of patient access to PNS therapy, as provided by the study device.

The results presented here provide clinical confidence in the application of PNS therapy to appropriate patients.

Introduction

Peripheral nerve stimulation (PNS) is an established modality for the treatment of chronic peripheral neuralgia/neuropathy. 1 The prevalence of neuropathic pain may be as high as 10% in the general population. 2 When more conservative methods (eg, physical therapy or over-the-counter pain medications) fail, then second-line therapies include nerve blocks and prescription medications. The last line of therapies involves PNS, which has been used as a treatment for chronic pain since the 1960s 3 and now is supported by a growing body of evidence. We report here the results from the first large, postmarket, multicentre, on-label, randomised control trial (RCT) documenting the effectiveness and safety of PNS and conventional medical management (CMM) versus CMM alone in the treatment of chronic peripheral neuropathic pain with a micro-implantable pulse generator (micro-IPG) PNS system.

The device evaluated in this RCT is an FDA-cleared (K183579 and K191435) system with a battery-free micro-IPG, a volume of <1.5 cm 3 and an 18-year service life (Nalu Neurostimulation System, Carlsbad, California, USA). The system is powered by a small, externally worn battery (therapy disc (TD)). Unlike other PNS systems, the micro-IPG system allows for a temporary trial lead placement. It also offers a broad menu of therapeutic stimulation parameters and waveforms. The system software is upgradeable without micro-IPG replacement (see Kalia et al 4 for a detailed device description).

The COMFORT (Clinical Study O f A Micro-Implantable Pulse Generator FOR the Treatment of Peripheral Neuropathic Pain) study was approved by the Institutional Review Board and conducted in compliance with local regulations and standards for good clinical practice. The study is registered on ClinicalTrials.gov ( NCT05287373 ; date of registration: 08 February 2022; https://classic.clinicaltrials.gov/ct2/results?cond=&term=NCT05287373&cntry=&state=&city=&dist= ).

Subjects who met the inclusion/exclusion criteria were randomised at 12 pain management centres across the USA, with enrollment commencing on 23 February 2022 and being completed on 29 March 2023. Full inclusion and exclusion are available on ClinicalTrials.gov. In brief, inclusion criteria included subjects diagnosed with one or more of the conditions listed below in the lower back, shoulder, knee or foot/ankle—postsurgical/post-traumatic peripheral neuralgia, including pain due to peripheral nerve injury; this was updated to include postsurgical scar formation, nerve entrapment, mononeuropathy and osteoarthritic pain, to align with the standard of care for PNS. Exclusion criteria included complex regional pain syndrome, peripheral neuralgia of metabolic origin and postherpetic origin; the subject is on ≥90 morphine mg equivalents per 24 hours.

The primary efficacy measure was the numeric rating scale (NRS) pain score captured in the Brief Pain Inventory Question 5 (BPI-Q5) from the target area of peripheral pain. Secondary outcome measures included the following patient-reported outcomes (PROs): Patient Global Impression of Change (PGIC), Brief Pain Inventory Short Form (BPI-SF), quality-of-life metric (EuroQoL 5 dimension 5 level (EQ-5D-5L)), Beck Depression Inventory (BDI) and Oswestry Disability Index (ODI). Patient safety, satisfaction, device comfort, usability and subject compliance with the therapy were also tracked.

The study design was intended to mimic real-world clinical practice as closely as possible.

Consented subjects received baseline evaluations per protocol and standard clinical practice. Eligible subjects were then randomised into one of two arms: the active arm, which received PNS and CMM, and the control arm, which received CMM alone ( figure 1 ). Allocation was concealed prior to randomisation, which was performed using a random permuted block design (block size of three) with a 2:1 allocation ratio (active vs control). Randomisation was stratified by investigational site and assigned via a centralised electronic system. The randomisation sequence was generated by SAS (V.9.4, SAS Institute, Cary, North Carolina, USA).

Download figure
Open in new tab
Download powerpoint

Subject disposition from consent to the 6-month endpoint. mITT, modified intention-to-treat.

Subjects randomised to the control arm continued to receive CMM alone for the next 3 months. Upon completion of the 3-month primary endpoint, subjects in the control arm were given the option to crossover into the active arm. Crossover subjects continued under the same follow-up visit schedule as those in the active arm. CMM was defined as the best standard of care for each individual subject, as determined by the investigator. CMM was standardised across institutions in both the active and control arms. See table 1 for a list of CMM administered during the study. Results from the crossover will be presented in a subsequent publication.

View inline

Subject demographics and baseline characteristics

Subjects randomised to the active arm underwent a temporary trial procedure per standard of care. Subjects needed to achieve ≥50% reduction in pain during the trial period (a ‘responder’) in order to be eligible for a permanent implant (52 of 57 clinically successful trials yielding a 91% success rate). Those who realised <50% improvement were considered trial failures and were exited from the study. The responders were implanted with a permanent system per standard clinical practice and were programmed with paresthesia-based and paresthesia-independent programmes. Subjects were then followed at prespecified time points up to 36 months; however, the current analysis was focused on the 3-month primary endpoint plus 6-month outcomes, as the study is ongoing.

Aside from the temporary trial and micro-IPG implant, both study arms were treated equally to ensure clinical equipoise. PROs and adverse events (AE) were captured at each of the follow-up visits.

Following the implant procedure, the system was programmed for optimal pain relief per standard clinical practice. The programming was performed by clinical personnel from the study sponsor, under the direction of a study physician. All programming was consistent with the device labelling and in a manner typically applied to patients outside of the clinical study. There were no off-label investigational devices or programming parameters used in this study. Interestingly, nearly all the programmes for the patients used complex programming, similar to the capabilities of spinal cord stimulation systems (pulse widths of ≥500 µs, frequencies ≥500 Hz, use of more than two electrodes, multiarea, cross-lead, current steering and/or proprietary waveforms). Approximately one-third used pulse widths ≥500 µs, frequencies ≥1000 Hz and/or >2 electrodes (anodes/cathodes combinations). A majority of programmes were multiarea, cross-lead, current steering and/or proprietary waveforms. Subjects were given a choice of up to eight sub-paresthesia and supra-paresthesia stimulation programmes, which they could cycle through based on the therapeutic benefit.

Statistical analysis

Primary endpoint analysis was carried out on the modified-intent-to-treat (mITT) population, as prespecified in the statistical analysis plan. The mITT population is defined as ‘all randomised subjects receiving a permanent implant and having an implant at the time of analysis in the active arm and all randomised subjects in the control arm’. The primary effectiveness endpoint was the percentage of responders (responders were defined as ≥50% reduction in pain relative to baseline) at 3 months captured in the NRS-BPI-Q5 for their primary area of pain relative to baseline. Comparisons were made between randomised arms. Missing data were assumed to be missing completely at random. Results were reported as mean±SD for continuous variables and as a percentage (count) for categorical variables, unless otherwise noted. Comparisons of responder rates between the active arm and control arm were conducted by a two-sample t-test; within-arm comparisons were conducted using the Wilcoxon signed-rank test. P values of <0.05 were regarded as statistically significant. For all outcomes, per cent reduction is calculated as a paired analysis within each subject and reported as mean±SD. Analyses were conducted using SAS.

The sample size for the study was based on power requirements for the primary effectiveness endpoint. A sample size of 87 randomised subjects was calculated based on a two-sample exact binomial test with a two-sided 0.05 alpha level, providing 90% power for a difference in responder rate between the arms.

131 subjects consented. Of these, 89 subjects were randomised to the active arm (58 subjects) or the control arm (31 subjects). Of these, 12 subjects exited early in the active arm and were not included in the mITT population. The mITT population included 46 active arm subjects and 31 control arm subjects. At 3 months, three subjects in the active arm missed the visit and two subjects in the control arm withdrew. The details of the final subject disposition are shown in figure 1 .

The demographic distribution of the subjects is detailed in table 1 . 49.4% (38/77) of subjects had chronic pain in the lower back, 20.8% (16/77) in the knee, 16.9% (13/77) in the foot/ankle and 13% (10/77) in the shoulder. Targeted nerves are listed in table 1 .

The responder rate was 84% (36/43) at 3 months and 88% (37/42) at 6 months in the active arm compared with 3% (1/29) in the control arm ( figure 2 ; p<0.001). Subjects in the active arm achieved a 67% improvement at 3 months and a 70% improvement at 6 months in pain as compared with baseline (p<0.001), whereas the control arm achieved a 6% improvement in pain. A comparison between the responder rates in the two arms at 3 months (primary endpoint) was statistically significant at p<0.001 ( figure 3 ). 30% (13/43) of active arm subjects and 3% (1/29) of control arm subjects were high responders, with ≥80% pain improvement from baseline ( figure 3 ).

Tornado plot. (A) Active arm at 3 months, (B) active arm at 6 months and (C) control arm at 3 months, showing per cent pain relief in each study subject. Responders were subjects with ≥50% pain reduction compared with their baseline NRS pain score. High responders were subjects with ≥80% pain reduction compared with their baseline pain score. NRS, numeric rating scale.

Mean NRS pain scores (BPI-Q5) and responder rates at 3 and 6 months. (A) Pain scores captured in the office at baseline and at 1 month, 3 months and 6 months for active and control arms. The mean per cent reduction in pain was statistically significant in the active arm compared with the control arm at 1, 3 and 6 months (p<0.001). Each data point represents mean±SEM. (B) Responder rates (≥50% improvement) and high responder rates (≥80% improvement) were statistically better in the active arm versus the control arm, at p<0.001 and p<0.05, respectively. Per cent pain reduction was also significantly better in the active arm versus the control arm at p<0.001. The sample size (N) is shown in parentheses. BPI-Q5, Brief Pain Inventory Question 5; NRS, numeric rating scale.

The PROs are shown in table 2 in the following areas: BPI-SF (both interference and severity), EQ-5D-5L, BDI and ODI. Each of these measures demonstrated a statistically significant (p<0.001) improvement at 3 months and 6 months following device activation, whereas none of the PROs in the control arm yielded statistical significance at 3 months.

Patient reported outcomes (PRO) at 3 and 6-months. BPI, EQ-5D-5L, BDI and ODI.

The PGIC was used to assess a subject’s overall impression of change (better or worse) following treatment. 98% of active arm subjects reported an improvement at both 3 and 6 months, compared with only 14% (4/29), in the control arm (p<0.001) at 3 months. In the active arm, 58% (25/43) of subjects reported very much improved, 30% (13/43) reported much improved, and 9% (4/43) reported minimally improved. None of the active arms reported minimally worse, 2.3% (1) reported much worse, and none reported very much worse. In the control arm, no subjects (0%) reported very much improved, 7% (2/29) reported much improved, 7% (2/29) reported minimally improved, 69% (20/29) reported no change, 10% (3/29) reported minimally worse and 7% (2/29) reported much worse. Similar results were seen at 6 months in the active arm.

Subjects in the active arm were also asked to rate their overall satisfaction with the PNS system on a five-point Likert scale. 77% (33/43) of active arm subjects were very satisfied with the system; 21% (9/43) were satisfied, whereas one subject (2%) was very dissatisfied at 3 months. At 6 months, 71% (30/42) of active arm subjects were very satisfied with the system; 26% (11/42) were satisfied, whereas one subject (2%) was dissatisfied.

At 3 months, 43 subjects in the active arm reported their comfort ratings related to the device. 81% (35/43) reported that the wearable was very comfortable or comfortable. 91% (39/43) of subjects reported the device as very easy or easy to use. 81% (35/43) of subjects reported using the device for a full day. At 6 months, 79% (33/42) of subjects continued to report the device to be very comfortable or comfortable. 90% of subjects found the device to be very easy or easy to use and 76% (32/42) reported using it for a full day.

Subjects in both study arms continued their CMM regimen as needed. At 3 months, 88% (38/43) of active arm subjects and 100% (29/29) of control arm subjects reported continued use of oral medications. Other CMM reported at 3 months include topical medications (12), physical therapy (4), psychological therapy (4) and other treatments (11; bracing, chiropractic, water aerobics and removal of bursa); one control arm subject reported using a transcutaneous nerve stimulation unit. At 6 months, in the active arm, 90% (38/42) of subjects continued to take oral medications, 11 reported using topical medications, four underwent physical therapy, five were in psychological therapy and four subjects used a brace.

No unanticipated serious adverse device effects have been reported in the study to date. There were no serious AEs (SAEs) related to the device or procedure. No reports of pocket pain have been reported to date. All non-serious adverse device effects were resolved with no sequelae. Lead migration was reported in one patient, which resulted in a revision. One additional patient had swelling and induration without an infection, which resulted in revision. One patient had a lead fracture in the knee, which resulted in a revision. One patient had a mild infection at the implant site that resolved without sequelae following treatment with antibiotics (oral cephalexin 500 mg four times a day for 15 days). One patient had an IPG migration that was revised. Two other patients had infections postimplant; both had their devices explanted, the infections resolved and the subjects discontinued study participation. Seven non-device-related SAEs were reported in the active arm at the 6-month timepoint, all resolving with no sequelae. In the control arm, two non-SAEs were reported, which were not related to their current CMM regimen.

The study was a success by meeting the primary endpoint. The 3-month responder rate was 84% with a 67% average pain reduction in the active arm, compared with a 3% responder rate and a 6% average pain reduction in the control arm (p<0.001). The results were maintained, where the responder rate at 6 months was 88% with a 70% pain reduction. The outcomes were consistent across the four areas of pain and the respective nerve targets included in the study. Favourable comfort, compliance and ease-of-use outcomes indicated that the wearable aspects of the system (see figure 4 for the system description) were well received by users. There was a strong safety profile with a complete lack of serious adverse device events and no reports of pocket pain. Subsequent publications will report on the 1-year, 2-year and 3-year outcomes of these subjects.

Peripheral nerve stimulation system used during the course of this study. The Nalu system consists of a micro-implantable pulse generator (<1.5 cc) that is powered by a therapy disc worn over the implant with an adhesive clip or a limb cuff. Bidirectional telemetry allows for optimal therapy delivery. There were three lead configurations employed during this study: four-contact leads with tines, four-contact leads without tines and eight-contact leads without tines. In addition, there were four micro-IPG configurations: Single port for four-contact leads, dual port for four-contact leads, single port for eight-contact leads and dual port for eight-contact leads.

The results of this RCT were significantly better than a separate PNS RCT with an older device (StimRouter, Bioventus). 5 In that study, the observed responder rates (30% responder rate criterion) were 38% in the active arm versus 10% in the control arm. The pain relief was 27% for the active arm versus 2.3% pain reduction in the control arm. These reductions in pain scores were smaller than seen in the current study, especially when the responder rate criterion is taken into account (ie, 30% vs 50%). If the 30% responder rate criterion was applied in the COMFORT study, instead of 50%, the responder rate would improve to 95% (41/43) in the active arm and to 10% (3/29) in the control arm.

The improvements in the COMFORT study were similar to or better than the prospectively collected values reported in the PNS literature. For example, Hassenbush et al 6 found a 63% (19/30) PNS responder rate (50% criterion) in Reflex Sympathetic Dystrophy/Chronic Regional Pain Syndrome (RSD/CRPS) with an average pain reduction of 59% (8.3±0.3 at baseline, prior to implant, to 3.5±0.4 at last follow-up; mean follow-up of 2.2±0.6 years). The target nerves were as follows: median/ulnar, radial, common peroneal and posterior tibial. In another study, Possover et al 7 demonstrated an 83% (19/23) PNS responder rate (50% criterion) in posthernia repair neuralgia, with an average pain reduction of 62% (8.1±8.1 at baseline to 3.1±2.8 postimplantation). The mean follow-up was 28.6±16.2 months. The target nerves were genitofemoral, ilioinguinal, iliohypogastric and lateral femoral cutaneous.

The outcomes reported here are also comparable to those reported in three separate retrospective studies. Eisenberg et al 8 studied 46 subjects with various forms of peripheral neuropathy and demonstrated a statistically and clinically significant improvement in pain scores following PNS (p<0.001). Law et al 9 demonstrated retrospective pain control in 13 of 22 (59%) traumatic peripheral neuropathic pain subjects out to 25 months post-PNS implant, and Schon et al 10 also demonstrated satisfactory pain reduction in 61% of lower extremity nerve injury pain in a retrospective study of 62 subjects.

The fact that the COMFORT study results are better than those of previous PNS studies cited here may be due in part to the advancement in processor technologies that allow for the miniaturised form factor of the micro-IPG while maintaining advanced programming capabilities that were lacking in the devices used in the other studies.

The lack of pocket pain in the COMFORT study is consistent with data from two other clinical studies investigating the same micro-IPG system for spinal cord stimulation, where the micro-IPG was placed in the lower back. 11 12 The reports in the literature of pocket pain associated with traditional IPGs can be as high as 64%. 13 14 Unlike large implants, which can be limited in their implant location, this micro-IPG is more versatile and can be placed in the location that best suits the subject, regardless of body mass index (BMI) (study BMI range: 20.5–64.3 kg/m 2 ) and can help avoid the need for leads crossing joints.

96% (126/131) of subjects who were screened liked or tolerated the wearable. The high satisfaction, comfort, compliance and usability scores reported here may be due to a unique patient-centric attribute of this micro-IPG system. Specifically, the ‘Wear Assessment’ ensures that the subject and the implanting physician agree upon the micro-IPG implant location and that the subject is comfortable with the external wearable. This process reduces the risk of revisions related to poor micro-IPG placement. Additionally, subjects had the opportunity to use the TD with a limb cuff and/or adhesive clip, regardless of the location of the micro-IPG implant. These favourable results are consistent with other studies involving the micro-IPG, 11 12 and they show the patient acceptability, comfort and usability of the system.

Limitations of this study include the fact that the control arm remained in CMM only for 3 months; a longer period was considered but was thought to be ethically problematic for those subjects with significant pain. The prevalence of females over males was unanticipated (70% females), but the randomisation addressed potential bias, and this reflected the real-world population at the clinical sites.

Conclusions

The study met the criterion for success—the active arm achieved statistical significance at the primary endpoint over the control arm in the responder rate. Treatment with this micro-IPG resulted in statistically significant improvement in pain (and in other PROs) relative to baseline values and between the active and control arms. The outcomes were consistent with, and in some cases superior to, results in the PNS literature for the treatment of pain associated with chronic peripheral neuropathy or neuralgia. There was a strong safety profile with no serious adverse device effects and no reports of pocket pain. Subjects also reported high ratings for comfort and ease of use while wearing the external components. The small size of this micro-IPG allowed it to be used in all four of the anatomic locations studied without regard to body habitus. The sponsor and investigators are dedicated to continuing the study and reporting the long-term outcomes when available.

Supplemental material

Ethics statements, patient consent for publication.

Not applicable.

Ethics approval

This study involves human participants and was approved by WCG IRB Tracking Number: 20215749. Participants gave informed consent to participate in the study before taking part.

Acknowledgments

We would like to thank the COMFORT study investigators, subinvestigators and coordinators at the following US sites for their participation and support in this study: Arizona Pain Specialists, DBPS Research, LLC, International Spine, Pain & Performance Center, The Center for Clinical Research, Institute of Precision Pain Medicine, Northwest Pain Care, PS, Stanford University, Pacific Sports and Spine, Comprehensive Spine and Pain Physicians, Pain Management and Injury Relief, Pain Specialists of America and Columbia Pain Management, PC, University of Wisconsin, University of Iowa and University of Arkansas. We would also like to thank our statistician Ping-Yu Liu.

van Hecke O ,
Austin SK ,
Khan RA , et al
Pritzlaff S ,
Li AH , et al
Benyamin R , et al
Hassenbusch SJ ,
Stanton-Hicks M ,
Schoppa D , et al
Eisenberg E ,
Waisbrod H ,
Gerbershagen HU
Easley ME , et al
Du Toit N , et al
Ung C , et al
Dietvorst S ,
Decramer T ,
Lemmens R , et al

Deceased Gary Heit passed away in February 2023.

Contributors All authors either made a substantial contribution to the study concept, design, and/or analysis, or they enrolled at least one study subject. All authors approved the final version of the manuscript. SK is responsible for the overall content as the guarantor and accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled decision to publish.

Funding This study was sponsored by Nalu Medical.

Competing interests GH is a consultant at Nalu Medical, Agitated Solutions, and a co-founder of Nesos. PS is a consultant for Nalu Medical, Saluda, SPR therapeutics and Medtronic. He is the Chief Medical Officer at electroCore. SK is an employee at Nalu Medical. JM is a consultant at Nalu Medical and owns stock in Nalu Medical. JH is a speaker and consultant for Nalu Medical. MJD consults for Avanos, Nalu, SPR Therapeutics; receives research support from Abbott, Avanos, Averitas, Mainstay, Nalu, Nature Cell, Saol, SPR Therapeutics and Vivex; and owns stock options in SPR Therapeutics, SynerFuse and Virdio.

Provenance and peer review Not commissioned; externally peer reviewed.

Read the full text or download the PDF:

Log in using your username and password

Search More Search for this keyword Advanced search
Latest content
Current issue
Write for Us
BMJ Journals More You are viewing from: Google Indexer

Tasmira Mohib 1 ,
http://orcid.org/0000-0002-7499-5050 Tanvir C Turin 1 , 2
1 Department of Community Health Sciences , University of Calgary Cumming School of Medicine , Calgary , Alberta , Canada
2 Department of Family Medicine , University of Calgary Cumming School of Medicine , Calgary , Alberta , Canada
Correspondence to Dr Tanvir C Turin, Department of Family Medicine, University of Calgary Cumming School of Medicine, Calgary, Alberta, T2N 4N, Canada; turin.chowdhury{at}ucalgary.ca

https://doi.org/10.1136/ebnurs-2023-103903

Statistics from Altmetric.com

Request permissions.

Patient-Centered Care

Commentary on: Feo R, Young JA, Urry K, Lawless M, Hunter SC, Kitson A, Conroy T. ‘I wasn’t made to feel like a nut case after all’: A qualitative story completion study exploring healthcare recipient and carer perceptions of good professional caregiving relationships. Health Expect . 2023 Oct 19;27(1):e13871. doi: 10.1111/hex.13871. Epub ahead of print.

Implications for practice and research

Healthcare providers can foster effective patient–provider relationships by addressing concerns early on and adopting key behaviours, such as showing interest in understanding the patient’s issues, validating their concerns and respecting their choices.

Future research should focus on identifying strategies to help healthcare providers develop effective patient–provider relationships. This requires a thorough understanding of these relationships from the perspectives of all involved parties, including healthcare providers, patients and their informal caregivers.

The patient–provider relationship is at the core of effective disease management. 1 An effective patient–provider relationship improves the compliance of the patients by developing a safe environment, tailoring treatment to the individual patient, improving emotional well-being and furthering patient-centred care. 1 Despite these benefits, there is a lack of evidence defining a standardised and effective patient–provider relationship that transcends disciplines and contexts. Consequently, optimised healthcare outcomes are often not achieved despite advances in medical sciences. Feo et al conducted this study with the aim of exploring how patients and their informal caregivers perceive the patient–provider relationship and what they consider an effective patient–provider relationship. 2

The median age of the participants was 41.5 years, ranging between 19 and 79 years. Majority (69.44%) of the participants were women and primarily were urban dwellers (87.5%). Among the informal caregivers, 18 caregivers provided care to their parents, 17 to their children, 8 to their spouse/partner, 3 to their friends and 3 to other family members. Two main themes were identified from the responses of the participants: (1) “meeting new healthcare providers can elicit a range of unwanted emotions for healthcare recipients and carers” and (2) “developing good relationships is achieved by relieving or minimising healthcare recipients’ and carers’ initial, unwanted emotions”. Theme 1 included identification of a range of unwanted emotions for both patients and their informal caregivers such as anxiety, fear and dread at the initial encounter with new healthcare providers. Theme 2 described four strategies suggested by the respondents to develop an effective patient–provider relationship. Those were: (a) “easing into the encounter”; (b) “demonstrating interest in and understanding of recipients’ presenting health problems”; (c) “validating recipients’ presenting health problems”; and (d) “enabling and respecting recipient choice”.

Patient-centred care is a transformative paradigm about how patients are treated, focusing on tailoring healthcare to each person’s needs. Developing personalised health solutions requires active shared decision-making partnership between providers and patients/caregivers. 3 Empowered interaction between them plays a pivotal role in formulating optimal personalised care plans, offering providers the opportunity to understand patients’ perspectives while simultaneously upholding the principles of evidence-based medicine. Therefore, provision of patient-centred care requires a strong patient–provider relationship, ensuring the flexibility to accommodate the unique needs, preferences and values of individual patients.

Despite the widely accepted significance of effective patient–provider relationship in theory and policy as well as the increasing evidence supporting its influence, research work not adequately focused on how they are defined and put into implementation. A possible reason for this gap is the limited guidance provided by theories and policy discussions on the effective development and maintenance of the patient–provider relationships in practical settings. It is very important to gain comprehensive understanding of this issue from the perspectives of providers, patients and caregivers, enabling providers to initiate proactive approaches. Some of the common approaches suggested in the literature for providers for ensuring development of an effective patient–provider relationship through empowered shared decision-making are actively listening to the patients, being compassionate to the patients, inviting them into the conversation, being non-judgemental and validating their emotions. 4 These provide the basis for the patient’s expectations of the provider’s competencies. Understanding of the provider’s perspective on achieving an effective patient–provider relationship will help solidify recommendations and strategies for enhancing the patient–provider relationship.

Urry K , et al
Dugas M , et al
Drossman DA ,

Competing interests None declared.

Provenance and peer review Commissioned; internally peer reviewed.

Read the full text or download the PDF:

COMMENTS

Homepage
A journal publishing case reports in all medical disciplines, including general medicine, drug interaction and adverse reactions. The largest online collection of medical case reports. Validation period: 6/2/2024, 8:57:04 PM - 6/3/2024, 2:57:04 AM
Writing a case report in 10 steps
First steps. Begin by sitting down with your medical team to discuss the interesting aspects of the case and the learning points to highlight. Ideally, a registrar or middle grade will mentor you and give you guidance. Another junior doctor or medical student may also be keen to be involved. Allocate jobs to split the workload, set a deadline ...
For authors
How to submit. When you submit to BMJ Case Reports you will be required to upload 4 documents: 1) Case report - using the relevant template as a Word document 2) Figures - a separate word document for each image 3) Patient consent form 4) Author statements. Read our Author Guide for more information.
How to write a medical case report
Two BMJ Case Reports journal editors take you through the process #### This article contains... During medical school, students often come across patients with a unique presentation, an unfamiliar response to treatment, or even an obscure disease. Writing a case report is an excellent way of documenting these findings for the wider medical community—sharing new knowledge that will lead to ...
How to present patient cases
Presenting patient cases is a key part of everyday clinical practice. A well delivered presentation has the potential to facilitate patient care and improve efficiency on ward rounds, as well as a means of teaching and assessing clinical competence. 1. The purpose of a case presentation is to communicate your diagnostic reasoning to the ...
Browse by collection
Respiratory medicine. Rheumatology. Sexual health. Sports and exercise medicine. Surgery. Urology. A journal publishing case reports in all medical disciplines, including general medicine, drug interaction and adverse reactions. The largest online collection of medical case reports.
PDF Writing and publishing a useful and interesting Case Report
Title of case. You do not need to include "a case report" in the title - you may be cryptic if you wish. Summary. This will be freely available online. Up to 150 words summarising the case presentation and outcome. We need a good flavour of the case - emphasise the learning points. Background.
Homepage
A journal publishing case reports in all medical disciplines, including general medicine, drug interaction and adverse reactions. The largest online collection of medical case reports. Validation period: 5/17/2024, 3:38:54 PM - 5/17/2024, 9:38:54 PM
PDF Methodological quality and synthesis of case series and case reports
BMJ Evidence-Based Medicine 2018;23:60-63. Abstract Case reports and case series are uncontrolled study designs known for increased risk of bias but have profoundly influenced the medical literature and continue to advance our knowledge. In this guide, we present a framework for appraisal, synthesis and application of evidence derived
Clinical course of a 66-year-old man with an acute ...
A 66-year-old man was admitted to hospital with a right frontal cerebral infarct producing left-sided weakness and a deterioration in his speech pattern. The cerebral infarct was confirmed with CT imaging. The only evidence of respiratory symptoms on admission was a 2 L oxygen requirement, maintaining oxygen saturations between 88% and 92%. In a matter of hours this patient developed a greater ...
Fundamentals of case study research in family medicine and community
The aim of this article is to introduce family medicine researchers to case study research, a rigorous research methodology commonly used in the social and health sciences and only distantly related to clinical case reports. The article begins with an overview of case study in the social and health sciences, including its definition, potential applications, historical background and core features.
Global Health
BMJ Case Reports is a repository of evidence regarding global health and the social determinants of health. Our global health case reports can be used for education and to improve clinical practice around the world. Our goal is to facilitate the teaching and learning of global health based on real patients. No one is a better advocate for your ...
Current Issue
Characterization of accelerated approval status, trial endpoints and results, and recommendations in guidelines for oncology drug treatments from the National Comprehensive Cancer Network: cross sectional study (5 April, 2024) Maryam Mooghali, Aaron P Mitchell, Joshua J Skydel, Joseph S Ross, Joshua D Wallach, Reshma Ramachandran.
What is a case study?
Case study is a research methodology, typically seen in social and life sciences. There is no one definition of case study research.1 However, very simply… 'a case study can be defined as an intensive study about a person, a group of people or a unit, which is aimed to generalize over several units'.1 A case study has also been described as an intensive, systematic investigation of a ...
Homepage
BMJ Medicine is a new international multispecialty journal that seeks to promote multidisciplinary collaboration through encouraging scientific debate, and the exchange of new knowledge and ideas to improve the health of patients and the public. Closely aligned with The BMJ , BMJ Medicine prioritises high impact research, specialist reviews ...
Home page
Journal of Medical Case Reports will consider any original case report that expands the field of general medical knowledge, and original research relating to case reports. Case reports should show one of the following: Unreported or unusual side effects or adverse interactions involving medications. Unexpected or unusual presentations of a disease.
Methodological quality and synthesis of case series and case reports
If a case series is prospective, differentiating it from a single-arm uncontrolled cohort study becomes difficult. In one clinical practice guideline, it was proposed that studies without internal comparisons can be labelled as case series unless they explicitly report having a protocol before commencement of data collection, a definition of inclusion and exclusion criteria, a standardised ...
Case studies
BMJ Library Resource Centre. /. Case studies. Making the most of your time. Dr Victor Chuprina. Improving organisation and communication for better diagnostic and management at Clinic Medical Center in Azerbaijan. Dr Hokuma Mammadova. 5 ways to make better clinical decisions. Dr Yaroslav Diakunchak.
Case reports and case series in prehospital emergency care research
Research begins with a clearly stated question, problem or hypothesis. The selection of a study design appropriate to the task is the next key step. This paper provides guidance for the use of case report and case series designs by describing the 'what', 'when' and 'how' of both designs. Also described is the use of case reports and case series study designs in prehospital ...
BMJ Case Reports overview
BMJ Case Reports is an online, peer-reviewed journal that publishes clinically-important cases on common and rare conditions from all specialties. Subscribe your institution to a fellowship and provide the faculty, staff and students the opportunity to have their work published, and access an invaluable library of case reports from around the ...
Covid-19: virology, variants, and vaccines
As of 25 January 2022, over 349 million individuals have received a confirmed diagnosis of covid-19, with over 5.59 million confirmed deaths associated with the SARS-CoV-2 virus. The covid-19 pandemic has prompted an extensive global effort to study the molecular evolution of the virus and develop vaccines to prevent its spread. Although rigorous determination of SARS-CoV-2 infectivity remains ...
Regular use of fish oil supplements and course of cardiovascular
Objective To examine the effects of fish oil supplements on the clinical course of cardiovascular disease, from a healthy state to atrial fibrillation, major adverse cardiovascular events, and subsequently death. Design Prospective cohort study. Setting UK Biobank study, 1 January 2006 to 31 December 2010, with follow-up to 31 March 2021 (median follow-up 11.9 years). Participants 415 737 ...
BMJ Best Practice academic institutional subscription case study
As part of its innovative approach to learning, the University took out a subscription for BMJ Best Practice in 2009 to provide medical students with online support for all aspects of medicine and surgery.
How to co-design a prototype of a clinical practice tool: a framework
Background. Clinical practice tools—ranging from medicine reconciliation charts through to diagnosis support tools and track-and-trigger charts—are endemic in healthcare.1-3 While much research and debate focus on the validity and reliability of such tools,4 far less attention has been given to how to optimise their design.5-8 Yet, features of design, including usability,9-11 are ...
Process mining to investigate the relationship between clinical
Objective This paper presents an exploratory case study focusing on the applicability and value of process mining in a professional sports healthcare setting. We explore whether process mining can be retrospectively applied to readily available data at a professional sports club (Football Club Barcelona) and whether it can be used to obtain insights related to care flows. Design Our study used ...
Clinical, endoscopic and therapeutic features of bleeding Dieulafoy's
Objective Dieulafoy's lesions (DLs) are a rare but potentially life-threatening source of gastrointestinal (GI) haemorrhage. They are responsible for roughly 1%-6.5% of all cases of acute non-variceal GI bleeding. Here, we describe retrospectively the clinical and endoscopic features, review the short-term and long-term outcomes of endoscopic management of bleeding DLs and we identify rate ...
Delayed development of spinal stenosis at the spinal cord stimulator
Case presentation A patient in her early 70s underwent SCS implantation with adequate therapeutic benefit for approximately 2 years before citing complaints of increasing lower back pain and lower extremity radicular pain. Lumbar spine X-rays excluded lead migration as a causative factor. An MRI of the lumbar spine obtained 30 months following SCS implantation demonstrated a marked interval ...
Gender medicine in the US: how the Cass review failed to land
A landmark investigation with bearing on the future of gender identity services for children and adolescents has been pivotal in the UK—and largely ignored by US medical organisations and media. Jennifer Block reports on how America has resisted the push for a more holistic approach The newly released Cass review on transgender care for under 18s has had a seismic effect across the United ...
Clinical study of a micro-implantable pulse generator for the treatment
Background We report the results from the first large, postmarket, multicentre, randomised controlled trial (RCT) evaluating peripheral nerve stimulation (PNS) for the treatment of chronic peripheral pain with a micro-implantable pulse generator (micro-IPG). Methods Subjects meeting eligibility were randomised (2:1) to either the active arm receiving PNS and conventional medical management ...
Effective patient-provider relationship can be achieved through a
Commentary on: Feo R, Young JA, Urry K, Lawless M, Hunter SC, Kitson A, Conroy T. 'I wasn't made to feel like a nut case after all': A qualitative story completion study exploring healthcare recipient and carer perceptions of good professional caregiving relationships. Health Expect . 2023 Oct 19;27(1):e13871. doi: 10.1111/hex.13871. Epub ahead of print. The patient-provider ...

Search the world's largest collection of clinical case reports

Publish in BMJ Case Reports

Case Reports by specialty

AltmetricsTEST4

Global Health Competition

Latest Articles

Log in using your username and password

You are here

Statistics from Altmetric.com

Significance statement

Introduction

Origins of case study research

Case study illustration from family medicine

A step-by-step description of the process of carrying out a case study

Step 1. Conduct a literature review

Step 2. Formulate the research questions

Step 3. Ensure that a case study is appropriate

Step 4. Determine the type of case study design

Step 5. Define the boundaries of the case(s) and select the case(s)

Step 6. Prepare to collect data

Step 7. Collect and organise the data

Step 8. Analyse the data

Step 9. Write the case study report

Step 10. Appraise quality

Other resources

Conclusions

Acknowledgments

Read the full text or download the PDF:

Global Health

Journal of Medical Case Reports

Join the Editorial Board

Requirements for case reports submitted to JMCR

Report of the Month

Case analysis of hepatotoxicity caused by vancomycin

Endovascular stenting using a sagittal sinus approach for sigmoid sinus wall dehiscence related to intractable pulsatile tinnitus: a case series

Surgical intervention of Lemierre’s syndrome: a case report and review of the literature

Severe hypotension and postoperative cardiac arrest caused by 5-aminolevulinic acid: a case report

Hemodynamic instability caused by pneumorrachis and pneumomediastinum following epidural analgesia: a case report

An itchy erythematous papular skin rash as a possible early sign of COVID-19: a case report

Red ear syndrome precipitated by a dietary trigger: a case report

How to choose the best journal for your case report

COVID-19 with repeated positive test results for SARS-CoV-2 by PCR and then negative test results twice during intensive care: a case report

Recurrent knee arthritis diagnosed as juvenile idiopathic arthritis with a 10-year asymptomatic period after arthroscopic synovectomy: a case report

A Guide to Writing and Using Case Reports

Aims and scope

Article accesses

Latest Tweets

Peer Review Mentoring Scheme

Call for Papers

About the Editor-in-Chief

Annual Journal Metrics

Log in using your username and password

You are here

Statistics from Altmetric.com

Definitions

Evaluating methodological quality

Proposed tool

Synthesis of case reports/series

Narrative synthesis

Quantitative synthesis

From evidence to decision

Read the full text or download the PDF:

Log in using your username and password

You are here

Statistics from Altmetric.com

The ‘what’ of case reports and case series

The ‘when’ of case reports and case series

The ‘how’ of case reports and case series

Use of case reports and case series in prehospital emergency care research

Conclusions

Acknowledgments

Supplementary materials

Read the full text or download the PDF:

BMJ Case Reports overview

Log in using your username and password

You are here

Data availability statement

Statistics from Altmetric.com

WHAT IS ALREADY KNOWN ON THIS TOPIC

WHAT THIS STUDY ADDS